Prevalence, management, and outcome of adverse rhythm disorders in takotsubo syndrome: insights from the international multicenter GEIST registry.

One important complication related to takotsubo syndrome (TTS) is adverse rhythm disorders. Our study was conducted to determine the incidence and management of adverse rhythm disorders in TTS and its long-term prognostic impact. We analyzed 906 TTS patients from 9 European centers. Patients were divided into the adverse rhythm disorders group (encompassing ventricular tachycardia, ventricular fibrillation, torsade de pointes, and asystole or complete atrioventricular block) and non-adverse rhythm disorders group. In our study cohort, we identified 67 (7.4%) patients with presence of adverse rhythm disorders. TTS patients were followed up over a period of 2.8 years. In the adverse rhythm disorders group, 18% of patients presented adverse rhythm disorders before hospital admission. Asystole and/or AV block were significantly more presented before admission (13 patients versus 8 patients; p < 0.01), whereas ventricular tachyarrhythmias were more presented in-hospital (4 patients versus 42 patients; p < 0.01). Adverse rhythm disorders patients suffered more frequently from cardiogenic shock (31% versus 7.6%, p < 0.01) and in-hospital death (10.9% versus 3.6%; p < 0.01). Furthermore, the long-term survival was significantly impaired in adverse rhythm disorders patients as compared with non-adverse rhythm disorders patients; (log-rank p < 0.01). Using multivariate Cox regression analysis, cardiogenic shock (HR 2.86, 95% CI 1.1-6.9; p = 0.02) was identified as independent predictors of adverse rhythm disorders. The short- and long-term mortality rate of TTS patients presenting with adverse rhythm disorders was significantly higher than in TTS patients presenting without it. Therefore, TTS patients with adverse rhythm disorders should be carefully monitored during hospital stay and at long-term follow-up.

Emerging pharmacotherapies for the treatment of atrial fibrillation.

INTRODUCTION: The main aim of current research on the field of atrial fibrillation (AF) treatment is to find new antiarrhythmic drugs with less side effects. Areas covered: Dronedarone and vernakalant showed promising result in term of efficacy and safety in selected patients. Ranolazine and colchicine are obtaining a role as a potential antiarrhythmic drug. Ivabradine is used in experimental studies for the rate control of AF. Moreover, new compounds (vanoxerine, moxonidine, budiodarone) are still under investigation. Monoclonal antibodies or selective antagonist of potassium channel are under investigation for long term maintenance of sinus rhythm. Clinical evidence and new pharmacological investigation on new drugs will be accurately reviewed in this article. Expert opinion: Dronedarone use is not recommended in patients with symptomatic heart failure (HF), NYHA class III-IV, depressed ventricular function and permanent AF, especially in patients assuming a concomitant therapy with digoxin. Vernakalant had superior efficacy than amiodarone, flecainide and propafenone in single studies and similar efficacy to direct current cardioversion. Several of the developing drugs examined in this paper show an interesting potential, in particular the research on selective ionic channel inhibition and on compounds which reduce the inflammation state, especially after ablation or surgery.

Safety and Efficacy of Dapagliflozin in Patients with Heart Failure with Reduced Ejection Fraction: Multicentre Retrospective Study on Echocardiographic Parameters and Biomarkers of Heart Congestion.

Objectives: Dapagliflozin has shown efficacy in clinical trials in patients with heart failure and reduced ejection fraction (HFrEF). However, real-world data on its use and outcomes in routine clinical practice are limited. We aimed to evaluate the utilisation and safety profile of dapagliflozin in a real-world population of HFrEF patients within the Marche region. Methods: Nine cardiology departments within the Marche region retrospectively included HFrEF patients who were initiated on dapagliflozin therapy in an outpatient setting. Data on medical history, comorbidities, echocardiographic parameters, and laboratory tests were collected at baseline and after 6 months. Telephone follow-up interviews were conducted at 1 and 3 months to assess adverse events. We defined the composite endpoint score as meeting at least 50% of four objective measures of improvement among: weight loss, NYHA decrease, ≥50% Natriuretic peptides (NP) decrease, and guideline/directed medical therapy (GDMT) up titration. Results: We included 95 HFrEF patients aged 66 ± 12 years, 82% were men, 48% had ischemic heart disease, and 20% had diabetes. At six months, glomerular filtration rate declined (p = 0.03) and natriuretic peptides levels decreased, on average, by 23% (p < 0.001). Echocardiographic measurements revealed a decrease in pulmonary artery pressure (p < 0.001) and E/e' (p < 0.001). In terms of drug therapy, furosemide dosage decreased (p = 0.001), and the percentage of the target dose achieved for angiotensin receptor-neprilysin inhibitors increased (p = 0.003). By multivariable Cox regression, after adjustment for age, sex, the presence of diabetes/prediabetes, and HF duration, higher baseline Hb concentrations (HR 1.347, 95% CI 1.038-1.746, p = 0.025), and eGFR levels (HR 1.016, 95% CI 1.000-1.033, p = 0.46). Conclusions: In a real-life HFrEF population, dapagliflozin therapy is safe and well-tolerated, improves echocardiographic parameters and biomarkers of congestion, and can also facilitate the titration of drugs with a prognostic impact.

Impact of intra-aortic balloon counterpulsation on all-cause mortality among patients with Takotsubo syndrome complicated by cardiogenic shock: results from the German-Italian-Spanish (GEIST) registry.

Aims: Takotsubo syndrome (TTS) is an acute and reversible left ventricular dysfunction and can be complicated by cardiogenic shock (CS). However, few data are available on optimal care in TTS complicated by CS. Aim of this study was to evaluate short- and long-term impact of intra-aortic balloon pumping (IABP) on mortality in this setting. Methods and results: In a multi-centre, international registry on TTS, 2248 consecutive patients were enrolled from 38 centres from Germany, Italy, and Spain. Of the 2248 patients, 212 (9.4%) experienced CS. Patients with CS had a higher prevalence of diabetes (27% vs. 19%), male sex (25% vs. 10%), and right ventricular involvement (10% vs. 5%) (P < 0.01 in all cases). Forty-three patients with CS (20% of 212) received IABP within 8 h (interquartile range 4-18) after admission. No differences in terms of age, gender, cardiovascular risk factors, and admission left ventricular ejection fraction were found among patients with and without IABP. There were no significant differences in terms of 30-day mortality (16% vs. 17%, P = 0.98), length of hospitalization (18.9 vs. 16.7 days, P = 0.51), and need of invasive ventilation (35% vs. 41%, P = 0.60) among two groups: 30-day survival was not significantly different even after propensity score adjustment (log-rank P = 0.73). At 42-month follow-up, overall mortality in patients with CS and TTS was 35%, not significantly different between patients receiving IABP and not (37% vs. 35%, P = 0.72). Conclusions: In a large multi-centre observational registry, the use of IABP was not associated with lower mortality rates at short- and long-term follow-up in patients with TTS and CS.

Incidence and Clinical Impact of Right Ventricular Involvement (Biventricular Ballooning) in Takotsubo Syndrome: Results From the GEIST Registry.

BACKGROUND: The short- and long-term prognosis of Takotsubo syndrome (TTS) presenting with right ventricular (RV) involvement remains poorly understood. RESEARCH QUESTION: What is the incidence and clinical outcome of RV involvement in TTS? STUDY DESIGN AND METHODS: This study analyzed 839 consecutive patients with TTS (758 female subjects and 81 male subjects) in a multicenter registry. RV involvement was defined as wall motion abnormality of the RV free wall, with or without apical involvement. The median long-term follow-up was 2.1 years (interquartile range, 0.3-4.5 years). The primary outcome was in-hospital and out-of-hospital all-cause mortality. The secondary end point was a composite of in-hospital death, thromboembolic events, cardiogenic shock, pulmonary edema, and malignant arrhythmias. RESULTS: The incidence of RV involvement in TTS was 11% (n = 93). More often patients with RV involvement were male compared with patients without RV involvement (P = .02). There was a slight difference in the left ventricular ejection fraction measured in patients with RV involvement vs those patients with isolated left ventricular TTS (38 ± 10% vs 40 ± 10%; P = .03). No major differences in terms of comorbidities were observed between groups except regarding a history of cancer, which was significantly more prevalent in patients with TTS presenting with RV involvement (P = .03). Physical stressors were more prevalent in the RV group (P < .01), whereas emotional stressors were less prevalent (P < .01). Patients with RV involvement had a higher incidence of in-hospital cardiogenic shock (P = .02). The primary outcome (in- and out-of-hospital all-cause mortality) was observed in 12.8% of patients without RV involvement compared with 29% of patients with RV involvement. Although the in-hospital mortality rate was similar in both groups, a higher out-of-hospital all-cause mortality rate (log-rank test, P = .008) was observed in the RV involvement group. The Cox multivariable regression analysis showed that physical triggers were independent predictors of RV involvement. INTERPRETATION: RV involvement defines a high-risk cohort of patients with TTS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04361994; URL: www.clinicaltrials.gov.

Incidence and Clinical Impact of Recurrent Takotsubo Syndrome: Results From the GEIST Registry.

Background Current literature only reports variable information from single-center studies on the recurrence rate, the complications, and the outcome of patients with Takotsubo syndrome ( TTS) experiencing recurrent TTS . Therefore, a detailed description of clinical characteristics, predictors, and the prognostic impact of patients with TTS and recurrences in a multicenter registry is needed. Methods and Results We analyzed 749 patients with TTS from 9 European centers being part of the international, multicenter GEIST (German Italian Stress Cardiomyopathy) Registry. Patients were divided into the recurrence group and the nonrecurrence group. The recurrence rate at a median follow-up of 830 days (interquartile range, 118-1701 days) was 4%. Most recurrences were documented in the first 5 years after the index TTS episode. Up to 2 TTS recurrences were documented in 2 of 30 patients (6%). A variable ballooning pattern (n=6, 0.8%) with, in particular, involvement of the right ventricular occurred in 3 cases (0.4%) at the recurrence event. Except for the higher presence of arterial hypertension (86.7% versus 68.3%; P=0.03) in the recurrence group, no other baseline characteristics were different between groups. Observation of TTS complications during follow-up, including stroke, thromboembolic events, in-hospital death, and cardiogenic shock, revealed no significant differences between groups ( P>0.05), except the higher presence of pulmonary edema in the recurrence group versus the nonrecurrence group (13.3% versus 4.9%; P=0.04). Conclusions The incidence of TTS recurrence is estimated to be 4% in this multicenter TTS registry. A variable TTS pattern at recurrence is common in up to 20% of recurrence cases.

The ECG in the differential diagnosis between takotsubo cardiomyopathy and acute coronary syndrome.

INTRODUCTION: Takotsubo cardiomyopathy (TC) is an acquired cardiomyopathy affecting mostly postmenopausal women mimicking an acute coronary syndrome (ACS). TC clinical presentation involves chest pain, elevated cardiac enzymes, wall motion abnormalities and electrocardiographic changes, all of which share striking similarities to ACS. Areas covered: Differential diagnosis between TC and ACS can be complex since there are no reliable and widely-accepted electrocardiographic criteria and, at the moment, only coronary angiography can rule out one of the two diagnoses with good certainty. The present review will discuss the pros and cons of the ECG in TC, focusing on how the signal changes through the acute phase, the hospitalization, and after discharge. Specific information will be provided for each component of the ECG trace, and potential pitfalls will be highlighted, in order get to the core of this important unmet clinical issue. Expert commentary: There are at least several reasons why the ECG is still not considered a useful tool in differential diagnosis between TC and ACS. These include recent awareness of the syndrome, lack of evidence-based therapy, and, more importantly, a wide range of ECG features according to race, patient characteristics, wall motion abnormalities, triggers, and time from symptoms onset.

Transient QRS amplitude attenuation is associated with clinical recovery in patients with takotsubo cardiomyopathy.

BACKGROUND/OBJECTIVES: Low voltage QRS complexes (LQRSV) and amplitude attenuation of QRS voltage (AAQRS) have been described in takotsubo (TC) patients, and postulated as valuable pre-angiographic markers. The aim of this observational study is to evaluate potential diagnostic and prognostic features of QRS amplitude in TC and acute coronary syndrome (ACS) patients. METHODS: Fifty-eight patients with TC were matched with 58 patients with ACS according to age, gender, and presence or absence of ST elevation at hospital admission. A 12-lead ECG was recorded within 12h after symptoms onset, the day after coronary angiography (CA) and before hospital discharge. When available, ECGs prior and subsequent to the acute event were also collected. RESULTS: QRS amplitude showed a time related trend, with a first phase characterized by an initial decrease in amplitude in both groups and a second phase, with a progressive recovery of QRS amplitude in TC patients up to pre-event levels, while QRS amplitude in ACS patients remained substantially unchanged from admission onwards. Rise in AAQRS during hospitalization showed a positive linear association with systolic function recovery and both troponin I and CK-MB decrease (all p<0.01) in TC patients. A 20% increase of mean AAQRS from admission is able to predict LVEF recovery and troponin I and CK-MB normalization in TC patients with good sensitivity and specificity. CONCLUSIONS: LQRSV and AAQRS are not reliable in differentiating ACS from TC. However, QRS amplitude attenuation in TC is transient, and is linearly associated with systolic function recovery and cardiac biomarkers normalization.

Differences and similarities of repolarization patterns during hospitalization for Takotsubo cardiomyopathy and acute coronary syndrome.

Takotsubo cardiomyopathy (TC) is characterized by an acute transient left ventricular systolic dysfunction mimicking acute coronary syndrome (ACS) without significant coronary stenosis. The aim of this study was to examine the electrocardiographic repolarization patterns of TC and ACS and to compare them from hospital admission to hospital discharge. Forty-five patients with TC were matched with 45 patients with ACS according to age, gender, and presence or absence of ST elevation at hospital admission. A complete 12-lead electrocardiography was performed within 12 hours after symptoms onset and then repeated after 3, 5, and 7 days. All patients underwent coronary angiography, and patients with ACS also underwent percutaneous revascularization. Within 12 hours from the symptoms' onset, patients with TC had a significantly fewer number of leads with ST elevation and a significantly more number of leads with T-wave inversion. These differences, however, were not present after 72 hours and a similar trend was seen over time during the 7-day follow-up. Patients with TC had a significant longer corrected QT interval at admission and during the whole follow-up. In conclusion, in the electrocardiograms collected 12 hours within symptoms onset, patients with TC and those with ACS showed significant differences in cardiac repolarization. However, the number of leads with either ST-segment deviation or T-wave alterations in patients with TC soon matched the ACS group undergoing percutaneous revascularization. In contrast, corrected QT interval was persistently longer in patients with TC and, despite a similar reduction in length over time in both groups, it was still significantly longer after 7 days.