Cardiac Tamponade

Non-invasive Assessment of Rheumatoid Arthritis Cardiac Involvement: A Systematic Review of Echocardiography

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disorder primarily characterized by joint degradation, with consequential cardiovascular ramifications significantly impacting patient mortality rates.

Methods: We systematically searched for full-text English-language journal articles from 1973 to 2025 in the PubMed and Web of Science databases. Utilizing keywords such as “Rheumatoid Arthritis,” “Autoimmune Diseases,” “Pathophysiology,” “Heart,” “Cardiac,” and “Echocardiography” to narrow the search results. Articles related to the evaluation of heart diseases in rheumatoid arthritis by echocardiography were included, while those with insufficient data or low data quality were excluded. Study quality was assessed using the CASP Quantitative Checklist (2018 version), and data were synthesized through thematic content analysis.

Results: We included 52 studies in this review after the primary analysis. The results show that traditional echocardiography can identify organic changes in the heart and ventricular function impairment of patients with rheumatoid arthritis. New ultrasound techniques, such as speckle tracking and pressure-strain loops, can detect ventricular function impairment earlier than traditional echocardiography.

Discussion: Echocardiography provides complementary diagnostic information for rheumatoid arthritis cardiac involvement through structural and functional assessment, yet limitations remain. Future work should establish multimodal ultrasound frameworks and develop AI-driven analytical platforms to enhance early detection and precision management.

Conclusion: The continuous progress of ultrasound technology has significantly improved the accuracy of assessing cardiac damage in patients with rheumatoid arthritis, and it has become an essential examination method for screening heart diseases in such patients, providing strong support for early diagnosis.

Multiple, Extensive Cardiac and Pulmonary Hydatid Cysts Managed by a Single-stage Surgical Removal: A Case Report

Background: Echinococcosis is a zoonotic infection that is characterised clinically by the development of hydatid cysts in different organs, mainly the liver and lungs. Cardiac involvement is rare but can lead to serious and fatal complications.

Case Report: We report a rare challenging case of multiple, extensive cardiac and pulmonary Echinococcal cysts that were treated by successful single-stage surgical resection via median sternotomy without additional thoracic incisions.

Conclusion: This article highlights the rare presentation of multiple, extensive cardiac and pulmonary Echinococcal cysts and how to overcome diagnostic challenges in the era of modern diagnostic imaging. Surgical removal remains the mainstay treatment, and a single-stage surgical approach is feasible in capable centres. Perioperative chemotherapy with Albendazole and the intraoperative use of scolicidal agents improved immediate surgical outcomes, although long-term effects could not be established in this case due to loss of follow-up.

Intensive Care Unit Management of Right Heart Failure and Lung Transplantation for Pulmonary Hypertension

Pulmonary hypertension is associated with worse outcomes across systemic and cardiopulmonary conditions. Right ventricular (RV) dysfunction often leads to poor outcomes due to a progressive increase in RV afterload. Recognition and management of RV dysfunction are important to circumvent hospitalization and improve patient outcomes. Early recognition of patients at risk for RV failure is important to ensure that medical therapy is optimized and, where appropriate, referral for lung transplant assessment is undertaken. Patients initiated on parenteral prostanoids and those with persistent intermediate to high risk for poor outcomes should be referred. For patients with RV failure, identifying reversible causes should be a priority in conjunction with efforts to optimize RV preload and strategies to reduce RV afterload. Admission to a monitored environment where vasoactive medications can treat RV failure and its sequelae, such as renal dysfunction, is essential in patients with severe RV failure. Exit strategies need to be identified early on, with consideration and implementation of extracorporeal support for those in whom recovery or transplantation are viable options. Enlisting the skills and support of a palliative care team may improve the quality of life for patients with limited options and those with ongoing symptoms from heart failure in the face of medical treatments.

Pharmacological Considerations during Percutaneous Treatment of Heart Failure

Heart Failure (HF) remains a global health challenge, marked by its widespread prevalence and substantial resource utilization. Although the prognosis has improved in recent decades due to the treatments implemented, it continues to generate high morbidity and mortality in the medium to long term. Interventional cardiology has emerged as a crucial player in HF management, offering a diverse array of percutaneous treatments for both acute and chronic HF. This article aimed to provide a comprehensive review of the role of percutaneous interventions in HF patients, with a primary focus on key features, clinical effectiveness, and safety outcomes. Despite the growing utilization of these interventions, there remain critical gaps in the existing body of evidence. Consequently, the need for high-quality randomized clinical trials and extensive international registries is emphasized to shed light on the specific patient populations and clinical scenarios that stand to benefit most from these innovative devices.

Body Fat Distribution Contributes to Defining the Relationship between Insulin Resistance and Obesity in Human Diseases

The risk for metabolic and cardiovascular complications of obesity is defined by body fat distribution rather than global adiposity. Unlike subcutaneous fat, visceral fat (including hepatic steatosis) reflects insulin resistance and predicts type 2 diabetes and cardiovascular disease. In humans, available evidence indicates that the ability to store triglycerides in the subcutaneous adipose tissue reflects enhanced insulin sensitivity. Prospective studies document an association between larger subcutaneous fat mass at baseline and reduced incidence of impaired glucose tolerance. Case-control studies reveal an association between genetic predisposition to insulin resistance and a lower amount of subcutaneous adipose tissue. Human peroxisome proliferator-activated receptorgamma (PPAR-γ) promotes subcutaneous adipocyte differentiation and subcutaneous fat deposition, improving insulin resistance and reducing visceral fat. Thiazolidinediones reproduce the effects of PPAR-γ activation and therefore increase the amount of subcutaneous fat while enhancing insulin sensitivity and reducing visceral fat. Partial or virtually complete lack of adipose tissue (lipodystrophy) is associated with insulin resistance and its clinical manifestations, including essential hypertension, hypertriglyceridemia, reduced HDL-c, type 2 diabetes, cardiovascular disease, and kidney disease. Patients with Prader Willi syndrome manifest severe subcutaneous obesity without insulin resistance. The impaired ability to accumulate fat in the subcutaneous adipose tissue may be due to deficient triglyceride synthesis, inadequate formation of lipid droplets, or defective adipocyte differentiation. Lean and obese humans develop insulin resistance when the capacity to store fat in the subcutaneous adipose tissue is exhausted and deposition of triglycerides is no longer attainable at that location. Existing adipocytes become large and reflect the presence of insulin resistance.

A Narrative Review of Emerging Therapies for Hypertrophic Obstructive Cardiomyopathy

Hypertrophic obstructive cardiomyopathy is a hereditary condition that affects myocardial contraction. In case of failure of pharmacological treatment, alternative approaches might be used that include surgical myectomy, percutaneous transluminal septal myocardial ablation, and radiofrequency ablation. In respect of long-term advantages, surgical septal myectomy remains the therapy of choice for symptomatic hypertrophic obstructive cardiomyopathy. Alcohol septal ablation has been considered an alternative to surgical myectomy, which confers the benefits of a shorter hospital stay, less discomfort, and fewer complications. However, only expert operators should perform it on carefully chosen patients. Further, radiofrequency septal ablation reduces the left ventricular outflow tract gradient and improves the NYHA functional class of patients with hypertrophic obstructive cardiomyopathy, despite complications like cardiac tamponade and atrioventricular block. Further research with a larger sample size is required to compare the radiofrequency approach with established invasive treatment methods for hypertrophic obstructive cardiomyopathy. Septal myectomy has low morbidity and mortality rates, making it the preferred procedure; however, the efficacy and morbidity remain debatable. Advances in invasive techniques, including percutaneous septal radiofrequency ablation and transcatheter myotomy, have provided alternative approaches for reducing left ventricular outflow tract (LVOT) obstruction in patients who are not candidates for traditional surgical septal myectomy. Candidates for alcohol and radiofrequency septal ablation include patients with symptomatic hypertrophic obstructive cardiomyopathy, older adults, and those with multiple comorbidities.

Biomarkers in Acute Heart Failure Syndromes: An Update

Heart failure is one of the leading healthcare problems in the world. Clinical data lacks sensitivity and specificity in the diagnosis of heart failure. Laboratory biomarkers are a non-invasive method of assessing suspected decompensated heart failure. Biomarkers such as natriuretic peptides have shown promising results in the management of heart failure. The literature does not provide comprehensive guidance in the utilization of biomarkers in the setting of acute heart failure syndrome. Many conditions that manifest with similar pathophysiology as acute heart failure syndrome may demonstrate positive biomarkers. The following is a review of biomarkers in heart failure, enlightening their role in diagnosis, prognosis and management of heart failure.

Efficacy and Complications of Subcutaneous versus Conventional Cardioverter Defibrillators: A Systematic Review and Meta-analysis

Background/Objectives: Implantable cardioverter defibrillators are used to prevent sudden cardiac death. The subcutaneous implantable cardioverter-defibrillator was newly developed to overcome the limitations of the conventional implantable cardioverter defibrillator-transvenous device. The subcutaneous implantable cardioverter defibrillator is indicated for young patients with heart disease, congenital heart defects, and poor venous access, who have an indication for implantable cardioverter defibrillator without the need for anti-bradycardic stimulation. We aimed to compare the efficacy and complications of subcutaneous with transvenous implantable cardioverter- defibrillator devices.

Methodology: A systematic review was conducted using different databases. The inclusion criteria were observational and clinical randomized trials with no language limits and no publication date limit that compared subcutaneous with transvenous implantable cardioverter-defibrillators. The selected patients were aged > 18 years with complex ventricular arrhythmia.

Results: Five studies involving 2111 patients who underwent implantable cardioverter defibrillator implantation were included. The most frequent complication in the subcutaneous device group was infection, followed by hematoma formation and electrode migration. For the transvenous device, the most frequent complications were electrode migration and infection. Regarding efficacy, the total rates of appropriate shocks were 9.04% and 20.47% in the subcutaneous and transvenous device groups, respectively, whereas inappropriate shocks to the subcutaneous and transvenous device groups were 11,3% and 10,7%, respectively.

Conclusion: When compared to the transvenous device, the subcutaneous device had lower complication rates owing to lead migration and less inappropriate shocks due to supraventricular tachycardia; nevertheless, infection rates and improper shocks due to T wave oversensing were comparable for both devices CRD42021251569.

Management of Unusual Not Scar Ectopic Pregnancy: A Multicentre Retrospective Case Series

Background: Management of unusual not scar ectopic pregnancies (UNSEPs) is an unexplored clinical field because of their low incidence and lack of guidelines.

Objective: To report the clinical presentation, the first- and second-line treatment and outcomes of UNSEPs.

Methods: We retrospectively collected patients treated for UNSEP (namely cervical, interstitial, ovarian, angular, abdominal, cornual and intramural), their baseline characteristics, risk factors, symptoms, diagnostic pathway and the type of first-line treatment (medical, surgical or combined). We further collected treatment failures and the type of second- line treatment. We assessed treatment outcomes, time to serum beta human chorionic gonadotropin (β-hCG) level negativity, length of recovery, follow up and return to a normal menstrual cycle.

Results: From 2009 to 2019, we collected 79 cases. Of them, 27 (34%), 23 (29%), 12 (15%), 8 (10%), 6 (8%) and 3 (4%) were cervical, interstitial, ovarian, angular, abdominal and cornual, respectively. Forty women (50.6%) were submitted to medical treatment, mostly methotrexate based; conversely, 36 patients (45.6%) underwent surgery and only 3 women (3.8%) received a combined treatment. The success of first-line treatment rate, regardless of UNSEP location, was 53% and 89% for medical and surgical treatment, respectively. Treatment failures (21 patients) were submitted to second-line treatment, respectively 47.6% and 52.4% to medical and surgical approach. Of interest, cervical pregnancies achieved the lowest rate of first-line medical treatment success (22%) and received more frequently (69%) a subsequent surgical approach with no hysterectomy. Interstitial pregnancies were submitted to surgery mostly for a matter of urgency (71%), otherwise, they were treated with a medical approach both at first- and second-line treatment. Ovarian pregnancies were treated with ovariectomy in 44% of the cases submitted to surgery. Angular pregnancies underwent surgery more often, while all the abdominal pregnancies underwent endoscopic or open surgery. Cornual pregnancies received cornuostomy in 75% of the cases. Overall, the need for blood transfusion was 23.1% among the patients submitted to surgery. The median length of hospitalisation was shorter for women submitted to surgical first-line treatment (5 vs. 10 days; p = 0.002). In case of first-line medical treatment and in case of failure, we found an increase of 3 days (CI95% 0.6-5.5; p = 0.01) and of 3.6 days (CI95% 0.89-6.30; p = 0.01) in the length of hospitalisation, respectively. Negative β-HCG levels were obtained earlier in the surgical group (median 25 vs. 51 days; p = 0.001), as well as the return to normal menstrual cycle (median 31 vs. 67 days; p < 0.000). Post-treatment follow-up, regardless of the failure of first-line treatment was shorter in the surgical group (median 32 versus 68 days; p= 0.003).

Conclusion: Cervical pregnancies were successfully managed with a surgical approach without hysterectomy, and hence, we suggest avoiding medical treatment. No consensus emerged for other UNSEPs. Ovarian, angular and interstitial pregnancies are burdened by a non-conservative approach on the utero-ovarian structures. The surgical approach led to shorter recovery, earlier β-hCG negativity and shorter follow-up, even though there is an increased risk for blood transfusion.

CTO in Contemporary PCI

Percutaneous Coronary Intervention (PCI) of Chronic Total Occlusions (CTO) represents the most challenging procedure in modern endovascular treatments. In recent years, the success rate of CTO PCI has substantially improved, owing to increasing operator expertise and advancements in CTO equipment and algorithms as well as the development of expert consensus documents. In this review, we summarize existing evidence for CTO PCI, its success/ risk prediction scoring tools, procedural principles and complications and provide an insight into the future role of CTO PCI.

Surgical Treatment of Pulmonary Embolism and Chronic Thromboembolic Pulmonary Hypertension

Venous thromboembolism clinically presents as deep venous thrombosis or acute pulmonary embolism and is globally recognized as the third most frequent acute cardiovascular syndrome after myocardial infarction and stroke. Although pulmonary embolism does not typically cause severe pulmonary hypertension in the acute setting, thrombus organization and fibrosis can lead to stenosis or obliteration of pulmonary arteries in a minority of patients, which in turn result in severe pulmonary hypertension and right heart failure. This disease is labeled chronic thromboembolic pulmonary hypertension and can occur after a single episode or multiple ones of pulmonary embolism. The cornerstone of pulmonary embolism treatment is medical therapy, whereas systemic thrombolytic therapy has to be considered for patients with hemodynamic instability. Given the current acceptable short-term surgical mortality, the potential of first-line surgical embolectomy as an alternative to medical thrombolysis has gained momentum as far as pulmonary embolism treatment is concerned. In contrast to pulmonary embolism, bilateral complete pulmonary endarterectomy under short deep hypothermic circulatory arrest intervals is the treatment of choice against chronic thromboembolic pulmonary hypertension, given patients’ operability. Pulmonary endarterectomy is suggested in every operable patient when the operation is offered by an experienced multidisciplinary team, including at least one experienced surgeon. Surgical embolectomy should also be limited to large institutions since it also requires an experienced heart team. This review concerns a thorough discussion regarding surgical treatment of pulmonary embolism and chronic thromboembolic pulmonary hypertension. Eligibility criteria, operation-related complications and postoperative outcomes are discussed in detail.

Constrictive Pericarditis Associated with Coronavirus Disease 2019 (COVID-19): A Case Report

Background: Since December 2019, there has been an increasing number of patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world. As of March 2020, the World Health Organization declared a global pandemic.

Case Presentation: To our best knowledge, this is the first report of a patient with SARS-CoV-2 infection presenting with constrictive pericarditis, possibly from the COVID infection. She was presented after a week of fever, persistent dry cough, and diarrhea. She received a single dose of hydroxychloroquine 400 mg, Oseltamivir 75 mg every 12 hours, lopinavir/ritonavir (Kaletra) 400/100 mg every 12 hours, and levofloxacin 750 mg daily. After 24 hours, she was immediately transferred to the Intensive Care Unit (ICU) because of dyspnea and progressive respiratory failure with a drop of the O2 saturation to 70%.

Conclusion: After a week of progress, her respiratory condition deteriorated again. She was re-admitted to the ICU and she expired. She died due to constrictive pericarditis, most probably caused by SARS-CoV-2.

Complications in Patients with Cardiac Penetrating Trauma

Background: Cardiac penetrating trauma is a medical emergency that mostly affects young people. Based on the type of injury and associated complications, it can present as a surgical challenge and can lead to mortality.

Objective: The aim of this study is to evaluate the complications of penetrating heart trauma among patients referred to Shahid Madani Hospital.

Methods: In this retrospective descriptive study, the data of penetrating cardiac trauma patients referred to Shahid Madani hospital, Karaj, Tehran, from 2016-2019, were investigated. Information, including age, sex, cause of trauma, traumatized area and complications, was extracted and recorded in a data collection form. The data were evaluated statistically using SPSS v18.

Results: A total of 44 patients were included in the study, where the mean age of the patients was 25 years. 73.3% of these patients were men and 26.7% were women. Knife stab wounds were the most prevalent cause of the trauma, present in 93.3% of patients. 73.3% of the patients had cardiac tamponade and 20% had a pneumothorax. The right ventricle was the most common site of the injury in 46.7% of the patients. A mortality rate of 3.4% was reported in this study.

Conclusion: The results of this study showed that the highest penetrating heart rate trauma occurred among young people, and the most common cause of the trauma was a knife stab. The most common area of the injury was the right ventricular, and cardiac tamponade was the most common complication.

Aortic Regurgitation as a Complication of Electrophysiologic Ablation Techniques: A Narrative Review

Background: Radiofrequency catheter ablation is a well-established treatment for several cardiac arrhythmias. Arrhythmias originating from the left side of the heart including ventricular and supraventricular tachycardia and ectopy can be successfully ablated through either transseptal or retrograde aortic approach. Although these techniques have a generally low rate of complications, aortic valve injury is a potential complication of ablation at the left cardiac side that warrants more investigation.

Objective: The purpose of this review is to evaluate the incidence of iatrogenic aortic valve regurgitation and explore the potential mechanisms and risk factors that might contribute to aortic valve injury during radiofrequency ablation. Additionally, the course and progression of aortic regurgitation in the reported cases will be described.

Methods: Authors searched PubMed for articles using the keywords “ablation” AND “aortic insufficiency” OR “aortic valve injury” OR “aortic regurgitation”. Case reports and series as well as retrospective and prospective studies were included, and relevant review articles and editorial comments were used as a supplementary source of data. A total of 19 references were used and a detailed description of patient characteristics, procedural techniques, and incidence, predictors, and fate of aortic regurgitation were reported by 11 clinical studies.

Results: There is a small risk of significant iatrogenic aortic regurgitation after radiofrequency ablation of left-sided cardiac arrhythmias, especially techniques performed via a retrograde aortic approach.

Conclusion: Although the risk is not confined to procedures applying direct energy to the aortic cusp region, a more aggressive ablation applied in the vicinity of the valvular complex seems to be associated with a higher risk. Routine post-procedural surveillance should be adopted to detect de novo aortic valve injury following radiofrequency ablation techniques.

Natural Products in Mitigation of SARS CoV Infections

Severe acute respiratory syndrome (SARS) is a critical respiratory disease caused by coronaviruses (CoV). The available antiviral agents or host-specific antiinflammatory therapies are the principal treatment modalities, with drug-repurposing as the most viable approach to timely tackle the CoV pandemic. Though these approaches are successful to some extent in reducing the mortality rate, however, it is too far to see a complete escape from the current SARS CoV-2 pandemic. Plants are the primary source of diet, dietary supplements, botanical drugs, and natural products (NPs). It has been well accepted and proved via several scientific studies that plant-based therapies play a vital role in managing such infections. The faulty immune system (compromised innate immunity or aberrant immune activation) determines the severity of the respiratory distress in CoV-2 infected patients. Natural products intervene at various stages of the virus replication cycle, including inhibition of virus entry into the host cells, inhibition of serine/ cysteine proteases, RNA-dependent RNA polymerase (RdRp) or helicase. Besides, several natural products or plant-based dietary supplements have a unique ability to strengthen the immune system or alleviate the hyper-inflammatory condition. Many plant-based formulations, dietary supplements, and NPs are being investigated in clinical trials in CoV-2 infected patients, and few have already shown positive results. The review has unearthed several NP leads for medicinal chemistry programs as well as some having direct opportunity of repurposing in SARS CoV infections.

Aortic Dissection: A Review of the Pathophysiology, Management and Prospective Advances

Aortic dissection is an emergent medical condition, generally affecting the elderly, characterized by a separation of the aortic wall layers and subsequent creation of a pseudolumen that may compress the true aortic lumen. Predisposing factors mediate their risk by either increasing tension on the wall or by causing structural degeneration. They include hypertension, atherosclerosis, and a number of connective tissue diseases. If it goes undetected, aortic dissection carries a significant mortality risk; therefore, a high degree of clinical suspicion and a prompt diagnosis are required to maximize survival chances. Imaging methods, most commonly a CT scan, are essential for diagnosis; however, several studies have also investigated the effect of several biomarkers to aid in the detection of the condition. The choice of intervention varies depending on the type of dissection, with open surgical repair remaining of choice in those with type. In dissections, however, the role of conventional open surgery has considerably diminished in complicated type B dissections, with endovascular repair, a much less invasive technique, proving to be more effective. In uncomplicated type B dissections, where medical choice reigned supreme as the optimal intervention, endovascular repair is being explored as a viable option which may reduce long- term mortality outcomes, although the ideal intervention in this situation is far from settled.

Cardiovascular Manifestations of COVID-19

Coronavirus disease 2019 (COVID-19) first emerged in a group of patients who presented with severe pneumonia in Wuhan, China, in December 2019. A novel virus, now called SARSCoV- 2 (Severe Acute Respiratory Syndrome Coronavirus-2), was isolated from lower respiratory tract samples. The current outbreak of infection has spread to over 100 countries and killed more than 340,000 people as of 25th May, 2020.

The predominant clinical manifestation of COVID-19 is a respiratory disease- ranging from mild flu-like symptoms to fulminant pneumonia and Acute Respiratory Distress Syndrome (ARDS). Patients with pre-existing cardiovascular risk factors are considered more susceptible to the virus, and these conditions are often worsened by the infection. Furthermore, COVID-19 infection has led to de novo cardiac complications, like acute myocardial injury and arrhythmias.

In this review, we have focused on the cardiovascular manifestations of COVID-19 infection that have been reported in the literature so far. We have also outlined the effect of pre-existing cardiovascular disease as well as risk factors on the clinical course and outcomes of COVID-19 infection.

Antiplatelet Therapy And Percutaneous Coronary Interventions

Dual antiplatelet therapy is one of the cornerstones of modern percutaneous coronary interventions. The development of new therapeutic agents has significantly reduced ischemic events at the risk of increased bleeding complications. Therefore, efforts are currently focused on optimizing therapeutic algorithms to obtain the greatest anti-thrombotic benefit associated with the lowest risk of bleeding, that is, the greater net clinical benefit.

A significant number of trials evaluating different drug combinations or adjustments in treatment duration have been completed. However, clinical translation of these results is often difficult due to the heterogeneity of the therapeutic approaches.

The aim of this manuscript is to provide an updated review of the literature regarding the use of dual antiplatelet therapy in patients undergoing coronary angioplasty and stenting.

A Review of Selected Adult Congenital Heart Diseases Encountered in Daily Practice

The advancement in corrective surgical procedures and anaesthesia technology has resulted in the increased survival of patients with Congenital Heart Diseases (CHD). Most of the surviving CHD patients have successfully reached adulthood and those surviving adults now outnumber the infants born with the CHD. Unfortunately, the surviving adults with CHD do not get proper care due to either inconsistent follow-up or not getting care from a specialist in the field of CHD. It is imperative for general practicing clinicians to be aware of the congenital diseases as well as the current clinical recommendations. This manuscript reviews some of the common congenital diseases seen in adults such as cardiac shunts, left heart obstructive lesions, and aortopathies.

Access-site Complications of the Transradial Approach: Rare But Still There

In the past decade, the Transradial Approach (TRA) has constantly gained ground among interventional cardiologists. TRA’s anatomical advantages, in addition to patients’ acceptance and financial benefits, due to rapid patient mobilization and shorter hospital stay, made it the default approach in most catheterization laboratories.

Access-site complications of TRA are rare and usually of little clinical impact, thus, they are often overlooked and underdiagnosed. Radial Artery Occlusion (RAO) is the most common, followed by radial artery spasm, perforation, hemorrhagic complications, pseudoaneurysm, arterio-venous fistula, and even rarer complications, such as nerve injury, sterile granuloma, eversion endarterectomy or skin necrosis. Most of them are conservatively treated, but rarely, surgical treatment may be needed and late diagnosis may lead to life-threatening situations, such as hand ischemia or compartment syndrome and tissue loss. Additionally, some complications may eventually lead to TRA failure and switch to a different approach.

On the other hand, it is the opinion of the authors that non-occlusive radial artery injury, commonly included in TRA’s complications in the literature, should be regarded more as an anticipated functional and anatomical cascade, following radial artery puncture and sheath insertion.

Cardiac Complications Attributed to Hydroxychloroquine: A Systematic Review of the Literature Pre-COVID-19

Introduction: Hydroxychloroquine has been used for rheumatological diseases for many decades and is considered a safe medication. With the COVID-19 outbreak, there has been an increase in reports associating cardiotoxicity with hydroxychloroquine. It is unclear if the cardiotoxic profile of hydroxychloroquine is previously underreported in the literature or is it a manifestation of COVID-19 and therapeutic interventions. This manuscript evaluates the incidence of cardiotoxicity associated with hydroxychloroquine prior to the onset of COVID-19.

Methods: PubMED, EMBASE, and Cochrane databases were searched for keywords derived from MeSH terms prior to April 9, 2020. Inclusion eligibility was based on appropriate reporting of cardiac conditions and study design.

Results: A total of 69 articles were identified (58 case reports, 11 case series). The majority (84%) of patients were female, with a median age of 49.2 (range 16-92) years. 15 of 185 patients with cardiotoxic events were in the setting of acute intentional overdose. In acute overdose, the median ingestion was 17,857 ± 14,873 mg. 2 of 15 patients died after acute intoxication. In patients with long-term hydroxychloroquine use (10.5 ± 8.9 years), new onset systolic heart failure occurred in 54 of 155 patients (35%) with median cumulative ingestion of 1,493,800 ± 995,517 mg. The majority of patients improved with the withdrawal of hydroxychloroquine and standard therapy.

Conclusion: Millions of hydroxychloroquine doses are prescribed annually. Prior to the COVID-19 pandemic, cardiac complications attributed to hydroxychloroquine were uncommon. Further studies are needed to understand the impact of COVID-19 on the cardiovascular system to understand the presence or absence of potential medication interactions with hydroxychloroquine in this new pathophysiological state.

Spontaneous Biliary Pericardial Tamponade: A Case Report and Literature Review

Background: Biliary pericardial tamponade (BPT) is a rare form of pericardial tamponade, characterized by yellowish-greenish pericardial fluid upon pericardiocentesis. Historically, BPT reported to occur in the setting of an associated pericardiobiliary fistula. However, BPT in the absence of a detectable fistula is extremely rare.

Learning objective: A biliary pericardial tamponade is a rare form of tamponade warranting a prompt workup (e.g., MRCP or HIDA scan) for a potential fistula between the biliary system and the pericardial space. A pericardio-biliary fistula can be iatrogenic or traumatic. People with a history of chest wall trauma, abdominal surgery, or chest surgery are at increased risk. The use of HIDA scanning plays a salient role in effectively surveilling for the presence of a fistula – especially when MRCP is contraindicated.

Case Presentation: A 75-year-old Hispanic male presenting with dyspnea and diagnosed with cardiac tamponade is the subject of the study. Subsequent pericardiocentesis revealed biliary pericardial fluid (bilirubin of 7.6 mg/dl). The patient underwent extensive workup to identify a potential fistula between the hepatobiliary system and the pericardial space, which was non-revealing. The mechanism of bile entry into the pericardial space remains to be unidentified.

Literature Review: A total of six previously published BPT were identified: all were males, with a mean age of 53.3 years (range: 31-73). Mortality was reported in two out of the six cases. The underlying etiology for pericardial tamponade varied across the cases: incidental pericardio-biliary fistula, traumatic pericardial injury, and presence of associated malignancy. -

Conclusion: Biliary pericardial tamponade is a rare form of tamponade that warrants a prompt workup (e.g., Hepatobiliary Iminodiacetic Acid – HIDA scan) for an iatrogenic vs. traumatic pericardio- biliary fistula. As a first case in the literature, our case exhibits a biliary tamponade in the absence of an identifiable fistula.

A Comprehensive Systemic Literature Review of Pericardial Decompression Syndrome: Often Unrecognized and Potentially Fatal Syndrome

Background: Pericardial Decompression Syndrome (PDS) is defined as paradoxical hemodynamic deterioration and/or pulmonary edema, commonly associated with ventricular dysfunction. This phenomenon was first described by Vandyke in 1983. PDS is a rare but formidable complication of pericardiocentesis, which, if not managed appropriately, is fatal. PDS, as an entity, has discrete literature; this review is to understand its epidemiology, presentation, and management.

Methodology: Medline, Science Direct and Google Scholar databases were utilized to do a systemic literature search. PRISMA protocol was employed. Abstracts, case reports, case series and clinical studies were identified from 1983 to 2019. A total of 6508 articles were reviewed, out of which, 210 were short-listed, and after removal of duplicates, 49 manuscripts were included in this review. For statistical analysis, patient data was tabulated in SPSS version 20. Cases were divided into two categories surgical and percutaneous groups. t-test was conducted for continuous variable and chi-square test was conducted for categorical data used for analysis.

Results: A total of 42 full-length case reports, 2 poster abstracts, 3 case series of 2 patients, 1 case series of 4 patients and 1 case series of 5 patients were included in the study. A total of 59 cases were included in this manuscript. Our data had 45.8% (n=27) males and 54.2% (n=32) females. The mean age of patients was 48.04 ± 17 years. Pericardiocentesis was performed in 52.5% (n=31) cases, and pericardiostomy was performed in 45.8% (n=27). The most common identifiable cause of pericardial effusion was found to be malignancy in 35.6% (n=21). Twenty-three 23 cases reported pre-procedural ejection fraction, which ranged from 20%-75% with a mean of 55.8 ± 14.6%, while 26 cases reported post-procedural ejection fraction which ranged from 10%-65% with a mean of 30% ± 15.1%. Data was further divided into two categories, namely, pericardiocentesis and pericardiostomy. The outcome as death was significant in the pericardiostomy arm with a p-value of < 0.00. The use of inotropic agents for the treatment of PDS was more common in needle pericardiocentesis with a p-value of 0.04. Lastly, the computed recovery time did not yield any significance with a p-value of 0.275.

Conclusion: Pericardial decompression syndrome is a rare condition with high mortality. Operators performing pericardial drainage should be aware of this complication following drainage of cardiac tamponade, since early recognition and expeditious supportive care are the only therapeutic modalities available for adequate management of this complication.

Cardiac Amyloid - A Hidden Contributor to Cardiac Dysfunction Following Cardiac Surgery: Case Report and Literature Review

We present two patients who underwent cardiac surgery followed by post-operative low cardiac output, diastolic dysfunction and resistance to inotropic support. Despite aggressive medical management, both patients died. At autopsy, the hearts were enlarged and showed previously undiagnosed myocardial and vascular amyloidosis. Occult cardiac amyloidosis is an uncommon, often occult, contributor to post-operative complications post cardiac surgery. Pre-operative or intraoperative myocardial biopsy may be useful in patients with unexplained diastolic dysfunction.

Brief Summary: We present two patients who underwent cardiac surgery followed by low cardiac output, diastolic dysfunction and resistance to inotropic support. Cardiac dysfunction was due to occult amyloidosis. Pre-operative or intra-operative myocardial biopsy may be useful in patients with unexplained diastolic dysfunction. With recent therapy advances, classification and possible treatment of amyloid are possible.

Cardiovascular Disease in Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA), is a term used to describe a group of inflammatory disorders beginning before the age of 16 years. Although for the majority of children remission is achieved early, those with systemic or polyarticular form of the disease may present persistent symptoms in adulthood. Considering that there is overlap in the pathogenesis of JIA with adult rheumatic diseases, concerns have been raised as to whether JIA patients could be at increased cardiovascular (CV) risk in the long-term. In this review, we summarize evidence for CV involvement in JIA and present data on CV risk factors and surrogate markers of arterial disease. We also provide information on beneficial and harmful CV effects of anti-inflammatory medications in the context of JIA and suggest strategies for CV screening. Overall, patients with systemic forms of JIA demonstrate an adverse lipid profile and early arterial changes relevant to accelerated arterial disease progression. Although there is paucity of data on CV outcomes, we recommend a holistic approach in the management of JIA patients, which includes CV risk factor monitoring and lifestyle modification as well as use, when necessary, of antiinflammatory therapies with documented CV safety.

Predictive Role of BNP/NT-proBNP in Non-Heart Failure Patients Undergoing Catheter Ablation for Atrial Fibrillation: An Updated Systematic Review

Atrial Fibrillation (AF) is a growing public health issue, associated with significant morbidity and mortality. In addition to pharmacological therapy, catheter ablation is an effective strategy in restoring and maintaining sinus rhythm. However, ablation is not without risk, and AF recurs in a significant proportion of patients. Non-invasive, easily accessible markers or indices that could stratify patients depending on the likelihood of a successful outcome following ablation would allow us to select the most appropriate patients for the procedure, reducing the AF recurrence rate and exposure to potentially life-threatening risks.

There has been much attention paid to Brain Natriuretic Peptide (BNP) and N-Terminal prohormone of Brain Natriuretic Peptide (NT-proBNP) as possible predictive markers of successful ablation. Several studies have demonstrated an association between higher pre-ablation levels of these peptides, and a greater likelihood of AF recurrence. Therefore, there may be a role for measuring brain natriuretic peptides levels when selecting patients for catheter ablation.

Antithrombotic Treatment after Atrial Fibrillation Ablation

Atrial fibrillation is a major cause of debilitating strokes and anticoagulation is an established and indispensable therapy for reducing their rate. Ablation of the arrhythmia has emerged as a putative means of disrupting its natural course by isolating its triggers and modifying its substrate, dependent on the chosen method. An important dilemma lies in the need for continuation of anticoagulation therapy in those previously receiving it following an, apparently, successful intervention, purportedly preventing arrhythmia recurrence with considerably high rates. Current guidance, given scarcity of high-quality data from randomized trials, focuses on established knowledge and recommends anticoagulation continuation based solely on estimated thromboembolic risk. In the present review, it will be attempted to summarize the pathophysiological rationale for maintaining anticoagulation post-successful ablation, along with the latter’s definition, including the two-fold effects of the procedure per se on thrombogenicity. Available evidence pointing to an overall clinical benefit of anticoagulation withdrawal following careful patient assessment will be discussed, including ongoing randomized trials aiming to offer definitive answers. Finally, the proposed mode of post-ablation anticoagulation will be presented, including the emerging, guideline-endorsed, role of direct oral anticoagulants in the field, altering cost/benefit ratio of anticoagulation and potentially affecting the very decision regarding its discontinuation.

Novel Perspective for Antithrombotic Therapy in TAVI

While surgical aortic valve replacement (SAVR) was for years the only available treatment for symptomatic aortic stenosis, the introduction of transcatheter aortic valve implantation (TAVI) in 2002 and the improvement of its technical aspects in the following years, has holistically changed the synchronous therapeutic approach of aortic valve stenosis. Recent evidence has expanded the indication of TAVI from high to lower surgical risk populations with symptomatic aortic stenosis. The administration of antithrombotic therapy periprocedurally and its maintenance after a successful TAVI is crucial for the prevention of complications and affects postprocedural survival. Randomized controlled trials investigating the appropriate combination and the duration of antithrombotic treatment after TAVI are for the moment scarce. This review article sheds light on the underlying pathogenetic mechanisms contributing in periprocedural TAVI thrombotic complications and discuss the efficacy of current antithrombotic policies as evaluated in randomized trials.

Effects of Simvastatin on the Metabolism of Fatty Acids in Combined Secondary Prevention of Coronary Heart Disease: Dosage and Gender Differences between the Effects

Background: Statins are currently used for secondary prevention of Coronary Heart Disease (CHD), as the lipid-lowering therapy with them is proven safe and effective.

Objective: The purpose of this research is to investigate the dose-dependent effect of statins used for secondary prevention of coronary heart disease, as well as mechanisms of quantitative and qualitative changes in lipoproteins, fatty acids and cholesterol in the blood and tissues of people of both sexes.

Methods: In a clinical trial (n=125, of which 89 patients belong to group 1 and 36 to group 2) and an experiment on laboratory animals (n = 100), simvastatin reduced the total level of fatty acids in blood plasma, when given in the amount that was within the therapeutic dose range.

Results: This effect was achieved through a drug-induced improvement in the capacity of hepatic cells to absorb Low-density (LDL) and Very-low-density (VLDL) lipoproteins.

Conclusion: Considering the formation of saturated fatty acids, statin performed better in males. With Omega-3 polyunsaturated fatty acids involved, changes in lipoproteins, cholesterol and fatty acids (liver and myocardium) were similar to those caused by small doses of a statin drug. Effects of the combination of bisoprolol and acetylsalicylic acid were completely different from those caused by the use of statin.

The Bleeding Risk in Antithrombotic Therapies: A Narrative Review

Bleeding represents the most important complication of antithrombotic treatment, including anticoagulant and antiplatelet therapies. A number of scores were proposed to evaluate the risk of bleeding both for anticoagulant and antiplatelet treatment. In the last decade, 5 bleeding risk scores were published for use in atrial fibrillation patients, and 3 scores for patients receiving anticoagulants for venous thromboembolism therapy or prophylaxis. In addition, 3 scores were recently developed to assess inhospital or short-term bleeding risk in patients receiving antiplatelet therapy after Acute Coronary Syndrome (ACS) and Percutaneous Coronary Intervention (PCI). Furthermore, 3 additional scores have focused on long-term bleeding in outpatients receiving dual antiplatelet therapy after PCI. The aim of this review is to consider the evidence on bleeding scores.

Tubular and Glomerular Biomarkers of Acute Kidney Injury in Newborns

Background: Acute Kidney Injury (AKI) is a sudden decrease in kidney function. In the early period, the highest percentage of AKI occurs among newborns hospitalized in the neonatal intensive care units, especially premature neonates. The prognosis of AKI depends on the type and severity of the cause of an injury, the accuracy and the time of diagnosis and treatment. The concentration of serum creatinine is still the main diagnostic test, although it changes in the course of AKI later than glomerular filtration rate GFR. In addition, the reliability of the determination of creatinine level is limited because it depends on many factors. New studies have presented other, more useful laboratory markers of renal function that can be measured in serum and/or in urine.

Objective: The aim of the work was to present the latest data about tubular and glomerular biomarkers of acute kidney injury in newborns.

Methods: We undertook a structured search of bibliographic databases for peer-reviewed research literature by using focused review topics. According to the conceptual framework, the main idea of research literature has been summarized and presented in this study.

Results: The concentrations of some novel biomarkers are higher in serum and/or urine of term and preterm newborns with AKI, especially in the course of perinatal asphyxia.

Conclusion: In this systematic review of the literature, we have highlighted the usefulness of biomarkers in predicting tubular and/or glomerular injury in newborns. However, novel biomarkers need to prove their clinical applicability, accuracy, and cost-effectiveness prior to their implementation in clinical practice.

Shock – Classification and Pathophysiological Principles of Therapeutics

The management of patients with shock is extremely challenging because of the myriad of possible clinical presentations in cardiogenic shock, septic shock and hypovolemic shock and the limitations of contemporary therapeutic options. The treatment of shock includes the administration of endogenous catecholamines (epinephrine, norepinephrine, and dopamine) as well as various vasopressor agents that have shown efficacy in the treatment of the various types of shock. In addition to the endogenous catecholamines, dobutamine, isoproterenol, phenylephrine, and milrinone have served as the mainstays of shock therapy for several decades. Recently, experimental studies have suggested that newer agents such as vasopressin, selepressin, calcium-sensitizing agents like levosimendan, cardiac-specific myosin activators like omecamtiv mecarbil (OM), istaroxime, and natriuretic peptides like nesiritide can enhance shock therapy, especially when shock presents a more complex clinical picture than normal. However, their ability to improve clinical outcomes remains to be proven. It is the purpose of this review to describe the mechanism of action, dosage requirements, advantages and disadvantages, and specific indications and contraindications for the use of each of these catecholamines and vasopressors, as well as to elucidate the most important clinical trials that serve as the basis of contemporary shock therapy.

Cancer Therapeutics-Related Cardiovascular Complications. Mechanisms, Diagnosis and Treatment

Background: Chemotherapy regimens have improved prognosis and mortality of patients with malignant diseases. The development of therapies, however, has widened the cardiotoxic spectrum and the cardiacrelated effects of antineoplastic drugs.

Methods: A review of the literature under the search terms anthracyclines, oncology, cardiotoxicity, cardiooncology, chemotherapy and heart failure was used for the identification of the most relevant articles.

Results: Considerable variability exists in patients’ characteristics, in mechanisms involved in cardiomyopathy progression and in its physical history, as well as in modalities used to screen myocardial competence. The anthracyclines and particularly doxorubicin are the most widely used antineoplastic drugs. Monoclonal antibodies, tyrosine kinase inhibitors and other targeted therapies have been associated with cardiovascular side-effects, such as cardiomyopathy and congestive heart failure. Moreover, some of these agents are associated with an increased risk of coronary artery disease with or without myocardial infarction. The current standard for the detection of cardiac toxicity is serial echocardiography. Biomarkers though could be proved helpful, they can be tested at closer intervals and are highly accurate and reproducible. Of note, a growing body of data has emerged suggesting that some agents could have cardioprotective properties.

Conclusion: Since the number of long-term survivors following the diagnosis and treatment of malignant disease will continue to increase, cardio-oncology will continue to evolve. Therefore, a better understanding of potential cardiovascular effects of chemotherapeutic regiments and the earlier identification and treatment of high-risk patients would be the focus of research in the future.

The Role of Percutaneous Coronary Intervention in the Treatment of Chronic Total Occlusions: Rationale and Review of the Literature

Background: Chronic total occlusion (CTO) of a coronary artery is defined as an occluded segment with no antegrade flow and a known or estimated duration of at least 12 weeks.

Objective: We considered the current literature describing the indications and clinical outcomes for denovo CTO- percutaneous coronary intervention (PCI), and discuss the role of CTO-PCI and future directions for this procedure.

Methods: Databases (PubMed, the Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL were searched and relevant studies of CTO-PCI were selected for review.

Results: The prevalence of coronary artery CTO’s has been reported to be ~ 20% among patients undergoing diagnostic coronary angiography for suspected coronary artery disease. Revascularization of any CTO can be technically challenging and a time-consuming procedure with relatively low success rates and may be associated with a higher incidence of complications, particularly at non-specialized centers. However, with an increase in experience and technological advances, several centers are now reporting success rates above 80% for these lesions. There is marked variability among studies in reporting outcomes for CTO-PCI with some reporting potential mortality benefit, better quality of life and improved cardiac function parameters. Anecdotally, properly selected patients who undergo a successful CTO-PCI most often have profound relief of ischemic symptoms. Intuitively, it makes sense to revascularize an occluded coronary artery with the goal of improving cardiovascular function and patient quality of life.

Conclusion: CTO-PCI is a rapidly expanding specialized procedure in interventional cardiology and is reasonable or indicated if the occluded vessel is responsible for symptoms or in selected patients with silent ischemia in whom there is a large amount of myocardium at risk and PCI is likely to be successful.

Recurrent Episodes of Pericardial Effusion as Isolated Manifestation of Tuberculosis: Case Report

Background: Recurrent episodes of isolated pericardial effusion due to tuberculosis, leading to reduced Left Ventricle Ejection Fraction (LVEF), are uncommon.

Methods: This is a case report of a previously healthy 32-years old male with tuberculous induced pericardial effusion as isolated manifestation. The only known exposure of tuberculosis was a brother with whom the patient did not have physical contact during the last year. The pericardial effusion repeatedly appeared after being drained a total of three times. Due to recurrent episodes of pericardial effusion, severe thickening of the pericardium, pericardial adherences and increasing affection on the heart, pericardiectomy was ultimately performed.

Results: Biochemical examination, chest X-ray, computed tomography of thorax and abdomen and cytology report did not reveal any signs of malignancy, connective tissue disease or other infections including extra-pulmonary/pulmonary tuberculosis. However, the pericardial biopsy was Polymerase Chain Reaction positive (PCR) for tuberculosis DNA and showed granulomatous inflammation with necrosis. After 6 months anti-tuberculous therapy, biochemical parameters, LVEF and the clinical condition of the patient were normalized.

Conclusion: Tuberculosis can be difficult to diagnose when it only manifests as pericardial effusion especially if the time for exposure is long before the appearance of symptoms and admission.

Fluid and Medication Considerations in the Traumatized Patient

This article reviews fluid therapy and medications in pediatric trauma. For resuscitation in the setting of hemorrhagic shock, isotonic crystalloid solution is the first-line agent of choice. Colloid solutions offer no additional benefit, introduce possible increased risks and cost more than crystalloids.

Blood products, starting with pRBCs, should be introduced after 20-40 ml/kg of crystalloid has been administered if there is ongoing need for volume replacement. The use of a massive transfusion protocol of 1:1:1 (if >30 kg) or 30:20:20 (if <30 kg) of pRBCs:FFP:platelets is suggested after an initial 30 ml/kg of pRBcs has been administered.

Cryoprecipitate should be given for documented low fibrinogen or ongoing bleeding after administration of 1 round of all 3 blood components. For patients at risk of massive hemorrhage, early administration of tranexamic acid with an initial loading dose of 15 mg/kg (maximum 1 g) is recommended. Choice of medication for intubation of the patient with Traumatic Brain Injury (TBI) may best be guided by physiology: in the TBI patient with a high mean arterial pressure, premedication with lidocaine, fentanyl and use of etomidate may be most appropriate, whereas in the hemodynamically compromised patient, use of ketamine alone may be considered.

If needed, norepinephrine has been recommended as a temporizing agent for vasopressor support in the setting of fluid-refractory shock.

Although controversial, in the setting of significant spinal cord injury, the potential benefits of administering 24-48 hours of steroids (initial 30 mg/kg of methylprednisolone within 8 hours of injury) may outweigh the risks especially in previously healthy pediatric patients.

Mechanical Support in Cardiogenic Shock Complicating Acute Coronary Syndrome: Ready for Prime Time?

Cardiogenic Shock (CS) is a major challenge in current cardiology. Over the last decade, cardiogenic shock mortality has decreased somewhat, but it still remains high, particularly when associated with ischaemic heart disease. The challenges are numerous and include prevention, accurate diagnosis, prompt management and effective therapies to support a failing heart and prevent multi-organ failure. Despite improvements in the care of Acute Coronary Syndrome (ACS), it remains the most common cause of CS. In addition to existing medical therapy, mechanical circulatory support has been proposed for the management of ventricular failure. The intra-aortic balloon pump was amongst the first widely used percutaneous mechanical support devices, and more recently, systems providing a higher level of support have been developed. Although the evidence supporting their use is limited, they have the potential to significantly reduce CS-associated mortality. In this narrative review, we summarize the available evidence and discuss the future directions regarding percutaneous mechanical circulatory support in patients with left ventricular dysfunction and CS complicating ACS.

Is there a Role for Oral Triple Therapy in Patients with Acute Coronary Syndromes Without Atrial Fibrillation?

Background: Acute Coronary Syndrome (ACS) patients, despite treatment with Dual Anti- Platelet Therapy (DAPT), have up to 10% risk of recurrent Major Adverse Cardiac Events (MACE) in the short term.

Methods: Here we review studies using more potent antithrombotic agent combinations to reduce this risk, namely Triple Therapy (TT) with the addition of an oral anticoagulant, PAR-1 antagonist, or cilostazol to DAPT (mainly aspirin and clopidogrel), and discuss the limitations of trials to date.

Results: Generally speaking, TT leads to an increase in bleeding. Vorapaxar showed a signal for reducing ischaemic events, but increased intracranial haemorrhage 3-fold in the subacute phase of ACS, although remains an option for secondary prevention beyond the immediate subacute phase, particularly if prasugrel or ticagrelor are not available. Non-Vitamin K Oral Anticoagulants (NOACs) all increased bleeding, with only modest reduction in MACE noted with low dose rivaroxaban. Rivaroxaban can be considered combined with aspirin and clopidogrel in ACS patients at high ischaemic and low bleeding risk, without prior stroke/TIA. The combination of P2Y12 inhibitor and NOAC, without aspirin, looks promising. DAPT may be replaced, not by TT, but by dual therapy comprising a NOAC with a P2Y12 inhibitor.

Conclusion: More potent antithrombotic regimens increase bleeding and should only be considered on an individual basis, after careful risk stratification. Accurate risk stratification of ACS patients, for both ischaemic and bleeding risk, is essential to allow individualised treatment.

Antithrombotic Therapy for Transcatheter Valvular Interventions: A Revisit

Background: The optimal antithrombotic therapies for transcatheter aortic valve implantation (TAVI) and MitraClip implantation have not been well established. We conducted a narrative review from currently available studies between January 2002 and May 2016 to highlight the advantages and disadvantages of antithrombotic therapy use in cardiac catheter-based therapeutic techniques. Recently, these techniques have dramatically altered the approach towards valvular heart diseases management. The introduction into clinical practice, of TAVI for severe aortic stenosis and MitraClip for mitral regurgitation, has revolutionized interventional cardiology. However, TAVI is associated with a risk of cerebral embolization and ischaemic vascular events leading to neurological impairment and even death. These ischaemic complications might occur perioperatively or much later, although the estimated rate of occurrence is variable.

Conclusion: We will discuss prior experience with MitraClip for antithrombotic use. It is imperative for patients undergoing transcatheter valvular interventions to have optimal antithrombotic therapy that balances between ischaemic and haemorrhagic complications. The appropriate timing, combination, and duration of antithrombotic medications need consensus to weigh between the efficacy, efficiency and adverse effects in patients with transcatheter valvular interventions.

Transseptal Access to the Left Atrium: Tips and Tricks to Keep it Safe Derived from Single Operator Experience and Review of the Literature

Background: Transseptal puncture (TSP) remains a demanding procedural step in accessing the left atrium with inherent risks and safety concerns, mostly related to cardiac tamponade.

Objective: Based on our own experience with 249 TSP procedures and in-depth literature review, we present our results and offer several tips and tricks that may render TSP successful and safe.

Methods: This prospective study comprised 249 consecutive patients (146 men), aged 41.6±17.4 years, undergoing TSP by a single operator for ablation of a variety of arrhythmias, mostly related to left accessory pathways (n=145) or left atrial tachycardias (n=33) and more recently, atrial fibrillation (n=70). TSP was guided by fluoroscopy alone in all patients without the use of echocardiography imaging. In addition, an extensive literature review of TSP-related topics was carried out in PubMed, Scopus and Google Scholar.

Results: Among 249 patients, 33 patients were children or young adolescents (aged 7-18 years); 14 patients were undergoing a repeat procedure. Patients with a manifest accessory pathway were the youngest (mean age 33.7±15.9) and patients with atrial fibrillation the oldest (mean age 56.0±10.8 years). A successful TSP was accomplished in 247 patients (99.2%). Two (0.8%) procedures were complicated by cardiac tamponade managed successfully with pericardiocentesis or surgical drainage. Review of the literature revealed no systematic reviews and meta-analyses of TSP studies; however, several patient series have documented that fluoroscopy-guided TSP, with various modifications in the technique employed in the present series, have been effective in 95-100% of the cases with a complication rate ranging from 0.0% to 6.7%, albeit with a mortality rate of 0.018%- 0.2%. Echo imaging techniques were employed in cases with difficult TSP.

Conclusion: Employing a standardized protocol with use of fluoroscopy alone minimized serious complications to 0.8% (2 patients) among 249 consecutive patients undergoing TSP for ablation of a variety of cardiac arrhythmias. Based on this single-operator experience and review of the literature, a list of practical tips and tricks is provided for a successful and safe procedure, reserving the more expensive and patient inconveniencing echo-imaging techniques for difficult or failed cases.

Chemotherapy and Cardiotoxicity in Hematologic Malignancies

Introduction: Antineoplastic agents affect the cardiovascular system, and the incidence of cardiotoxicity is continuously growing in patients with hematologic malignancies and treated with antineoplastic therapy.

Methods: In this mini-review, we analyzed existing literature which evaluates the likelihood of cardiotoxicity related to the main agents employed in the treatment of hematologic malignancies.

Results: There is a significant need to optimize the early identification of patients who are at risk of cardiotoxicity. The conventional echocardiographic measurements used to detect cardiac alterations, such as LVEF, fractional shortening, diameters and volumes, allow only a late diagnosis of cardiac dysfunction, which might be already irreversible. The early identification of patients at risk for rapid progression towards irreversible cardiac failure has a primary purpose, the opportunity for them to benefit from early preventive and therapeutic measures. A useful imaging technique that points in this direction detecting subclinical LVD may be the speckle tracking echocardiography, that has demonstrated a previous detection of myocardial contractile dysfunction compared to the traditional left ventricular ejection fraction. In this view, the discovery of new biomarkers to identify patients at a high risk for the development of these complications is another priority.

Conclusion: Cardiotoxicity induced by anticancer drugs is always the outcome of several concurrent factors. It is plausible that an asymptomatic dysfunction precedes clinical events. During this asymptomatic phase, an early treatment prepares the patient for cardiovascular “safety” conditions; on the other hand, a late or missing treatment paves the ground for the development of future cardiac events.

Traditional and Alternative Therapies for Refractory Angina

Refractory angina (RFA) is an unfavourable condition that is characterized with persistent angina due to reversible myocardial ischemia in patients with coronary artery disease that remains uncontrollable despite an optimal combination of pharmacological agents and revascularization. Despite significant advances in revascularization techniques and agents used in pharmacological therapy, there is still a significant population suffering from RFA and the global prevalence is even increasing. Anti- anginal treatment and secondary risk-factor modification are the traditional approaches for this group of patients. Furthermore, now there is still a large number of alternative treatment options. In order to review traditional and alternative treatment strategies in patients with RFA, we searched Pubmed for articles in English using the search terms “pharmacological therapy, refractory angina”, “alternative therapy, refractory angina” between inception to June 2016. We also went through separately for each alternative treatment modality on Pubmed. To identify further articles, we handsearched related citations in review articles and commentaries. We also included data from the European Society of Cardiology (2013), and the Canadian Society of Cardiology/ Canadian Pain Society (2012) guidelines. Data show that besides traditional pharmacological agents, such as nitrates, beta- blockers or calcium channel blockers, novel antiischemic drugs and if symptoms persist, several non- invasive and/ or invasive alternative strategies may be considered. Impact of some pharmacological agents, such as rho- kinase inhibitors, and novel alternative treatment modalities, such as coronary sinus reducers, stem cell therapy, gene and protein therapy, on outcomes are still under investigation.

Pathophysiology of Myocardial Infarction and Acute Management Strategies

On an annual basis, 13.2% of all deaths are attributable to coronary artery disease (CAD), which makes CAD - with 7.4 million deaths – the leading cause of death in the world. In this review, we discuss current knowledge in the pathophysiology of atherosclerosis with its progression to stable CAD and its destabilization and complication with thrombus formation – myocardial infarction (MI). Next, we describe mechanisms of myocardial cell death in MI, the ischemia-reperfusion injury, leftventricular remodeling and complications of MI. Furthermore, we add acute management strategies concentrating on medical therapy, a decision on the reperfusion strategy, timing and cardiac protection by ischemic preconditioning, post-conditioning and remote ischemic conditioning.

Helminth Infections and Cardiovascular Diseases: Toxocara Species is Contributing to the Disease

Toxocariasis is the clinical term used to describe human infection with either the dog ascarid Toxocara canis or the feline ascarid Toxocara cati. As with other helminths zoonoses, the infective larvae of these Toxocara species cannot mature into adults in the human host. Instead, the worms wander through organs and tissues, mainly the liver, lungs, myocardium, kidney and central nervous system, in a vain attempt to find that, which they need to mature into adults. The migration of these immature nematode larvae causes local and systemic inflammation, resulting in the “larva migrans” syndrome. The clinical manifestations of toxocariasis are divided into visceral larva migrans, ocular larva migrans and neurotoxocariasis. Subclinical infection is often referred to as covert toxocariasis. One of the primary causes of death all around the world is cardiovascular disease that accounted for up to 30 percent of all-cause mortality. Cardiovascular disease and more precisely atherosclerotic cardiovascular disease, is predicted to remain the single leading cause of death (23.3 million deaths by 2030). A-quarter of people presenting the disease does not show any of the known cardiovascular risk factors. Therefore, there is considerable interest in looking for novel components affecting cardiovascular health, especially for those that could improve global cardiovascular risk prediction. This review endeavours to summarize the clinical aspects, new diagnostic and therapeutic perspectives of toxocaral disease with cardiovascular manifestations.

Deep Inspiration Breath-hold (DIBH) Technique to Reduce Cardiac Radiation Dose in the Management of Breast Cancer

With advances in diagnosis and treatment, breast cancer has become an increasingly survivable disease with a growing population of long-term survivors. As an essential component of breast conservation therapy, radiotherapy is a standard treatment for many women with stage I/II breast cancer. Cardiac radiation exposure has been associated with an increased risk of cardiovascular diseases. Among these are coronary artery disease, cardiomyopathy, valvular heart disease, and pericardial disease. Microvascular changes and accelerated atherosclerosis are likely the primary underlying mechanisms of radiation induced cardiovascular damage. A simple and highly effective technique, deep inspiration breath-hold (DIBH), has been shown to decrease cardiac radiation exposure without compromising target coverage. This brief review focuses on the effects of radiation therapy on the heart, radiation-induced cardiovascular diseases in breast cancer survivors, and the DIBH technique as a means for reducing cardiac radiation exposure.

A Practical Comprehensive Approach to Management of Acute Decompensated Heart Failure

Heart failure (HF) has a high incidence and prevalence in the USA and worldwide. It is a very common cause of significant morbidity and mortality with serious cost implications on the US health sector. The primary focus of this review is to synthesize an effective comprehensive care plan for patients in acute decompensated heart failure (ADHF) based on the most current evidence available. It begins with a brief overview of the pathophysiology, clinical presentation and evaluation of patients in ADHF. It then reviews management goals and treatment guidelines, with emphasis on challenges presented by diuretic resistance and worsening renal function (WRF). It provides information on recognition of advanced HF even during acute presentation, estimation of prognosis and proactive identification of patients that will benefit from mechanical cardiac devices, transplantation and palliative care/hospice. In addition, it presents strategies to address the problem of readmissions, which is an ominous prognostic factor with enormous economic burden.

Therapeutic Utilities of Pediatric Cardiac Catheterization

In an era when less invasive techniques are favored, therapeutic cardiac catheterization constantly evolves and widens its spectrum of usage in the pediatric population. The advent of sophisticated devices and well-designed equipment has made the management of many congenital cardiac lesions more efficient and safer, while providing more comfort to the patient. Nowadays, a large variety of heart diseases are managed with transcatheter techniques, such as patent foramen ovale, atrial and ventricular septal defects, valve stenosis, patent ductus arteriosus, aortic coarctation, pulmonary artery and vein stenosis and arteriovenous malformations. Moreover, hybrid procedures and catheter ablation have opened new paths in the treatment of complex cardiac lesions and arrhythmias, respectively. In this article, the main therapeutic utilities of cardiac catheterization in children are discussed.

Are Some Anticoagulants More Equal Than Others? - Evaluating the Role of Novel Oral Anticoagulants in AF Ablation

Left atrial ablation strategies are being increasingly performed as a Class 1 therapeutic indication for drug refractory paroxysmal atrial fibrillation (AF). Traditionally AF ablation has been performed with patients on uninterrupted warfarin therapy, however over the last few years, novel oral anticoagulants (NOACs) have emerged as attractive alternatives to warfarin in order to reduce stroke risk due to AF. NOACs are therefore increasingly being used instead of warfarin in the management of AF. There is also mounting evidence mainly in the form of small randomised studies and meta-analysis that have demonstrated that the use of NOACs for AF ablation is efficacious, safe and convenient. However the peri-procedural dosing protocols used in various studies especially in terms of whether NOAC use is interrupted or uninterrupted during AF ablation, have significant inter-operator and inter-institution variability. Currently there is also a lack of randomised controlled trials to validate the data obtained from meta-analyses. There is also evidence that use of NOACs may increase the requirement of unfractionated heparin during the procedure. This review article shall examine the currently available evidence-base, appraise the gaps in the current evidence and also underscore the need for larger randomised clinical trials in this rapidly developing field.

Twenty Years of Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy

Hypertrophic obstructive cardiomyopathy is the most common genetic cardiac disease and is generally characterised by asymmetric septal hypertrophy and intraventricular obstruction. Patients with severe obstruction and significant symptoms that persist despite optimal medical treatment are candidates for an invasive septal reduction therapy. Twenty years after its introduction, percutaneous transluminal alcohol septal ablation has been increasingly preferred for septal reduction in patients with drug refractory hypertrophic obstructive cardiomyopathy. Myocardial contrast echocardiography and injection of reduced alcohol volumes have increased safety, while efficacy is comparable to the surgical alternative, septal myectomy, which has for decades been regarded as the ‘gold standard’ treatment. Data on medium- and long-term survival show improved prognosis with survival being similar to the general population. Current guidelines have supported its use by experienced operators in centres specialised in the treatment of patients with hypertrophic obstructive cardiomyopathy.

Obstetrical Hemorrhage Review

Obstetrical hemorrhage is the leading cause of maternal mortality worldwide. Management of obstetrical hemorrhage involves medical knowledge and surgical skill. Uterotonics for the prevention and treatment of uterine atony remain the cornerstone of medical management. The rising rate of placenta accreta emphasizes the importance of definitive surgical management. Proficiency of uterinesparing techniques for the management of uterine atony or placenta accreta allow alternative options for those who wish to preserve fertility. New concepts in the management of severe obstetrical hemorrhage have changed how we care for this unique emergent condition. The use of massive transfusion protocols in conjunction with products such as tranexamic acid, fibrinogen concentrates and prothrombin complex concentrates are emerging techniques to reduce morbidity and mortality.

A Successful Treatment of Cervical Ectopic Pregnancy with Multidose Methotrexate

Background and Aim: Cervical pregnancy is a rare form of ectopic pregnancy. Treatment approach depends on hemodynamic status; so, it could be medical therapy or more aggressive treatment like emergent hysterectomy.

Case report: We present an interesting case of cervical ectopic pregnancy with high level of βhCG which was successfully treated with multidose methotrexate.

Conclusion: In cases of early diagnosis of cervical pregnancy in patients with stable hemodynamic status, medical therapy could successfully treat cervical ectopic pregnancy even with high level of βhCG.

Molecular Pharmacology of Malignant Pleural Mesothelioma: Challenges and Perspectives From Preclinical and Clinical Studies

Malignant pleural mesothelioma (MPM) is one of the deadliest and most heterogeneous tumors, highly refractory to multimodal therapeutic approach, including surgery, chemo- and radiotherapy. Preclinical and clinical studies exploring the efficacy of drugs targeting tyrosine kinases, angiogenesis and histone deacetylases, did not fulfil the expected clinical benefits. Thus, novel molecular targets should be identified from a definite knowledge of the unique biology and most relevant transduction pathways of MPM cells. Cancer stem cells (CSCs) are a subset of malignant precursors responsible for initiation, progression, resistance to cytotoxic drugs, recurrence and metastatic diffusion of tumor cells. CSCs are putative driving factors for MPM development and contribute to its clinical and biological heterogeneity; hence, targeted eradication of CSCs represents an ineludible goal to counteract MPM aggressiveness. In this context, innovative preclinical models could be exploited to identify novel intracellular pathway inhibitors able to target CSC viability. Novel drug targets have been identified among key factors responsible for the oncogenic transformation of mesothelial cells, often directly induced by asbestos. These include mitogenic and anti-apoptotic signaling that may also be activated by autocrine and paracrine cytokine pathways controlling cell plasticity. Both signaling pathways affecting proto-oncogene and transcription factor expression, or genetic and epigenetic alterations, such as mutations in cell cycle genes and silencing of tumor suppressor genes, represent promising disease-specific targets. In this review we describe current knowledge of MPM cell biology, focusing on potential targets to be tested in pharmacological studies, and highlighting results and challenges of clinical translation.

Atrial Fibrillation During or After TAVI: Incidence, Implications and Therapeutical Considerations

Introduction: Aortic stenosis is one of the most frequent valvulopathy of modern time necessitating interventional therapy when symptoms arise and stenosis becomes severe. First line treatment has traditionally been surgical aortic valve replacement (SAVR). However in the last decade transcatheter aortic valve implantation (TAVI) with bioprosthetic valves has proved to be a sound solution for high-risk for SAVR or inoperable patients. As expected implantation of the bioprosthetic device requires administration of antiplatelet regimen to the patients for a certain period. Atrial fibrillation (AF) may occur frequently during the peri-procedural period. In this background, the occurrence of AF after device implantation may be a challenging issue.

Methods: We performed a literature search of PubMed and Embase database. Published articles reporting the incidence, clinical implications and description of antithrombotic regimen of New-onset atrial fibrillation (NOAF) in individuals undergoing TAVI were considered eligible.

Incidence, Implications and Antithrombotic Regimen: The overall occurrence of NOAF is reported to be 1%-32% after TAVI. Left atrial enlargement and transapical approach constitute independent predictors for NOAF. Additionally it has been shown that patients with AF face an increased risk of death irrespective of the type of AF. Patients, with a history of AF, present greater rate of death than individuals with NOAF. NOAF is responsible for cerebrovascular events (CVE) occurring in the subacute phase (days 1–30) after the procedure. The risk of stroke/transient ischemic attack after TAVI is increased at least two fold by the presence of atrial fibrillation. Empirically, a dual antiplatelet strategy has been used for patients undergoing TAVR, including aspirin and a thienopyridine. In cases where patients are in need of oral anticoagulation after TAVI a combination of aspirin or thienopyridine with acenocoumarol has been the preferred regimen.

Discussion: Despite the continuously crescent use of TAVI for patients with symptomatic severe aortic stenosis, there are still many aspects of this procedure to be clarified. A lack of data exists from the available clinical trials regarding the appropriate anticoagulation therapy for patients with greater risk for thromboembolic events. As a result, patient’s treatment remains at the discretion of the physician.

Conclusion: Limited data are available regarding the optimal therapeutic regimen in patients undergoing TAVI who need therapy for AF. Carefully designed clinical studies might further clarify the incidence and interrelation between atrial fibrillation and TAVI. The balance between the efficacy and risk of anticoagulation needs to be further clarified in patients undergoing TAVI.

Mechanisms And Prevention Of TAVI-Related Cerebrovascular Events

Introduction of transcatheter aortic valve implantation (TAVI) has resulted in a paradigm shift in the treatment of patients with high risk or inoperable severe aortic stenosis. This article aims to comprehensively review the mechanisms of neurological injury per se, the read-outs of cerebrovascular events, and strategies currently used to predict and prevent stroke in transcatheter aortic valve implantation.

Transcatheter Aortic Valve Implantation versus Surgical Aortic Valve Replacement: Meta-Analysis of Clinical Outcomes and Cost-Effectiveness

Objective: Transcatheter aortic valve implantation (TAVI) has emerged as a feasible alternative treatment to conventional surgical aortic valve replacement (AVR) for high-risk patients with aortic stenosis. The present systematic review aimed to assess the comparative clinical and cost-effectiveness outcomes of TAVI versus AVR, and meta-analyse standardized clinical endpoints.

Methods: An electronic search was conducted on 9 online databases to identify all relevant studies. Eligible studies had to report on either periprocedural mortality or incremental cost-effectiveness ratio (ICER) to be included for analysis.

Results: The systematic review identified 24 studies that reported on comparative clinical outcomes, including three randomized controlled trials and ten matched observational studies involving 7906 patients. Meta-analysis demonstrated no significant differences in regards to mortality, stroke, myocardial infarction or acute renal failure. Patients who underwent TAVI were more likely to experience major vascular complications or arrhythmias requiring permanent pacemaker insertion. Patients who underwent AVR were more likely to experience major bleeding. Eleven analyses from 7 economic studies reported on ICER. Six analyses defined TAVI to be low value, 2 analyses defined TAVI to be intermediate value, and three analyses defined TAVI to be high value.

Conclusion: The present study demonstrated no significant differences in regards to mortality or stroke between the two therapeutic procedures. However, the cost-effectiveness and long-term efficacy of TAVI may require further investigation. Technological improvement and increased experience may broaden the clinical indication for TAVI for low-intermediate risk patients in the future.

Association of Genetic Polymorphisms of CYP2C9 and VKORC1 with Bleeding Following Warfarin: A Case-Control Study

Introduction: Various factors have been shown to increase the risk of bleeding with warfarin. This study aimed to assess the association of CYP2C9 and VKORC1 with the development of bleeding following warfarin.

Study Methods: A case control study was initiated after obtaining institutional ethics committee clearance and written informed consent from patients. Cases were defined as those who bled within three months of warfarin initiation and controls as those who did not have any episode of bleeding within three months. Genotyping for CYP2C9 (*1, *2, *3) and VKORC1 1639 (GG, GA and AA) was performed by PCRRFLP. Chi square test was used to find out the association and trend of CYP2C9 and VKORC1 genotypes with odds ratio (95% CI) for strength of association. A binary logistic regression model was developed associating age, body weight, sex, CYP2C9 and VKORC1 status with risk of bleeding.

Results: A total of 100 controls and 38 cases were studied from Oct 2009 to July 2011. A significant association (P < 0.0001) and trend (P = 0.027) of mutant alleles of CYP2C9 and VKORC1 were noted with bleeding with odds ratios of 7.8 [3.4, 17.9] and 2.7 [1.3, 5.7] respectively. Weekly dose requirement was significantly lower with the presence of *3 allele relative to *1 in CYP2C9 (P < 0.001). The regression model showed an accuracy of 80% and could explain 35.3% of the variability.

Conclusion: A significant association between CYP2C9 (*1,*2,*3) genotype and VKORC1 (1639 G>A) haplotype status has been found with increased bleeding tendency to warfarin. This may help to individualize therapy.

The Role of Protease-Activated Receptors for the Development of Myocarditis: Possible Therapeutic Implications

Protease-activated receptors (PARs) are a unique group of four G-protein coupled receptors. They are widely expressed within the cardiovascular system and the heart. PARs are activated via cleavage by serine proteases. In vitro and in vivo studies showed that the activation of PAR1 and PAR2 plays a crucial role in virus induced inflammatory diseases. The receptors enable cells to recognize pathogen-derived changes in the extracellular environment. An infection with Coxsackie-virus B3 (CVB3) can cause myocarditis. Recent studies have been shown that PAR1 signaling enhanced the antiviral innate immune response via interferon β (IFNβ) and thus limited the virus replication and cardiac damage. In contrast, PAR2 signaling decreased the antiviral innate immune response via IFNβ und thus increased the virus replication, which caused severe myocarditis. Along with CVB3 other viruses such as influenza A virus (IAV) and herpes simplex virus (HSV) can induce myocarditis. The role of PAR signaling in IAV infections is contrarily discussed. During HSV infections PARs facilitate the virus infection of the host cell. These studies show that PARs might be interesting drug targets for the treatment of virus infections and inflammatory heart diseases. First studies with PAR agonists, antagonists, and serine protease inhibitors have been conducted in mice. The inhibition of thrombin the main PAR1 activating protease decreased the IFNβ response and increased the virus replication in CVB3-induced myocarditis. This indicates that further studies with direct PAR agonists and antagonists are needed to determine whether PARs are useful drug targets for the therapy of virus-induced heart diseases.

The Role of the Metabolism of Anticancer Drugs in Their Induced-Cardiotoxicity

Cardioncology is a major topic of the day, since cardiotoxicity of chemotherapy agents can limit its real use and it can also become a clinical problem years after the end of anticancer therapy. These cardiac problems largely increase the mortality and morbidity of cancer-treated patients. Actually, as the number of cancer survivors is increasing each decade, late cardiotoxicity related to anticancer therapy is expected to grow exponentially in the fore coming years. The mechanisms of cardiotoxicity of anticancer drugs are still largely unknown. The metabolism of some drugs can lead to more active anticancer metabolites but those metabolites can likewise contribute to the observed cardiotoxicity. The alcohols and aglycone metabolites of anthracyclines are known to be cardiotoxic, while regarding 5-fluorouracil, fluoroacetate is considered one of the major metabolites responsible for its cardiotoxicity. Regarding mitoxantrone, the toxicity of the majority of the metabolites has not been assessed so far and concerning cyclophosphamide metabolites, both hydroxycyclophosphamide and acrolein are shown to be more cardiotoxic than the parent drug. Still, the contribution of drug metabolism to the cardiotoxicity of chemotherapy agents is largely unknown and poorly discussed. This review presents a new link between several cardiotoxic anticancer drugs and their drug metabolites, as they can play an important role in the widely reported heart damage inflicted by chemotherapy. Anthracyclines, cyclophosphamide, mitoxantrone, and 5- fluorouracil will be mainly focused, given the vast literature and clinical use. The current knowledge shows the possible involvement of drug metabolism in bioactivation mechanisms that can contribute to their cardiotoxicity.

Novel Oral Anticoagulation During Pulmonary Vein Isolation and Cardioversion

Atrial fibrillation is an age-dependent disease with symptomatic and prognostic implications. Treatment options include rhythm as well as rate control. However, there is a need for anticoagulation depending on calculated individual annual risk. Treatment options include antiplatelet therapy, oral anticoagulation and the use of novel oral anticoagulation (NOACs). To date, the safety and efficacy of NOACs in atrial fibrillation is established in large mega-trials. However, there is still concern on the use of NOACs in invasive procedures such as coronary angiography, electrophysiological procedures, and general surgical procedures. This review will give an overview about current data of NAOCs in procedures for rhythm control (pulmonary vein isolation and current cardioversion).

Pathophysiology of Post-Operative Low Cardiac Output Syndrome

Low cardiac output syndrome frequently complicates the post-operative care of infants and children following cardiac surgery. The onset of low cardiac output follows a predictable course in the hours following cardiopulmonary bypass, as myocardial performance declines in the face of an elevated demand for cardiac output. When demand outstrips supply, shock ensues, and early recognition and intervention can decrease mortality. Multifactorial in etiology, this article will discuss the pathophysiology of low cardiac output syndrome, including myocardial depression following bypass, altered cardiac loading conditions, and inflammation driving a hypermetabolic state. Contributions from altered neurohormonal, thyroid, and adrenal axes will also be discussed. Sources included the clinical experiences of four cardiac intensivists, supported throughout by primary sources and relevant reviews obtained through PubMed searches and from seminal textbooks in the field. This article addresses the second of eight topics comprising the special issue entitled “Pharmacologic strategies with afterload reduction in low cardiac output syndrome after pediatric cardiac surgery”.

COMPLICATIONS OF RECANALIZATION OF CHRONIC TOTAL OCCLUSION

Percutaneous Coronary Intervention (PCI) of Chronic Total Occlusions (CTO) is an accepted revascularization procedure. These complex procedures carry with them certain risks and potential complications. Complications of PCI such as contrast induced renal dysfunction, radiation, etc, assume more relevance given the length and complexity of these procedures. Further, certain complications such as donor vessel injury, foreign body entrapment are unique to CTO PCI. A thorough understanding of the potential complications is important in mitigating risk during these complex procedures.

Retrograde Coronary Chronic Total Occlusion Intervention

Coronary chronic total occlusion (CTO) is a frequent finding in patients with coronary artery disease. It remains one of the most challenging subsets, accounting for 10-20% of all percutaneous coronary interventions (PCI). Although remarkable progress in PCI has been made, it is reasonable to state that successful recanalization of CTO represents the “last frontier" of PCI. PCI of CTOs has been limited historically by technical success rates of 50-70%. The introduction of enhanced guidewires, microcatheter, channel dilatator with increasing operator experience, and innovative techniques such as the retrograde approach have raised hopes for better outcomes. This article goes into depth into various strategies of retrograde approach in CTO.

Applied Pathology for Interventions of Coronary Chronic Total Occlusion

Percutaneous coronary intervention of chronically occluded vessels can result in significant improvement in symptoms, relieve myocardial ischemia, and affect a reduction in major adverse cardiac events. Likelihood of achieving successful revascularization can be significantly enhanced with a thorough understanding of the pathology of these occluded coronary arteries. In this chapter, various steps and techniques to cross the CTO lesion and recanalize it are discussed in details.

Collateral Circulation in Chronic Total Occlusions – an interventional perspective

Human coronary collaterals are inter-coronary communications that are believed to be present from birth. In the presence of chronic total occlusions, recruitment of flow via these collateral anastomoses to the arterial segment distal to occlusion provide an alternative source of blood flow to the myocardial segment at risk. This mitigates the ischemic injury. Clinical outcome of coronary occlusion ie. severity of myocardial infarction/ischemia, impairment of cardiac function and possibly survival depends not only on the acuity of the occlusion, extent of jeopardized myocardium, duration of ischemia but also to the adequacy of collateral circulation. Adequacy of collateral circulation can be assessed by various methods. These coronary collateral channels have been used successfully as a retrograde access route for percutaneous recanalization of chronic total occlusions. Factors that promote angiogenesis and further collateral remodeling ie. arteriogenesis have been identified. Promotion of collateral growth as a therapeutic target in patients with no suitable revascularization option is an exciting proposal.

Imaging of Chest and Abdominal Trauma in Children

Trauma is the commonest cause of death in children over a year old. The injuries sustained and management of these children differs to adults, due to differences in anatomy and physiology. Careful thought must also be given to exposing children to radiation, and CT scans should be performed only in select patients. This article reviews these important points and explains the imaging findings in chest and abdominal trauma.

Thoracic Trauma in Combat or Austere Environments

Major traumatic injuries to the thorax can present significant challenges at even the most modern and well-equipped trauma centers. Additional significant challenges regarding the evaluation and management of these injuries arise in more resource-constrained environment such as the rural setting or on the battlefield during combat operations. The recent prolonged combat operations in Iraq and Afghanistan have resulted in a large body of experience and lessons learned related to combat thoracic trauma, and much of this can be applied to the civilian setting. Although advances in protective equipment and vehicles, as well as changes in the common mechanisms of wounding on the modern battlefield have impacted the incidence and severity of these injuries, they remain relatively common and carry a high morbidity and mortality. Initial evaluation and interventions should focus on identification and control of ongoing hemorrhage, rapidly determining the need for operative intervention, and then appropriate surgical decision-making including the need for an abbreviated initial damage-control procedure with more definitive repairs/reconstruction delayed until after the patient is stabilized and adequately resuscitated. Additional operational factors that must be considered and can alter management decisions include the tactical situation, the local supply and personnel situation, the need for evacuation to the next higher level of care, and the needs of other casualties in a mass casualty scenario.

Thoracic Surgical Approaches in the Trauma Setting: A Basic Review

The most common surgical intervention following chest injury is simply tube thoracostomy. Despite the fact that it is uncommon for more complex interventions to be required acutely, the overall mortality and complication rate following chest injury is as high as 25%. Complications in the post resuscitation phase not uncommon, and surgeons managing these patients must be facile with a number of exposures and techniques, the choice of which will be affected by the patients injury mechanism, stability and the setting in which the patient is initially resuscitated.

Point-of-Care Thoracic Ultrasound in Trauma

Point-of-care ultrasound is an increasingly utilized technology in the management of the acutely injured patient. Ultrasonography has demonstrated utility and improved outcomes in rapidly detecting pnemothorax, intrapericardial blood and assessing cardiac function in the hemodynamically unstable patient. Examination of the thorax incorporated into the FAST exam (termed E-FAST, or extended FAST exam) enables rapid recognition of pathology within the trauma bay, permitting earlier intervention.

Cardiovascular Involvement in Pediatric Systemic Autoimmune Diseases: The Emerging Role of Noninvasive Cardiovascular Imaging

Cardiac involvement in pediatric systemic autoimmune diseases has a wide spectrum of presentation ranging from asymptomatic to severe clinically overt involvement. Coronary artery disease, pericardial, myocardial, valvular and rythm disturbances are the most common causes of heart lesion in pediatric systemic autoimmune diseases and cannot be explained only by the traditional cardiovascular risk factors. Therefore, chronic inflammation has been considered as an additive causative factor of cardiac disease in these patients.

Rheumatic fever, juvenile idiopathic arthritis, systemic lupus erythematosus, ankylosing spondylitis/spondyloarthritides, juvenile scleroderma, juvenile dermatomyositis/polymyositis, Kawasaki disease and other autoimmune vasculitides are the commonest pediatric systemic autoimmune diseases with heart involvement.

Noninvasive cardiovascular imaging is an absolutely necessary adjunct to the clinical evaluation of these patients. Echocardiography is the cornerstone of this assessment, due to excellent acoustic window in children, lack of radiation, low cost and high availability. However, it can not detect disease acuity and pathophysiologic background of cardiac lesions. Recently, the development of cardiovascular magnetic resonance imaging holds the promise for early detection of subclinical heart disease and detailed serial evaluation of myocardium (function, inflammation, stress perfusion-fibrosis) and coronary arteries (assessment of ectasia and aneurysms).

Imaging in Drug Side Effects

Drug side effects are common in clinical practice and its diagnosis and radiologic manifestations are not always evident or known. Adverse effects may cause medical complications and negatively affect prognosis and outcome of patients. In this setting, an early diagnosis might have relevant clinical and therapeutic implications. Different studies have shown that adverse drug reactions related hospital admissions comprise up to 10% of the total number of hospitalizations and are an important cause of morbidity and mortality in adults. Most adverse drugs reactions have no distinctive radiological features. However, certain iatrogenic disorders have distinctive imaging characteristics that allow their recognition. We illustrate the imaging findings of drugs side effects and review those complications that radiologists may diagnose.

Molecularly Imprinted Sol-Gel Materials for Medical Applications

The present review deals with the sol-gel imprinting of both drug and non-drug templates of medical relevance, namely neurotransmitters, biomarkers, hormones, proteins and cells. Nearly a hundred recent works, either developmental or applied in a medical-related context, were critically analyzed. It may be concluded that, although research is still at an early stage, the potential of these sol-gel materials was well demonstrated in a few applications of critical interest for medicinal/biomedical science. The vast room left for expansion and improvement envisages a continuously growing interest by researchers in the future, eventually resulting in important medical applications able to enter the professional and consumer medical markets.

Cardiovascular Magnetic Resonance for Evaluation of Heart Involvement in ANCA-Associated Vasculitis. A Luxury or a Valuable Diagnostic Tool?

Antineutrophil cytoplasmic antibody (ANCA)-related vasculitis is a systemic small-vessel vasculitis, including 3 clinical syndromes: granulomatosis with polyangiitis, known as Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and the Churg-Strauss syndrome (CSS). ANCA-related vasculitis usually presents with severe kidney or pulmonary disease, has a mortality of 28% at 5 years, and also contributes to increased morbidity in vasculitis patients.

Cardiac involvement in this entity may have different forms, including coronary vessels, pericarditis, myocarditis, endocarditis, myocardial infarction and subendocardial vasculitis that can contribute to reduced life expectancy.

Cardiovascular magnetic resonance using oedema and fibrosis imaging can early reveal, noninvasively and without radiation, heart involvement during vasculitis, undetected by other imaging techniques and guide further risk stratification and treatment of these patients.

Hybrid Therapy in the Management of Atrial Fibrillation

Atrial fibrillation is the most common sustained arrhythmia. Because of the sub-optimal outcomes and associated risks of medical therapy as well as the recent advances in non-pharmacologic strategies, a multitude of combined (hybrid) algorithms have been introduced that improve efficacy of standalone therapies while maintaining a high safety profile. Antiarrhythmic administration enhances success rate of electrical cardioversion. Catheter ablation of antiarrhythmic drug-induced typical atrial flutter may prevent recurrent atrial fibrillation. Through simple ablation in the right atrium, suppression of atrial fibrillation may be achieved in patients with previously ineffective antiarrhythmic therapy. Efficacy of complex catheter ablation in the left atrium is improved with antiarrhythmic drugs. Catheter ablation followed by permanent pacemaker implantation is an effective and safe treatment option for selected patients. Additional strategies include pacing therapies such as atrial pacing with permanent pacemakers, preventive pacing algorithms, and/or implantable dual-chamber defibrillators are available. Modern hybrid strategies combining both epicardial and endocardial approaches in order to create a complex set of radiofrequency lesions in the left atrium have demonstrated a high rate of success and warrant further research. Hybrid therapy for atrial fibrillation reviews history of development of non-pharmacological treatment strategies and outlines avenues of ongoing research in this field.

Catheter Ablation of Lone Atrial Fibrillation

Atrial fibrillation is the most common sustained arrhythmia in clinical practice, associated with increased mortality, risk of stroke and heart failure, as well as the reduction of the quality of life. Atrial fibrillation may be encountered in young otherwise healthy individuals, due to the isolated electrophysiological disorder limited mostly to the pulmonary veins and posterior left atrial wall, or associated with the presence of advanced underlying heart disease and numerous cardiac and non-cardiac comorbidities with significant structural remodeling of the atrial myocardium. Due to limited efficacy and serious side effects of antiarrhythmic drugs, catheter ablation of atrial fibrillation, based on the pulmonary vein isolation for paroxysmal atrial fibrillation and adjunctive substrate modification for persistent atrial fibrillation, has emerged as an attractive and promissing alternative therapeutic option for selected patients with atrial fibrillation. In this review article, we discuss the electrophysiological left atrial abnormalities underlying lone atrial fibrillation and the role of pulmonary veins in pathophysiology of arrhythmia, and we summarize results of the studies on the long term outcome of catheter ablation of atrial fibrillation, as well as the studies on comparison of antiarrhythmic drugs with catheter ablation for treatment of atrial fibrillation. In addition, we present available data that provide better understanding of mechanisms, diagnosis, prevention and treatment of specific procedure-related complications and discuss current periprocedural anticoagulation strategies and their impact on the thromboembolic risk reduction.

Pharmacological Therapy of Pericardial Diseases

(117 words) Acute and recurrent pericarditis, isolated pericardial effusion, and constrictive pericarditis represent the main pericardial syndromes and therapy of these conditions should be targeted as much as possible at the specific aetiology, but unfortunately many cases still remain idiopathic with current diagnostic methods and should be empirically treated according to best available evidence. Unfortunately, treatment is often empirical since there are few clinical trials available. Nevertheless as for hypertension, even if we do not know the precise cause of the syndrome in all cases, we may provide excellent management for most cases. The aim of the present paper is to review current medical therapy for the main pericardial syndromes.

The Evidence Base for Revascularisation of Chronic Total Occlusions

When patients with ischaemic heart disease are considered for revascularisation the Heart Team’s aim is to choose a therapy that will provide complete relief of angina for an acceptable procedural risk. Complete functional revascularisation of ischaemic myocardium is thus the goal and for this reason the presence of a chronic total occlusion (CTO) - which remain the most technically challenging lesions to revascularise percutaneously - is the most common reason for selecting coronary artery bypass surgery [1]. From the behaviour of Heart Teams it is clear that physicians believe that CTOs are important. Yet when faced with patients with CTOs for whom surgery appears excessive (e.g. nonproximal LAD) or too high risk, there remains a reluctance to undertake CTO PCI, despite significant recent advances in procedural success and safety and a considerable body of evidence supporting a survival benefit following successful CTO PCI. This article reviews the relationship between CTOs, symptoms of angina, ischaemia and left ventricular dysfunction and further explores the evidence relating their treatment to improved quality of life and prognosis in patients with these features.

Advances in Procedural Techniques - Antegrade

There have been many technological advances in antegrade CTO PCI, but perhaps most importantly has been the evolution of the “hybrid’ approach where ideally there exists a seamless interplay of antegrade wiring, antegrade dissection re-entry and retrograde approaches as dictated by procedural factors. Antegrade wire escalation with intimal tracking remains the preferred initial strategy in short CTOs without proximal cap ambiguity. More complex CTOs, however, usually require either a retrograde or an antegrade dissection re-entry approach, or both. Antegrade dissection re-entry is well suited to long occlusions where there is a healthy distal vessel and limited “interventional” collaterals. Early use of a dissection re-entry strategy will increase success rates, reduce complications, and minimise radiation exposure, contrast use as well as procedural times. Antegrade dissection can be achieved with a knuckle wire technique or the CrossBoss catheter whilst re-entry will be achieved in the most reproducible and reliable fashion by the Stingray balloon/wire. It should be avoided where there is potential for loss of large side branches. It remains to be seen whether use of newer dissection re-entry strategies will be associated with lower restenosis rates compared with the more uncontrolled subintimal tracking strategies such as STAR and whether stent insertion in the subintimal space is associated with higher rates of late stent malapposition and stent thrombosis. It is to be hoped that the algorithms, which have been developed to guide CTO operators, allow for a better transfer of knowledge and skills to increase uptake and acceptance of CTO PCI as a whole.

Procedure Planning: Anatomical Determinants of Strategy

In contemporary practice there are three main methods that can be employed when attempting to open a chronic total occlusion (CTO) of a coronary artery; antegrade or retrograde wire escalation, antegrade dissection re-entry and retrograde dissection re-entry. This editorial will attempt to clarify the anatomical features that can be identified to help when deciding which of these strategies to employ initially and help understand the reasons for this decision.

Steerable Sheath Technology in the Ablation of Atrial Fibrillation

Steerable sheaths have been shown to reduce procedure time in the catheter ablation of atrial fibrillation (AF), where catheter positioning and stability is typically challenging. This review critically addresses and highlights the recent developments in design of sheaths used to manipulate the ablation catheter and how these developments may impact on the ablation procedure itself, in particular the likelihood of first-time success. Patents relating to steerable sheaths are reviewed and discussed to gauge potential future developments in this area.

Emerging Evidence that Radial is Safer than Femoral Percutaneous Coronary Intervention in Subjects with ST Segment Elevation Myocardial Infarction.

Bleeding complications in patients with acute coronary syndromes are a significant predictor of mortality. Trans-radial approach (TRA) is a promising strategy to reduce bleedings in patients undergoing invasive coronary procedures. Recently, two multicentre prospective randomized trials aimed to test whether TRA, compared to trans-femoral approach (TFA), may improve clinical outcome in patients with ST-elevation myocardial infarction: the RIFLE STEAC and STEMI-RADIAL.

In the RIFLE STEACS, the primary endpoint of 30-day NACEs occurred in 68 patients (13.6%) in the TRA arm and 105 patients (21.0%) in the TFA arm (p = 0.003). In particular, compared with TFA, TRA was associated with significantly lower rates of cardiac mortality (5.2% vs. 9.2% , p = 0.020), bleeding (7.8% vs. 12.2%, p = 0.026), and shorter hospital stay (5 days, [range, 4 to 7 days]; vs. 6 [range, 5 to 8 days]; p = 0.03). In the STEMI-RADIAL, the primary endpoint of major bleeding or access site complications occurred in 7.2 percent of the TFA patients and 1.4 percent of the TRA patients (p=0.0001). The rate of MACE at 30 days was 4.2 percent in the TFA group, and 3.5 percent in the TRA group (p=0.7). The results of two recent trials support the systematic adoption of TRA instead of TFA approach to improve the clinical outcome of STEMI patients. In the present paper, we overview the results of these two trials and put them in the context of previous scientific evidences collected in this field.

Management of Retained Intervention Guide-wire: A Literature Review

Percutaneous coronary angioplasty is increasingly employed in the treatment of patients with complex coronary artery disease.

Different steerable guide wires used to open occluded vessel and facilitate balloon and stent deployment. However, the guide-wire itself is not without hazard: it may perforate or dissect the vessel, but fracture or entrapment is uncommon. Its management depends on the clinical situation of the patient, as well as the position and length of the remnant.

In this review we discuss the angioplasty guide-wire fracture and entrapment risk factors, potential risks and management.

The LIM Protein fhlA is Essential for Heart Chamber Development in Zebrafish Embryos

Four-and-a-half LIM proteins FHL1-3 play important roles in cardiovascular pathophysiology. However, their roles in heart development remain unclear. Here, we report that fhlA, the zebrafish homolog of human FHL1, was found to be expressed around the 22-somite stage. After 24 hpf, expression was restricted to the heart. fhlA knockdown caused an enlarged cardiac chamber phenotype with up-regulated expression of the cardiac markers, but fhlA overexpression reduced the sizes of the cardiac chambers and down-regulated expression of the markers. The morphology associated with the cmlc2, amhc, and vmhc expression patterns at the 22 somite and 24 hpf stages included a broadened domain in embryos lacking fhlA and a smaller domain in embryos overexpressing fhlA. The changes in the sizes of the chambers were attributed to the changes in the number of ventricular and atrial cells. Loss of fhlA caused a longer heart period and pause between heartbeats in M-modes than in controls, but fhlA overexpression caused shorter systolic and diastolic intervals. Abnormal cardiac chambers and physiological function were found to be largely rescued. We also showed the expression of fhlA in the heart to be increased by retinoic acid (RA) and decreased by the RA synthase inhibitor DEAB. Both fhlA and RA signaling caused a phenotype characterized by the morphological alterations in the chamber sizes, suggesting that the role of fhlA in heart development is probably regulated by RA signaling. Taken together, these results showed that fhlA regulates the size of the heart chamber by reducing the number of cardiac cells.

Herpetic (Non-Cytomegalovirus) Retinal Infections in Patients with the Acquired Immunodeficiency Syndrome

Human herpes viruses cause significant morbidity in patients with the acquired immunodeficiency syndrome. Even after the introduction of highly active anti-retroviral therapy (HAART), herpes viruses remain the leading causes of blindness in AIDS patients. Cytomegalovirus (CMV) retinitis and the closely-related immune reconstitution uveitis syndrome are the most common causes of blindness, but progressive outer retinal necrosis and acute retinal necrosis due to varicella zoster and herpes simplex are also important causes of vision loss. Successful treatment of these conditions requires an aggressive approach with multi-drug intravenous therapy or repeated intravitreal antiviral injections. Since the rate of retinal detachment is alarmingly high despite successful antiviral therapy, internists and ophthalmologists must work closely together to recognize and treat complications as they arise. Fortunately, Epstein-Barr virus is a rare cause of retinal infection and human herpes virus (HHV)-6, HHV-7, and HHV-8 do not appear to be primary pathogens. However, increasing evidence suggests that HHV-6 and HHV-7 play important roles in modulating the immune system and potentiating infection by CMV.

Heart Failure in Sub-Saharan Africa

The heart failure syndrome has been recognized as a significant contributor to cardiovascular disease burden in sub-Saharan African for many decades. Seminal knowledge regarding heart failure in the region came from case reports and case series of the early 20^th century which identified infectious, nutritional and idiopathic causes as the most common. With increasing urbanization, changes in lifestyle habits, and ageing of the population, the spectrum of causes of HF has also expanded resulting in a significant burden of both communicable and non-communicable etiologies. Heart failure in sub-Saharan Africa is notable for the range of etiologies that concurrently exist as well as the healthcare environment marked by limited resources, weak national healthcare systems and a paucity of national level data on disease trends. With the recent publication of the first and largest multinational prospective registry of acute heart failure in sub-Saharan Africa, it is timely to review the state of knowledge to date and describe the myriad forms of heart failure in the region. This review discusses several forms of heart failure that are common in sub-Saharan Africa (e.g., rheumatic heart disease, hypertensive heart disease, pericardial disease, various dilated cardiomyopathies, HIV cardiomyopathy, hypertrophic cardiomyopathy, endomyocardial fibrosis, ischemic heart disease, cor pulmonale) and presents each form with regard to epidemiology, natural history, clinical characteristics, diagnostic considerations and therapies. Areas and approaches to fill the remaining gaps in knowledge are also offered herein highlighting the need for research that is driven by regional disease burden and needs.

Post-cardiac Arrest Syndrome in Children

Although sustained return of spontaneous circulation (ROSC) can be initially established after resuscitation in children, many of the children do not survive to discharge because they developped a post cardiac arrest syndrome.

The post-cardiac arrest syndrome includes systemic ischaemia/reperfusion response, post-cardiac arrest brain injury, postcardiac arrest myocardial dysfunction, and persistent precipitating pathology. The main cause of death after ROSC in children is brain injury.

Physiopathology and management are reviewed in regards of pediatric specificities. Management according to ABCDE includes airway and ventilation management, oxygen therapy, hemodynamic management with early goal directed therapy and protection of the brain against secondary injury by therapeutic hypothermia, management of seizures and control of glycemia.

Complications Associated with Recombinant Tissue Plasminogen Activator Therapy for Acute Ischaemic Stroke

Intravenous recombinant human tissue plasminogen activator (rtPA, formulated as alteplase) is the primary therapy for acute ischaemic stroke by breaking down a clot of an occluded vessel. There are several randomised controlled trials and observational studies that support the use of rtPA to improve functional outcome following acute ischaemic stroke. However, thrombolytic therapy with rtPA can be associated with a number of complications. Many of the rtPArelated complications result from its thrombolytic action including bleeding (intracerebral and systemic haemorrhage), reperfusion injury with oedema, and angioedema. Other rtPA complications such as reocclusion and secondary embolisation are related to ineffective thrombolysis or redistribution of the lysed clot. In addition to its thrombolytic properties, rtPA can act upon the brain parenchyma leading to seizures and neurotoxicity. Many of these complications have been reported in both pre-clinical experiments and in clinical trials. In animal studies, these complications of rtPA can confound the experimental results achieved, and have to be taken into account in future experiments. In the clinical setting, these complications are not always life-threatening, but can be serious and often lead to prolonged stays in intensive care units, increase the need for medical treatment, lengthen hospital stays, delay rehabilitation and increase morbidity and mortality. Some of these complications could be prevented through adherence to treatment guidelines or at least minimised through early detection and proper management. It is imperative that physicians caring for stroke patients have knowledge of these complications associated with rtPA treatment, and their management.

Clinical Management of the Cardiovascular Failure in Sepsis

Cardiovascular failure in sepsis involves a combination of hypovolemia, decreased vascular tone, myocardial depression and microcirculatory alterations. Fluids represent the first line therapeutic intervention, with controversy regarding the type of fluid. Recent data indicate that albumin is safe and might even be beneficial in specific subgroups. Starches may be an alternative, although concerns exist on potential detrimental effects on renal function of old generation starches. Trials testing new generation starches are ongoing. When fluids fail to correct hypotension, vasopressor agents are used. Various adrenergic agents increase blood pressure, especially dopamine, noradrenaline and adrenaline, by stimulating alpha-adrenergic receptors. They also variably stimulate beta-adrenergic receptors, increasing cardiac contractility, heart rate, and splanchnic perfusion, but with increased risk of arrhythmias, immunomodulation and increased metabolism. Furthermore, dopamine stimulates dopaminergic receptors, resulting in doubtful effects on splanchnic and renal perfusion, but also in endocrine alterations. Do these pharmacologic differences among the various alpha-adrenergic agents translate into clinical differences? Several randomized trials tested the effects of these agents on outcome. Epinephrine produces more undesired effects than norepinephrine, but no clear cut differences on outcome were observed in underpowered trials. Norepinephrine should be preferred over dopamine, as suggested in one large trial and confirmed in a meta-analysis. Vasopressin may be considered as an alternative or in addition to adrenergic agents. In one large trial, no significant difference in outcome was observed, and the exact role of vasopressin still needs clarification. Finally, various inotropic agents can counteract septic myocardial depression. So far, no study supports their routine use, but these may be justified on an individual basis.

Microvascular Obstruction After Primary Percutaneous Coronary Intervention: Pathogenesis, Diagnosis and Prognostic Significance

The primary goal in reopening an infarct-related artery is the restoration of myocardial tissue-level perfusion. In a variable proportion of patients with ST-elevation myocardial infarction, however, microcirculatory impairment may persist after epicardial coronary artery recanalization. This phenomenon is known as microvascular obstruction (MVO). Ischemic injury, reperfusion injury, and distal embolization along with the individual response to each of these mechanisms are variably involved in the pathogenesis of MVO in the single patient. Importantly, MVO is associated with a worse prognosis both at short- and long-term follow-up. MVO can be assessed in the cath-lab by simple angiographic indexes, such as Thrombolysis in Myocardial Infarction grade score and Myocardial Blush Grade, or by invasive measures of coronary flow pattern. Imaging techniques, such as myocardial contrast echocardiography or cardiac magnetic resonance, and ST-segment resolution on standard electrocardiogram are used in the days following reperfusion with the patient in the coronary care unit. In this article, we review the available data regarding pathogenesis, diagnosis and the prognostic significance of MVO after primary percurtaneous coronary intervention in ST-elevation myocardial infarction patients, with a brief highlighting on the crucial role of its prevention and its early detection.

Neonatal Ultrasound in Transport

Current practices for monitoring the haemodynamics of critically ill newborns whilst in transport to tertiary care are poorly validated. These include arterial blood pressure monitoring, capillary return and urine output. Clinician performed ultrasound (CPU) has been validated in the NICU and is currently being trialled in transport. This case based discussion describes the retrieval of four newborn infants utilising CPU assessment of the newborn systemic blood flow and investigation of intracranial blood flow and pathology. Case one describes a baby with subgaleal haemorrhage who was pre arrest where the CPU (cardiac) allowed the treating team to effectively change the inotropes and alter the clinical course. Case two is a baby with the classical diagnostic dilemma of persistent pulmonary hypertension of the newborn (PPHN) versus cyanotic congenital heart disease (CCHD) – the screening CPU (cardiac) was able to define CCHD and the transport was re-directed to tertiary paediatric cardiac services. The CPU (cardiac) in case three, a baby born at 25 weeks, also assisted in the choice of therapeutic options for the treating team. Both case three and four were born at 25 week gestation and the CPU (cranial) provided information prior to transport that aided in the counselling of the parents.

Indications of Anti-Inflammatory Drugs in Cardiac Diseases

Throughout the history of cardiology, physicians have attempted to treat cardiac inflammatory diseases in a multitude of different ways. In recent years, three major developments have confirmed the important role of antiinflammatory drugs in cardiology: the development of new, more powerful drugs, the advent of evidence-based medicine, and the decline of rheumatic disease in western countries. Thus, we aim to review the indications for anti-inflammatory drugs in pericarditis and myocarditis. The management of pericarditis has been improved following the publication of the European guidelines in 2004. Indeed, recent randomized controlled trials highlighted the role of colchicine to i) prevent and treat recurrences of acute pericarditis and ii) prevent post pericardiectomy syndrome and its complications. With regard to the management of myocarditis, significant advances have been made towards further understanding the mechanisms involved, and in the identification of its underlying causes (especially viral vs. autoimmune). In addition, cardiac MRI and endomyocardial biopsy are now used to detect rare etiologies of myocarditis, which may benefit from immunosuppressive therapy (giant cell and eosinophilic myocarditis, cardiac sarcoidosis). Although broad consensus has yet to be reached regarding the management of acute myocarditis, identifying viral vs. autoimmune myocarditis allows a tailored treatment using antiviral or immunosuppressive drugs.

Colchicine: An Old Wine in a New Bottle?

Although colchicine, a natural product, is one of the oldest drugs still currently available, its possible functions seem to be surprisingly not well-known. Beyond its present medicinal use (gout, familial Mediterranean fever, Behcet’s disease, chondrocalcinosis and other crystal arthritis), numerous other conditions have been recently proposed for the use of this drug, including pericardial diseases. However, colchicine appears as a double-edged sword, with underestimated toxicity and frequent side effects. In this review, we present the main pharmacologic features of this drug, with an emphasis on toxicity and highlight its possible applications in the cardiovascular field.

Recent Advances in Transcatheter Heart Valve Replacement: A Review on Aortic and Mitral Implantation

Heart valve disease is a serious problem, especially in aging societies. If left untreated, many patients can die from the disease itself or complications associated with it. However, many are denied open-heart replacement surgeries due to advanced age and co-morbidities. Thus, other solutions had to be explored. One successful solution is transcatheter heart valve implantation and is now seen as the only viable treatment. Transcatheter heart valve implantation is a minimally invasive technique of inserting an artificial heart valve by means of a catheter without requiring open heart surgery. However, challenges are always there with every successful technology. Obstacles that need to be overcome include anatomical constraints, appropriate delivery technique, satisfactory performance of the transcatheter heart valve and so on. In this review, these challenges associated with aortic and mitral valve will be analyzed due to the prevalence of the diseases associated with them. On top of that, design considerations, hemodynamic performance and current stateof- the-art and recent patents of aortic and mitral valves are discussed, with particular emphasis on their engineering aspects.

Anesthesia for Bronchoscopy

Bronchoscopic procedures are at times intricate and the patients often very ill. These factors and an airway shared with the pulmonologist present a clear challenge to anesthesiologists. The key to success lies in the understanding of both the underlying pathology and procedure being performed combined with frequent two-way communication between the anesthesiologist and the pulmonologist. Above all, vigilance and preparedness are paramount.

Topics discussed in this review include anesthesia for advanced diagnostic procedures as well as for interventional/ therapeutic procedures. The latter includes bronchoscopic tracheal balloon dilation, tracheobronchial stenting, endobronchial electrocautery, bronchoscopic cryotherapy and other techniques. Special situations, such as tracheoesophageal fistula and mediastinal masses, are also considered.

Atrial Fibrillation in Acute St-Elevation Myocardial Infarction: Clinical and Prognostic Features

Atrial fibrillation (AF) is a common arrhythmia in the setting of acute coronary syndrome and acute ST-elevation myocardial infarction (STEMI). This review summarizes recent evidence on the clinical and prognostic significance of pre-existent and new-onset AF in acute STEMI patients and highlights new emerging predictors of AF development in the era of contemporary treatment.

Advances in Catheter Ablation: Atrial Fibrillation Ablation in Patients With Mitral Mechanical Prosthetic Valve

Atrial fibrillation (AF) is common in patients with mitral valve replacement (MVR). Treatment of AF in these subjects is challenging, as the arrhythmia is often refractory to antiarrhythmic drug therapy. Radiofrequency catheter ablation (RFCA) is usually avoided or delayed in patients with MVR due to the higher perceived risks and difficulty of left atrial catheter manipulation in the presence of a mechanical valve. Over the last few years, several investigators have reported the feasibility and safety of RFCA of AF in patients with MVR. Five case-control studies have evaluated the feasibility and safety of RFCA of AF or perimitral flutter (PMFL) in patients with MVR. Overall, a total of 178 patients with MVR have been included (21 undergoing ablation of only PMFL), and have been compared with a matched control group of 285 patients. Total procedural duration (weigthed mean difference [WMD] = +24.5 min, 95% confidence interval [CI] +10.2 min to +38.8 min, P = 0.001), and fluoroscopy time (WMD = +13.5 min, 95% CI +3.7 min to +23.4 min, P = 0.007) were longer in the MVR group. After a mean follow-up of 11.5 ± 8.6 months, 64 (36%) patients in the MVR group experienced recurrence of AF/PMFL, as compared to 73 (26%) patients in the control group, accounting for a trend toward an increased rate of recurrences in patients with MVR (odds ratio [OR] = 1.66, 95% CI 0.99 to 2.78, P = 0.053). Periprocedural complications occurred in 10 (5.6%) patients in the MVR group, and in 8 (2.8%) patients in the control group (OR = 2.01, 95% CI 0.56 to 7.15, P = 0.28). In conclusion, a quantitative analysis of the available evidence supports a trend toward a worse arrhythmia-free survival and a higher absolute rate of periprocedural complications in patients with MVR undergoing RFCA of AF or PMFL, as compared to a matched control group without mitral valve disease. These data would encourage the adoption of RFCA of AF in MVR patients mostly by more experienced Institutions.

Risk of Bleeding Related to Antithrombotic Treatment in Cardiovascular Disease

Antithrombotic therapy is a cornerstone of treatment in patients with cardiovascular disease with bleeding being the most feared complication. This review describes the risk of bleeding related to different combinations of antithrombotic drugs used for cardiovascular disease: acute coronary syndrome (ACS), atrial fibrillation (AF), cerebrovascular (CVD) and peripheral arterial disease (PAD). Different risk assessment schemes and bleeding definitions are compared. The HAS-BLED risk score is recommended in patients with AF and in ACS patients with AF. In patients with ACS with or without a stent dual antiplatelet therapy with a P2Y12 receptor antagonist and acetylsalicylic acid (ASA) is recommended for 12 months, preferable with prasugrel or ticagrelor unless there is an additional indication of warfarin or increased risk of bleeding. In patients with AF, warfarin is recommended if the risk of stroke is moderate to high, but newer emerging antithrombotic drugs will be recommended along with/or preferred to warfarin in the nearby future. Patients with CVD (without cardiogenic causes) are recommended clopidogrel treatment for secondary prevention, where as patients with PAD are recommended ASA or clopidogrel. With future implementation of new antithrombotic treatment regimens as monotherapy and in combinations with antiplatelet therapy, increased focus on risk of thromboembolic events and bleeding and individual tailoring of antithrombotic therapy is warranted.

Lung Ultrasound in the Critically Ill Neonate

Critical ultrasound is a new tool for first-line physicians, including neonate intensivists. The consideration of the lung as one major target allows to redefine the priorities. Simple machines work better than up-to-date ones. We use a microconvex probe. Ten standardized signs allow a majority of uses: the bat sign (pleural line), lung sliding and the A-line (normal lung surface), the quad sign and sinusoid sign indicating pleural effusion regardless its echogenicity, the tissuelike sign and fractal sign indicating lung consolidation, the B-line artifact and lung rockets (indicating interstitial syndrome), abolished lung sliding with the stratosphere sign, suggesting pneumothorax, and the lung point, indicating pneumothorax. Other signs are used for more sophisticated applications (distinguishing atelectasis from pneumonia for instance...). All these disorders were assessed in the adult using CT as gold standard with sensitivity and specificity ranging from 90 to 100%, allowing to consider ultrasound as a reasonable bedside gold standard in the critically ill. The same signs are found, with no difference in the critically ill neonate. Fast protocols such as the BLUE-protocol are available, allowing immediate diagnosis of acute respiratory failure using seven standardized profiles. Pulmonary edema e.g. yields anterior lung rockets associated with lung sliding, making the B-profile. The FALLS-protocol, inserted in a Limited Investigation including a simple model of heart and vessels, assesses acute circulatory failure using lung artifacts. Interventional ultrasound (mainly, thoracocenthesis) provides maximal safety. Referrals to CT can be postponed. CEURF proposes personnalized bedside trainings since 1990. Lung ultrasound opens physicians to a visual medicine.

The Patient with a Single Cardiac Ventricle

Patients born with a single cardiac ventricle are one of the most complex and challenging subgroups of congenital heart disease to manage, from their initial diagnosis to their long-term post-surgical sequelae. Advances in antenatal detection, operative techniques, and post-operative strategies have led to improved outcomes over the past two decades, yet morbidity and mortality remain high relative to other congenital heart lesions. Optimal management and outcome depend in part on a thorough understanding of the anatomy and physiology unique to these infants by all caregivers that may be involved including neonatologists, primary care pediatricians, emergency medicine physicians, and pediatric intensivists. This review will discuss in detail the course of these infants, from their birth through to their three stage surgical palliations and beyond. This review will also highlight many of the most recent medical and surgical innovations available to these infants.

Descending Necrotizing Mediastinitis: Current Strategies for Diagnosis and Treatment

Descending necrotizing mediastinitis is an acute, polymicrobial infection. Originating in the pharynx or neck, this necrotizing process descends into the chest producing widespread tissue necrosis. Despite the introduction of modern antimicrobial therapy and computed tomographic imaging, this form of mediastinitis has continued to produce reported mortality rates of 25% to 40%. This review discusses the pathophysiology, diagnosis and treatment of descending necrotizing mediastinitis with recommendations for treating physicians based on the modern literature.

Hemothorax

Hemothorax is most commonly seen following trauma or iatrogenic injury, but can be related to underlying medical issues. The primary issue to be determine dis whether or not the patient is stable and/or has ongoing hemorrhage. Simple tube thoracostomy usually suffices to manage the problem, but specific subsets of patients are at increased risk of complications, notably empyema. The role, type and timing of surgical intervention depends upon patient stability, underlying etiology and co-existing medical variables.