Diagnosis and Treatment of Right Heart Failure in Pulmonary Vascular Diseases: A National Heart, Lung, and Blood Institute Workshop

Abstract

Right ventricular dysfunction is a hallmark of advanced pulmonary vascular, lung parenchymal, and left heart disease, yet the underlying mechanisms that govern (mal)adaptation remain incompletely characterized. Owing to the knowledge gaps in our understanding of the right ventricle (RV) in health and disease, the National Heart, Lung, and Blood Institute commissioned a working group to identify current challenges in the field. These included a need to define and standardize normal RV structure and function in populations; access to RV tissue for research purposes and the development of complex experimental platforms that recapitulate the in vivo environment; and the advancement of imaging and invasive methodologies to study the RV within basic, translational, and clinical research programs. Specific recommendations were provided, including a call to incorporate precision medicine and innovations in prognosis, diagnosis, and novel RV therapeutics for patients with pulmonary vascular disease.

Coronary blood flow in heart failure: cause, consequence and bystander

“…The right ventricle, however, is more affected in pulmonary hypertension. The failing right ventricle has only recently received more attention, [ 79 , 130 , 261 ] and the coronary circulation in right ventricular failure has received little attention at all. Yet, there are some special considerations to the coronary circulation in the right ventricle, [ 35 ] since coronary perfusion pressure is above right ventricular pressure throughout the cardiac cycle such that extravascular compression and diastolic duration during tachycardia are of lesser importance than in the LV.…”

“…Patients with chronic pulmonary hypertension have reduced right coronary artery blood flow in proportion to right ventricular hypertrophy [ 257 ] and reduced adenosine-recruitable coronary reserve on MRI [ 262 ]. A recent NIH consensus workshop recommended directions for future research on the genetic, molecular and cellular processes in right heart failure, [ 130 ] but further research on the coronary circulation in right heart failure is also warranted. Arrhythmogenic right ventricular cardiomyopathy is a relatively infrequent form of human heart failure, caused by genetic mutations mostly in desmosomal proteins and characterized morphologically by diffuse fibrosis and inflammatory infiltration [ 68 ].…”

Right ventricular function across the spectrum of health and disease

“…These knowledge gaps impair patient management and may adversely impact clinician decision-making and overall clinical outcomes. It remains to be determined how factors such as demographics, comorbidities and modifiable risk factors influence RV function across the lifespan 5 6. Also unclear is how variations in genomic, proteomic and metabolomic profiles influence RV physiology in normal and diseased states, which may guide identification of novel therapeutic targets 6.…”

“…Early on, it was concluded that a normally functioning RV ‘is not necessary for the maintenance of a normal circulation’3 and one whose function was limited to that of a conduit between the venous and pulmonary circuits 4. However, the centrality of the RV to normal cardiovascular and pulmonary physiology, as well as symptom burden and overall outcomes in cardiovascular and pulmonary disease, is increasingly recognised 5 6. Nevertheless, large gaps in knowledge persist regarding function of the RV in normal healthy individuals, as well as RV pathophysiology in cardiovascular and pulmonary disease, and finally, effective methods for managing RV dysfunction in these populations 5 6.…”

“…However, the centrality of the RV to normal cardiovascular and pulmonary physiology, as well as symptom burden and overall outcomes in cardiovascular and pulmonary disease, is increasingly recognised 5 6. Nevertheless, large gaps in knowledge persist regarding function of the RV in normal healthy individuals, as well as RV pathophysiology in cardiovascular and pulmonary disease, and finally, effective methods for managing RV dysfunction in these populations 5 6. The American Heart Association recently emphasised that ‘It is remarkable how misunderstood are some basic concepts of right sided heart dysfunction among practicing clinicians and the impact that such misunderstanding can have on appropriate patient management’ 5.…”