Title:The Right Ventricle in Pulmonary Arterial Hypertension: An Organ at
the “Heart of the Problem”
Volume: 20
Issue: 3
Author(s): Siddharth Singh and Michael I. Lewis*
Affiliation:
- Department of Cardiology, Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
- Department of Medicine, Pulmonary & Critical Care Medicine, Cedars Sinai Medical Center, Los Angeles, CA
90048, United States
Keywords:
Right ventricle, pulmonary arterial hypertension, adaptive RV hypertrophy, maladaptive RV hypertrophy, RV systolic and diastolic dysfunction, pathobiology of RV muscle, workup of RV function, right heart catheterization, echocardiogram, cardiac magnetic resonance scan, BNP, pulmonary artery elastance, RV functional reserve, chronic right heart failure, novel therapies.
Abstract: Pulmonary Arterial Hypertension (PAH) is a progressive disease with no cure. A major
determinant of outcome is the function of the right ventricle (RV). Unfortunately, progressive RV
dysfunction and failure can occur despite PAH-specific therapies. While initial adaptive hypertrophic
changes occur to maintain cardiac output and preserve contractile function and reserve,
maladaptive changes occur in the RV muscle that contribute to RV systolic and diastolic dysfunction
and failure. These include impaired angiogenesis / decreased capillary density with ischemia,
fibrosis, cardiomyocyte apoptosis and impaired autophagy, inflammation, enhanced oxidative
stress, altered metabolism, etc. Of note, there are no therapies currently approved that offset these
changes and treatment of RV dysfunction is largely supportive only. Further patients often do not
qualify for bilateral lung transplantation because of co-morbidities such as renal impairment.
Thus, a dire unmet need exists regarding the management of RV dysfunction and failure in patients
with PAH. In this State-of-the-Art review, we comprehensively outline the unique features
of the RV compared to the left ventricle (LV) under normal circumstances and highlight the
unique challenges faced by the RV when confronted with increased afterload as occurs in PAH.
We provide detailed insights into the basis for the adaptive hypertrophic phase as well as detailed
commentary into the pathophysiology of the maladapted dysfunctional state as well as the pathobiological
aberrations occurring in the RV muscle that underlines the progressive dysfunction and
failure that commonly ensues. We also review comprehensively the evaluation of RV function using
all currently employed imaging, hemodynamic and other modalities and provide a balanced
outline of strengths and limitations of such approaches with the treating clinician in mind. We outline
the current approaches, albeit limited to chronic multi-modal management of RV dysfunction
and failure. We further outline new possible approaches to treatment that include novel pharmacologic
approaches, possible use of cellular/stem cell therapies and mechanical approaches. This review
is directed to the treating clinician to provide comprehensive insights regarding the RV in patients
with PAH.
