Determinants of cardiopulmonary exercise test responses in hypertrophic cardiomyopathy
Authors: Foccardi G , Chernis K , Quinto G , Baioccato V , Vecchiato M , Ortolan S , Battista F , Neunhaeuserer D , Ermolao A , Gasperetti A 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Exercise capacity and ventilatory efficiency are often altered in hypertrophic cardiomyopathy (HCM) and several factors have been advocated as possible causes.

Aim
This study investigates the determinants of cardiopulmonary exercise test (CPET) prognostic markers for HCM (VO2Peak, VE/VCO2 Slope and PETCO2 apex), by considering echocardiographic and cardiac magnetic resonance (CMR) parameters. Secondly, it scopes if myocardial fibrosis at CMR leads to clinical and functional differences.

Methods
64 patients with HCM underwent a clinical assessment, including maximal CPET, echocardiography, and CMR. Exclusion criteria were the corrective surgery for cardiac hypertrophy and heart failure stage.

Results
The study included 66% males, age 40±17 years, NYHA class I or II 91%. Mean left ventricle (LV) ejection fraction was 63,8±7,7%, with a mean LV maximal wall thickness (MVT) of 20,2±5,6 mm; LVOT gradient was &gt;30mmHg in 14% of patients. Late gadolinium enhancement (LGE) was described in 70,3% of cases with a mean LGE extension on bullseye plot of 11%. 39% of patients had a VO2 peak &lt;80% of predicted, 35% a reduced PETCO2 apex and 26% an increased VE/VCO2 Slope.
At the stepwise multivariate analysis, age (β=-0,33; p=0,00), BMI (β=-0,80; p=0,002), systolic blood pressure increase (β=0,22; p=0,02), left atrial volume (β=-0,15; p=0,02) and BB therapy (β=-0,45; p=0,00) were independently associated with VO2 peak (R2-adjusted index 0,95).
Concerning ventilatory efficiency, sex (β=-0,41; p=0,03), left atrial volume (β=0,46; p=0,01) and LGE extension (β=0,33; p=0,01) were independently associated with VE/VCO2 Slope (R2-adjusted index 0,46). Similar data, with reversed correlations, emerged for PETCO2 apex.
Patients with LGE had a LV mass index (mean 104,6 vs 82,7 g/m2, p=0,04), MWT (mean 21,8 vs 16,2 mm, p=0,00) and diastolic function (mean E/e’ 13,4 vs 10,0, p=0,01) worse that the counterpart. No differences were found in sex, age, therapy, CPET parameters and arrhythmic burden.
BB+ patients were older, had more LV hypertrophy, worse diastolic parameters, and functional capacity while ventilatory efficiency was similar.

Conclusions
This study supports previous data about VO2 peak determinants.
The correlation between the extension of the LGE and ventilatory efficiency in patients with HCM is an original finding. It confirms the pathophysiological explanation of a lung ventilation/perfusion mismatch due to the increased left atrium pressure that is secondary to a more severe LV diastolic disfunction in patients with LGE.
The reduced VO2 in BB+ compared to BB- patients is not inferable given the different age and severity of disease. Moreover, the negative chronotropic effect of BB during exercise prolongs the diastolic filling time, thus, improving stroke volume and alleviating the LV filling pressures, thus normalising, in the less advanced stages of pathology, the ventilatory efficiency in HCM patients.