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OBJECTIVES: Myocardial infarction without significant stenosis or occlusion of the coronary arteries carries a high risk of recurrent major adverse cardiovascular events and poor prognosis. This study aimed to investigate the association between body mass index and outcomes in patients with a suspected myocardial infarction with nonobstructive coronary artery disease (MINOCA). METHODS: Patients were recruited at Bergmannsheil University Hospital from January 2010 to April 2021. The primary outcomes were in-hospital and long-term mortality. Secondary outcomes consisted of adverse events during hospitalization and during follow-up. RESULTS: A total of 373 patients were included in the study, with a mean follow-up time of 6.2 years. The patients were divided into different BMI groups: < 25 kg/m² (n = 121), 25-30 kg/m² (n = 140), and > 30 kg/m² (n = 112). In-hospital mortality was 1.7% versus 2.1% versus 4.5% (p = 0.368). However, long-term mortality tended to be higher in the < 25 kg/m² group compared to the 25-30 and > 30 kg/m² groups (log-rank p = 0.067). Subgroup analysis using Kaplan-Meier analysis showed a higher rate of cardiac cause of death in the < 25 kg/m² group compared to the 25-30 and > 30 kg/m² groups: 5.7% versus 1.1% versus 0.0% (log-rank p = 0.042). No significant differences were observed in other adverse events between the different BMI groups during hospitalization and long-term follow-up. CONCLUSIONS: Patients with a BMI < 25 kg/m² who experience a suspected myocardial infarction without significant coronary artery disease may have higher all-cause mortality and cardiovascular cause of death. However, further data are needed to confirm these findings.

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INTRODUCTION: Coronary sclerosis is a risk factor for the progression to obstructive coronary artery disease (CAD). However, understanding its impact on the outcomes of patients with myocardial infarction and non-obstructive coronary arteries is limited. This study aimed to explore the prognostic influence of coronary sclerosis on in- and out-of-hospital events in troponin-positive patients with non-obstructive coronary arteries. METHODS: This study was a retrospective cohort analysis based on prospectively collected data. A total of 24,775 patients who underwent coronary angiography from 2010 to 2021 in a German university hospital were screened, resulting in a final study cohort of 373 troponin-positive patients with non-obstructive coronary arteries and a follow-up period of 6.2 ± 3.1 years. Coronary sclerosis was defined as coronary plaques without angiographically detectable stenotic lesions of 50% or more in the large epicardial coronary arteries. The primary study endpoint was the occurrence of in-hospital events. Secondary endpoints included events during follow-up. RESULTS: Patients with coronary sclerosis were significantly older (70 ± 12 vs. 58 ± 16 years, p < 0.001), had ST-segment elevation less frequently on electrocardiogram (9.4% vs. 18.7%, p = 0.013), and suffered more often from diabetes mellitus (23.3% vs. 13.1%, p = 0.009), arterial hypertension (79.6% vs. 59.8%, p < 0.001), chronic obstructive pulmonary disease (17.1% vs. 9.4%, p = 0.028), chronic kidney disease (22.2% vs. 8.4%, p < 0.001), atrial fibrillation (19.8% vs. 12.2%, p = 0.045), and valvular diseases than patients without CAD. Patients with coronary sclerosis were more likely to receive medication for primary/secondary prevention on admission and at discharge. The incidence of in- and out-of-hospital events was significantly higher in patients with coronary sclerosis (in-hospital: 42.8% vs. 29.9%, p = 0.010; out-of-hospital: 46.0% vs. 26.1%, p < 0.001). Mortality rates tended to be higher in the coronary sclerosis group (29.4% vs. 20.0%, p = 0.066). CONCLUSION: Patients diagnosed with coronary sclerosis presented a higher incidence of comorbidities and increased medication use, and experienced higher rates of both in-hospital and out-of-hospital events, primarily due to the clustering of cardiovascular risk factors.

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BACKGROUND AND AIMS: Wearable cardioverter defibrillator (WCD) can protect patients from sudden cardiac death due to ventricular tachyarrhythmias and serve as a bridge to decision of definite defibrillator implantation. The aim of this analysis from an international, multicenter WCD registry was to identify predictors of sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) in this population. METHODS: One thousand six hundred seventy-five patients with WCD were included in a multicenter registry from 9 European centers, with a median follow-up of 440 days (IQR 120-893). The primary study end point was the occurrence of sustained VT/VF. RESULTS: Sustained VT was detected by WCD in 5.4% and VF in 0.9% of all patients. Of the 30.3% of patients receiving ICD implantation during follow-up, sustained VT was recorded in 9.3% and VF in 2.6%. Non-ischemic cardiomyopathy (HR 0.5, p < 0.001), and medication with angiotensin-converting enzyme inhibitors (HR 0.7, p = 0.027) and aldosterone antagonists (HR 0.7, p = 0.005) were associated with a significantly lower risk of VT/VF. CONCLUSIONS: Patients who received WCD due to a transient increased risk of sudden cardiac death have a comparatively lower risk of VT/VF in the presence of non-ischemic cardiomyopathy. Of note, optimal medical treatment for heart failure not only results in an improvement in left ventricular ejection fraction but also in a reduction in the risk for VT/VF.

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Background: Data on the use of the wearable cardioverter defibrillator in patients suffering from inherited and congenital heart disease are limited. Consequently, evidence for guideline recommendations in this patient population is lacking. Methods: In total 1,675 patients were included in a multicenter registry of eight European centers. In the present cohort, we included 18 patients suffering from congenital and inherited heart disease. Results: Nine patients (50%) were male with a mean age of 41.3 ± 16.4 years. Four patients suffered from hypertrophic cardiomyopathy (HCM), four patients suffered from non-compaction cardiomyopathy (NCCM), two patients were diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC) and one patient suffered from muscular dystrophy of the limb-girdle type with cardiac involvement, secondary cardiomyopathy. Three patients presented with Brugada syndrome (BrS). One patient suffered from long-QT syndrome type 1 (LQTS1). Furthermore, two patients had congenital heart defects and one patient suffered from cardiac sarcoidosis (CS). There were no appropriate/inappropriate shocks with the WCD in this cohort. One patient had recurrent self-limiting sustained ventricular tachycardia during the wear time, but actively inhibited a shock and was hospitalized. The compliance rate in this cohort was 77.8% with a mean wear time of 45.3 ± 26.9 days with a mean follow-up time of 570 ± 734 days. 55.6% (10/18) of the patients received an ICD after WCD wear time. Conclusions: This retrospective study of patients with inherited and congenital heart disease shows that WCD use is not beneficial in the majority of patients with inherited and congenital heart disease.

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OBJECTIVE: The study investigates the characteristics and prognostic impact of different heart failure (HF) etiologies in patients with heart failure with mildly reduced ejection fraction (HFmrEF). BACKGROUND: Data regarding the characterization of patients with HFmrEF and their outcomes is scarce. METHODS: Consecutive patients 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. Patients with ischemic cardiomyopathy (ICM) were compared to patients without ischemic cardiomyopathy (non-ICM). The primary endpoint was all-cause mortality at 30 months (median follow-up). Statistical analyses included Kaplan-Meier, multivariable Cox proportional regression analyses and propensity score matching. RESULTS: From a total of 1,832 patients hospitalized with HFmrEF, ICM was the most common HF etiology in 68.7 %, followed by hypertensive (9.7 %) and primary non-ischemic cardiomyopathies (NICM) (8.1 %). Within the entire study cohort, the presence of ICM was not associated with the risk of all-cause mortality (HR = 0.864; 95 % CI 0.723 - 1.031), however after multivariable adjustment (HR = 0.792; 95 % CI 0.646 - 0.972; p = 0.026) and propensity score matching (25.7% vs. 31.4 %; log rank p = 0.050), the presence of ICM was associated with lower risk of all-cause mortality at 30 months compared to patients without ICM. CONCLUSION: ICM is the most common etiology of HF in HFmrEF and may be associated with favorable outcomes. This may be related to better adherence to pharmacological treatment and improved revascularization strategies for HFmrEF patients with ICM.

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AIMS: The study investigates the prognosis of atrial fibrillation (AF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Data concerning the prognostic impact of AF in patients with HFmrEF is scarce. METHODS AND RESULTS: Consecutive patients with HFmrEF [i.e. left ventricular ejection fraction 41-49% and signs and/or symptoms of heart failure (HF)] were retrospectively included at one institution from 2016 to 2022. Patients with AF were compared with patients without with regard to the primary composite endpoint of all-cause mortality and HF-related rehospitalization at 30 months (median follow-up). Statistical analyses included Kaplan-Meier, multivariable Cox proportional regression analyses, and propensity score matching. A total of 2148 patients with HFmrEF were included with an overall prevalence of AF of 43%. The presence of AF was associated with a higher risk of the primary composite endpoint all-cause mortality and HF-related rehospitalization at 30 months [hazard ratio (HR) = 2.068; 95% confidence interval (CI) 1.802-2.375; P = 0.01], which was confirmed after propensity score matching (HR = 1.494; 95% CI 1.216-1.835; P = 0.01). AF was an independent predictor of both all-cause mortality (HR = 1.340; 95% CI 1.066-1.685; P = 0.01) and HF-related rehospitalization (HR = 2.061; 95% CI 1.538-2.696; P = 0.01). Finally, rhythm control may be associated with lower risk of all-cause mortality compared with rate control for AF (HR = 0.342; 95% CI 0.199-0.587; P = 0.01). CONCLUSION: Atrial fibrillation affects 43% of patients with HFmrEF and represents an independent predictor of adverse long-term prognosis.

By now, limited data regarding the prognostic impact of comorbidities in heart failure with mildly reduced ejection fraction (HFmrEF) are available, contributing to the overall limited evidence regarding the treatment of patients with HFmrEF. The present study investigates the prognostic impact of the presence of atrial fibrillation (AF) on the long-term prognosis of patients with HFmrEF using a large retrospective study of 2148 patients hospitalized with HFmrEF from 2016 to 2022. Atrial fibrillation was prevalent in 43% of patients with HFmrEF and independently associated with an increased risk of the composite of long-term all-cause mortality and heart failure-related rehospitalization. Adverse prognosis in patients with concomitant AF was confirmed using multivariable Cox regression analyses and propensity score matching. Finally, the achievement of rhythm control may be associated with a lower risk of long-term all-cause mortality. Further studies are needed to demonstrate the effect of rhythm control and catheter ablation for AF in patients with HFmrEF.

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Background: The development and course of myocardial infarction with non-obstructive coronary artery (MINOCA) disease is still not fully understood. In this study, we aimed to examine the baseline characteristics of in-hospital outcomes and long-term outcomes of a cohort of troponin-positive patients without obstructive coronary artery disease based on different left ventricular ejection fractions (LVEFs). Methods and results: We included a cohort of 254 patients (mean age: 64 (50.8-75.3) years, 120 females) with suspected myocardial infarction and no obstructive coronary artery disease (MINOCA) in our institutional database between 2010 and 2021. Among these patients, 170 had LVEF ≥ 50% (84 females, 49.4%), 31 patients had LVEF 40-49% (15 females, 48.4%), and 53 patients had LVEF < 40% (20 females, 37.7%). The mean age in the LVEF ≥ 50% group was 61.5 (48-73) years, in the LVEF 40-49% group was 67 (57-78) years, and in the LVEF < 40% group was 68 (56-75.5) years (p = 0.05). The mean troponin value was highest in the LVEF < 40% group, at 3.8 (1.7-4.6) µg/L, and lowest in the LVEF ≥ 50% group, at 1.1 (0.5-2.1) µg/L (p = 0.05). Creatine Phosphokinase (CK) levels were highest in the LVEF ≥ 50% group (156 (89.5-256)) and lowest in the LVEF 40-49% group (127 (73-256)) (p < 0.05), while the mean BNP value was lowest in the LVEF ≥ 50% group (98 (48-278) pg/mL) and highest in the <40% group (793 (238.3-2247.5) pg/mL) (p = 0.001). Adverse in-hospital cardiovascular events were highest in the LVEF < 40% group compared to the LVEF 40-49% group and the LVEF ≥ 50% group (56% vs. 55% vs. 27%; p < 0.001). Over a follow-up period of 6.2 ± 3.1 years, the all-cause mortality was higher in the LVEF < 40% group compared to the LVEF 40-49% group and the LVEF ≥ 50% group. Among the different factors, LVEF < 40% and LVEF 40-49% were associated with an increased risk of in-hospital cardiovascular events in the multivariable Cox regression analysis. Conclusions: LVEF has different impacts on in-hospital cardiovascular events in this cohort. Furthermore, LVEF influences long-term all-cause mortality.

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Background: The occurrence of ventricular tachyarrhythmias represents an established risk factor of mortality in heart failure (HF). However, data concerning their prognostic impact in heart failure with mildly reduced ejection fraction (HFmrEF) is limited. Therefore, the present study aims to investigate patient characteristics associated with ventricular tachyarrhythmias and their prognostic impact in patients with HFmrEF. Methods: 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 HFmrEF and different types of ventricular tachyarrhythmias (i.e., non-sustained ventricular tachycardia (nsVT), sustained VT (sVT), and ventricular fibrillation (VF) was investigated for the primary endpoint of long-term all-cause mortality at 30 months. Secondary endpoints included in-hospital all-cause mortality and long-term HF-related rehospitalization at 30 months. Results: From a total of 2184 patients with HFmrEF, 4.4% experienced ventricular tachyarrhythmias (i.e., 2.0% nsVT, 0.7% sVT, and 1.6% VF). The occurrence of nsVT was associated with higher New York Heart Association (NYHA) functional class, whereas the incidence of sVT/VF was associated with acute myocardial infarction and ischemic heart disease. However, nsVT (25.0%; HR = 0.760; 95% CI 0.419-1.380; p = 0.367) and sVT/VF (28.8%; HR = 0.928; 95% CI 0.556-1.549; p = 0.776) were not associated with a higher risk of long-term all-cause mortality compared to patients with HFmrEF without ventricular tachyarrhythmias (31.5%). In-hospital cardiovascular mortality was more frequently observed in patients with HFmrEF and sVT/VF compared to those with HFmrEF but without sustained ventricular tachyarrhythmias (7.7% vs. 1.5%; p = 0.004). Finally, the risk of rehospitalization for worsening HF was not affected by the presence of ventricular tachyarrhythmias. Conclusions: The occurrence of ventricular tachyarrhythmias in patients hospitalized with HFmrEF was low and not associated with long-term prognosis.

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AIMS: As there is limited evidence regarding the prognostic impact of prior left ventricular ejection fraction (LVEF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF), this study investigates the prognostic impact of longitudinal changes in LVEF in patients with HFmrEF. METHODS: Consecutive patients with HFmrEF (i.e. LVEF 41-49% with signs and/or symptoms of HF) were included retrospectively in a monocentric registry from 2016 to 2022. Based on prior LVEF, patients were categorized into three groups: stable LVEF, improved LVEF, and deteriorated LVEF. The primary endpoint was 30-months all-cause mortality (median follow-up). Secondary endpoints included in-hospital and 12-months all-cause mortality, as well as HF-related rehospitalization at 12 and 30 months. Kaplan-Meier and multivariable Cox proportional regression analyses were applied for statistics. RESULTS: Six hundred eighty-nine patients with HFmrEF were included. Compared to their prior LVEF, 24%, 12%, and 64% had stable, improved, and deteriorated LVEF, respectively. None of the three LVEF groups was associated with all-cause mortality at 12 (p ≥ 0.583) and 30 months (31% vs. 37% vs. 34%; log rank p ≥ 0.376). In addition, similar rates of 12- (p ≥ 0.533) and 30-months HF-related rehospitalization (21% vs. 23% vs. 21%; log rank p ≥ 0.749) were observed. These findings were confirmed in multivariable regression analyses in the entire study cohort. CONCLUSION: The transition from HFrEF and HFpEF towards HFmrEF is very common. However, prior LVEF was not associated with prognosis, likely due to the persistently high dynamic nature of LVEF in the follow-up period.

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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.

Although heart failure (HF) with mildly reduced ejection fraction (HFmrEF) affects one out of four patients with HF, limited evidence regarding HF pharmacotherapies in these patients is available. The present study investigates the treatment with beta-blockers (BB), angiotensin-converting enzyme inhibitors, receptor blockers, or receptor-neprilysin inhibitor (ACEi/ARB/ARNI), mineralocorticoid receptor antagonists (MRA), and sodium­glucose-linked transport protein 2 inhibitors (SGLT2i) on long-term outcomes using a large registry-based data set of 2109 patients hospitalized with HFmrEF. Treatment with BB, ACEi/ARB/ARNI, and SGLT2i was independently associated with a lower risk of long-term all-cause mortality, even after multivariable adjustment and propensity score matching, specifically when applied in combination. In contrast, MRA treatment was not associated with outcomes in the present study. The present study supports the evidence that patients with HFmrEF may benefit from HF pharmacotherapies similar than patients with HF with reduced ejection fraction.

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BACKGROUND: Although mitral valve regurgitation (MR) is a common valvular heart disease in patients with heart failure (HF), there is a paucity of data on the characterization and outcomes of patients with HF with mildly reduced ejection fraction (HFmrEF) and concomitant MR. METHODS: From 2016 to 2022, consecutive patients hospitalized with HFmrEF (i.e., left ventricular ejection fraction from 41% to 49% and signs and/or symptoms of HF) were retrospectively included at one institution. Patients with MR were compared with patients without MR. Further risk stratification was performed according to MR severity and etiology (i.e., primary vs. secondary MR). The primary end point was all-cause mortality at 30 months (median follow-up), and the key secondary end point was hospitalization for worsening HF. RESULTS: Of 2181 patients hospitalized with HFmrEF, 59% presented with mild, 10% with moderate, and 2% with severe MR. MR was associated with increased all-cause mortality at 30 months (HR = 1.756; 95% CI 1.458-2.114; p = 0.001), with higher risk in more advanced stages. Furthermore, MR patients had higher risk of HF-related re-hospitalization at 30 months (HR = 1.560; 95% CI 1.172-2.076; p = 0.002). Even after multivariable adjustment, mild, moderate, and severe MR were still associated with all-cause mortality. Finally, the risk of all-cause mortality was lower in patients with secondary MR compared with patients with primary MR (HR = 0.592; 95% CI 0.366-0.956; p = 0.032). CONCLUSION: MR is common in HFmrEF and independently associated with higher risk of all-cause mortality and HF hospitalization.

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Objective: The study investigates the prognostic impact of body mass index (BMI) in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). Background: Limited data regarding the prognostic impact of BMI in patients with HFmrEF is available. Methods: Consecutive patients with HFmrEF (ie, left ventricular ejection fraction 41-49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. Risk stratification was performed according to WHO-defined BMI groups. The primary endpoint was all-cause mortality at 30 months (median follow-up). Kaplan-Meier, uni- and multivariable Cox proportional regression analyses were applied for statistics. Results: 1832 consecutive patients with HFmrEF were included with a median BMI of 26.7 kg/m2 (IQR 24.0-30.8 kg/m2). Patients with lowest BMI (ie, 18.5-24.9 kg/m2) were associated with highest risk of all-cause mortality at 30 months compared to patients with higher BMI values (40.0% vs 29.0% vs 21.4% vs 20.9%; log rank p = 0.001; HR = 0.721; 95% CI 0.656-0.793; p = 0.001). Even after multivariable adjustment, higher BMI values were associated with improved survival at 30 months (HR = 0.963; 95% CI 0.943-0.985; p = 0.001). In contrast, the risk of HF- related rehospitalization at 30 months was not affected by BMI (log rank p = 0.064). Conclusion: In patients hospitalized with HFmrEF, lower BMI was associated with increased risk of all-cause mortality at 30 months, suggesting an obesity paradox in HFmrEF.

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BACKGROUND: Recently, abnormal thyroid function was shown to be common in patients with Takotsubo syndrome (TTS), being classified into "endocrine-type" and "stress-type" responses. The aim of this study was to investigate the association between thyroid homeostasis and TTS in a larger international registry. METHODS: In total 288 patients with TTS were enrolled through the GEIST multicentre registry from Germany, Italy and Spain. Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at admission. Data were collected both retrospectively and prospectively from 2017 onwards. Primary endpoints included in-hospital and all-cause fatality, determined by cluster analysis using an unsupervised machine learning algorithm (k-medoids). FINDINGS: Three clusters were identified, classifying TTS with low (TSLT), high (TSHT) and normal (TSNT) thyroid output, based on TSH and FT4 levels in relation to the median thyroid's secretory capacity (SPINA-GT). Although TSH and FT4 concentrations were similar among survivors and non-survivors, these clusters were significantly associated with patient outcomes. In the longitudinal Kaplan-Meier analysis including in- and out-of-hospital survival, the prognosis related to concentrations of TSH, FT4, and FT3 as well as SPINA-GT, deiodinase activity (SPINA-GD) and clusters. Patients in the TSHT cluster and with cardiogenic shock had a lower initial left ventricular ejection fraction (LVEF). INTERPRETATION: This study suggests that thyroid hormones may impact the evolution and prognosis of TTS. The findings indicate that thyroid-derived biomarkers may help identify high-risk patients and pave the way for novel personalized and preventive therapeutic options. FUNDING: This research was not funded by any public, commercial, or not-for-profit agencies.

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Background: Diabetes mellitus is a major cardiovascular risk factor for the development of coronary artery disease, but knowledge about the impact of diabetes mellitus on the outcome of patients with myocardial infarction with non-obstructive coronary arteries is limited. The aim of this study was to investigate the prognostic impact of diabetes mellitus on in- and out-of-hospital adverse events in troponin-positive patients with non-obstructive coronary arteries. Methods and Results: A total of 373 troponin-positive patients with non-obstructive coronary arteries between 2010 and 2021 at Bergmannsheil University Hospital Bochum were enrolled, including 65 diabetics and 307 nondiabetics. The median follow-up was 6.2 years. The primary study end point was a composite of in-hospital major adverse cardiovascular events (MACE). Secondary endpoints covered MACE during follow-up.Mean age of the study cohort was 62.9 years and 49.3 % were male. Although the overall rate of in-hospital MACE was higher in diabetics (41.5 %) than in non-diabetics (33.9 %), this difference did not reach statistical significance (p = 0.240). The in-hospital mortality rate was low in both groups, 0 % of diabetes group versus 2.9 % of non-diabetic patients. During follow-up, diabetic patients had a significantly higher rate of MACE (51.9 % vs. 31.1 %, p = 0.004) and a significantly higher all-cause mortality rate than non-diabetic patients (42.3 % vs. 20.1 %, p < 0.001). Conclusion: Our study reveals that the impact of diabetes mellitus on cardiovascular outcomes in troponin-positive patients with non-obstructive coronary arteries intensifies over the long term, leading to increased rates of both cardiovascular adverse events and overall mortality.

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BACKGROUND: Data regarding the characterization and outcomes of diabetics with heart failure with a mildly reduced ejection fraction (HFmrEF) is scarce. This study investigates the prevalence and prognostic impact of type 2 diabetes in patients with HFmrEF. METHODS: Consecutive patients 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. Patients with type 2 diabetes (dia-betics) were compared to patients without (i.e., non-diabetics). The primary endpoint was all-cause mortality at 30 months. Statistical analyses included Kaplan-Meier, multivariable Cox regression analyses and propensity score matching. RESULTS: A total of 2169 patients with HFmrEF were included. The overall prevalence of type 2 diabetes was 36%. Diabetics had an increased risk of 30-months all-cause mortality (35.8% vs. 28.6%; HR = 1.273; 95% CI 1.092-1.483; p = 0.002), which was confirmed after multivariable adjustment (HR = 1.234; 95% CI 1.030-1.479; p = 0.022) and propensity score matching (HR = 1.265; 95% CI 1.018-1.572; p = 0.034). Diabetics had a higher risk of HF-related rehospitalization (17.8% vs. 10.7%; HR = 1.714; 95% CI 1.355-2.169; p = 0.001). Finally, the risk of all-cause mortality was increased in diabetics treated with insulin (40.7% vs. 33.1%; log-rank p = 0.029), whereas other anti-diabetic pharmacotherapies had no prognostic impact in HFmrEF. CONCLUSIONS: Type 2 diabetes is common and independently associated with adverse long-term prognosis in patients with HFmrEF.

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BACKGROUND: The role of age in the short- and long-term prognosis of takotsubo syndrome (TTS) is controversial. The aim of the present study was to evaluate age-related differences and prognostic implications among patients with TTS. METHODS AND RESULTS: In total, 2492 consecutive patients with TTS enrolled in an international registry were stratified into 4 groups (<45, 45-64, 65-74, and ≥75 years). The median long-term follow-up was 480 days (interquartile range, 83-1510 days). The primary outcome was all-cause mortality (in-hospital and out-of-hospital mortality). The secondary end point was TTS-related in-hospital complications. Among the 2479 patients, 58 (2.3%) were aged <45 years, 625 (25.1%) were aged 45 to 64 years, 733 (29.4%) were aged 65 to 74 years, and 1063 (42.6%) were aged ≥75 years. Young patients (<45 years) had a higher prevalence of men (from youngest to oldest, 24.1% versus 12.6% versus 9.7% versus 11.4%; P<0.01), physical triggers (46.6% versus 27.5%, 33.9%, and 38.4%; P<0.01), and non-apical forms of TTS (25.9% versus 23.7%, 12.7%, and 9%; P<0.01) than those aged 45 to 64, 65 to 74, and ≥75 years. During hospitalization, young patients experienced a higher rate of in-hospital complications (32.8% versus 23.4%, 27.4%, and 31.9%; P=0.01), but in-hospital mortality was higher in the older group (0%, 1.6%, 2.9%, and 5%; P=0.001). Long-term all-cause mortality was significantly higher in the older cohort (5.6%, 6.4%, 11.3%, and 22.3%; log-rank P<0.001), as was long-term cardiovascular mortality (0%, 0.9%, 1.9%, and 3.2%; log-rank P=0.01). CONCLUSIONS: Young patients with TTS have a typical phenotype characterized by a higher prevalence of male sex, non-apical ballooning patterns, and in-hospital complications. However, in-hospital and long-term mortality are significantly lower in young patients with TTS. REGISTRATION: URL: https://classic.clinicaltrials.gov/ct2/show/NCT04361994. Unique identifier: NCT04361994.

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Limited data concerning the diagnostic and prognostic value of blood-derived biomarkers in heart failure with mildly reduced ejection fraction (HFmrEF) is available. This study investigates the diagnostic and prognostic value of aminoterminal prohormone of brain natriuretic peptide (NT-proBNP) in patients with HFmrEF, stratified by the estimated glomerular filtration rate (eGFR). Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. First, the diagnostic value of NT-proBNP for acute decompensated heart failure (ADHF) was tested. Thereafter, the prognostic value of NT-proBNP levels was tested for 30-months all-cause mortality in patients with ADHF. From a total of 755 patients hospitalized with HFmrEF, the rate of ADHF was 42%. Patients with ADHF revealed higher NT-proBNP levels compared to patients without (median 5394 pg/mL vs. 1655 pg/mL; p = 0.001). NT-proBNP was able to discriminate ADHF with an area under the curve (AUC) of 0.777 (p = 0.001), with the highest AUC in patients with eGFR ≥ 60 mL/min (AUC = 0.800; p = 0.001), and no diagnostic value was seen in eGFR < 30 mL/min (AUC = 0.576; p = 0.210). Patients with NT-proBNP levels > 3946 pg/mL were associated with higher rates of all-cause mortality at 30 months (57.7% vs. 34.4%; HR = 2.036; 95% CI 1.423-2.912; p = 0.001), even after multivariable adjustment (HR = 1.712; 95% CI 1.166-2.512; p = 0.006). In conclusion, increasing NT-proBNP levels predicted the risk of ADHF and all-cause mortality in patients with HFmrEF and preserved renal function; however, NT-proBNP levels were not predictive in patients with HFmrEF and eGFR < 30 mL/min.

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Cardiac remodeling is frequently observed in patients with heart failure (HF) and serves as an indicator of disease progression and severity. Septal hypertrophy represents an aspect of remodeling that can be easily assessed via an echocardiographic measurement of the interventricular septal end diastole (IVSd), but it has not been evaluated for its prognostic value, particularly in patients with heart failure with mildly reduced ejection fraction (HFmrEF). We retrospectively included 1881 consecutive patients hospitalized with HFmrEF (i.e., a left ventricular ejection fraction of 41-49% and signs and/or symptoms of HF) at one institution during a study period from 2016 to 2022. Septal hypertrophy, defined as an IVSd > 12 mm, was prevalent in 34% of the HFmrEF patients. Although septal hypertrophy was not associated with all-cause mortality at 30 months (median follow-up) (HR = 1.067; 95% CI: 0.898-1.267; p = 0.460), it was associated with an increased risk of hospitalization due to worsening HF at 30 months (HR = 1.303; 95% CI: 1.008-1.685; p = 0.044), which was confirmed even after multivariable adjustment (HR = 1.340; 95% CI: 1.002-1.792; p = 0.049) and propensity score matching (HR = 1.399; 95% CI: 1.002-1.951; p = 0.048). Although septal hypertrophy was not associated with the risk of all-cause mortality in patients with HFmrEF, it was identified as an independent predictor of long-term HF-related rehospitalization.

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BACKGROUND: The aging population has led to a significant increase in heart failure (HF) patients. Related to demographic changes, the burden with comorbidities was shown to increase in patients with HF. Whereas chronic obstructive pulmonary disease (COPD) was yet demonstrated to be associated with adverse outcomes in patients with HF, the prognostic impact of COPD in HF with mildly reduced ejection fraction (HFmrEF) has not yet been clarified. OBJECTIVE: The study investigates the prognostic impact of COPD in patients hospitalized with HFmrEF. METHODS: Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Patients with COPD were compared to patients without with regard to the primary endpoint all-cause mortality at 30 months (median follow-up). Secondary endpoints comprised in-hospital mortality, HF-related re-hospitalization, cardiac re-hospitalization and major adverse cardiac and cerebrovascular events (MACCE) at 30 months. RESULTS: A total of 2184 patients with HFmrEF were included with a prevalence of COPD of 12.0 %. Patients with COPD were older (median 77 vs. 75 years; p = 0.025), had increased burden of cardiovascular comorbidities and more advanced HF symptoms. At 30 months, patients with COPD had an increased risk of all-cause mortality compared to patients without (45 % vs. 30 %; HR = 1.667; 95 % CI 1.366-2.034; p = 0.001), alongside with a higher risk of re-hospitalization for worsening HF (20 % vs. 12 %; HR = 1.658; 95 % CI 1.218-2.257; p = 0.001). CONCLUSION: COPD is independently associated with adverse outcomes in patients hospitalized with HFmrEF.

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Aims: To assess the influence of tobacco on acute and long-term outcomes in Takotsubo syndrome (TTS). Methods: Patients with TTS from the international multicenter German Italian Spanish Takotsubo registry (GEIST) were analyzed. Comparisons between groups were performed within the overall cohort, and an adjusted analysis with 1:1 propensity score matching was conducted. Results: Out of 3,152 patients with TTS, 534 (17%) were current smokers. Smoker TTS patients were younger (63 ± 11 vs. 72 ± 11 years, p < 0.001), less frequently women (78% vs. 90%, p < 0.001), and had a lower prevalence of hypertension (59% vs. 69%, p < 0.01) and diabetes mellitus (16% vs. 20%, p = 0.04), but had a higher prevalence of pulmonary (21% vs. 15%, p < 0.01) and/or psychiatric diseases (17% vs. 12%, p < 0.01). On multivariable analysis, age less than 65 years [OR 3.85, 95% CI (2.86-5)], male gender [OR 2.52, 95% CI (1.75-3.64)], history of pulmonary disease [OR 2.56, 95% CI (1.81-3.61)], coronary artery disease [OR 2.35, 95% CI (1.60-3.46)], and non-apical ballooning form [OR 1.47, 95% CI (1.02-2.13)] were associated with smoking status. Propensity score matching (PSM) 1:1 yielded 329 patients from each group. Smokers had a similar rate of in-hospital complications but longer in-hospital stays (10 vs. 9 days, p = 0.01). During long-term follow-up, there were no differences in mortality rates between smokers and non-smokers (5.6% vs. 6.9% yearly in the overall, p = 0.02, and 6.6%, vs. 7.2% yearly in the matched cohort, p = 0.97). Conclusions: Our findings suggest that smoking may influence the clinical presentation and course of TTS with longer in-hospital stays, but does not independently impact mortality.