Testing the degree of right ventricle exercise contractile reserve (RVECR) may reveal different phenotypes in heart failure (HF), and impaired RV function at rest may not necessarily lead to an unfavorable RVECR and exercise RV to pulmonary circulation (PC) coupling, according to a study that examined severely failing RV, published in JACC: Heart Failure.
As the study authors explained, the development of RV dysfunction and failure is considered a “turning point” in a patient’s history of heart failure and signifies a worsening outcome. They sought to determine whether the severely failing RV at rest might still improve function during maximal exercise, to find the hemodynamic and cardiac correlates of RVECR, and ultimately, to identify the cardiopulmonary exercise testing phenotype commonly associated with preserved or impaired RVECR.
A total of 97 patients with heart failure reserved ejection fraction (HFrEF) were enrolled in the study between September 2012 and June 2015. Researchers divided the patients into 3 groups based on tricuspid annular plane systolic excursion (TAPSE) at rest, with a cutoff at 16 mm: 60 patients in Group A had a TAPSE ≥16 mm at rest and 37 patients had a TAPSE <16 mm. In the latter group, 2 phenotypes were identified by the patients’ RVECR, which was defined as a median exercise-induced TAPSE increase (15.5 mm). In Group B, 19 patients had a preserved RVECR and in Group C, 18 patients had an impaired RVECR.
Echocardiography was conducted at rest and during exercise to assess systolic, diastolic, and valvular functions, while Doppler echocardiography was utilized to measure early mitral peak (E) and late wave flow velocity (A). LV end diastolic volume indexed and LV mass were measured at rest, while relative wall thickness, left atrial volume, and LV ejection fraction (EF) were measured at rest and during exercise. Finally, RV dimensions were determined by the RV end-diastolic area.
Patients were followed up every 6 months after enrollment via hospital and outpatient medical chart review for major cardiac-related events (both hospitalization and mortality).
With regard to age, sex, and risk factors, the 3 groups were similar. However, a more severe degree of dyspnea and a higher use of potassium-sparing diuretics were seen in Group C. All patients reached a peak exercise RER > 1.1, though Group C had worse exercise tolerance compared with Group B (lower maximal workload, peak VO2, and peak O2 pulse).
In addition, Group C had severely impaired ventilatory efficiency (steeper VE/VCO2 slope and lower peak end-tidal CO2) and lower ventilatory power. Exercise oscillatory ventilation rates were not different among the groups, but a higher trend was observed in Group C. Patients in Group C also exhibited lower peak systolic, diastolic, and pulse pressures.
Group C exhibited significantly worse remodeling with increased left atrium and LV mass index, though there were no group differences in the LVEF at rest and at peak exercise. While patients in Group C presented higher grade III diastolic dysfunction rates, increased pulmonary veins S/D and E/e’ ratios, Groups B and C showed significantly reduced TAPSEs, RV fractional areas, and s’.
At a median period of 16 months, the hospitalization and cardiac-related mortality rates did not reach statistical significance in any of the 3 groups, although Group C had a higher mortality rate.
Based on these results, researchers concluded that HF with similar LV function impairment is associated with RV contractile reserve phenotypes, and that a lack of RVECR is associated with worse ventilation and aerobic efficiency. They also concluded that correlates of worse RV to PC coupling during exercise are the net-change in pulmonary artery systolic pressure increase and severe functional mitral regurgitation at rest.
“Our findings have possibly shifted the paradigm from an isolated RV systolic performance assessment to a RV contractile functional reserve analysis, thus allowing to phenotype different RV adaptive patterns that are unpredictable at rest,” researchers noted. “Specifically, the identification of those RV chambers that, despite a depressed function at rest, are still responsive to inotropic stimuli might provide best insights on clinical decision making such as indications for valve surgery, LVAD [left ventricular assist device] implantation, and transplantation.”
Further investigation is required to determine the value of “unmasking exercise-induced RV to PC adaptive response” in patients with severely compromised RV function at rest. Researchers concluded that while no specific pharmacological therapies have been identified, their study may help provide a clearer characterization of right heart disease and its reversibility in HF.
Guazzi M, Villani S, Generati G, et al. Right ventricular contractile reserve and pulmonary circulation uncoupling during exercise challenge in heart failure: pathophysiology and clinical phenotypes. JACC Heart Fail. 2016. doi:10.1016/j.jchf.2016.03.007.