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.

Global Longitudinal Strain as a Predictor of First and Subsequent Arrhythmic Events in Remotely Monitored ICD Patients With Structural Heart Disease.

OBJECTIVES: This study sought to assess speckle-tracking-derived parameters as predictors of first and subsequent ventricular events in patients with structural heart disease and implantable cardioverter-defibrillators (ICD). BACKGROUND: Left ventricular ejection fraction (LVEF), the current primary parameter of risk stratification for ventricular arrhythmias (VAs) in structural heart diseases is burdened by many limitations. METHODS: In this retrospective, observational study, all consecutive patients with structural heart disease were admitted for ICD implantation. Patients not followed by a home-monitoring system were excluded. Two-dimensional (2D) speckle-tracking analysis was used to derive global longitudinal strain (GLS), mechanical dispersion (MD), and delta contraction duration (DCD) of all patients at enrollment. Home monitoring was checked weekly to detect all VAs and ICD therapies. A recurrent event statistical approach (Prentice, Williams, and Peterson model) was applied to evaluate subsequent events after the first ones. RESULTS: A total of 203 patients were consecutively enrolled and followed for a median of 2.2 years. Kaplan-Meier curves showed an increased risk of antitachycardia pacing or shock (log-rank p = 0.003) and VAs (log-rank p = 0.001) associated with lower quartiles of GLS. An impaired GLS was independently associated with an increased risk for the first ICD therapy (hazard ratio [HR]: 1.94; 95% confidence interval [CI]: 1.30 to 2.91; p = 0.001) and (HR: 1.42; 95% CI: 1.01 to 1.98; p = 0.04) for the first VA. GLS impairment was not significantly associated with an increased risk of recurrent ICD therapies or VAs. LVEF, MD, and DCD were not associated with an increased risk of first, second, and third ICD therapies or VA. CONCLUSIONS: Impaired GLS is associated with an increased risk of VAs and appropriate ICD therapies in a consecutive "real-world," unselected population of remotely monitored patients with structural heart disease, although it does not seem reliable in predicting further arrhythmic events after the first one. MD and DCD do not predict first or subsequent arrhythmic events in ICD patients with structural heart disease.

Cardiac resynchronization therapy and electrical storm: results of the OBSERVational registry on long-term outcome of ICD patients (OBSERVO-ICD).

Aims: Electrical storm (ES) is a condition defined as three or more episodes of ventricular fibrillation (VF) or ventricular tachycardia (VT) within 24 h, and usually coexist with advanced heart failure in patients with structural heart disease. The aim of the present study is to test whether cardiac resynchronization therapy (CRT) can be associated with a lower incidence of ES. Methods and results: The OBSERVO-ICD (NCT02735811) is a multicentre, retrospective registry, enrolling all consecutive patients undergoing ICD or CRT-D implantation from 2010 to 2012 in five Italian high-volume arrhythmia centres. Propensity score matching was used to compare two equally sized cohorts of ICD and CRT-D patients with similar characteristics. The primary endpoint was the time free from ES. Secondary endpoints were time free from unclustered VT/VF episodes and time free from ES in CRT-D patients according to clinical or echographic response. CRT-D was associated with a 45% relative risk reduction in ES when compared with ICD (5.6% vs. 12.3%; log rank P = 0.014). CRT-responders presented lower rates of ES when compared with non-responders and negative responders according to both clinical and echographic criteria (log-rank P = 0.017 and 0.023, respectively). No ES was detected in any of the 133 full responders to CRT-D. Clinical and echographic positive responses, but not CRT-implant per se, were associated with lower estimate rates of unclustered VTs/VFs. Conclusion: Patients with CRT had a lower incidence of ES when compared with propensity-matched ICD patients. The long-term benefit of CRT seems to be due to the improved haemodynamics, as CRT-responders performed markedly better over a long-term follow-up.

Temporal Trends and Temperature-Related Incidence of Electrical Storm: The TEMPEST Study (Temperature-Related Incidence of Electrical Storm).

BACKGROUND: The occurrence of ventricular tachyarrhythmias seems to follow circadian, daily, and seasonal distributions. Our aim is to identify potential temporal patterns of electrical storm (ES), in which a cluster of ventricular tachycardias or ventricular fibrillation, negatively affects short- and long-term survival. METHODS AND RESULTS: The TEMPEST study (Circannual Pattern and Temperature-Related Incidence of Electrical Storm) is a patient-level, pooled analysis of previously published data sets. Study selection criteria included diagnosis of ES, absence of acute coronary syndrome as the arrhythmic trigger, and ≥10 patients included. At the end of the selection and collection processes, 5 centers had the data set from their article pooled into the present registry. Temperature data and sunrise and sunset hours were retrieved from Weather Underground, the largest weather database available online. Total sample included 246 patients presenting with ES (221 men; age: 65±9 years). Each ES episode included a median of 7 ventricular tachycardia/ventricular fibrillation episodes. Fifty-nine percent of patients experienced ES during daytime hours (P<0.001). The prevalence of ES was significantly higher during workdays, with Saturdays and Sundays registering the lowest rates of ES (10.4% and 7.2%, respectively, versus 16.5% daily mean from Monday to Friday; P<0.001). ES occurrence was significantly associated with increased monthly temperature range when compared with the month before (P=0.003). CONCLUSIONS: ES incidence is not homogenous over time but seems to have a clustered pattern, with a higher incidence during daytime hours and working days. ES is associated with an increase in monthly temperature variation. CLINICAL TRIAL REGISTRATION: https://www.crd.york.ac.uk. Unique identifier: CRD42013003744.

IntErnationaL eLeCTRicAl storm registry (ELECTRA): Background, rationale, study design, and expected results.

Electrical storm (ES) is defined as three or more episodes of ventricular fibrillation (VF) or ventricular tachycardia (VT) within 24 h and is associated with an increased cardiac and all-cause mortality. ES is a full arrhythmic emergency, its prevalence steadily increasing along with the number of implantable cardioverter-defibrillator implanted every year in developed countries. Nowadays, little evidence exists regarding clinical predictors of ES and their potential association on mortality and heart failure (HF), nor optimal pharmacological and non-pharmacological treatment has ever been codified. The intErnationaL eLeCTRicAl storm registry (ELECTRA) is a multicentre, observational, prospective clinical study with two major aims. First, to create an international database on ES encompassing clinical features, pharmacological management, and interventional treatment strategies. Second, to describe mortality and rehospitalization rates in patients with ES over a long follow-up. The primary endpoint is all-cause mortality 3 years after the ES index event. The main secondary endpoint is hospitalization for all causes 3 years after the ES index event. Other secondary endpoints includes ES recurrences, unclustered VTs/VFs recurrences, and hospitalizations for HF worsening. A minimum of 500 patients will be included in the registry, and all patients will be followed-up for a minimum of three years. The present paper describes the background and current rationale of the ELECTRA study and details the study design, from enrolment strategy to data collection methods to planned data analysis. A brief overview of the expected results and their potential clinical and research implications will also be presented (NCT02882139).

Implantable cardioverter-defibrillator programming and electrical storm: Results of the OBSERVational registry On long-term outcome of ICD patients (OBSERVO-ICD).

BACKGROUND: Electrical storm (ES) is defined as 3 or more episodes of ventricular fibrillation (VF) or ventricular tachycardia (VT) within 24 hours and is associated with increased cardiac and all-cause mortality. OBJECTIVE: The purpose of this study was to test whether aggressive implantable cardioverter-defibrillator (ICD) programming can be associated with ES. METHODS: The OBSERVational registry On long-term outcome of ICD patients (OBSERVO-ICD) is a multicenter, retrospective registry enrolling all consecutive patients undergoing ICD implantation from 2010 to 2012 in 5 Italian high-volume arrhythmia centers. Clinical history and risk factors were collected for all patients, as were ICD therapy-related variables such as detection zones and delays. The total number of arrhythmic episodes and therapies delivered by the ICD were collected through out-of-hospital visits and remote monitoring. RESULTS: The registry enrolled 1319 consecutive patients, of whom 62 (4.7%) experienced at least 1 ES during follow-up (median 39 months). Patients who experienced ES had a significantly lower VF detection zone (P = .002), more frequently had antitachycardia pacing therapies programmed off during capacitor charge (P = .001), and less frequently had an ICD set with delayed therapies for VT zones (P = .042) and VF zone (P = .036). Patients who experienced ES had a significantly higher incidence of death and heart failure-related death compared to patients with no ventricular arrhythmias and patients with unclustered VTs/VFs (P = .025 and P <.001, respectively). CONCLUSION: Patients with ES had a more aggressive ICD programming setup, including lower VF detection rates, shorter detection times, and no antitachycardia pacing therapies during capacitor charge. This kind of ICD programming potentially could increase the likelihood of ES and the related risk of death.

Electrical storm and heart failure worsening in implantable cardiac defibrillator patients.

AIMS: In patients with an implantable cardiac defibrillator (ICD), electrical storm (ES) is associated with increased sudden and non-sudden cardiac mortality, the latter largely due to worsening heart failure (HF). Aim of this study is to test the association between ES and impending pump failure in patients with known chronic HF and ICD. METHODS AND RESULTS: Inclusion criteria were a previous history of chronic HF, former ICD implant, and hospital admission for HF worsening, or ES, or unclustered ventricular tachyarrhythmias (VTs/VFs). Patients with concomitant stable HF or HF worsening due to another specific cause were excluded. Primary endpoint was all cause mortality. Main secondary endpoint was time to first rehospitalization. Prospective, observational study on 146 patients: 34 with ES, 30 with unclustered VTs/VFs, and 82 with HF worsening. During the 5 years of follow-up, there was no significant difference between survival estimates between ES and HF worsening (P = 0.7), while both were significantly lower than survival of unclustered VT/VF patients (all log rank P < 0.05). Hospitalization-free time was significantly lower in both the ES group and in the HF worsening group when compared with unclustered VT/VF patients (all log rank P < 0.05). There was no significant difference between hospitalization estimates between ES and HF worsening. CONCLUSION: Heart failure patients admitted for ES have major similarities with patients admitted for HF clinical decompensation such as similar survival, cause of death and time to first rehospitalization. There is evidence suggesting that, in this population, ES could be considered as a clinical manifestation of HF worsening.