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Objective: The study investigates the prognostic impact of the severity and etiology of chronic kidney disease (CKD) in patients with heart failure with mildly reduced ejection fraction (HFmrEF)., Background: Data regarding the outcomes in patients with CKD in HFmrEF is scarce., Methods: Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Prognosis of patients with different stages and etiologies of CKD was investigated with regard to the primary endpoint of all-cause mortality at 30 months., Results: A total of 2155 consecutive patients with HFmrEF were included with an overall prevalence of CKD of 31%. Even milder stages of CKD (i.e., KDIGO stage 3a) were associated with an increased risk of 30-months all-cause mortality (HR = 1.242; 95% CI 1.147-1.346; p = 0.001). However, long-term prognosis did not differ in patients with KDIGO stage 5 compared to patients with stage 4 (HR = 0.886; 95% CI 0.616-1.275; p = 0.515). Furthermore, the highest risk of HF-related rehospitalization was observed in patients with KDIGO stages 3b and 4 (log rank p ≤ 0.015), whereas patients with KDIGO stage 5 had a lower risk of HF-related rehospitalization compared to patients with KDIGO stage 4 (HR = 0.440; 95% CI 0.228-0.849; p = 0.014). In contrast, the etiology of CKD was not associated with the risk of 30-month all-cause mortality (log rank p ≥ 0.347) and HF-related rehospitalization (log rank p ≥ 0.149)., Conclusion: In patients with HFmrEF, even milder stages of CKD were independently associated with increased risk of 30-months all-cause mortality., (© 2024. The Author(s).)

Aims: The study sought to comprehensively investigate the effect of heart failure (HF) pharmacotherapies in patients with HF with mildly reduced ejection fraction (HFmrEF). In the absence of randomized controlled trials, guideline recommendations concerning HF-related therapies in patients with HFmrEF are limited., Methods and Results: Consecutive patients hospitalized with HFmrEF were retrospectively included at one institution from 2016 to 2022. The prognostic value of treatment with beta-blockers (BB), angiotensin-converting enzyme inhibitors, receptor blockers, or receptor-neprilysin inhibitor (ACEi/ARB/ARNI), mineralocorticoid receptor antagonists (MRA), and sodium-glucose-linked transport protein 2 inhibitors (SGLT2i) was investigated for all-cause mortality at 30 months (a median follow-up) and HF-related rehospitalization. A total of 2109 patients with HFmrEF were included. Treatment with BB [27.0 vs. 35.0%; hazard ratio (HR) = 0.737; 95% confidence interval (CI) 0.617-0.881; P = 0.001], ACEi/ARB/ARNI (25.9 vs. 37.6%; HR = 0.612; 95% CI 0.517-0.725; P = 0.001), and SGLT2i (11.9 vs. 29.5%; HR = 0.441; 95% CI 0.236-0.824; P = 0.010) was associated with a lower risk of 30-month all-cause mortality, which was still demonstrated after multivariable adjustment and propensity score matching. In contrast, MRA treatment was not associated with long-term prognosis. The risk of HF-related rehospitalization was not affected by HF pharmacotherapies. Finally, the lowest risk of long-term all-cause mortality was observed in patients with combined use of BB, ACEi/ARB/ARNI, and SGLT2i (HR = 0.456; 95% CI 0.227-0.916; P = 0.027)., Conclusion: Beta-blockers, ACEi/ARB/ARNI, and SGLT2i were independently associated with a lower risk of all-cause mortality in patients with HFmrEF, specifically when applied as combined 'HF triple therapy'. Randomized studies are needed to investigate the effect of HF-related pharmacotherapies in patients with HFmrEF., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: The present study aims to clarify the prevalence and prognostic impact of anaemia and iron deficiency in patients with heart failure with mildly reduced ejection fraction (HFmrEF)., Background: The prognostic impact of anaemia and iron deficiency in HFmrEF has not yet been clarified., Methods: Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Patients with anaemia (i.e. haemoglobin <13 g/dL in males and < 12 g/dL in females) were compared to patients without, respectively patients with or without iron deficiency. The primary endpoint was all-cause mortality at 30 months (median follow-up), secondary endpoints comprised HF-related rehospitalisation., Results: Two thousand one hundred and fifty four patients with HFmrEF with a median haemoglobin level of 12.2 g/dL were included. Anaemia was present in 52% of patients with HFmrEF and associated with a higher risk of all-cause mortality (44% vs. 18%; HR = 3.021; 95% CI 2.552-3.576; p =.001) and HF-related rehospitalisation (18% vs. 8%; HR = 2.351; 95% CI 1.819-3.040; p =.001) at 30 months, which was confirmed after multivariable adjustment. Although iron status was infrequently assessed in anaemics with HFmrEF (27%), the presence of iron deficiency was associated with higher risk of rehospitalisation for worsening HF (25% vs. 15%; HR = 1.746; 95% CI 1.024-2.976; p =.038), but not all-cause mortality (p =.279) at 30 months., Conclusion: Anaemia and iron deficiency are very common in atleast half of patients with HFmrEF and independently associated with adverse long-term prognosis., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Aims: This study sought to determine the prognostic impact of acute decompensated heart failure (ADHF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). ADHF is a major complication in patients with heart failure (HF). However, the prognostic impact of ADHF in patients with HFmrEF has not yet been clarified., Methods and Results: Consecutive patients hospitalized with HFmrEF (i.e. left ventricular ejection fraction 41-49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. The prognosis of patients with ADHF was compared with those without (i.e. non-ADHF). The primary endpoint was long-term all-cause mortality. Secondary endpoints included in-hospital all-cause mortality and long-term HF-related re-hospitalization. Kaplan-Meier, multivariable Cox proportional regression, and propensity score matched analyses were performed for statistics. Long-term follow-up was set at 30 months. A total of 2184 patients with HFmrEF were included, ADHF was present in 22%. The primary endpoint was higher in ADHF compared to non-ADHF patients with HFmrEF [50% vs. 26%; hazard ratio (HR) = 2.269; 95% confidence interval (CI) 1.939-2.656; P = 0.001]. Accordingly, the secondary endpoint of long-term HF-related re-hospitalization was significantly higher (27% vs. 10%; HR = 3.250; 95% CI 2.565-4.118; P = 0.001). A history of previous ADHF before the index hospitalization was associated with higher rates of long-term HF-related re-hospitalization (42% vs. 23%; HR = 2.073; 95% CI 1.420-3.027; P = 0.001), but not with long-term all-cause mortality (P = 0.264)., Conclusion: ADHF is a common finding in patients with HFmrEF associated with an adverse impact on long-term prognosis., Competing Interests: Conflict of interest: The authors declare that they do not have any conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sex hormones influence the prevalence and the outcome of heart diseases. The conversion of testosterone to its more active metabolite dihydrotestosterone drives cardiac growth and dysfunction, while inhibition of this step by the anti-androgenic drug finasteride counteracts these pathological processes in preclinical models. In this retrospective, observational study, we aim to investigate whether finasteride, which is in clinical use mainly for prostate disease, might ameliorate cardiac hypertrophy and heart failure in patients. Retrospective chart review of 1041 medical cases with heart failure between 1995 and 2015 was conducted. Stratification was performed by concomitant prostate treatment status (tamsulosin versus finasteride). A propensity score analysis yielded a total of 328 matched medical cases without residual differences in the baseline patient characteristics. In this propensity score matched samples, anti-androgenic therapy with finasteride was associated with significantly reduced left ventricular hypertrophy (interventricular septal thickness 13.3 ± 2.4 mm control vs. 12.6 ± 2.1 mm finasteride group (p = 0.029); estimated average treatment effects on the treated: -0.7 mm, 95% CI mean difference -1.3 to -0.1). In this retrospective analysis anti-androgenic therapy with finasteride for prostate disease was associated with attenuated cardiac hypertrophy in patients with heart failure. Therefore, our data encourage further analysis of this approach in larger heart failure patient cohorts.

Objective: This study sought to assess the impact of treatment with digitalis on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients with atrial fibrillation (AF) and heart failure (HF)., Background: The data regarding outcomes of digitalis therapy in ICD recipients are limited., Methods: A large retrospective registry was used, including consecutive ICD recipients with episodes of ventricular tachyarrhythmia between 2002 and 2016. Patients treated with digitalis were compared to patients without digitalis treatment. The primary prognostic outcome was first recurrence of ventricular tachyarrhythmia at 5 years. Kaplan-Meier and multivariable Cox regression analyses were applied., Results: A total of 394 ICD recipients with AF and/or HF was included (26% with digitalis treatment and 74% without). Digitalis treatment was associated with decreased freedom from recurrent ventricular tachy-arrhythmias (HR = 1.423; 95% CI 1.047-1.934; p = 0.023). Accordingly, digitalis treatment was associated with decreased freedom from appropriate ICD therapies (HR = 1.622; 95% CI 1.166-2.256; p = 0.004) and, moreover, higher rates of rehospitalization (38 vs. 21%; p = 0.001) and all-cause mortality (33 vs. 20%; p = 0.011)., Conclusion: Among ICD recipients suffering from AF and HF, treatment with digitalis was associated with increased rates of recurrent ventricular tachyarrhythmias and ICD therapies. However, the endpoints may also have been driven by interactions between digitalis, AF, and HF., (© 2019 S. Karger AG, Basel.)

Background: To comparatively evaluate long-term prognostic values of fibrotic biomarkers galectin-3, gremlin-1 and osteopontin in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF)., Methods: Patients with acute dyspnea or peripheral edema were enrolled in the ED. Biomarkers were measured and added to prognostic models including 11 conventional risk factors plus NT-proBNP assessing state-of-the-art statistics of discrimination, calibration, reclassification and Cox regression analyses. Prognostic outcomes were long-term all-cause mortality (ACM) and AHF-related rehospitalization (AHF-RH) at 1 and 5 years., Results: 401 patients including 122 AHF patients were enrolled (mean age 67 years, males 51%). During 5 years follow-up 129 patients (30%) died and 73 (18%) were re-hospitalized because of AHF. In multivariate analysis, galectin-3 (hazard ratios (HR) range 1.4–1.9; p = 0.03) and osteopontin (HR range 1.2–1.4; p = 0.001) remained associated with ACM overall and in the AHF population at 5 years, whereas gremlin-1 remained associated with AHF-RH at 1 year in AHF patients (HR 1.3; p = 0.002). ACM in whole cohort was best discriminated (AUC = 0.85, p = 0.0001), calibrated and re-classified (NRI + 0.50 to + 0.56, p = 0.0001) by galectin-3, whereas in AHF patients ACM was best discriminated by osteopontin (AUC range: 0.82–0.84, p = 0.0001; NRI + 0.34 to + 0.38, p < 0.1) and AHF-RH at 1 year by gremlin-1 (AUC range: 0.82–0.92, p = 0.0001; NRI + 0.59 to + 0.60, p = 0.006)., Conclusions: A panel of fibrotic biomarkers, including osteopontin, galectin-3 and gremlin-1, might be useful for long term risk-stratification of symptomatic ED patients being suspected of AHF.

Background: To evaluate diagnostic and long-term prognostic values of hFABP compared to NT-proBNP and troponin I (TnI) in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF)., Methods: 401 patients with acute dyspnea or peripheral edema, 122 suffering from AHF, were prospectively enrolled and followed up to 5 years. hFABP combined with NT-proBNP versus NT-proBNP alone was tested for AHF diagnosis. Prognostic value of hFABP versus TnI was evaluated in models predicting all-cause mortality (ACM) and AHF related rehospitalization (AHF-RH) at 1 and 5 years, including 11 conventional risk factors plus NT-proBNP., Results: Additional hFABP measurements improved diagnostic specificity and positive predictive value (PPV) of sole NT-proBNP testing at the cutoff <300 ng/l to "rule out" AHF. Highest hFABP levels (4th quartile) were associated with increased ACM (hazard ratios (HR): 2.1-2.5; p = 0.04) and AHF-RH risk at 5 years (HR 2.8-8.3, p = 0.001). ACM was better characterized in prognostic models including TnI, whereas AHF-RH was better characterized in prognostic models including hFABP. Cox analyses revealed a 2 % increase of ACM risk and 3-7 % increase of AHF-RH risk at 5 years by each unit increase of hFABP of 10 ng/ml., Conclusions: Combining hFABP plus NT-proBNP (<300 ng/l) only improves diagnostic specificity and PPV to rule out AHF. hFABP may improve prognosis for long-term AHF-RH, whereas TnI may improve prognosis for ACM., Trial Registration: ClinicalTrials.gov identifier: NCT00143793 .

Aims: To analyze long-term efficacy and survival in patients with chronic heart failure treated with cardiac contractility modulation., Methods: 81 patients implanted with a CCM device between 2004 and 2012 were included in this retrospective analysis. Changes in NYHA class, ejection fraction (EF), Minnesota Living with Heart Failure Questionnaire, NT-proBNP and peak VO₂ were analyzed during a mean follow up of 34.2 ± 28 months (6-123 months). Observed mortality rate was compared with that predicted by the MAGGIC Score., Results: Patients were 61 ± 12 years old with EF 23 ± 7%. Heart failure was due to ischemic (n=48, 59.3%) or idiopathic dilated (n=33, 40.7%) cardiomyopathy. EF increased from 23.1 ± 7.9 to 29.4 ± 8.6% (p<0.05), mean NT-proBNP decreased from 4395 ± 3818 to 2762 ± 3490 ng/l (p<0.05) and mean peak VO2 increased from 13.9 ± 3.3 to 14.6 ± 3.5 ml/kg/min (p=0.1). The overall clinical responder rate (at least 1 class improvement of NYHA within 6 months or last follow-up) was 74.1%. 21 (25.9%) patients died during follow up, 11 (52.4%) due to cardiac conditions and 10 (47.6%) due to non-cardiac conditions. Mortality rates at 1 and 3 years were 5.2% and 29.5% compared to mortality rates estimated from the MAGGIC risk score of 18.4% (p<0.001) and 40% (p=ns), respectively. Log-Rank analysis of all events through 3 years of follow-up, however, was significantly less than predicted (p=0.022)., Conclusions: CCM therapy improved quality of life, exercise capacity, NYHA class, EF and NT-proBNP levels during long-term follow up. Mortality rates appeared to be lower than estimated from the MAGGIC score., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Background: To evaluate the diagnostic and prognostic value of sensitive troponin I (TnI) in patients with acute dyspnea and/or peripheral edema suspected of having acute heart failure (AHF)., Methods: This single centre prospective clinical study evaluates 372 patients presenting with acute dyspnea and/or peripheral edema to the emergency department (ED). Measurements of TnI and NT-proBNP were performed at the initial presentation in the ED. All patients were followed up to 5 years. The diagnostic value of TnI compared to NT-proBNP for AHF diagnosis as well as long-term prognostic values for all cause mortality and AHF related rehospitalization were evaluated., Results: TnI plus NT-proBNP improved the diagnosis of AHF (improvement of accuracy (75%, 95% CI 71% - 79%), specificity (68%, 95% CI 62% - 74%), PPV (54%, 95% CI 47% - 62%), and NRI +0.15) compared to NT-proBNP alone (p = 0.0001). TnI levels showed independent prognostic value for all-cause mortality and AHF related rehospitalization after 1 and 5 years (range of AUCs 0.64 - 0.72; p = 0.03 or lower). Highest TnI levels of the 4th quartile revealed an up to 5.5 times higher risk of death within 1 and 5 years (range of HRs: 2.5 - 5.5; p = 0.0001). TnI added significantly to multivariable Cox prediction models even after adjusting for NT-proBNP, particularly in AHF patients (range of HRs: 2.1 - 2.7; p ≤ 0.05)., Conclusions: TnI improves AHF diagnosis when combined with NT-proBNP. TnI identifies patients with high 1- and 5-year all-cause mortality and AHF-related rehospitalization risk and adds prognostic value to NT-proBNP.

Background: As a mediator of ECM homeostasis, connective tissue growth factor (CTGF) appears to be involved in adverse structural remodeling processes in the heart. However, the diagnostic and prognostic value of CTGF levels in acute heart failure (AHF) in addition to natriuretic peptide testing has not yet been evaluated., Methods and Results: A total of 212 patients presenting with acute dyspnea and/or peripheral edema to the Emergency Department were evaluated. CTGF and NT-proBNP plasma levels were measured at the initial presentation. All patients were followed up to 1 and 5 years. The first endpoint tested was the diagnostic non-inferiority of combined CTGF plus NT-proBNP compared to NT-proBNP alone for AHF diagnosis. Afterwards, the additional diagnostic value of CTGF plus NT-proBNP was tested. CTGF levels were higher in NYHA class III/IV and AHA/ACC class C/D patients compared to lower class patients (p = 0.04). Patients with HFREF revealed highest CTGF levels (median 93.3 pg/ml, IQR 18.2-972 pg/ml, n = 48) compared to patients with a normal heart function (i.e., without HFREF and HFPEF) (median 25.9, IQR <1-82.2 pg/ml, n = 37) (p < 0.05), followed by patients with HFPEF (median 82.2 pg/ml, IQR 11.5-447 pg/ml, n = 32) as assessed by echocardiography. Finally, CTGF levels were higher in patients with AHF (median 77.3 pg/ml, IQR 22.5-1012 pg/ml, n = 66) compared to those without (p = 0.002). CTGF plus NT-proBNP was non-inferior to NT-proBNP testing alone for AHF diagnosis (AUC difference 0.01, p > 0.05). CTGF plus NT-proBNP improved the diagnostic capacity for AHF (accuracy 82 %, specificity 83 %, positive predictive value 66 %, net reclassification improvement +0.11) compared to NT-proBNP alone (p = 0.0001). CTGF levels were not able to differentiate prognostic outcomes after 1 and 5 years., Conclusions: Additional CTGF measurements might lead to a better discrimination of higher functional and structural heart failure stages and might identify patients of an increased risk for an acute cardiac decompensation.

Aims: To evaluate the diagnostic and prognostic value of osteopontin in patients with acute dyspnoea and/or peripheral oedema suspected of having acute congestive heart failure (aCHF)., Methods and Results: A total of 401 patients presenting with acute dyspnoea and/or peripheral oedema to the emergency department were prospectively enrolled and followed up for up to 5 years. Blood samples for biomarker measurements were collected on admission to the emergency department. Osteopontin combined with NT-proBNP vs. NT-proBNP alone for diagnosis of aCHF was tested. Additionally, osteopontin vs. NT-proBNP for prognostic outcomes (i.e. all-cause mortality, aCHF-related rehospitalization, and both in combination) was tested. The diagnostic and prognostic capacity of osteopontin was tested by C-statistics, reclassification indices, and multivariable Cox prediction models. Osteopontin plus NT-proBNP improved the diagnostic capacity for aCHF diagnosis [accuracy 76%, 95% confidence interval (CI) 72-80%; specificity 74%, 95% CI 69-79%, net reclassification improvement (NRI) +0.10] compared with NT-proBNP alone in the emergency department (P = 0.0001). Osteopontin independently predicted all-cause mortality and aCHF-related rehospitalization after 1 and 5 years. Compared with NT-proBNP, osteopontin was of superior prognostic value, specifically in aCHF patients and for the prognostic outcome of aCHF-related rehospitalization., Conclusion: Osteopontin improves aCHF diagnosis when combined with NT-proBNP. Osteopontin identifies aCHF patients with high 1- and 5-year mortality and rehospitalization risk, and adds prognostic value to NT-proBNP. Trial registration NCT00143793.

Purpose: Atrial fibrillation (AF) and acute congestive heart failure (aCHF) are characterized by an adverse cardiac remodeling. Arrhythmogenic or structural remodeling can be caused by interstitial fibrosis. Transforming growth factor beta 1 (TGF-beta 1) represents a central regulator of cardiac fibrosis. This study investigates serum levels of TGF-beta 1 in patients with AF and aCHF., Methods: 401 patients presenting with symptoms of dyspnea or peripheral edema were prospectively enrolled. Blood samples for measurement of TGF-beta 1 (R&D Systems, Inc.) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) (DadeBehring ltd.) were collected after the initial clinical evaluation., Results: Median TGF-beta 1 levels were lower in patients with AF (21.0 ng/ml, interquartile range (IR) 15.4-27.6 ng/ml, n = 107) compared to those without (25.0 ng/ml, IR 18.5-31.6 ng/ml, n = 294) (p = 0.009). Patients with aCHF had lower TGF-beta 1 levels (median 22.0 ng/ml, IR 15.6-27.1 ng/ml, n = 122) than those without (median 24.9 ng/ml, IR 18.1-31.9 ng/ml, n = 279) (p = 0.0005). In logistic regression models TGF-beta 1 was still associated with AF (odds ratio (OR) 3.00, 95% CI 1.37-6.61, p = 0.0001) and aCHF (OR 3.98, 95% CI 1.55-10.19, p = 0.004). TGF-beta 1 inversely correlated with left atrial diameter (r = -0.30, p = 0.007) and NT-proBNP (r = -0.14, p = 0.007)., Conclusions: Low serum levels of TGF-beta 1 are associated with AF and aCHF. This decrease may result from a higher consumption of TGF-beta 1 within the impaired myocardium or antifibrotic functions of natriuretic peptides.

Background: The purpose of this study was to determine the diagnostic power of a newly available assay for amino-terminal pro-brain natriuretic peptide (NT-proBNP) to identify patients with acute heart failure. In addition, the influence of initial NT-proBNP measurements on economic consequences, diagnostic procedures and staff involvement was evaluated., Methods and Results: 401 patients presenting with acute dyspnea or peripheral edema in the emergency department were enrolled. NT-proBNP was measured after initial clinical evaluation. Clinical routine care and diagnostic assessment were blinded to NT-proBNP results. Two cardiologists independently validated the period of hospitalization, clinical examinations and medical therapies of each patient considering NT-proBNP results. The median NT-proBNP level among patients with acute congestive heart failure (CHF) (n=122) was 3497 pg/ml as compared to 320 pg/ml in patients without (n=279) (p<0.0001). An NT-proBNP cutoff level <300 pg/ml was optimal to rule out acute CHF (negative predictive value 96%; sensitivity 96%). NT-proBNP >or=300 pg/ml could strongly predict acute CHF when compared to patients' history or physical examination (odds ratio 9.5; p<0.0001) and diagnostic technical findings (odds ratio 14.7; p<0.05). In patients with NT-proBNP<300 pg/ml, 14% of the period of hospitalization could be saved, corresponding to savings of US $481 per patient. In addition, 9% of the number and time of staff involvement of clinical examinations and therapies could be saved, 10% of the costs of clinical examinations. Chest X-rays were saved in 34%, echocardiography in 9%., Conclusions: Measurement of NT-proBNP leads to multiple saving amounts and optimizes diagnostic pathways and resource allocation.

The article focuses on FORTA [Fit fOR The Aged] List which addresses both over- and undertreatment, leading to patients' medical needs being comprehensively met. It mentions highest percentage of disease-related entries with changed FORTA classifcations was observed for arterial hypertension; and also mentions SGLT2 inhibitors were labeled as FORTA B for heart failure while their classifcation for type 2 diabetes remained FORTA C.

Objective: This study evaluates the impact of left ventricular ejection fraction (LVEF) on recurrences of ventricular tachyarrhythmias in recipients of implantable cardioverter defibrillator (ICD). Background: Data regarding recurrences of ventricular tachyarrhythmias in ICD recipients according to LVEF is limited. Methods: A large retrospective registry was used, including all consecutive ICD recipients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2016. Patients with LVEF <35% were compared to patients with LVEF ≥35%. The primary end point was first recurrences of ventricular tachyarrhythmias at 5 years. Secondary end points were ICD-related therapies, rehospitalization, and all-cause mortality at 5 years. Cox regression, Kaplan Meier, and propensity score matching analyses were applied. Results: A total of 528 consecutive ICD recipients were included (51% with LVEF ≥35% and 49% with LVEF <35%). LVEF <35% was associated with reduced freedom from recurrent ventricular tachyarrhythmias (40 vs. 49%, log rank p = 0.014; hazard ratio [HR] = 1.381; 95% confidence interval [CI] 1.066–1.788; p = 0.034), mainly attributed to recurrent sustained VT in primary preventive ICD recipients. Accordingly, LVEF <35% was associated with reduced freedom from first appropriate ICD therapies (28 vs. 41%, log rank p = 0.001; HR = 1.810; 95% CI 1.185–2.766; p = 0.001). Finally, LVEF <35% was associated with a higher rate of rehospitalization (23 vs. 34%; p = 0.005) and all-cause mortality at 5 years (13 vs. 29%; p = 0.001). Conclusion: LVEF <35% was associated with reduced freedom from recurrent ventricular tachyarrhythmias, appropriate device therapies, rehospitalization and all-cause mortality secondary to index ventricular tachyarrhythmias. [ABSTRACT FROM AUTHOR]

Objective: The study sought to assess the impact of ischemic (ICMP) compared to non-ischemic cardiomyopathy (NICMP) on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients.Background: Data comparing recurrences of ventricular tachyarrhythmias in ICD recipients with ischemic or non-ischemic cardiomyopathy is limited.Methods: A large retrospective registry was used including all consecutive ICD recipients with first episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2016. Patients with ICMP were compared to patients with NICMP. The primary prognostic endpoint was first recurrences of ventricular tachyarrhythmias at one year. Secondary endpoints comprised ICD-related therapies, rehospitalization and all-cause mortality at one year. Statistics Kaplan-Meier survival and multivariable Cox regression analyses.Results: A total of 387 consecutive ICD recipients were included retrospectively (ICMP: 82%, NICMP: 18%). At one year of follow-up, freedom from first recurrences of ventricular tachyarrhythmias was lower in NICMP (81% vs. 71%, log-rank p = 0.063; HR = 1.760; 95% CI 0.985-3.002; p = 0.080), mainly attributed to higher rates of sustained VT (20% versus 12%, p = 0.054). Accordingly, freedom from first appropriate device therapies was lower in NICMP (74% vs. 85%, log rank p = 0.004; HR = 1.951; 95% CI 1.121-3.397; p = 0.028), especially in patients with sustained VT or VF at index. Both groups revealed comparable rates of rehospitalization and all-cause mortality at one year.Conclusion: NICMP was associated with higher rates of recurrent ventricular tachyarrhythmias and appropriate ICD therapies compared to ICMP at one year of follow-up, whereas rates of rehospitalization and all-cause mortality were comparable.Condensed Abstract: This study retrospectively compared the impact of cardiomyopathy types (ICMP versus NICMP) on recurrences of ventricular tachyarrhythmias in 387 ICD recipients. Freedom from first episodes of ventricular tachyarrhythmias and first appropriate device therapies were lower in patients with NICMP compared to ICMP. [ABSTRACT FROM AUTHOR]

Background: Data regarding the prognostic impact of atrial fibrillation (AF) in patients with electrical storm (ES) is rare. Objectives: This study sought to assess the prognostic impact of AF in patients with ES on mortality, rehospitalization, major adverse cardiovascular events (MACE) and recurrence of ES (ES-R). Methods: All consecutive implantable cardioverter defibrillator (ICD) patients presenting with ES were included retrospectively from 2002 to 2016. Patients with AF were compared to non-AF patients. The primary prognostic endpoint was all-cause mortality. Secondary endpoints were in-hospital mortality, rehospitalization rates, MACE and ES-R. Results: A total of 87 ES patients with ICD were included and followed up to 2.5 years; 43% suffered from AF. The presence of AF was associated with increased all-cause mortality (47 vs. 29%, log-rank p = 0.052; hazard ratio [HR] 1.969, 95% confidence interval [CI] 0.981–3.952, p = 0.057), which was no longer present after multivariable adjustment for age, diabetes and dilated cardiomyopathy. Furthermore, AF was associated with increased rates of overall rehospitalization (61 vs. 31%, log-rank p = 0.013; HR 2.381, 95% CI 1.247–4.547, p = 0.009), especially due to AF (14 vs. 0%, p = 0.001) and acute heart failure (AHF) (28 vs. 10%, p = 0.018; HR 3.754, 95% CI 1.277–11.038, p = 0.016). Notably, AF was not associated with differences in MACE (55 vs. 37%, log rank p = 0.339) and ES-R (28 vs. 25%, log rank p = 0.704). Conclusion: In ES patients, presence of AF was univariably associated with increased rates of all-cause mortality at 2.5 years. Furthermore, AF was multivariably associated with overall rehospitalization, especially due to AF and AHF. [ABSTRACT FROM AUTHOR]

Because data on electrical storm (ES) is limited, this study sought to compare the prognosis of patients with ES to those with ventricular tachyarrhythmias on mortality, rehospitalization and major adverse cardiac events (MACE). In this retrospective study consecutive implantable cardioverter defibrillator (ICD) recipients presenting with ES were compared to patients surviving ventricular tachyarrhythmias (ventricular tachycardia (VT) or fibrillation (VF); non-ES) on admission from 2002 to 2016. The primary endpoint was all-cause mortality, secondary endpoints were rehospitalization and MACE at 2.5 years of follow-up. 764 consecutive patients with an ICD were included (11% with ES, 89% with VTA). ES was associated with higher rates of all-cause mortality (37% vs. 20%, log-rank p = 0.001; HR 2.084; 95% CI 1.416–3.065, p = 0.001). However, only in secondary preventive ICD recipients, ES remained significantly associated with mortality (39% vs. 20%; log rank p = 0.001; HR 2.235, 95% CI 1.378–3.625, p = 0.001). Furthermore, ES was associated with higher rates of rehospitalization (44% vs. 12%, log-rank p = 0.001; HR 4.763, 95% CI 3.237–7.009, p = 0.001), mainly due to VT (22% vs. 4%, p = 0.001) and acute heart failure (AHF) (17% vs. 4%, p = 0.001) and higher rates of MACE (40% vs. 23%; log rank p = 0.001; HR 1.838; 95% CI 1.273–2.654, p = 0.002). Increasing risks of death and rehospitalization were still observed even after multivariable adjustment. ES was associated with increased rates of all-cause mortality, rehospitalization, respectively due to VT and AHF, as well as MACE at 2.5 years compared to patients with ventricular tachyarrhythmias apart from ES. • ES is associated with increased rates of long-term all-cause mortality. • ES is not associated with all-cause mortality in primary preventive ICD recipients. • ES is associated with increased rates of VT and AHF related rehospitalization. • ES is associated with increased rates of MACE. [ABSTRACT FROM AUTHOR]

Abstract: Background: Amyloidosis is a life-threatening protein misfolding disease and affects cardiac tissue, leading to heart failure, myocardial ischemia and arrhythmia. Amyloid deposits result in oxidative stress, inflammation and apoptosis. The purpose of this study was to examine the role of innate defense components, i.e., Deleted in Malignant Brain Tumors 1 (DMBT1) and the complement system, in different types of cardiac amyloidosis. Methods: Expression of DMBT1 and of the complement proteins C1q, C3d and C4d in cardiac specimens of patients with different types of amyloidosis were determined by immunohistochemistry and correlated with amyloid deposits stained by Congo red dye. Results: Strong DMBT1 staining adjacent to amyloid deposits was detected in different amyloidosis types, depending on the extent of the deposits. DMBT1 is localized in the endomysium and perimysium, in the endocardium, in the myocytes and in endothelial cells of affected transmural vessels. C1q, C3d and C4d were detected in the amyloid deposits but also in the endomysium and perimysium, in some myocytes, in endothelial cells, in the endocardium, and around the amyloid deposits. Conclusions: Up-regulated DMBT1 and complement activation in cardiac amyloidosis may be part of the activated pathways induced by protein aggregation and the consecutive inflammatory reaction. [Copyright &y& Elsevier]