Background: Efficacy of chronic drug therapy in prevention of stress-induced cardiomyopathy recurrences is not well established. We therefore aimed to evaluate in this meta-analysis whether pharmacological treatment can effectively prevent takotsubo cardiomyopathy (TTC) recurrences, according to available studies. Hypothesis: There is no evidence for preventing TTC recurrence by drug therapy. Methods: After a PubMed search, we conducted a meta-analysis of available studies (clinical nonrandomized registries) on efficacy of drug therapy in preventing recurrence of TTC. Results: A total of 23 (4.5%) TTC recurrences occurred in the 511 patients included in the analysis. Seven studies on the effects of β-blockers on prevention of TTC recurrence were evaluated; the odds ratio (OR) was 0.44 and the 95% confidence interval (CI) was 0.15-1.31. In 5 studies on the effects of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, the OR was 0.42 and the 95% CI was 0.08-2.36; in 3 studies on statins, the OR was 0.74 and the 95% CI was 0.07-7.3; and in 4 studies on aspirin, the OR was 0.33 with a 95% CI of 0.05-2.17 (P value not significant in all cases). Conclusions: A meta-analysis of the efficacy of different medications through the clinical TTC registries available showed no clinical evidence for a standard drug treatment in the chronic management of TTC. β-Blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins, and aspirin do not seem to significantly reduce recurrences of TTC. Randomized, adequately powered studies are needed to further assess this issue. IntroductionTakotsubo cardiomyopathy (TTC) is a rapidly reversible form of acute heart failure occurring mainly in postmenopausal women after an episode of physical or emotional stress 1 and is associated with a typical left ventricular (LV) contraction pattern. 2 Increased catecholamine levels were thought to be the primary precipitator of the condition, 3 but the exact mechanism is still not well elucidated. 4,5 The initial treatment for TTC is usually the same as adopted for acute heart failure, except for contraindication to β-adrenergic inotropes 6 ; data on the efficacy of chronic pharmacological therapy, however, are scanty. Despite its relatively good long-term prognosis, 7 recurrences of TTC are not infrequent, with a rate ranging from 5% to 11.4% within the first 4 years and an incidence per year of 2.4%. 8,9 β-Blockers are commonly used chronically to prevent TTC recurrence, but, given the rarity of TTC, there are no randomized studies supporting this approach.We therefore conducted a meta-analysis of currently available studies to evaluate whether drug therapy can effectively prevent TTC recurrences.

SUMMARYBackground: Left ventricular outflow tract obstruction (LVOTO) may complicate an episode of Takotsubo cardiomyopathy (TTC), potentially leading to cardiogenic shock. Betablockers are considered the most suitable treatment for such complication. Aim of the study: The objective of this study was to evaluate the hemodynamic effects, safety, and feasibility of a selective beta-blocker (b1) with a short half-life, esmolol, in subjects with a TTC episode. Methods: Ninety-six consecutive patients with TTC were enrolled in a multicenter registry. The hemodynamic and echocardiographic effects of esmolol (0.15-0.3 mg/kg/min) were analyzed in nine consecutive patients with LVOTO. Clinical course of patients, hemodynamics, days of hospitalization, LV function, and adverse events at follow-up were recorded. Results: Left ventricular outflow tract obstruction was present in 10 (10.4%) of 96 patients. Patients with LVOTO were older and had higher values of troponin-I at admission. LV ejection fraction at admission (36.1 AE 8.4%) significantly improved at discharge (51.4 AE 6.9%, P = 0.001). Among patients treated with esmolol infusion, LVOT pressure gradient before treatment was 47.6 AE 16.6 mmHg and after 18.2 AE 2.3 mmHg (P = 0.0091). Systolic blood pressure decreased from 123.8 AE 29.1 to 112.6 AE 12.7 mmHg (P = 0.1537). Mean hospital stay was 9 AE 2 days. No adverse events were observed during hospitalization and at follow-up. Conclusions: Esmolol infusion was temporally associated with reduction in intraventricular gradient and systemic blood pressure in patients with TTC and LVOTO. Further controlled studies are warranted to confirm these preliminary findings.

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Background Prolonged QTc interval and life-threatening arrhythmias (LTA) are potential drug induced complications previously reported with antimalarial, antivirals and antibiotics. Objectives To evaluate prevalence and predictors of QTc interval prolongation and incidence of LTA during hospitalization for COVID-19 among patients with normal admission QTc. Methods 110 consecutive patients were enrolled in a multicenter international registry. 12-lead ECG was performed at admission, after 7 and 14 days; QTc values were analyzed. Results Fifteen (14%) patients developed a prolonged-QTc (pQT) after 7 days (mean QTc increase 66±20msec, +16%, p<0.001); these patients were older, had higher basal heart rates, higher rates of paroxysmal atrial fibrillation, lower platelet count. QTc increase was inversely proportional to baseline QTc levels and leukocyte count and directly to basal heart rates(p<0.01).At multivariate stepwise analysis including age, male gender, paroxysmal atrial fibrillation, basal QTc values, basal heart rate and dual antiviral therapy, age(OR 1.06, 95% C.I. 1.00-1.13, p<0.05), basal heart rate(OR 1.07, 95% C.I. 1.02-1.13, p<0.01) and dual antiviral therapy(OR 12.46, 95% C.I. 2.09-74.20, p<0.1) were independent predictors of QT-prolongation.Incidence of LTA during hospitalization was 3.6%. One patient experienced cardiac arrest and three non-sustained ventricular tachycardia. LTAs were recorded after a median of 9 days from hospitalization and were associated with 50% of mortality rate. Conclusions After 7 days of hospitalization, 14% of patients with Covid-19 developed pQTc; age, basal heart rate and dual antiviral therapy were found as independent predictor of pQTc. Life threatening arrhythmias have an incidence of 3.6% and were associated with poor outcome.