Cardiac function, haemodynamics, and valve competence with exercise in patients with heart failure with preserved ejection fraction and mild to moderate secondary mitral regurgitation

Abstract

Aims: This study aimed to evaluate the clinical significance of secondary mitral regurgitation (MR) in patients with heart failure with preserved ejection fraction (HFpEF).

Methods and results: We conducted a prospective study enrolling consecutively evaluated patients with HFpEF undergoing invasive haemodynamic exercise testing with simultaneous echocardiography. Compared to HFpEF without MR (n = 145, 79.7%), those with mild or moderate MR (n = 37, 20.3%) were older, more likely to be women, had more left ventricular (LV) systolic dysfunction, and more likely to have left atrial (LA) myopathy reflected by greater burden of atrial fibrillation, more LA dilatation, and poorer LA function. Pulmonary artery (PA) wedge pressure was higher at rest in HFpEF with MR (17 ± 5 mmHg vs. 20 ± 5 mmHg, p = 0.005), but there was no difference with exercise. At rest, only 2 (1.1%) patients had moderate MR, and none developed severe MR. Pulmonary vascular resistance was higher, and right ventricular (RV)-PA coupling was more impaired in patients with HFpEF and MR at rest and exercise. LV and LA myocardial dysfunction remained more severe in patients with MR during stress compared to those without MR, characterized by greater LA dilatation during all stages of exertion, lower LA emptying fraction and compliance, steeper and rightward-shifted LA pressure-volume relationships, and reduced LV longitudinal contractile function.

Conclusions: Patients with HFpEF and mild or moderate MR have more severe LV systolic dysfunction, LA myopathy, RV-PA uncoupling, and more severe pulmonary vascular disease. Mitral valve incompetence in this setting is a phenotypic marker of more advanced disease but is not a causal factor in development of HFpEF.

Keywords: Echocardiography; Exercise; Haemodynamics; Heart failure with preserved ejection fraction; Mitral regurgitation.

Figure 1.. Grading the severity of MR.

MR severity was assessed according to the guidelines using a combination of visual and quantitative assessment when technically feasible. LA, left atrial; LAVI, left atrial volume index; MR, mitral regurgitation; and VCW, vena contracta width.

Figure 2.. MR severity throughout exercise.

(A) Among 182 patients with HFpEF who could be evaluated for MR both at rest and during peak exercise, only 2 cases (1%) showed moderate MR at rest, while the majority (n=145, 80%) did not show any MR. During 20W exercise, MR severity could not be evaluated due to poor image quality in 6 (3%) patients. The proportion of MR severity during exercise was as follows: 20W: absent 132 (75%), mild 42 (24%), moderate 2 (1%), and Peak: absent 134 (74%), mild 46 (25%), moderate 2 (1%). (B) Sankey diagrams illustrate the change in MR severity throughout exercise. At least 1 grade worsening in MR severity with exercise was observed in 15 cases (absent to mild, n=14; mild to moderate, n=1) at up to 20W and in 15 (absent to mild, n=14; mild to moderate, n=1) at peak exercise. HFpEF, heart failure with preserved ejection fraction; and other abbreviations as in Figure 1.

Figure 3.. Tissue Doppler velocity, LV and LA strains, and LA sizes and function at each stage of exercise.

(A) While medial e’ velocity was not different between the two groups, patients with HFpEF and MR had lower medial s’ velocity during all stages than in those without. (B) At rest, LA reservoir strain was comparable among the group, while LV longitudinal strain was reduced in patients with HFpEF and MR. During exercise, both were lower in patients with HFpEF and MR than in those without MR. (C) LA volumes were larger, and (D) LA emptying fraction was lower in patients with HFpEF and MR during all stages than in those without MR. *Age, sex, and BMI adjusted p<0.05 versus HFpEF without MR. ^†Age, sex, and BMI adjusted p<0.01 versus HFpEF without MR. Error bars reflect SEM. LV, left ventricular; and other abbreviations as in Figures 1 and 2.

Figure 4.. LA pressure-volume relationships.

In patients with HFpEF and MR, there was a greater limitation in the change in LA volume (LA max volume – LA min volume) to that in LA pressure (PAWP v-wave – nadir x-descent) during ventricular systole at rest (A) (LA volume compliance, 3.6 [1.9, 6.6] mL/mmHg vs. 2.2 [0.7, 3.5], adjusted p=0.004*) and during exercise (B) (1.8 [1.0, 3.4] mL/mmHg vs. 1.1 [0.6, 1.6], adjusted p=0.02*), suggesting more reduced LA compliance. Error bars reflect SEM. *: Adjusted for age, sex, and body mass index. LA max/min vol; LA max/minimal volume, PAWPv; PAWP v-wave, PAWPx, PAWP nadir x-descent; and other abbreviations as in Figures 1 and 2.