Impact of discontinuing afterload-reducing medication on left ventricular outflow tract gradient in hypertrophic obstructive cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetic heart disease, affecting around one in 500 people. Depending on the presence of left ventricular outflow tract obstruction (LVOTO), HCM is categorized into hypertrophic non-obstructive cardiomyopathy (HNCM) or hypertrophic obstructive cardiomyopathy (HOCM). Patients with HOCM often face a higher likelihood of developing comorbidities such as arterial hypertension (AH) and symptoms of heart failure (HF). For this reason, they might be prescribed medication to reduce afterload, intended to treat HF or AH. Paradoxically, this medication can worsen both - symptoms and LVOTO. Current guidelines for HOCM treatment advise against the use of afterload-reducing drugs. Nevertheless, clinical data on this are scarce. This study aims to demonstrate the advantages of discontinuing such medication in HOCM patients.

Twenty-four patients diagnosed with HOCM, who were taking afterload-reducing medication during their first outpatient visit, were included in this single-centre retrospective analysis. Angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and dihydropyridine-type calcium channel blockers (CCB-DHPs) were classified as afterload-reducing medications. The study investigated the effects of discontinuing afterload-reducing medication in comparison to patients who persisted in their usage despite medical advice. These groups were analyzed to assess changes in LVOTO following the discontinuation or continuation of medication.

Twenty-four patients with HOCM and receiving afterload-reducing medication (43.8% male, median age 65.8 ± 7.5 years) were included in this study. Out of these, sixteen patients discontinued their afterload-reducing medication resulting in a significant decrease in the median LVOT gradient from 86.5 [60.5-109.3] mmHg to 61.5 [28.3-97.5] mmHg (p = 0.0004). Among these cases, beta-blocker therapy was either initiated or its dose was increased concomitantly in six patients. However, the reduction in LVOT gradient remained significant in the residual ten patients (p = 0.001). In contrast, the eight patients who continued their afterload-reducing medication did not show a significant change in the gradient (56.5 [41.5-63.3] mmHg to 67.5 [47.5-77.3] mmHg; p = 0.14).

Discontinuation of afterload-reducing drugs leads to a significant reduction in LVOTO in patients with HOCM, regardless of whether beta-blocker therapy is initiated simultaneously. Our study emphasizes the importance of abstaining from afterload-reducing drugs in HOCM patients. This straightforward therapeutic strategy alleviates symptoms and LVOTO, aligning with the recommendations of the recently published European guidelines that suggest beta-blockers, non-dihydropyridine calcium channel blockers, or mavacamten for treating HOCM patients.

Figure 1: Changes in maximum left ventricular outflow tract (LVOT) gradient in HOCM patients after discontinuation of afterload-reducing medication (n=16) and remaining on afterload-reducing medication (n=8).