Right Ventricular Failure | NEJM
Highlights
- The right ventricle and left ventricle are not distinct structures but rather are integrated anatomically and physiologically through the interventricular septum, with the right ventricle depending on the left ventricle for a substantial portion of its contractile function. This interaction is intensified in the context of right ventricular failure (View Highlight)
- The helical orientation of the myofibrils in the septum produces a primarily longitudinal contractile pattern, whereas the circumferential fibers in the right ventricular free wall contribute a transverse shortening pattern. The latter is less prominent in normal physiology. (View Highlight)
- Mechanical mechanisms contributing to right ventricular failure can be conceptualized in four primary categories: excessive preload, excessive afterload, reduced contractility, and reduced lusitropy (View Highlight)
- Myocyte hypertrophy serves initially as a compensatory mechanism. Progressive hypertrophy increases oxygen demand in excess of supply, which ultimately results in right ventricular dilatation, impaired contractility, and decompensation (View Highlight)
- The right ventricular metabolic substrate utilization in patients with pulmonary arterial hypertension is characterized by an increase in glycolysis and glucose oxidation and a reduction in beta-oxidation. This switch is relatively oxygen-efficient at the cost of lower ATP production (View Highlight)
- Delivery of fatty acid substrates in excess of mitochondrial oxidative capacity may result in accumulation of toxic lipid species, known as lipotoxicity (View Highlight)
- Chronically increased afterload from any cause results in right ventricular hypertrophy,9 which is initially adaptive and accompanied by an increase in contractility and preserved stroke volume (homeometric adaptation). These early compensatory mechanisms are achieved in part by neurohormonal activation with increased adrenergic tone. As in left heart failure, neurohormonal activation ultimately becomes maladaptive, characterized by reduced right ventricular beta1-adrenergic receptor density, depletion of tissue adrenergic effectors, and failure of myocyte adenylate cyclase stimulation in response to beta agonists (View Highlight)
- Over time, as contractility declines or afterload further increases, the right ventricle must dilate to maintain stroke volume (heterometric adaptation). Right ventricular ischemia may result from a mismatch between increased oxygen demand and reduced coronary arterial perfusion due to increased wall stress with hypertrophy and capillary rarefaction.11 Right ventricular ischemia and reduced right coronary artery flow are reported in patients with pulmonary hypertension and are proportional to right ventricular mass and end-diastolic pressure (i.e., wall stress).12,13 Eventually, oxygen demand exceeds supply and contractility further declines, resulting in a state of ventriculoarterial uncoupling and right ventricular failure (View Highlight)
- Mechanical stress, ischemia, and neurohormonal activation stimulate the production and proliferation of cardiac fibroblast collagen.15 Early in the disease, increased collagen production may provide protection against right ventricular dilatation. As fibrosis progresses, right ventricular diastolic function and excitation–contraction coupling worsen and contractility is impaired. Right ventricular fibrosis is most prominent at the septal insertion points where mechanical stress is highest but is also observed in the right ventricular free wall. (View Highlight)
- Lusitropic abnormalities occur not only from increased collagen and fibrosis but also from intrinsic stiffening of the right ventricular cardiomyocyte sarcomeres (View Highlight)
- In adults, the right ventricle derives energy primarily through fatty acid oxidation, which accounts for 60 to 90% of ATP production (View Highlight)
- Patients with chronic pulmonary hypertension have marked right ventricular glucose uptake, which correlates inversely with right ventricular function and is partially reversed with pulmonary vasodilator therapy. These observations suggest dynamic substrate utilization by the right ventricle (View Highlight)
- Diabetes is associated with worse right ventricular systolic and diastolic function in patients with dilated cardiomyopathy or pulmonary arterial hypertension, and right ventricular remodeling is present in patients with uncomplicated diabetes or prediabetes.20,21 Potential contributing mechanisms include promotion of myocardial fibrosis, inflammation, microvascular ischemia, and lipotoxicity. (View Highlight)
- The optimal Ees:Ea ratio, meaning the ratio at which maximal transfer of potential energy from the ventricle to the circulation occurs, is 1.5 to 2.0 (View Highlight)
- In pulmonary hypertension, Ees initially increases to offset the increase in Ea, maintaining RV-PA coupling. Eventually, lack of additional contractile reserve leads to an increase in Ea that is out of proportion to Ees. RV-PA uncoupling is indicated by a ratio below 0.6 to 0.826,27 and has been associated with worse outcomes (View Highlight)
- As compared with pulmonary vascular resistance, arterial elastance is a more comprehensive description of afterload because it accounts for both resistive and pulsatile components (View Highlight)