In response to high ventricular afterload, the thin-walled RV hypertrophies but then quickly dilates and fails. The initial adaptive response of the RV is to hypertrophy, tested in a goat model of pulmonary trunk banding to increase RV afterload.13
This increase in RV mass comes at a greater oxygen requirement. In a canine study, Saito et al.30
showed that both normal and hypertrophied RVs are able to augment coronary flow to meet oxygen requirements but that the hypertrophied myocardium has a lower oxygen extraction reserve ultimately making it less efficient at oxygen utilization despite higher demand. Following further increase in RV mass, the contractile force decreases with subsequent chamber dilatation to maintain stroke volume in the face of decreasing fractional shortening. Ultimately, the RV fails with rising filling pressures and decreasing stroke volume due to a vicious cycle of increasing wall tension with increasing myocardial oxygen demand that leads to further decreased contractility and dilatation.31
Pulmonary arterial hypertension (PAH) remains a deadly disease characterized by vasoconstriction and remodeling of the pulmonary vascular bed with subsequent increase in pulmonary vascular resistance. This presents a higher afterload on the RV, with RV function a primary predictor of long-term survival in this disease.32
The mechanism underlying progression from adaptive RV hypertrophy in this setting to maladaptive remodeling is not clear, but based on experiences with lung transplant patients, RV failure appears to be reversible in most cases following RV pressure unloading.33
In cases of ventricular pressure overload with hypertrophied myocardium, animal models show that myocardial glucose uptake and glycolytic rate are increased while fatty acid metabolism is decreased.34,26
Therefore, metabolic changes in the hypertrophied RV mimic changes in metabolism demonstrated in the hypertrophied and failing LV. Evaluation with magnetic resonance spectroscopy can correlate cardiac structure with metabolic function and Nagaya et al.28
assessed 21 patients with RV hypertrophy due to pulmonary hypertension and found disproportionately decreased RV contractility in patients with impaired myocardial fatty acid uptake. Bokhari et al.35
have validated PET imaging as a viable method for quantifying myocardial glucose uptake and utilization in a study of 16 patients with idiopathic PAH. They found that RV glucose use correlates with hemodynamic parameters including mean PA pressure, presumably indicating RV functional impairment with the shift in myocardial glucose uptake serving as a marker of RV dysfunction. Similar findings were shown by Can et al.36
who studied 23 patients with PAH and 16 healthy controls studied by PET. They found that increased fludeoxyglucose accumulation in the RV myocardium was correlated with increased RV loading conditions and the presence but not severity of elevated pulmonary artery pressures.
So far, little is known on lipid storage in the normal or failing RV. Localized 1
H magnetic resonance spectroscopy is the only imaging modality at this time that can measure triglyceride content in tissue.37,38
Szczepaniak et al.37
found that increased myocardial triglyceride content is associated with elevated LV mass and suppressed septal wall thickening.37
Magnetic resonance spectroscopy measurement of myocardial triglyceride content has been shown to have good statistically significant correlation with triglyceride levels by RV biopsy, proving it a reliable tool in metabolic imaging of cardiac disease.39
However, no study has quantified levels of lipid intermediates in the RV.