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Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with preserved ejection fraction, but additional data are needed about its effect on inpatient and outpatient heart failure events.Methods: We randomly assigned 5988 patients with class II through IV heart failure with an ejection fraction of >40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to usual therapy, for a median of 26 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite end points.Results: Empagliflozin reduced the combined risk of cardiovascular death, hospitalization for heart failure, or an emergency or urgent heart failure visit requiring intravenous treatment (432 versus 546 patients [empagliflozin versus placebo, respectively]; hazard ratio, 0.77 [95% CI, 0.67-0.87]; P<0.0001). This benefit reached statistical significance at 18 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (hazard ratio, 0.71 [95% CI, 0.52-0.96]; P=0.028) and the total number of all hospitalizations that required a vasopressor or positive inotropic drug (hazard ratio, 0.73 [95% CI, 0.55-0.97]; P=0.033). Compared with patients in the placebo group, fewer patients in the empagliflozin group reported outpatient intensification of diuretics (482 versus 610; hazard ratio, 0.76 [95% CI, 0.67-0.86]; P<0.0001), and patients assigned to empagliflozin were 20% to 50% more likely to have a better New York Heart Association functional class, with significant effects at 12 weeks that were maintained for at least 2 years. The benefit on total heart failure hospitalizations was similar in patients with an ejection fraction of >40% to <50% and 50% to <60%, but was attenuated at higher ejection fractions.Conclusions: In patients with heart failure with preserved ejection fraction, empagliflozin produced a meaningful, early, and sustained reduction in the risk and severity of a broad range of inpatient and outpatient worsening heart failure events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977. [ABSTRACT FROM AUTHOR]

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but additional data are needed about the effect of the drug on inpatient and outpatient events that reflect worsening heart failure.Methods: We randomly assigned 3730 patients with class II to IV heart failure with an ejection fraction of ≤40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to recommended treatments for heart failure, for a median of 16 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite end points.Results: Empagliflozin reduced the combined risk of death, hospitalization for heart failure or an emergent/urgent heart failure visit requiring intravenous treatment (415 versus 519 patients; empagliflozin versus placebo, respectively; hazard ratio [HR], 0.76; 95% CI, 0.67-0.87; P<0.0001). This benefit reached statistical significance at 12 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (HR, 0.67; 95% CI, 0.50-0.90; P=0.008) and that required a vasopressor or positive inotropic drug or mechanical or surgical intervention (HR, 0.64; 95% CI, 0.47-0.87; P=0.005). As compared with placebo, fewer patients in the empagliflozin group reported intensification of diuretics (297 versus 414 [HR, 0.67; 95% CI, 0.56-0.78; P<0.0001]). Additionally, patients assigned to empagliflozin were 20% to 40% more likely to experience an improvement in New York Heart Association functional class and were 20% to 40% less likely to experience worsening of New York Heart Association functional class, with statistically significant effects that were apparent 28 days after randomization and maintained during long-term follow-up. The risk of any inpatient or outpatient worsening heart failure event in the placebo group was high (48.1 per 100 patient-years of follow-up), and it was reduced by empagliflozin (HR, 0.70; 95% CI, 0.63-0.78; P<0.0001).Conclusions: In patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk and total number of inpatient and outpatient worsening heart failure events, with benefits seen early after initiation of treatment and sustained for the duration of double-blind therapy. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is associated with impaired health-related quality of life (HRQoL), an increased risk of morbidity, and mortality. Traditional AF-related outcomes (e.g., AF recurrence) primarily demonstrate the physiological benefits of AF management but do not focus on the benefits experienced subjectively by the patient (i.e., patient-reported outcomes), which have been suggested as optimal endpoints in AF intervention studies. The aim of this study is to identify medical and psychological factors associated with impaired HRQoL at 1-year follow-up. Using data from the prospective observational multicenter ARENA study in patients with AF, we analyzed associations between medical factors, anxiety, and HRQoL at 1-year follow-up assessed using 5-level EuroQoL-5D. In 1353 AF patients (mean age 71.4 ± 10.3 years, 33.8% female), none of the medical predictors (e.g., heart disease) or history of cardioversion were associated with HRQoL at the 1-year follow-up. Higher generalized anxiety (β = -0.114, p <.001) but not cardiac anxiety (β = -0.006, p =.809) at baseline predicted decreased HRQoL, independent of confounding variables and patients' medical status. Furthermore, the worsening of patients' generalized anxiety was associated with decreased HRQoL (ß = -0.091, p <.001). In contrast, the improvement of generalized anxiety over time predicted higher HRQoL (ß = 0.097, p <.001). Finally, the worsening of patients' cardiac anxiety over time was associated with decreased HRQoL (ß = -0.081, p <.001). Our results highlight the importance of anxiety as a predictor of future HRQoL in patients with AF. Additional studies to examine the impact of anxiety treatment on HRQoL in this population are needed. The investigators registered on ClinicalTrials.gov (NCT02978248) on November 30, 2016 https://clinicaltrials.gov/ct2/show/NCT02978248. • Screening of anxiety might identify AF patients at elevated risk for impaired HRQoL. • Anxiety is a robust and independent predictor of future HRQoL in individuals with AF. • None of the medical predictors were associated with HRQoL at 1-year FU in AF patients. • Treatment of anxiety symptoms might lead to improvements of HRQoL in AF patients. [ABSTRACT FROM AUTHOR]

Background: Chronic heart failure (CHF) patients suffer from multiple and agonizing symptoms like shortness of breath and reduced functional status, the latter of which is usually assessed using New York Heart Association (NYHA) functional class. Purpose: In order to identify potentially modifiable factors of reduced functional status in patients with CHF, we investigated somatic and psychosocial correlates of NYHA functional class. We subsequently compared the results to correlates of left ventricular ejection fraction (LVEF) as an objective parameter of disease severity. Methods: The cross-sectional study ( n = 314) was part of the German Heart Failure Network. Data were analysed using a logistic regression modelling process. Results: In the final regression model, NYHA functional class was only significantly associated with depression (odds ratio (OR) = 1.18; 95 % confidence interval (CI) = 1.09-1.27) and multimorbidity (OR = 1.17; 95 % CI = 1.04-1.32). LVEF was associated with amino-terminal pro-brain natriuretic peptide (NT-proBNP) (OR = 0.60; 95 % CI = 0.44-0.82), aetiology of CHF (OR = 2.08; 95 % CI = 1.11-3.90), and smoking (OR = 2.21; 95 % CI = 1.25-3.91). Conclusions: Whereas LVEF was not related to depression, our data revealed a close association between functional status (as assessed by NYHA functional class) and depression in patients with CHF, even after adjusting for cardiac and socio-demographic variables. Different forms of underlying causal mechanisms could be suspected; it appears promising to further investigate this specific interaction. In any event, pending further investigation, our results underscore the need to examine CHF patients with respect to both somatic symptom burden and potential depressive disorders. [ABSTRACT FROM AUTHOR]

In preclinical studies, endothelin receptor A (ETA) antagonists (ETAi) attenuated the progression of heart failure (HF). However, clinical HF trials failed to demonstrate beneficial effects of ETAi. These conflicting data may be explained by the possibility that established HF drugs such as adrenergic receptor blockers interfered with the mechanism of ETAi action in clinical trials. Here we report that mice lacking ETA only in sympathetic neurons (SN-KO) showed less adverse structural remodeling and cardiac dysfunction in response to pathological pressure overload induced by transverse aortic constriction (TAC). In contrast, mice lacking ETA only in cardiomyocytes (CM-KO) were not protected. TAC led to a disturbed sympathetic nerve function as measured by cardiac norepinephrine (NE) tissue levels and [124l]-metaiodobenzylguani-dine-PET, which was prevented in SN-KO. In a rat model of HF, ETAi improved cardiac and sympathetic nerve function. In cocultures of cardiomyocytes (CMs) and sympathetic neurons (SNs), endothelin-1 (ET1) led to a massive NE release and exaggerated CM hypertrophy compared with CM monocultures. ETA-deficient CMs gained a hypertrophic response through wild-type SNs, but ETA-deficient SNs failed to mediate exaggerated CM hypertrophy. Furthermore, ET1 mediated its effects indirectly via NE in CM-SN cocultures through adrenergic receptors and histone deacetylases, resulting in activation of the prohypertrophic transcription factor myocyte enhancer factor 2. In conclusion, sympathetic ETA amplifies ET1 effects on CMs through adrenergic signaling pathways. Thus, anti-adrenergic therapies may blunt potentially beneficial effects of ETAi. Taken together, this may indicate that patients with β blocker intolerance or disturbed sympathetic nerve function could be evaluated for a potential benefit from ETAi. [ABSTRACT FROM AUTHOR]

Background Congestive heart failure (CHF) is a complex clinical syndrome with autonomic dysbalance and increased plasma levels of inflammatory cytokines, which further worsen the syndrome. Experimental data have shown that stimulation of certain acupoints decreases autonomic dysbalance. Objective To test the therapeutic potential of acupuncture for life-threatening diseases such as CHF. Methods 17 stable patients with CHF (New York Heart Association class II-III, ejection fraction <40%) receiving optimised heart failure medication were randomised into a verum acupuncture (VA) and placebo acupuncture (PA) group. Cardiopulmonary function, heart rate variability and quality of life were explored. Results No improvements of the cardiac ejection fraction or peak oxygen uptake were observed, but the ambulated 6 min walk distance was remarkably increased in the VA group (+32±7 m) but not the PA group (∧1±11 m; p<0.01). Accordingly, post-exercise recovery after maximal exercise and the VE/VCO2 slope, a marker of ventilatory efficiency, were improved after VA but not PA. Furthermore, heart rate variability increased after VA, but decreased after PA. The 'general health⇔tm) score and 'body pain⇔tm) score of the quality-of-life questionnaire SF-36 tended to be improved after VA. Conclusion Acupuncture may become an additional therapeutic strategy to improve the exercise tolerance of patients with CHF, potentially by improving skeletal muscle function. [ABSTRACT FROM AUTHOR]

Objective: To determine the factors, which are associated with suicidal ideation and ideas of self-harm in patients with congestive heart failure (CHF). Methods: We examined 294 patients with documented CHF, New York Heart Association (NYHA) functional class II-IV, in a cross sectional study at three cardiac outpatient departments. Measures included self-reports of suicidal ideation and self-harm (PHQ-9), depression (SCID), health-related quality of life (SF-36), multimorbidity (CIRS-G), consumption of alcoholic beverages, as well as comprehensive clinical status. Data were analyzed using logistic regression analyses. Results: 50 patients (17.1%) reported experiencing suicidal ideation and/or ideas of self-harm on at least several days over the past two weeks. The final regression model revealed significant associations with health-related quality of life, physical component (odds ratio [OR] 0.56; 95% confidence interval [CI]: 0.35–0.91), and mental component (OR 0.50; 95% CI: 0.31–0.82), consumption of alcoholic beverages (OR 1.27; 95% CI: 1.05–1.54), first-episode depression (OR 3.92; 95% CI: 1.16–13.22), and lifetime depression (OR 10.89; 95% CI: 2.49–47.72). Age was only significant in the univariable (P=.03) regression analysis. NYHA functional class, left ventricular ejection fraction (LVEF), etiology of CHF, medication, cardiovascular interventions, multimorbidity, gender, and living situation were not significantly associated with suicidal ideation or ideas of self-harm. Conclusions: Lifetime depression, in particular, increases the risk of suicidal ideation and ideas of self-harm in CHF patients. Furthermore, the findings of our study underline the necessity of differentiating between first-episode and lifetime depression in CHF-patients in future research and clinical practice. Depression and Anxiety, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with impaired health-related quality of life (HRQoL), high symptom severity, and poor cardiovascular outcomes. Both clinical and psychological factors may contribute to symptom severity and HRQoL in AF. Methods: Using data from the observational Atrial Fibrillation Rhine-Neckar Region (ARENA) trial, we identified medical and psychosocial factors associated with AF-related symptom severity using European Heart Rhythm Association symptom classification and HRQoL using 5-level EuroQoL- 5D. Results: In 1218 AF patients (mean age 71.1 ± 10.5 years, 34.5% female), female sex (OR 3.7, p < 0.001), preexisting coronary artery disease (CAD) (OR 1.7, p = 0.020), a history of cardioversion (OR 1.4, p = 0.041), cardiac anxiety (OR 1.2; p < 0.001), stress from noise (OR 1.4, p = 0.005), work-related stress (OR 1.3, p = 0.026), and sleep disturbance (OR 1.2, p = 0.016) were associated with higher AF-related symptom severity. CAD (β = −0.23, p = 0.001), diabetes mellitus (β = −0.25, p < 0.001), generalized anxiety (β = −0.30, p < 0.001), cardiac anxiety (β = −0.16, p < 0.001), financial stress (β = −0.11, p < 0.001), and sleep disturbance (β = 0.11, p < 0.001) were associated with impaired HRQoL. Conclusions: Psychological characteristics, preexisting CAD, and diabetes may play an important role in the identification of individuals at highest risk for impaired HRQoL and high symptom severity in patients with AF. [ABSTRACT FROM AUTHOR]

Background: The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. Methods: A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. Results: The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was ≤5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between −5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to 582 μmol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L), biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175 ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140–165 μL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. Conclusions: The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting. Clin Chem Lab Med 2006;44:1269–77. [ABSTRACT FROM AUTHOR]

Abstract: Background: There is minimal evidence that HMG-CoA reductase inhibitors (statins) are beneficial in patients with chronic heart failure (CHF). Treatment with statins may lead to a lower mortality in CHF, independent of cholesterol levels, CHF etiology and clinical status. Methods: In a first study, we included 3132 patients with CHF from the ELITE 2 study in whom information on body mass index (BMI) and statin use at baseline were available. In a second study, we pooled the databases of 5 tertiary referral centers with 2068 CHF patients. In this cohort 705 patients were on a statin (34%), 585 of 1202 (49%) patients with ischemic etiology, and 120 of 866 (14%) patients with non-ischemic etiology (established by coronary angiography). Findings: Patients in ELITE 2 who received statin therapy at baseline (n =397, 13%) had lower mortality (hazard ratio [HR] 0.61, 95% CI 0.45–0.83; p =0.0007). In univariate analysis, increasing age, NYHA class, creatinine, and decreasing BMI, LVEF, and cholesterol, as well as lack of beta-blocker treatment and ischemic etiology (all p <0.002) related to higher mortality. In multivariable analysis, statin therapy related to lower mortality independently of all these variables (adjusted HR 0.66, 95% CI 0.47–0.93; p =0.017). In the second study CHF patients on statins had lower mortality (adjusted HR 0.58, 95% CI 0.44–0.77; p =0.0001). Both in patients with ischemic (p <0.0001) and non-ischemic etiology (p =0.028) statin treatment related to better survival. Interpretation: In chronic heart failure, treatment with statins is related to lower mortality, independent of cholesterol levels, disease etiology and clinical status. [Copyright &y& Elsevier]

Abstract: A prospective multicenter study including 1410 chest pain patients with suspected acute coronary syndromes was carried out to examine the predictive value of biological cardiac markers for adverse events measured by a point-of-care system. Admission cardiac troponin T (cTnT) and myoglobin were measured in parallel on a point-of-care system in the emergency department and – together with CK-MB mass – on lab analyzers. In a one-year follow-up, cardiac and non-cardiac death, acute myocardial infarction, unstable angina pectoris and need for revascularization were registered. Median time between onset of symptoms and admission was 285 min; 172 patients (12.2%) had no event during follow-up. If the cTnT, measured either by the point-of-care system or a conventional lab analyzer, was >0.05 μg/L, then the chance of a cardiac event during the follow-up period was doubled (18% vs. 9%). Serial cTnT measurement did not add any further value to the predictive power of the admission cTnT. Myoglobin and CK-MB mass identified increasing risk with increasing concentration quartiles; cardiac event rates were 2.8- to 4.4-fold higher between the quartiles with the lowest and those with the highest analyte concentration, respectively. There was no difference in non-cardiac death rates between any concentration quartiles. In conclusion, the prediction of clinical events by cardiac troponin T and myoglobin measured with a point-of-care analyzer in the emergency department was as good as that of the same cardiac markers and CK-MB mass measured on lab analyzers. [Copyright &y& Elsevier]

Background: Community-based interventions may promote awareness and adherence to atrial fibrillation (AF)-related therapies, potentially reducing adverse events. The ARENA project investigated the health status, therapies and events in AF patients in the Rhein-Neckar Region, Germany. The subproject "ARENA intervention" studied the effect of community-based interventions on AF-associated outcomes., Methods: From 2016 onward, patients with diagnosed AF were recruited for the observational ARENA registry. In 2018, an intervention period was initiated involving population-based information campaigns on AF diagnosis and therapies. The "control group" was recruited prior to initiation, and the "intervention group" afterward. Patients underwent standardized follow-up > 1 year after recruitment. Clinical outcomes, therapy and quality of life were compared between the two groups., Results: A total of 2769 patients were included. This real-world cohort showed high adherence to oral anticoagulation therapy (OAC) and an increased use of NOACs over vitamin K antagonists over time. In the intervention group (n = 1362), more patients continued OAC at follow-up (87.1% vs. 81.5%, P = 0.002). However, this difference was not significant in the patient subgroup with class I/IIa indications for OAC (90.1% vs. 87.5%, P = 0.11). AF-related re-hospitalization was lower in the intervention group (6.8% vs. 12.3%, P < 0.001). There was no significant difference in quality of life. AF-related anxiety was reduced at follow-up. Of note, nearly a quarter of all patients stated that ARENA had influenced their health perception., Conclusion: Tailored community-based campaigns may raise awareness for AF-related health issues, supporting therapy adherence. Future public strategies to improve quality of life in AF patients should be investigated, as the ARENA project hints at a potential benefit of population-based campaigns., Trial Registration: ClinicalTrials.gov (Identifier: NCT02978248)., (© 2024. The Author(s).)

Background: Patients with chronic heart failure (CHF) frequently suffer from depressive comorbidity. CHF and depressive comorbidity can cause somatic symptoms. The correct attribution of somatic symptoms is important. Thus, we aimed to assess potential differences in somatic symptom severity between CHF patients with and without depressive comorbidity., Methods: We evaluated depressive comorbidity using the Patient Health Questionnaire-9 (PHQ-9), somatic symptom severity with the Patient Health Questionnaire-15 (PHQ-15), and sociodemographic and medical variables in 308 CHF outpatients. To compare somatic symptom severity between CHF patients with and without depressive comorbidity, we conducted item-level analyses of covariance., Results: Of the 308 participating patients, 93 (30.3%) met the PHQ-9 criteria for depressive comorbidity. These patients did not differ from those without depressive comorbidity with regard to age, sex, left ventricular function, and multimorbidity. Patients with depressive comorbidity scored significantly higher on ten out of thirteen PHQ-15 items than patients without depressive comorbidity. The largest effect sizes (0.71-0.80) were shown for symptoms of headache, chest pain, shortness of breath, and palpitations, and the latter three were potentially attributable to heart failure., Conclusions: Among patients with CHF, somatic symptoms are more pronounced in those with depressive comorbidity than those without depressive comorbidity. This finding is especially true for cardiac symptoms independent of CHF severity. The potential interpretation of somatic symptoms as correlates of depressive comorbidity must be recognized in clinical practice., Competing Interests: TM-T reports support from the German Ministry of Education and Research BMBF for the submitted work. BL received grants or, contracts from the German Research Foundation DFG, the BMBF, the German, Innovation Committee at the Joint Federal Committee, the European Commission: Horizon 2020 Framework Programme, the European Joint Programme for Rare Diseases EJP, and the Ministry of Education and Research of the Free and Hanseatic City of Hamburg, Germany. He receive royalties or licenses from Elsevier, Thieme Publishing, Clett Cobra Publishing, and Hogrefe Publishing for book chapters or self-report questionnaires. He received payments from Norddeutscher Rundfunk NDR for interviews and from the Department of Clinical Medicine, Aarhus University for expert testimony. NF received payments from Astra Zeneca, Boehringer Ingelheim, Novartis, and Pfizer, but these payments were not related to the content of this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Müller-Tasch, Löwe, Frankenstein, Frey, Haass and Friederich.)

Aims: Epidemiological surveillance has raised safety concerns for mRNA SARS-CoV-2-vaccination-related myocarditis. We aimed to analyze epidemiological, clinical and imaging findings associated with clinical outcomes in these patients in an international multi-center registry (NCT05268458)., Methods and Results: Patients with clinical and CMR diagnosis of acute myocarditis within 30 days after mRNA SARS-CoV-2-vaccination were included from five centers in Canada and Germany between 05/21 and 01/22. Clinical follow-up on persistent symptoms was collected. We enrolled 59 patients (80% males, mean age 29 years) with CMR-derived mild myocarditis (hs-Troponin-T 552 [249-1,193] ng/L, CRP 28 [13-51] mg/L; LVEF 57 ± 7%, LGE 3 [2-5] segments). Most common symptoms at baseline were chest pain (92%) and dyspnea (37%). Follow-up data from 50 patients showed overall symptomatic burden improvement. However, 12/50 patients (24%, 75% females, mean age 37 years) reported persisting symptoms (median interval 228 days) of chest pain ( n  = 8/12, 67%), dyspnea ( n  = 7/12, 58%), with increasing occurrence of fatigue ( n  = 5/12, 42%) and palpitations ( n  = 2/12, 17%). These patients had initial lower CRP, lower cardiac involvement in CMR, and fewer ECG changes. Significant predictors of persisting symptoms were female sex and dyspnea at initial presentation. Initial severity of myocarditis was not associated with persisting complaints., Conclusion: A relevant proportion of patients with mRNA SARS-CoV-2-vaccination-related myocarditis report persisting complaints. While young males are usually affected, patients with persisting symptoms were predominantly females and older. The severity of the initial cardiac involvement not predicting these symptoms may suggest an extracardiac origin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Schroth, Garg, Bocova, Hansmann, Haass, Yan, Fernando, Chacko, Oikonomou, White, Alhussein, Giusca, Ochs, Korosoglou, Andre, Friedrich and Ochs.)

Background: There is limited published information on outcome adjudication in heart failure (HF)., Objectives: The authors sought to compare investigator reports (IRs) to a Clinical Events Committee (CEC) and the impact of SCTI (Standardized Clinical Trial Initiative) criteria., Methods: In the EMPEROR-Reduced trial, the authors compared IRs to the CEC for concordance; treatment effect on primary composite outcome events; and the components first event hospitalization primarily for HF or cardiovascular mortality (CVM), prognosis after hospitalization for heart failure (HHF), total HHFs, and trial duration with and without SCTI criteria., Results: The CEC confirmed 76.3% of IR events for the primary outcome (CVM: 89.1%; HHF: 73.7%). The HR for treatment effect did not differ between adjudication methods for the primary outcome (IR: 0.75 [95% CI: 0.66-0.85]; CEC: 0.75 [95% CI: 0.65-0.86]), its components, or total HHFs. The prognosis after first HHF for all-cause mortality and CVM also did not differ between IR or CEC. Interestingly, IR primary HHF with different CEC primary cause had the highest subsequent fatal event rate. Full SCTI criteria were present in 90% of CEC HHFs-with a similar treatment effect to non-SCTI. The IR primary event reached the protocol target number (841) 3 months earlier than CEC (4 months with full SCTI criteria)., Conclusions: Investigator adjudication is an alternative to a CEC with similar accuracy and faster event accumulation. The use of granular (SCTI) criteria did not improve trial performance. Finally, our data suggest that consideration be given to broadening the HHF definition to include "for or with" worsening disease. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977)., Competing Interests: Funding Support and Author Disclosures The EMPEROR-Reduced trial was funded by the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance. Dr Carson has received consulting fees from Boehringer Ingelheim and IQVIA related to work on the Clinical Events Committee during the conduct of the study. Dr Teerlink has received research support and/or has been a consultant for Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics. Dr Komajda has received consulting fees from Boehringer Ingelheim related to work on the Clinical Events Committee during the conduct of the study and personal fees from Novartis, Servier, Amgen, Sanofi, Bayer, AstraZeneca, Lilly, and Torrent. Dr Anand has received consulting fees from Boehringer Ingelheim related to work on the Clinical Events Committee during the conduct of the study and personal fees from Novartis, Servier, Amgen, Sanofi, Bayer, AstraZeneca, Lilly, and Torrent. Dr Anker has received grants and personal fees from Vifor International and Abbott Vascular; personal fees from AstraZeneca, Bayer, Brahms, Boehringer Ingelheim, Cardiac Dimensions, Novartis, Occlutech, Servier, and Vifor International; and is a Trial Executive Committee member of the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Butler has received consulting fees from Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sanofi, Sequana Medical, VWave Ltd, and Vifor; and is a Trial Executive Committee member of the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Doehner has received consulting fees from Boehringer Ingelheim related to work on the Clinical Events Committee during the conduct of the study; personal fees from Aimediq, Bayer, Boehringer Ingelheim, Medtronic, Pfizer, Sanofi-Aventis, Sphingotec, Vifor Pharma; and research support from the European Union (Horizon2020), German ministry of Education and Research, German Center for Cardiovascular Research, Vifor Pharma, and ZS Pharma. Dr Ferreira has received consulting fees from Boehringer Ingelheim and is a Trial Executive Committee member of Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Filippatos has received lecture fees and/or committee member contributions in clinical trials sponsored by Bayer, Medtronic, Vifor, Servier, Novartis, and Amgen; research support from the European Union; and is a Trial Executive Committee member of the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Haass has received consulting fees from Boehringer Ingelheim related to work on the Clinical Events Committee during the conduct of the study. Dr Miller has received consulting fees from Abbott, Boehringer Ingelheim, Respicardia, CVRx, Pfizer, and AbbVie. Dr Pehrson has received consulting fees and/or lecture fees from Boehringer Ingelheim, GlaxoSmithKline, Celgene, Bristol Myers Squibb, Bayer, and Johnson & Johnson. Dr Pocock has received consulting fees and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Boehringer Ingelheim; and is a Trial Executive Committee member of Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Mr Schnaidt and Dr Schnee are employees of Boehringer Ingelheim. Dr Zannad has recently received Steering Committee or Advisory Board fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cardior, CVRx, Janssen, Livanova, Merck, Mundipharma, Novartis, Novo Nordisk, and Vifor Fresenius; and is a Trial Executive Committee member of the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Packer has received consulting fees from AbbVie, Actavis, Amgen, Amarin, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Casana, CSL Behring, Cytokinetics, Johnson & Johnson, Eli Lilly and Company, Moderna, Novartis, ParatusRx, Pfizer, Relypsa, Salamandra, Synthetic Biologics, and Theravance; and is a Trial Executive Committee member of Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Myocardial strain is a convenient parameter to quantify left ventricular (LV) function. Fast strain-encoding (fSENC) enables the acquisition of cardiovascular magnetic resonance images for strain-measurement within a few heartbeats during free-breathing. It is necessary to analyze inter-vendor agreement of techniques to determine strain, such as fSENC, in order to compare existing studies and plan multi-center studies. Therefore, the aim of this study was to investigate inter-vendor agreement and test-retest reproducibility of fSENC for three major MRI-vendors. fSENC-images were acquired three times in the same group of 15 healthy volunteers using 3 Tesla scanners from three different vendors: at the German Heart Institute Berlin, the Charité University Medicine Berlin-Campus Buch and the Theresien-Hospital Mannheim. Volunteers were scanned using the same imaging protocol composed of two fSENC-acquisitions, a 15-min break and another two fSENC-acquisitions. LV global longitudinal and circumferential strain (GLS, GCS) were analyzed by a trained observer (Myostrain 5.0, Myocardial Solutions) and for nine volunteers repeatedly by another observer. Inter-vendor agreement was determined using Bland-Altman analysis. Test-retest reproducibility and intra- and inter-observer reproducibility were analyzed using intraclass correlation coefficient (ICC) and coefficients of variation (CoV). Inter-vendor agreement between all three sites was good for GLS and GCS, with biases of 0.01-1.88%. Test-retest reproducibility of scans before and after the break was high, shown by ICC- and CoV values of 0.63-0.97 and 3-9% for GLS and 0.69-0.82 and 4-7% for GCS, respectively. Intra- and inter-observer reproducibility were excellent for both parameters (ICC of 0.77-0.99, CoV of 2-5%). This trial demonstrates good inter-vendor agreement and test-retest reproducibility of GLS and GCS measurements, acquired at three different scanners from three different vendors using fSENC. The results indicate that it is necessary to account for a possible bias (< 2%) when comparing strain measurements of different scanners. Technical differences between scanners, which impact inter-vendor agreement, should be further analyzed and minimized.DRKS Registration Number: 00013253.Universal Trial Number (UTN): U1111-1207-5874.

Background: Psychosocial factors in cardiovascular diseases are increasingly acknowledged by patients, health care providers and payer organizations. Due to the rapidly increasing body of evidence, the German Cardiac Society has commissioned an update of its 2013 position paper on this topic. The German version was published in 2018 and the current manuscript is an extended translation of the original version., Methods: This position paper provides a synopsis of the state of knowledge regarding psychosocial factors in the most relevant cardiovascular diseases and gives recommendations with respect to their consideration in clinical practice., Results: Psychosocial factors such as low socioeconomic status, acute and chronic stress, depression, anxiety and low social support are associated with an unfavorable prognosis. Psychosocial problems and mental comorbidities should be assessed routinely to initiate targeted diagnostics and treatment. For all patients, treatment should consider age and gender differences as well as individual patient preferences. Multimodal treatment concepts should comprise education, physical exercise, motivational counseling and relaxation training or stress management. In cases of mental comorbidities, brief psychosocial interventions by primary care providers or cardiologists, regular psychotherapy and/or medications should be offered. While these interventions have positive effects on psychological symptoms, robust evidence for possible effects on cardiac outcomes is still lacking., Conclusions: For coronary heart disease, chronic heart failure, arterial hypertension, and some arrhythmias, there is robust evidence supporting the relevance of psychosocial factors, pointing to a need for considering them in cardiological care. However, there are still shortcomings in implementing psychosocial treatment, and prognostic effects of psychotherapy and psychotropic drugs remain uncertain. There is a need for enhanced provider education and more treatment trials.

Objectives: The aim of this study was to investigate prognosis in patients with heart failure (HF) with preserved ejection fraction and the causes of hospitalization and post-hospitalization mortality., Background: Although hospitalizations in patients with HF with preserved ejection fraction are common, there are limited data from clinical trials on the causes of admission and the influence of hospitalizations on subsequent mortality risk., Methods: Patients (n = 4,128) with New York Heart Association functional class II to IV HF and left ventricular ejection fractions >45% were enrolled in I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction). A blinded events committee adjudicated cardiovascular hospitalizations and all deaths using predefined and standardized definitions. The risk for death after HF, any-cause, or non-HF hospitalization was assessed using time-dependent Cox proportional hazard models., Results: A total of 2,278 patients had 5,863 hospitalizations during the 49 months of follow-up, of which 3,585 (61%) were recurrent hospitalizations. For any-cause hospitalizations, 26.5% of patients died during follow-up, with an incident mortality rate of 11.1 deaths per 100 patient-years (PYs) and an adjusted hazard ratio of 5.32 (95% confidence interval: 4.21 to 6.23). Overall, 53.6% of hospitalizations were classified as cardiovascular and 43.7% as noncardiovascular, with 2.7% not classifiable. HF was the largest single cause of initial (17.6%) and overall (21.1%) hospitalizations, although, after HF hospitalization, a substantially higher proportion of readmissions were due to primary HF causes (40%). HF hospitalization occurred in 685 patients, with 41% deaths during follow-up, an incident mortality rate of 19.3 deaths per 100 PYs. The adjusted hazard ratio was 2.93 (95% confidence interval: 2.40 to 3.57) relative to patients who were not hospitalized for HF and was greater in those with longer durations of hospitalization. There were 1,593 patients with only non-HF hospitalizations, 21% of whom died during follow-up, with an incident mortality rate of 8.7 deaths per 100 PYs and an adjusted hazard ratio of 4.25 (95% confidence interval: 3.27 to 5.32). The risk for death was highest in the first 30 days and declined over time for all hospitalization categories. Patients not hospitalized for HF or for any cause had observed incident mortality rates of 3.8 and 1.3 deaths per 100 PYs, respectively., Conclusions: In I-PRESERVE, HFpEF patients hospitalized for any reason, and especially for HF, were at high risk for subsequent death, particularly early. The findings support the need for careful attention in the post-discharge time period including attention to comorbid conditions. Among those hospitalized for HF, the high mortality rate and increased proportion of readmissions due to HF (highest during the first 30 days), suggest that this group would be an appropriate target for investigation of new interventions., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Impairment of the cardiac norepinephrine (NE) reuptake by the neuronal NE transporter contributes to enhanced cardiac NE net release in congestive heart failure. Elevated plasma levels of aldosterone (AL) promote sympathetic overstimulation in failing hearts by unclear mechanisms. Our aim was to evaluate if elevated AL and/or alterations in Na(+) intake regulate cardiac NE reuptake. To test the effects of AL and Na(+) on cardiac NE reuptake, Wistar rats were fed a normal-salt (NS) diet (0.2% NaCl), a low-salt (LS) diet (0.015% NaCl), or a high-salt (HS) diet (8% NaCl). Another group of animals received AL infusion alone (0.75 μg/h) or AL infusion plus HS diet. Specific cardiac [(3)H]NE uptake via the NE transporter in a Langendorff preparation and AL plasma levels were measured at different time points between 5 and 42 days of treatment. To compare these findings from healthy animals with a disease model, Dahl salt-sensitive rats were investigated as a model of congestive heart failure with endogenously elevated AL. In summary, neither exogenous nor endogenous elevations of AL alone were sufficient to reduce cardiac NE reuptake. Only the HS diet induced a reduction of NE reuptake by 26%; additional infusion of AL augmented this effect to a further reduction of NE reuptake by 36%. In concordance, Dahl salt-sensitive rats treated with a HS diet displayed elevated AL and a marked reduction of NE reuptake. We conclude that exogenous or endogenous AL elevations alone do not reduce cardiac NE reuptake, but AL serves as an additional factor that negatively regulates cardiac NE reuptake in concert with HS intake., (Copyright © 2014 the American Physiological Society.)

Background: The rapid progress of psychosomatic research in cardiology and also the increasing impact of psychosocial issues in the clinical daily routine have prompted the Clinical Commission of the German Heart Society (DGK) to agree to an update of the first state of the art paper on this issue which was originally released in 2008., Methods: The circle of experts was increased, general aspects were implemented and the state of the art was updated. Particular emphasis was dedicated to coronary heart diseases (CHD), heart rhythm diseases and heart failure because to date the evidence-based clinical knowledge is most advanced in these particular areas. Differences between men and women and over the life span were considered in the recommendations as were influences of cognitive capability and the interactive and synergistic impact of classical somatic risk factors on the affective comorbidity in heart disease patients., Results: A IA recommendation (recommendation grade I and evidence grade A) was given for the need to consider psychosocial risk factors in the estimation of coronary risks as etiological and prognostic risk factors. Furthermore, for the recommendation to routinely integrate psychosocial patient management into the care of heart surgery patients because in these patients, comorbid affective disorders (e.g. depression, anxiety and post-traumatic stress disorder) are highly prevalent and often have a malignant prognosis. A IB recommendation was given for the treatment of psychosocial risk factors aiming to prevent the onset of CHD, particularly if the psychosocial risk factor is harmful in itself (e.g. depression) or constrains the treatment of the somatic risk factors. Patients with acute and chronic CHD should be offered anti-depressive medication if these patients suffer from medium to severe states of depression and in this case medication with selective reuptake inhibitors should be given. In the long-term course of treatment with implanted cardioverter defibrillators (ICDs) a subjective health technology assessment is warranted. In particular, the likelihood of affective comorbidities and the onset of psychological crises should be carefully considered., Conclusions: The present state of the art paper presents an update of current empirical evidence in psychocardiology. The paper provides evidence-based recommendations for the integration of psychosocial factors into cardiological practice and highlights areas of high priority. The evidence for estimating the efficiency for psychotherapeutic and psychopharmacological interventions has increased substantially since the first release of the policy document but is, however, still weak. There remains an urgent need to establish curricula for physician competence in psychodiagnosis, communication and referral to ensure that current psychocardiac knowledge is translated into the daily routine.

Vasopressin plays a physiological role in regulation of blood pressure, fluid volume, and serum osmolality. In heart failure inadequate release of vasopressin may result in excess fluid retention and hyponatremia. Vasopressin receptor antagonists are a new class of orally active drugs targeted to inhibit one or more of three distinct vasopressin receptors, namely V1a- (-->vasoconstriction), V1b- (-->release of ACTH) und V2-receptors (-->inhibition of free water reabsorption in the kidney). In cardiac decompensation with fluid overload selective V2- (Lixivaptan, satavaptan and tolvaptan) and non-selective V1a/V2-receptor blockers (Conivaptan) have been shown to be superior to standard therapy, as they allow for a faster weight loss and a more rapid symptomatic improvement (i.e. reduction in dyspnea). Inhibiting free water reabsorption without affecting renal sodium excretion vasopressin receptor antagonists allow for a controlled normalisation of serum natrium in euvolemic and hypervolemic hyponatremia. Vasopressin antagonists are well tolerated and have--in contrast to diuretics--no negative influence on renal function and serum potassium. Heart rate and blood pressure are not affected by vasopressin receptor antagonists. However, despite its excellent acute clinical effects long-term treatment with tolvaptan did not result in a reduced mortality and morbidity in heart failure patients over a mean follow-up of 9.9 months in the EVEREST trial.

Background: Although chronic heart failure (CHF) is often complicated by comorbid depression and poor self-care, little is known about their specific association in patients with CHF., Objective: To investigate self-care behavior among patients with CHF with different degrees of depression severity., Methods: A total of 287 patients with documented CHF, New York Heart Association functional class II to IV, completed the European Heart Failure Self-Care Behavior Scale. The Structured Clinical Interview for DSM (SCID) IV served as the criterion standard for the presence of a depressive disorder., Results: Analyses of covariance and linear regression analyses revealed that patients with CHF with minor depression reported significantly lower levels of self-care than patients with major depression (P = .003) and nondepressed patients (P = .014). In addition to minor depression, age (P < or = .001), multimorbidity (P = .01), left ventricular ejection fraction (P = .001), and family status (P = .01) were determinants of self-care., Conclusion: Our results demonstrate that patients with CHF with minor depression and not major depression are at higher risk for poor self-care and its resulting consequences, such as symptom deterioration and frequent hospitalization.

Background: In congestive heart failure (CHF), an activation of the cardiac sympathetic nervous system results in depleted cardiac norepinephrine (NE) stores. The underlying regulatory mechanisms are discussed controversially and were investigated in the present study in CHF resulting from volume overload., Methods and Results: Aorto-caval shunt (AVS) was performed in rats. Plasma NE levels were determined by radioenzymatic assay, left ventricular NE by high-performance liquid chromatography, endothelin-1 by enzyme-linked immunosorbent assay. Tyrosine-hydroxylase (TH)- and nerve growth factor (NGF)-mRNA was determined by Northern blot analysis and ribonuclease-assay. Cardiac [3H]-NE uptake was measured in isolated perfused hearts. Glyoxylic acid-induced histofluorescence was used to quantify cardiac sympathetic nerves. Compared with sham-operated animals (SH), AVS rats were characterized by depleted cardiac NE stores and enhanced NE plasma levels. Neither TH-mRNA levels in stellate ganglia, nor cardiac [3H]-NE-uptake were reduced in AVS. The left ventricular density of sympathetic nerves was markedly decreased. Gene expression of myocardial NGF (a positive regulator of NE reuptake and cardiac sympathetic nerve density) and left ventricular endothelin-1 (a negative regulator of NE reuptake and positive regulator of cardiac NGF expression) were unchanged., Conclusion: In volume-overloaded hypertrophic hearts, depletion of cardiac NE stores is caused by a reduction of the sympathetic nerve density, whereas cardiac NE reuptake is preserved.

An impairment of cardiac norepinephrine (NE) reuptake via the neuronal NE transporter (NET) enhances the effects of increased cardiac NE release in heart failure patients. Increasing evidence suggests that aldosterone and endothelins promote sympathetic overstimulation of failing hearts. Salt-sensitive Dahl rats (DS) fed a high-salt diet developed arterial hypertension and diastolic heart failure as well as elevated plasma levels of endothelin-1 and NE. Cardiac NE reuptake and NET-binding sites, as assessed by clearance of bolus-injected [(3)H]NE in isolated perfused rat hearts and [(3)H]mazindol binding, were reduced. Treatment of DS with the mineralocorticoid receptor antagonist spironolactone preserved the plasma levels of endothelin-1 and NE, cardiac NE reuptake, and myocardial NET density. Moreover, the ventricular function and survival of spironolactone-treated DS were significantly improved compared with untreated DS. The alpha(1)-inhibitor prazosin decreased blood pressure in DS similar to spironolactone treatment, but did not normalize the plasma levels of endothelin-1 and NE, NE reuptake, or ventricular function. In a heart failure-independent model, Wistar rats that were infused with aldosterone and fed a high-salt diet developed impaired cardiac NE reuptake. Treatment of these rats with the endothelin A receptor antagonist darusentan attenuated the impairment of NE reuptake. In conclusion, spironolactone preserves NET-dependent cardiac NE reuptake in salt-dependent heart failure. Evidence is provided that aldosterone inhibits NET function through an interaction with the endothelin system. Selective antagonism of the mineralocorticoid and/or the endothelin A receptor might represent therapeutic principles to prevent cardiac sympathetic overactivity in salt-dependent heart failure.

Aims: Improved prognosis of patients with chronic systolic heart failure by treatment with beta-blockers has been shown in several randomized controlled multicentre trials. However, in clinical practice only a part of heart failure patients meet the inclusion criteria of these trials. The present study evaluates whether reduction of mortality by beta-blockers also can be achieved in patients presenting one or more exclusion criteria of the MERIT-HF trial., Methods and Results: From the Ludwigshafen Heart Failure Registry 675 patients with chronic systolic heart failure consecutively enrolled between January 1995 and June 2004 were divided in two groups either meeting the inclusion criteria of the MERIT-HF trial ('trial patients': n = 278, 60% treated with beta-blockers) or not ('non-trial patients': n = 397; 51% treated with beta-blockers). The distribution of the MERIT-HF exclusion criteria in the group of 'non-trial patients' was as follows: acute myocardial infarction 9.6%; systolic blood pressure <100 mmHg 7.5%; chronic obstructive lung disease 33.2%; other serious diseases potentially limiting prognosis 16.9%; acutely performed or planned ICD, bypass surgery, PCI, heart transplantation: 17.1, 15.9, 7.8, and 4.8%, respectively. Median follow-up was 31.3 months (upper/lower quartile 16.3/50.0 months). All-cause mortality was significantly reduced by beta-blocker treatment not only in 'trial patients' (adjusted hazard ratio 0.57, 95% CI 0.38-0.86) but also in 'non-trial patients' (adjusted hazard ratio 0.72, 95% CI 0.53-0.97)., Conclusion: In clinical practice only the smaller part of the population to be treated for chronic systolic heart failure meets the inclusion criteria of the MERIT-HF study. However, beta-blocker treatment is associated with a significantly reduced long-term mortality even in patients meeting one or more exclusion criteria of the MERIT-HF study.

Background: The prognostic role of asymptomatic nonsustained ventricular tachycardia (NSVT) and programmed ventricular stimulation (PVS) in patients with idiopathic dilated cardiomyopathy (IDC) remains controversial., Methods: The prognostic significance of ventricular arrhythmias, ejection fraction, NYHA class, atrial fibrillation and age for overall and sudden death mortality was prospectively studied in 157 patients with IDC (group 1) free of documented sustained ventricular arrhythmia and syncope. In 99 patients with asymptomatic NSVT (group 2), PVS with 2 - 3 extrastimuli was performed. Non-inducible patients were discharged without specific antiarrhythmic therapy, whereas those with inducible monomorphic ventricular tachycardia were implanted with an ICD., Results: In group 1, 48% of patients had NSVT. Overall and sudden death mortality were significantly higher in patients with NSVT (34.2 vs. 9.8%, p = 0.0001 and 15.8 vs. 3.7%, p = 0.0037; follow-up 22 +/- 14 months). Multivariate analysis revealed that NSVT independently predicts both overall and sudden death mortality (p = 0.0021 and.0221, respectively; adjusted for EF, NYHA class and age). In group 2, inducibility of sustained ventricular tachyarrhythmia was 7%, but sustained monomorphic VT occurred in 3% only. Two of 7 inducible patients experienced arrhythmic events during a follow-up of 25 +/- 21 months (positive predictive value 29%). Overall and sudden death mortality were 29% and 0% in the inducible group vs. 17 and 4% in the non-inducible group. Both overall and sudden death mortality were significantly lower in non-inducible patients from group 2 as compared to patients from group 1 with NSVT (p = 0.0043 and 0.0048), most likely due to a more common use of betablockers and a higher EF in the former group (p < 0.001, respectively)., Conclusions: In patients with IDC, NSVT independently predicts both overall and sudden death mortality. Due to a low inducibility rate and a poor positive predictive value, PVS seems inappropriate for further arrhythmia risk assessment. However, in spite of documented NSVT, the incidence of SCD in patients on optimized medical treatment including betablockers seems to be very low, questioning the need for specific arrhythmia risk stratification.