Prognosis and Treatment Strategies for Atrial Fibrillation in Heart Failure with Mildly Reduced Ejection Fraction.

OBJECTIVE: The study investigates the prognosis of atrial fibrillation (AF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). BACKGROUND: Data concerning the prognostic impact of AF in patients with HFmrEF 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 AF were compared to 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 analyses, multivariable Cox proportional regression analyses and propensity score matching. RESULTS: 2,148 patients with HFmrEF were included with an overall prevalence of AF of 43%. The presence of AF was associated with higher risk of the primary composite endpoint all-cause mortality and HF-related rehospitalization at 30 months (HR = 2.068; 95% 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 to rate control for AF (HR = 0.342; 95% CI 0.199-0.587; p = 0.01). CONCLUSION: AF 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) is 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 2,148 patients hospitalized with HFmrEF from 2016 to 2022. AF 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 HF-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 demonstrated the effect of rhythm control and catheter ablation for AF in patients with HFmrEF.

Characteristics Associated with Ventricular Tachyarrhythmias and Their Prognostic Impact in Heart Failure with Mildly Reduced Ejection Fraction.

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.

Effect of severity and etiology of chronic kidney disease in patients with heart failure with mildly reduced ejection fraction.

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.

Influence of tricuspid regurgitation on the prognosis of patients with cardiogenic shock.

OBJECTIVE: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations. However, data regarding the prognostic impact in patients with cardiogenic shock (CS) is limited. The study investigates the prognostic impact of pre-existing TR in patients with CS. METHODS: Consecutive patients with CS from 2019 to 2021 were included in a monocentric registry. Every patient's medical history, including echocardiographic data, was recorded. The influence of pre-existing TR on prognosis was investigated. Furthermore, Kaplan-Meier analyses based on TR severity were conducted. Statistical analyses comprised univariable t-test, Spearman's correlation, Kaplan-Meier analyses, as well as multivariable Cox proportional regression models. Analyses were stratified by the underlying cause of CS such as acute myocardial infarction (AMI), or the need for mechanical ventilation. RESULTS: 105 patients with CS and pre-existing TR were included. In Kaplan Meier analyses, it could be demonstrated that patients with severe TR (TR III°) had the highest 30-day all-cause mortality compared to mild (TR I°) and moderate TR (TR II°) (44% vs. 52% vs. 77%; log rank p = .054). In the subgroup analyses of CS-patients without AMI, TR II°/TR III° showed a higher all-cause mortality after 30 days compared to TR I° (39% vs. 64%; log rank p = .027). In multivariable Cox regression TR II°/TR III° was associated with 30-day all-cause mortality in CS-patients without AMI (HR = 2.193; 95% CI 1.007-4.774; p = .048). No significant difference could be found in the AMI group. Furthermore, TR II°/III° was linked to an increased 30-day all-cause mortality in non-ventilated CS-patients (6% vs. 50%, log rank p = .015), which, however, could not be confirmed in multivariable Cox regression. CONCLUSION: The occurrence of pre-existing TR II°/III° was independently related with 30-day all-cause mortality in CS-patients without AMI. However, no prognostic influence was observed in CS-patients with AMI.

Effect of Heart Failure Pharmacotherapies in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

OBJECTIVE: The study sought to comprehensively investigate the effect of heart failure (HF) pharmacotherapies in patients with heart failure with mildly reduced ejection fraction (HFmrEF). BACKGROUND: In the absence of randomized controlled trials, guideline recommendations concerning HF-related therapies in patients with HFmrEF are limited. METHODS: 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 transport protein 2 inhibitors (SGLT2i) was investigated for all-cause mortality at 30 months (median follow-up) and HF-related rehospitalization. RESULTS: 2,109 patients with HFmrEF were included. Treatment with BB (27.0% vs. 35%; HR = 0.737; 95% 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 lower risk of 30-months 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: BB, ACEi/ARB/ARNI and SGLT2i were independently associated with 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 with mildly reduced ejection fraction (HFmrEF) affects one out of four patients with heart failure (HF), limited evidence regarding HF pharmacotherapies for the treatment of patients with HFmrEF 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 sodium-glucose transport protein 2 inhibitors (SGLT2i) on long-term outcomes using a large registry-based dataset of 2,109 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 (HFrEF).

Obesity Paradox in Heart Failure with Mildly Reduced Ejection Fraction.

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.

Prognostic Implications of Type 2 Diabetes Mellitus in Heart Failure with Mildly Reduced Ejection Fraction.

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.

Prognostic impact of chronic obstructive pulmonary disease in patients with heart failure with mildly reduced ejection fraction.

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.

Diagnostic and Prognostic Value of Aminoterminal Prohormone of Brain Natriuretic Peptide in Heart Failure with Mildly Reduced Ejection Fraction Stratified by the Degree of Renal Dysfunction.

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.

Prognostic Implications of Septal Hypertrophy in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

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.

Sex-Based Differences in Rotational Atherectomy and Long-Term Clinical Outcomes.

Present research on the influence of gender on the treatment of coronary artery disease (CAD) and the outcome after percutaneous coronary intervention (PCI) is inconsistent. Sex differences in the presentation of CAD and the success after treatment have been described. We intend to compare the male and female sex in the procedure and the long-term outcome of Rotational Atherectomy (RA). A total of 597 consecutive patients (20.3% female and 79.7% male, mean age 75.3 ± 8.9 years vs. 72.7 ± 9 years, p < 0.001) undergoing Rotational Atherectomy between 2015 and 2020 were enrolled in the analysis. Demographic and clinical data were registered. In-hospital, 1-year, and 3-year MACCEs (major adverse cardiac and cerebrovascular events) were calculated. Women presented more often with myocardial infarction (23.9% vs. 14.9%, p = 0.017). The intervention was mainly performed via femoral access compared to radial access (65.4% vs. 33.6%, p = 0.002). Women had a smaller diameter of the balloon predilatation compared to men (2.8 ± 0.5 mm vs. 3.15 ± 2.4 mm, p < 0.05) and a smaller maximum diameter of the implanted stent (3.5 ± 1.2 mm vs. 4.10 ± 6.5 mm, p = 0.01). In-hospital, 1-year-, and 3-year MACCEs did not differ between the sexes. After a multivariate analysis, no difference between men and women could be detected. In conclusion, this analysis shows differences between women and men in periprocedural characteristics but does not show any differences after RA regarding in-hospital, 1-year-, and 3-year MACCEs.

Prognostic Value of the AST/ALT Ratio versus Bilirubin in Patients with Cardiogenic Shock.

This study investigates the prognostic value of the aspartate-to-alanine aminotransferase ratio (i.e., AST/ALT ratio) and bilirubin in patients with cardiogenic shock (CS). Despite ongoing improvements regarding the treatment of CS patients, invasive care unit (ICU) mortality in CS patients remains unacceptably high. Limited data regarding the prognostic value of the AST/ALT ratio and bilirubin in patients suffering from CS is available. The authors hypothesize the measurement of liver enzymes during the course of CS may be an easy and feasible method to assess right-heart dysfunction and prognosis in patients with CS. Consecutive patients with CS from 2019 to 2021 were included. Blood samples were retrieved from the day of disease onset (day 1), days 2, 3, 4 and 8. The prognostic value of the AST/ALT ratio and bilirubin was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman's correlations, Kaplan-Meier analyses, as well as multivariable Cox proportional regression analyses. A total of 157 CS patients were included, with an overall rate of all-cause mortality at 30 days of 51%. The median AST/ALT ratio on day 1 was 1.4, and the median bilirubin was 0.63 mg/dL. No association of the baseline AST/ALT ratio (HR = 1.005; 95% CI 0.649-1.558; p = 0.981) and bilirubin (HR = 1.320; 95% CI 0.834-2.090; p = 0.236) with the risk of 30-day all-cause mortality was found. In contrast, the AST/ALT ratio on day 4 was associated with the risk of 30-day all-cause mortality (HR = 2.826; 95% CI 1.227-6.510; p = 0.015), which was still evident after the multivariable adjustment (HR = 2.830; 95% CI 1.054-7.690; p = 0.039). The AST/ALT ratio during the course of ICU hospitalization from day 4-but not the baseline AST/ALT ratio and bilirubin-was associated with an increased risk of 30-day all-cause mortality in CS patients.

Effect of Cardiovascular Risk Factors on 30-Day All-Cause Mortality in Cardiogenic Shock.

Although previous studies investigated the influence of cardiovascular risk (CVR) factors in patients with acute coronary syndrome, data concerning the effect of CVR factors on the prognosis of patients with cardiogenic shock (CS) is scarce. Consecutive patients with CS were prospectively included from 2019 to 2021. The prognosis of patients with "low CVR" (i.e., 0-1 CVR factors) was compared to patients with "high CVR" (i.e., 2-4 CVR factors) according to presence or absence of arterial hypertension, diabetes mellitus, hyperlipidaemia or smoking. The primary endpoint was 30-day all-cause mortality. Statistical analyses included Kaplan-Meier and Cox proportional regression analyses. 273 consecutive patients with CS were included. 28% presented with low CVR and 72% with high CVR. Within the entire study cohort, the risk of 30-day all-cause mortality did not differ between patients with high and low CVR (55% vs. 57%; log rank p = 0.727; HR = 0.942; 95% CI 0.663-1.338; p = 0.738). Even after multivariable adjustment, high CVR was not associated with an elevated risk of 30-day all-cause mortality (HR = 1.039; 95% CI 0.648-1.667; p = 0.873). The presence of arterial hypertension (55% vs. 58%; log rank p = 0.564; HR = 0.906; 95% CI 0.638-1.287; p = 0.582), diabetes mellitus (60% vs. 52%; log rank p = 0.215; HR = 1.213; 95% CI 0.881-1.671; p = 0.237) and a history of smoking (56% vs. 56%; log rank p = 0.725; HR = 0.945; 95% CI 0.679-1.315; p = 0.737) did not significantly influence short-term prognosis.. Only the absence of hyperlipidaemia significantly decreased the risk of all-cause mortality (65% vs. 51%; log rank p = 0.038; HR = 0.718; 95% CI 0.516-0.998; p = 0.049), which was no longer observed after multivariable adjustment (HR = 0.801; 95% CI 0.536-1.195; p = 0.277). In conclusion, neither the overall CVR nor individual CVR factors were associated with the risk of 30-day all-cause mortality in patients with CS.

Prognostic Value of Different Levels of Uric Acid in Patients with Coronary Chronic Total Occlusion Undergoing Percutaneous Coronary Intervention.

Recent data suggest that uric acid (UA) might be an independent predictor of clinical outcomes following percutaneous coronary intervention (PCI). The predictive value of uric acid in patients undergoing PCI for chronic total occlusions (CTO) is unknown. We included patients with CTO who underwent PCI at our center in 2005 and 2012, with available uric acid levels before angiography. Subjects were divided into groups according to uric acid tertiles (<5.5 mg/dL, 5.6-6.9 mg/dL, and >7.0 mg/dL), and outcomes were compared among the groups. Out of the 1963 patients (mean age 65.2 ± 11 years), 34.7% (n = 682) had uric acid concentrations in the first tertile, 34.3% (n = 673) in the second tertile, and 31% (n = 608) in the third tertile. Median follow-up was 3.0 years. Uric acid levels in the first tertile were associated with significantly lower all-cause mortality, as compared to the third tertile, with an adjusted hazard ratio (HR) of 0.67 (95% confidence interval (CI): 0.49 to 0.92; p = 0.012). No significant differences regarding all-cause mortality were found between patients in the first and second tertiles (HR: 0.96 [95% CI: 0.71 to 1.3; p = 0.78]). High levels of uric acid emerged as an independent predictor of all-cause mortality in patients with chronic total occlusion treated with PCI. Hence, uric acid levels should be incorporated into the risk assessment of patients with CTO.

Impact of age on the prognosis of patients with ventricular tachyarrhythmias and aborted cardiac arrest.

BACKGROUND: This study evaluated the prognostic impact of age on patients presenting with ventricular tachyarrhythmias (VTA) and aborted cardiac arrest. MATERIAL AND METHODS: The present registry-based, monocentric cohort study included all consecutive patients presenting at the University Medical Center Mannheim (UMM) between 2002 and 2016 with ventricular tachycardia (VT), ventricular fibrillation (VF) and aborted cardiac arrest. Middle-aged (40-60 years old) were compared to older patients (> 60 years old). Furthermore, age was analyzed as a continuous variable. The primary endpoint was all-cause mortality at 2.5 years. The secondary endpoints were cardiac death at 24 h, all-cause mortality at index hospitalization, all-cause mortality after index hospitalization and the composite endpoint at 2.5 years of cardiac death at 24 h, recurrent VTA, and appropriate implantable cardioverter defibrillator (ICD) treatment. RESULTS: A total of 2259 consecutive patients were included (28% middle-aged, 72% older). Older patients were more often associated with all-cause mortality at 2.5 years (27% vs. 50%; hazard ratio, HR = 2.137; 95% confidence interval, CI 1.809-2.523, p = 0.001) and the secondary endpoints. Even patient age as a continuous variable was independently associated with mortality at 2.5 years in all types of VTA. Adverse prognosis in older patients was demonstrated by multivariate Cox regression analyses and propensity score matching. Chronic kidney disease (CKD), systolic left ventricular dysfunction (LVEF) < 35%, cardiopulmonary resuscitation (CPR) and cardiogenic shock worsened the prognosis for both age groups, whereas acute myocardial infarction (STEMI/NSTEMI) and the presence of an ICD improved prognosis. CONCLUSION: The results of this study suggest that increasing age is associated with increased mortality in VTA patients. Compared to the middle-aged, older patients were associated with higher all-cause mortality at 2.5 years and the secondary endpoints.

Therapeutic Hypothermia Following Cardiac Arrest After the TTM2 trial - More Questions Raised Than Answered.

For almost 20 years, therapeutic hypothermia has been a cornerstone of modern post-cardiac arrest care lowering mortality, and improvin neurologic outcome compared to conventional therapy. This was challenged by the first TTM-trial in 2013, which did not show a benefit for hypothermia at 33°C compared to controlled normothermia at 36°C. Now, the TTM2 trial showed no benefit of hypothermia compared to fever prevention alone. While TTM1 and TTM2 suggest that hypothermia might not be helpful, a deep dive into the trials reveals that this conclusion does not hold true. Here, we focus on patient selection, suboptimal application of hypothermia, interaction of standard sedation with hypothermia, high incidence of post-arrest fever, and withdrawal of life support based on per-protocol neurologic prognostication in the TTM2-trial. Of particular interest, contemporary trials and registries using intravascular cooling in TTM-like patients repeatedly reported much lower mortality rates than those described in both TTM1 and TTM2.

Novel Therapeutic Strategies to Reduce Reperfusion Injury After Acute Myocardial Infarction.

For almost 30 years, urgent revascularization termed primary percutaneous coronary intervention has been a cornerstone of modern care for acute myocardial infarction (AMI). It lowers mortality and improved cardiovascular outcome compared to conservative therapy including thrombolysis. Reperfusion injury, which occurs after successful re-opening of the formerly occluded coronary artery, had been exploited as a potential therapeutic target. When revascularization became faster and primary percutaneous coronary intervention was successfully performed within 60-90 minutes of symptom onset, the interest in a potential additive effect of targeting reperfusion injury vanished. More recently, several meta-analyses indicated that limiting reperfusion injury prevents microvascular obstruction and reduces final infarct size, thereby lowering the probability of heart failure events and improving quality of life in AMI survivors. Here, we describe the current strategies to limit reperfusion injury and to improve post-AMI outcomes such as systemic or intracoronary hypothermia, left-ventricular unloading, intracoronary infusion of super-saturated oxygen, intermittent coronary sinus occlusion, and C-reactive protein apheresis.

Additive Impact of Interleukin 6 and Neuron Specific Enolase for Prognosis in Patients With Out-of-Hospital Cardiac Arrest - Experience From the HAnnover COoling REgistry.

Background: Patients after out-of-hospital cardiac arrest (OHCA) are at increased risk for mortality and poor neurological outcome. We assessed the additive impact of interleukin 6 (IL-6) at admission to neuron-specific enolase (NSE) at day 3 for prognosis of 30-day mortality and long-term neurological outcome in OHCA patients. Methods: A total of 217 patients from the HAnnover COoling REgistry with return of spontaneous circulation (ROSC) after OHCA and IL-6 measurement immediately after admission during 2017-2020 were included to investigate the prognostic value and importance of IL-6 in addition to NSE obtained on day 3. Poor neurological outcome was defined by cerebral performance category (CPC) ≥ 3 after 6 months. Results: Patients with poor outcome showed higher IL-6 values (30-day mortality: 2,224 ± 524 ng/l vs 186 ± 15 ng/l, p < 0.001; CPC ≥ 3 at 6 months: 1,440 ± 331 ng/l vs 180 ± 24 ng/l, p < 0.001). IL-6 was an independent predictor of mortality (HR = 1.013/ng/l; 95% CI 1.007-1.019; p < 0.001) and poor neurological outcome (HR = 1.004/ng/l; 95% CI 1.001-1.007; p = 0.036). In ROC-analysis, AUC for IL-6 was 0.98 (95% CI 0.96-0.99) for mortality, but only 0.76 (95% CI 0.68-0.84) for poor neurological outcome. The determined cut-off value for IL-6 was 431 ng/l for mortality (NPV 89.2%). In patients with IL-6 > 431 ng/l, the combination with NSE < 46 µg/l optimally identified those individuals with potential for good neurological outcome (CPC ≤ 2). Conclusion: Elevated IL-6 levels at admission after ROSC were closely associated with 30-day mortality. The combination of IL-6 and NSE provided clinically important additive information for predict poor neurological outcome at 6 months.

Prognostic Value of Cardiac Troponin I in Patients with Ventricular Tachyarrhythmias.

Besides the diagnostic role in acute myocardial infarction, cardiac troponin I levels (cTNI) may be increased in various other clinical conditions, including heart failure, valvular heart disease and sepsis. However, limited data are available regarding the prognostic role of cTNI in the setting of ventricular tachyarrhythmias. Therefore, the present study sought to assess the prognostic impact of cTNI in patients with ventricular tachyarrhythmias (i.e., ventricular tachycardia (VT) and fibrillation (VF)) on admission. A large retrospective registry was used, including all consecutive patients presenting with ventricular tachyarrhythmias from 2002 to 2015. The prognostic impact of elevated cTNI levels was investigated for 30-day all-cause mortality (i.e., primary endpoint) using Kaplan-Meier, receiver operating characteristic (ROC), multivariable Cox regression analyses and propensity score matching. From a total of 1104 patients with ventricular tachyarrhythmias and available cTNI levels on admission, 46% were admitted with VT and 54% with VF. At 30 days, high cTNI was associated with the primary endpoint (40% vs. 22%; log rank p = 0.001; HR = 2.004; 95% CI 1.603-2.505; p = 0.001), which was still evident after multivariable adjustment and propensity score matching (30% vs. 18%; log rank p = 0.003; HR = 1.729; 95% CI 1.184-2.525; p = 0.005). Significant discrimination of the primary endpoint was especially evident in VT patients (area under the curve (AUC) 0.734; 95% CI 0.645-0.823; p = 0.001). In contrast, secondary endpoints, including all-cause mortality at 30 months and a composite arrhythmic endpoint, were not affected by cTNI levels. The risk of cardiac rehospitalization was lower in patients with high cTNI, which was no longer observed after propensity score matching. In conclusion, high cTNI levels were associated with increased risk of all-cause mortality at 30 days in patients presenting with ventricular tachyarrhythmias.