Therapeutic Window for Calcium-Channel Blockers in the Management of Dilated Cardiomyopathy: A Prospective, Two-Centre Study on Non-Advanced Disease

Abstract

Objective: This study aimed to investigate the usefulness of the calcium-channel blocker verapamil in non-advanced dilated cardiomyopathy (DCM). Methods: This was a randomised trial of 70 DCM patients treated with carvedilol (36 patients) and verapamil (instead of β-blocker; 34 patients) for 12 months. The remaining heart failure (HF) therapy was constant in both groups. The primary outcomes were to determine selected echocardiography parameters and functional status of patients. The secondary outcome included death, heart transplantation and re-hospitalisation due to HF progression. Results: Of the primary outcomes, only the mean ratio of early to late transmitral flow velocities increased significantly in the verapamil-treated patients as compared with the carvedilol-based therapy (1.1 ± 0.3 vs. 0.7 ± 0.2; 95% CI –0.6 to –0.1; p = 0.015). Simultaneously, the Minnesota Quality of Life improved significantly in the verapamil group (95% CI 5.2–19.9; p = 0.002). It was accompanied by the favourable effect of verapamil therapy on exercise capacity in the 6-min walk test (95% CI 21.3–110.7; p = 0.005). Conclusion: The addition of verapamil to angiotensin-converting enzyme and aldosterone inhibitors in non-advanced DCM patients has been shown to have a neutral or even positive effect in a few patients.

Pharmacological Modulation of Calcium Homeostasis in Familial Dilated Cardiomyopathy: An In Vitro Analysis From an RBM20 Patient‐Derived iPSC Model

“…In conclusion, familial DCM hiPSC‐CMs display increased susceptibility to β‐adrenergic stimulation by defective Ca 2+ homeostasis, apoptotic changes, and sarcomeric disarray, and pretreatment with carvedilol or verapamil mitigates this stress response. Accordingly, clinical studies indicate that addition of verapamil in patients with nonadvanced DCM improved their Minnesota Quality of Life score and exercise capacity in the 6‐min walk test compared with standard carvedilol‐based therapeutic management . Here, we provide the first comprehensive in vitro analysis of β‐adrenergic stress in RBM20 ‐deficient familial DCM hiPSC‐CMs, allowing for further development of therapeutic interventions that modify heart disease progression.…”

“…Accordingly, clinical studies indicate that addition of verapamil in patients with nonadvanced DCM improved their Minnesota Quality of Life score and exercise capacity in the 6-min walk test compared with standard carvedilol-based therapeutic management. 24 Here, we provide the first comprehensive in vitro analysis of β-adrenergic stress in RBM20-deficient familial DCM hiPSC-CMs, allowing for further development of therapeutic interventions that modify heart disease progression.…”

“…Individuals with DCM caused by RBM20 mutations are generally treated with standard heart‐failure therapies, including β‐blockers. Additionally, L‐type Ca 2+ channel‐blocking drugs, which show vasospasm prevention and restoration of impaired Ca 2+ handling, are promising with respect to treatment of heart failure secondary to DCM . Although genotype‐positive family members can be identified preclinically, no preventative interventions have been studied.…”

Blockade of ICa suppresses early afterdepolarizations and reduces transmural dispersion of repolarization in a whole heart model of chronic heart failure

“…As regards the use of verapamil in heart failure, trials showed at least no increase in mortality rates, compared with placebo (Danish Verapamil Infarction Trial, 1990). In addition, in small trials in patients with CHF due to diastolic dysfunction (Hung et al, 2001) or only mild CHF (Wojnicz et al, 2010), verapamil had neutral clinical effects or even improved CHF. According to the present data, it might be reasonable to re-evaluate Ca 2+ channel blockade at least in stable CHF patients.…”

Comparative Efficacy of Different Drugs for the Treatment of Dilated Cardiomyopathy: A Systematic Review and Network Meta-analysis

“…LVEDD improvement was the difference of LVEDD before and after treatment. A total of 27 studies [ 16 , 17 , 19 , 21 , 26 , 27 , 29 , 31 – 33 , 37 , 41 , 42 , 44 – 46 , 51 – 55 , 57 , 58 , 63 – 66 ] involving 18 drugs reported LVEDD. The I 2 of the meta-analysis was 11%, and the fixed-effects model was used.…”