Cardiopulmonary Responses and Prognosis in Hypertrophic Cardiomyopathy

Abstract

Objectives

This study sought to discover the key determinants of exercise capacity, maximal oxygen consumption (oxygen uptake [Vo₂]), and ventilatory efficiency (ventilation/carbon dioxide output [VE/Vco₂] slope) and assess the prognostic potential of metabolic exercise testing in hypertrophic cardiomyopathy (HCM).

Background

The intrinsic mechanisms leading to reduced functional tolerance in HCM are unclear.

Methods

The study sample included 156 HCM patients consecutively enrolled from January 1, 2007 to January 1, 2012 with a complete clinical assessment, including rest and stress echocardiography and cardiopulmonary exercise test (CPET) with impedance cardiography. Patients were also followed for the composite outcome of cardiac-related death, heart transplant, and functional deterioration leading to septal reduction therapy (myectomy or septal alcohol ablation).

Results

Abnormalities in CPET responses were frequent, with 39% (n = 61) of the sample showing a reduced exercise tolerance (Vo₂ max <80% of predicted) and 19% (n = 30) characterized by impaired ventilatory efficiency (VE/Vco₂ slope >34). The variables most strongly associated with exercise capacity (expressed in metabolic equivalents), were peak cardiac index (r = 0.51, p < 0.001), age (r = –0.25, p < 0.01), male sex (r = 0.24, p = 0.02), and indexed right ventricular end-diastolic area (r = 0.31, p = 0.002), resulting in an R² of 0.51, p < 0.001. Peak cardiac index was the main predictor of peak Vo₂ (r = 0.61, p < 0.001). The variables most strongly related to VE/VCO2 slope were E/E′ (r = 0.23, p = 0.021) and indexed left atrial volume index (LAVI) (r = 0.34, p = 0.005) (model R² = 0.15). The composite endpoint occurred in 21 (13%) patients. In an exploratory analysis, 3 variables were independently associated with the composite outcome (mean follow-up 27 ± 11 months): peak Vo₂ <80% of predicted (hazard ratio: 4.11; 95% confidence interval [CI]: 1.46 to 11.59; p = 0.008), VE/Vco₂ slope >34 (hazard ratio: 3.14; 95% CI: 1.26 to 7.87; p = 0.014), and LAVI >40 ml/m² (hazard ratio: 3.32; 95% CI: 1.08 to 10.16; p = 0.036).

Conclusions

In HCM, peak cardiac index is the main determinant of exercise capacity, but it is not significantly related to ventilatory efficiency. Peak Vo₂, ventilatory inefficiency, and LAVI are associated with an increased risk of major events in the short-term follow-up.