Prognostic Impact of Anemia and Hemoglobin Levels in Unselected Patients Undergoing Coronary Angiography.

Background/Objectives: This study investigates the prevalence and prognostic impact of concomitant anemia in unselected patients undergoing invasive coronary angiography (CA). The spectrum of patients undergoing CA has significantly changed during the past decades, related to ongoing demographic changes and improved treatment strategies for patients with cardiovascular disease. Methods: Consecutive patients undergoing invasive CA from 2016 to 2022 were retrospectively included at one institution. Patients with anemia (i.e., hemoglobin < 13.0 g/dL for males and <12.0 g/dL for females) were compared with patients without anemia (i.e., nonanemics). The primary endpoint was rehospitalization for heart failure (HF) at 36 months. Secondary endpoints comprised the risk of rehospitalization for acute myocardial infarction (AMI) and coronary revascularization. Statistical analyses included Kaplan-Meier, multivariable Cox proportional regression analyses, and propensity score matching. Results: From 2016 to 2022, 7645 patients undergoing CA were included with a median hemoglobin level of 13.2 g/dL. Anemics had a higher prevalence of coronary artery disease (CAD) (76.3% vs. 74.8%; p = 0.001), alongside an increased need for percutaneous coronary intervention (PCI) (45.3% vs. 41.5%; p = 0.001). At 36 months, the risk of rehospitalization for HF was higher in anemic patients (27.4% vs. 18.4%; p = 0.001; HR = 1.583; 95% CI 1.432-1.750; p = 0.001), which was still evident after multivariable adjustment (HR = 1.164; 95% CI 1.039-1.304; p = 0.009) and propensity score matching (HR = 1.137; 95% CI 1.006-1.286; p = 0.040). However, neither the risk of AMI (8.4% vs. 7.4%, p = 0.091) nor the risk of coronary revascularization at 36 months (8.0% vs. 8.5%, p = 0.447) was higher in anemic compared with nonanemic patients. Conclusions: In consecutive patients undergoing CA, concomitant anemia was independently associated with an increased risk of rehospitalization for HF, but not AMI or coronary revascularization. Patients with LVEF ≥ 35% and multivessel disease were especially susceptible to anemia-induced HF-related rehospitalization.

Influence of Right and Left Bundle Branch Block in Patients With Cardiogenic Shock and Cardiac Arrest.

OBJECTIVES: The study investigates the prognostic impact of right bundle branch block (RBBB) and left bundle branch block (LBBB) in patients with cardiogenic shock (CS) compared with no bundle branch block (BBB). In patients with heart failure, existence of RBBB and LBBB has influence on prognosis. DESIGN: Prospective registry-study. SETTING: ICU of a tertiary academic hospital in Germany. PATIENTS: Adult patients with CS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Consecutive patients with CS were included. The prognostic impact of RBBB and LBBB on 30-day all-cause mortality was tested within the entire cohort and in the subgroup of CS patients with cardiac arrest at admission. The final study cohort comprised 248 patients. Patients with RBBB showed the highest 30-day all-cause mortality followed by LBBB and no BBB (72.5% vs. 52.9% vs. 50.0%; log-rank p = 0.015). These findings were consistent even after solely including CS patients with cardiac arrest (90.0% vs. 73.3% vs. 62.2%; log-rank p = 0.008). After adjustment for lactate, norepinephrine, troponin I, Acute Physiology Score, Society of Cardiovascular Angiography & Interventions shock stage, and heart rate in a multivariable Cox regression analysis, RBBB still revealed a negative impact on 30-day all-cause mortality (hazard ratio [HR], 1.807; 95% CI, 1.107-2.947; p = 0.018), whereas LBBB was not associated with 30-day all-cause mortality. In this multivariable Cox regression model lactate (HR, 1.065; 95% CI, 1.018-1.115; p = 0.006), troponin I (HR, 1.003; 95% CI, 1.001-1.005; p = 0.001), and Acute Physiology Score (HR, 1.033; 95% CI, 1.001-1.066; p = 0.041) were as well associated with 30-day all-cause mortality. Finally, no association of RBBB was found with the incidence of liver or severe renal failure. CONCLUSIONS: Besides the Acute Physiology Score, lactate, and troponin levels, RBBB was associated with an increased 30-day all-cause mortality in consecutive CS patients with and without cardiac arrest, whereas LBBB showed no prognostic impact.

Age-Related Outcomes in Heart Failure with Mildly Reduced Ejection Fraction.

Objective: This study investigates age-related differences and outcomes in patients hospitalized with heart failure with a mildly reduced ejection fraction (HFmrEF). Background: The characterization of patients with HFmrEF and the prognostic value of age has rarely been investigated. Methods: Patients with HFmrEF were retrospectively included at one institution between 2016 and 2022. The distribution of HF aetiology and prognostic outcomes were investigated comparing patients with ≤40, >40 to ≤60, >60 to ≤80, and >80 years of age. The primary endpoint was long-term all-cause mortality. Kaplan-Meier and multivariable Cox proportional regression analyses were applied for statistics. Results: For the present study, 2184 patients with HFmrEF with a median age of 76 years were included. Non-ischemic cardiomyopathy was the most common HF aetiology in patients <40 years of age, whereas patients with 60-80 years of age (60.2%) and >80 years of age (58.2%) had the higher rates of ischemic cardiomyopathies. The risk of long-term all-cause mortality at 30 months was highest in patients with >80 years of age (HR = 2.167; 95% CI 1.928-2.436; p = 0.001), even after multivariable adjustment. Furthermore, patients with >80 years of age had the highest risk of HF-related rehospitalization (HR = 1.529; 95% CI 1.293-1.807; p = 0.001). Conclusions: Ischemic cardiomyopathy represents the most common cause of HF in elderly patients with HFmrEF, whereas younger patients were more likely to suffer from non-ischemic HF aetiologies. Increasing age was an independent predictor of long-term all-cause mortality in patients hospitalized with HFmrEF.

Distribution and Prognostic Impact of Different Heart Failure Etiologies in Patients with Heart Failure with Mildly Reduced Ejection Fraction

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.

Left ventricular diastolic dysfunction in patients with heart failure with mildly reduced ejection fraction.

OBJECTIVE: This study investigates the prevalence and prognostic impact of diastolic dysfunction (DD) in patients hospitalized with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) in sinus rhythm. BACKGROUND: Data regarding the prognostic impact of DD in patients with HFmrEF is limited. METHODS: From 2016 to 2022, all 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. Patients with DD were compared to patients without (i.e., non-DD), further risk stratification was performed according to the severity of DD. The primary endpoint was all-cause mortality at 30 months (interquartile range (IQR) 15-61 months), key secondary endpoint was rehospitalization for worsening HF. RESULTS: From a total of 1154 patients (median age 68 years, 68% males) hospitalized with HFmrEF, concomitant DD was present in 72% (grade I: 56%, grade II: 14%, grade III: 2%). Patients with DD were older (71 years vs. 65 years; p = 0.001) and presented with higher rates of cardiovascular comorbidities. The presence of DD was not associated with the risk of long-term all-cause mortality (adjusted HR = 0.815; 95% CI 0.612-1.085; p = 0.161) or HF-related rehospitalization (adjusted HR = 0.736; 95% CI 0.442-1.225; p = 0.238). Furthermore, the outcome did not differ in patients with more advanced stages of DD. CONCLUSION: DD is commonly prevalent in patients with HFmrEF, but not associated with long-term prognosis.

Prognosis and treatment strategies for atrial fibrillation in heart failure with mildly reduced ejection fraction.

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.

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 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.

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 anaemia and iron deficiency in heart failure with mildly reduced ejection fraction.

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.

Prognostic impact of prior LVEF in patients with heart failure with mildly reduced ejection fraction.

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.

Prognostic value of mitral valve regurgitation in patients with heart failure with mildly reduced ejection fraction.

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.

Effect of heart failure pharmacotherapies in patients with heart failure with mildly reduced ejection fraction.

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.

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.

Predictors and Prognostic Impact of Early Acute Kidney Injury in Cardiogenic Shock: Results from a Monocentric, Prospective Registry.

INTRODUCTION: The presence of acute kidney injury (AKI) was shown to increase the risk of mortality following acute myocardial infarction; however, data regarding the prognostic impact of early AKI in patients with concomitant cardiogenic shock (CS) is limited. The study investigates predictors and the prognostic impact of AKI in patients with CS. METHODS: Consecutive patients with CS from 2019 to 2021 were included at one institution. Laboratory values were retrieved from day of disease onset (day 1) and days 2, 3, 4, and 8 thereafter. Predictors for AKI (defined as an increase of plasma creatinine >50% within 48 h referring to pre-admission or baseline creatinine on day 1 and/or the need for continuous veno-venous hemodiafiltration [CVVHDF]) and the prognostic impact of early AKI with regard to 30-day all-cause mortality were assessed. Statistical analyses included t test, Spearman's correlation, C-statistics, Kaplan-Meier, and Cox proportional regression analyses. RESULTS: A total of 219 CS patients were included with an incidence of early CS-related AKI of 52%. With an area under the curve of up to 0.689 (p = 0.001), creatine discriminated 30-day mortality in CS. Increasing lactate levels (OR = 1.194; 95% CI: 1.083-1.316; p = 0.001; per increase of 1 mmol/L) was associated with the occurrence of AKI. The presence of AKI was associated with an increased risk of 30-day all-cause mortality (63% vs. 36%; HR = 2.138; 95% CI: 1.441-3.171; p = 0.001), even after multivariable adjustment (HR = 1.861; 95% CI: 1.207-2.869; p = 0.005). Finally, highest risk of all-cause mortality was observed in patients with AKI requiring CVVHDF (75% vs. 44%; log rank p = 0.001; HR = 2.211; 95% CI: 1.315-3.718; p = 0.003). CONCLUSION: Early AKI affects more than half of patients with CS and is independently associated with 30-day all-cause mortality in CS, with highest risk of death among patients with AKI requiring CVVHDF.

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 Impact of Left Compared to Right Heart Function in Sepsis and Septic Shock.

This study investigates the prognostic impact of left ventricular ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE) in patients with sepsis and septic shock. Consecutive patients with sepsis and septic shock were included from 2019 to 2021. LVEF and TAPSE were assessed during the first 24 hours of intensive care unit (ICU) treatment. Patients were stratified by LVEF of less than 45% and greater than or equal to 45%. The primary endpoint was 30 day all-cause mortality. Two hundred ninety-two consecutive patients were included, of which 26% presented with LVEF of less than 45%. Within the entire study cohort (60% vs. 48%; hazard ratio [HR] = 1.414; 95% confidence interval [CI] = 0.999-2.001; p = 0.050) and specifically in patients with sepsis (58% vs. 36%; HR = 1.919; 95% CI = 1.148-3.208; p = 0.013), LVEF of less than 45% was associated with an increased risk of 30 day all-cause mortality, whereas TAPSE of less than 17 mm was not (56% vs. 52%; log rank p = 0.798). Even after multivariable adjustment, LVEF of less than 45% was accompanied by a worse prognosis in septic patients (HR = 1.944; 95% CI = 1.084-3.485; p = 0.026). Contrarily, LVEF < 45% was not accompanied with increased mortality in septic shock patients (63% vs. 67%; log rank p = 0.847; HR = 0.956; 95% CI 0.596-1.533; p = 0.853). In conclusion, impaired LVEF was associated with increased mortality in septic patients without shock, but not in patients with septic shock. In contrast, impaired right ventricular function was not associated with adverse prognosis in both conditions.

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.

Association of body mass index with 30-day all-cause mortality in cardiogenic shock.

BACKGROUND AND AIMS: This study investigates the prognostic impact of body mass index (BMI) on the risk of 30-day all-cause mortality in patients with cardiogenic shock (CS). Due to ongoing epidemiological developments, the characteristics of patients with cardiovascular disease are consistently changing. Especially increasing rates of obesity and associated comorbidities have been observed. However, data regarding the prognostic value of BMI in patients with CS remains inconclusive. METHODS AND RESULTS: Consecutive patients with CS were included from 2019 to 2021. The prognostic value of BMI (i.e., BMI 18.5-<25; 25-30 and >30 kg/m2) was analyzed using Kaplan-Meier and multivariable Cox proportional regression analyses regarding the primary endpoint of 30-day all-cause mortality. Additional risk stratification was performed based on the presence or absence of CS related to acute myocardial infarction (AMI). 256 patients with a median BMI of 26.4 kg/m2 were included. The overall risk of 30-day all-cause mortality was 53.5%. Within the entire study cohort, BMI was not associated with the risk of 30-day all-cause mortality (log rank p ≥ 0.107). In contrast, BMI >30 kg/m2 was associated with higher risk of 30-day all-cause mortality when compared to BMI <25 kg/m2 in patients with AMI-CS (78% vs 47%; log rank p = 0.017), which was confirmed after multivariable adjustment (HR = 2.466; 95% CI 1.126-5.399; p = 0.024). However, BMI was not associated with mortality in patients with non-AMI-CS. CONCLUSION: BMI >30 kg/m2 was associated with increased risk of 30-day all-cause mortality in patients with AMI-CS, but not in non-AMI-CS.

C-reactive protein and procalcitonin during course of sepsis and septic shock.

OBJECTIVE: The study investigates the diagnostic and prognostic value of C-reactive protein (CRP) and procalcitonin (PCT) in patients with sepsis and septic shock. BACKGROUND: Limited data regarding the prognostic value of CRP and PCT during the course of sepsis or septic shock is available. METHODS: Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from the day of disease onset (day 1), day 2, 3, 5, 7, and 10. Firstly, the diagnostic value of CRP and PCT for the diagnosis of a septic shock, as well as for the discrimination of positive blood cultures, was tested. Secondly, the prognostic value of the CRP and PCT was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman's correlations, C-statistics, and Kaplan-Meier analyses. RESULTS: A total of 349 patients were included, of which 56% had a sepsis and 44% a septic shock on day 1. The overall rate of all-cause mortality at 30 days was 52%. With an area under the curve (AUC) of 0.861 on day 7 and 0.833 on day 10, the PCT revealed a superior AUC than the CRP (AUC 0.440-0.652) with regard to the discrimination between patients with sepsis and septic shock. In contrast, the prognostic AUCs for 30-day all-cause mortality were poor. Both higher CRP (HR = 0.999; 95% CI 0.998-1.001; p = 0.203) and PCT levels (HR = 0.998; 95% CI 0.993-1.003; p = 0.500) were not associated with the risk of 30-day all-cause mortality. During the first 10 days of ICU treatment, both CRP and PCT declined irrespective of clinical improvement or impairment. CONCLUSION: PCT was a reliable diagnostic tool for the diagnosis of septic shock compared to CRP. Both CRP and PCT were shown to have poor predictive value with regard to 30-day all-cause mortality and were not associated with the risk of all-cause mortality in patients admitted with sepsis or septic shock.