Polymorphic Variants of SCN5A Gene (rs41312433 and rs1805124) Associated with Coronary Artery Affliction in Patients with Severe Arrhythmias.

Several mutations in this gene for the α subunit of the cardiac sodium channel have been identified in a heterogeneous subset of cardiac rhythm syndromes, including Brugada syndrome, progressive cardiac conduction defect, sick sinus node syndrome, atrial fibrillation and dilated cardiomyopathy. The aim of our study was to associate some SCN5A polymorphic variants directly with confirmed coronary stenoses in patients with non-LQTS ventricular fibrillation/flutter treated by an implantable cardioverter defibrillator. MATERIALS AND METHODS: A group of 32 unrelated individuals, aged 63 ± 12 years, was included in the study. All the patients were examined, diagnosed and treated with an implantable cardioverter defibrillator at the Department of Internal Cardiology Medicine, Faculty Hospital Brno. The control group included 87 persons of similar age without afflicted coronary circulation, which was confirmed coronagraphically. Genomic DNA was extracted from samples of peripheral blood according to the standard protocol. Two SCN5A polymorphisms-IVS9-3C/A (rs41312433) and A1673G (rs1805124, H558R)-were examined in association with coronary artery stenosis in the patients. RESULTS: In the case-control study, no significant differences in genotype distribution/allelic frequencies were observed for IVS9-3c>a and A1673G gene polymorphisms between patients with severe arrhythmias and healthy persons. The distribution of SCN5A double genotypes was not significantly different among different types of arrhythmias according to their ejection fraction in arrhythmic patients (p = 0.396). The ventricular arrhythmias with an ejection fraction below 40% were found to be 10.67 times more frequent in patients with multiple coronary stenosis with clinically valid sensitivity, specificity and power tests. In the genotype-phenotype study, we observed a significant association of both SCN5A polymorphisms with the stenosis of coronary vessels in the patients with severe arrhythmia. The double genotype of polymorphisms IVS9-3C/A together with A1673G (CCAA) as well as their simple genotypes were associated with significant multiple stenosis of coronary arteries (MVS) with high sensitivity and specificity (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.70; specificity 0.682; power test 0.359) Moreover, when a concrete stenotic coronary artery was associated with SCN5A genotypes, the CCAA double genotype was observed to be five times more frequent in patients with significant stenosis in the right coronary artery (RCA) compared to those without affliction of this coronary artery (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.682; specificity 0.700; power test 0.359). The CCAA genotype was also more frequent in patients without RCA affliction with MVS (p = 0.008); in patients with ACD affliction but without MVS (p = 0.008); and in patients with both ACD affliction and MVS compared to those without ACD affliction and MVS (p = 0.005). CONCLUSIONS: Our study presents a highly sensitive and specific association of two polymorphisms in SCN5A with significant coronary artery stenoses in patients with potentially fatal ventricular arrhythmias. At the same time, these polymorphisms were not associated with arrhythmias themselves. Thus, SCN5A gene polymorphic variants may form a part of germ cell gene predisposition to ischemia.

Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved.

The EMPEROR-Preserved trial showed that the sodium-glucose co-transporter 2 inhibitor empagliflozin significantly reduces the risk of cardiovascular death or hospitalization for heart failure (HHF) in heart failure patients with left ventricular ejection fraction (LVEF) > 40%. Here, we report the results of a pre-specified analysis that separately evaluates these patients stratified by LVEF: preserved (≥ 50%) (n = 4,005; 66.9%) or mid-range (41-49%). In patients with LVEF ≥ 50%, empagliflozin reduced the risk of cardiovascular death or HHF (the primary endpoint) by 17% versus placebo (hazard ratio (HR) 0.83; 95% confidence interval (CI): 0.71-0.98, P = 0.024). For the key secondary endpoint, the HR for total HHF was 0.83 (95%CI: 0.66-1.04, P = 0.11). For patients with an LVEF of 41-49%, the HR for empagliflozin versus placebo was 0.71 (95%CI: 0.57-0.88, P = 0.002) for the primary outcome (Pinteraction = 0.27), and 0.57 (95%CI: 0.42-0.79, P < 0.001) for total HHF (Pinteraction = 0.06). These results, together with those from the EMPEROR-Reduced trial in patients with LVEF < 40%, support the use of empagliflozin across the full spectrum of LVEF in heart failure.

What do the new ESC Guidelines for the treatment of heart failure bring to internists?

Chronic heart failure is in european countries in 0,4-2,0% population with an increase with age. The improved care of acute cases enables to decrease the number of patients with chronic heart failure.The disease has a bad prognosis, the diagnosis therapy are demanding. European guidelines for diagnosis and treatment heart failure stress, that patients should have all 4 drugs with class 1 reccomendation (ACE I/ARNI, betablockers, MRA and SGLT2) in reccomended doses. These drugs will be given step by step with dose titration.

Betablockers after myocardial infarction and chronic coronary heart disease.

Treatment with beta-blockers has been an essential part of secondary prevention after myocardial infarction or chronic CHD for several decades. Studies that have shown a beneficial prognostically beneficial effect of beta-blockers were conducted in the period prior to the routine use of reperfusion therapy. In patients who have been treated with fibrinolytic therapy, their contribution is less pronounced. The situation is even less clear in patients who are treated with primary percutaneous coronary intervention, as prospective studies and observational data from registries do not yet give a clear view of the indications and clinical contribution of beta-blockers, especially in the group with normal ejection fraction, without signs of heart failure. Here are the latest different studies from the South Korean and Danish national registries in patients with CHD without heart failure and the effect of beta-blockers on the long-term prognosis.

Relation between Mid-Regional Pro-Adrenomedullin in Patients with Chronic Heart Failure and the Dose of Diuretics in 2-Year Follow-Up-Data from FAR NHL Registry.

Background and Objectives: The aim of this paper is to evaluate the impact of humoral substance mid-regional pro-adrenomedullin (MR-proADM) on the two-year survival of patients with chronic heart failure and relate it to the dosage of furosemide. Materials and Methods: The data is taken from the stable systolic heart failure (EF < 50%) FAR NHL registry (FARmacology and NeuroHumoraL activation). The primary endpoint at two-year follow-up was death, heart transplantation, or LVAD implantation. Results: A total of 1088 patients were enrolled in the FAR NHL registry; MR-proADM levels were available for 569 of them. The mean age was 65 years, and 81% were male. The aetiology of HF was ischemic heart disease in 53% and dilated cardiomyopathy in 41% of patients. The mean EF was 31 ± 9%. Statistically significant differences (p < 0.001) were obtained in several parameters: patients with higher MR-proADM levels were older, rated higher in NYHA class, suffered more often from lower limb oedema, and had more comorbidities such as hypertension, atrial fibrillation, diabetes, and renal impairment. MR-proADM level was related to furosemide dose. Patients taking higher doses of diuretics had higher MR-proADM levels. The mean MR-proADM level without furosemide (n = 122) was 0.62 (±0.55) nmol/L, with low dose (n = 113) 1−39 mg/day was 0.67 (±0.30) nmol/L, with mid dose (n = 202) 40−79 mg/day was 0.72 (±0.34) nmol/L, with high dose (n = 58) 80−119 mg/day was 0.85 (±0.40) nmol/L, and with maximum dose (n = 74) ≥120 mg/day was 1.07 (±0.76) nmol/L, p < 0.001. Patients with higher MR-proADM levels were more likely to achieve the primary endpoint at a two-year follow-up (p < 0.001) according to multivariant analysis. Conclusions: Elevated plasma MR-proADM levels in patients with chronic heart failure are associated with an increased risk of death and hospitalization. Higher MR-proADM levels in combination with increased use of loop diuretics reflect residual congestion and are associated with a higher risk of severe disease progression.

Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B.

BACKGROUND: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction. METHODS: REAL-TIMI 63B (A Randomized, Placebo­controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. RESULTS: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, [IQR, 4.92-16.61], 1-sided P=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA-1.10], 1-sided P=0.30). There was no significant difference in treatment emergent serious adverse events. CONCLUSIONS: Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03578809.

Soluble urokinase-type plasminogen activator receptor improves early risk stratification in cardiogenic shock.

AIMS: Soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker reflecting the level of immune activation. It has been shown to have prognostic value in acute coronary syndrome and heart failure as well as in critical illness. Considering the complex pathophysiology of cardiogenic shock (CS), we hypothesized suPAR might have prognostic properties in CS as well. The aim of this study was to assess the kinetics and prognostic utility of suPAR in CS. METHODS AND RESULTS: SuPAR levels were determined in serial plasma samples (0-96 h) from 161 CS patients in the prospective, observational, multicentre CardShock study. Kinetics of suPAR, its association with 90-day mortality, and additional value in risk-stratification were investigated. The median suPAR-level at baseline was 4.4 [interquartile range (IQR) 3.2-6.6)] ng/mL. SuPAR levels above median were associated with underlying comorbidities, biomarkers reflecting renal and cardiac dysfunction, and higher 90-day mortality (49% vs. 31%; P = 0.02). Serial measurements showed that survivors had significantly lower suPAR levels at all time points compared with nonsurvivors. For risk stratification, suPAR at 12 h (suPAR12h) with a cut-off of 4.4 ng/mL was strongly associated with mortality independently of established risk factors in CS: OR 5.6 (95% CI 2.0-15.5); P = 0.001) for death by 90 days. Adding suPAR12h > 4.4 ng/mL to the CardShock risk score improved discrimination identifying high-risk patients originally categorized in the intermediate-risk category. CONCLUSION: SuPAR associates with mortality and improves risk stratification independently of other previously known risk factors in CS patients.

Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE-TIMI 58 trial.

AIMS: We investigated the associations between obesity, cardiorenal events, and benefits of dapagliflozin in patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: DECLARE-TIMI 58 randomized patients with T2DM and either atherosclerotic cardiovascular (CV) disease or multiple risk factors to dapagliflozin vs. placebo. Patients were stratified by body mass index (BMI, kg/m2): normal (18.5 to <25), overweight (25 to <30), moderately obese (30 to <35), severely obese (35 to <40), and very-severely obese (≥40). Outcomes analysed were CV death, hospitalization for heart failure (HHF), renal-specific composite outcome, and atrial fibrillation or flutter (AF/AFL). Of 17 134 patients, 9.0% had a normal BMI, 31.5% were overweight, 32.4% were moderately, 17.2% severely, and 9.8% were very-severely obese. Higher BMI was associated with a higher adjusted risk of HHF and AF/AFL (hazard ratio 1.30 and 1.28, respectively, per 5 kg/m2; P < 0.001 for all). Dapagliflozin reduced body weight by similar relative amounts consistently across BMI categories (percent difference: -1.9 to -2.4%). Although relative risk reductions in CV and renal-specific composite outcomes with dapagliflozin did not significantly differ across the range of BMI (P for interaction ≥0.20 for all outcomes), obese patients (BMI ≥ 30 kg/m2) tended to derive greater absolute risk reduction in HHF and AF/AFL (P for interaction 0.02 and 0.09, respectively) than non-obese patients. CONCLUSIONS: In DECLARE-TIMI 58, patients with T2DM and higher BMI were more likely to have HHF and AF/AFL. Whereas relative risk reductions in CV and renal outcomes with dapagliflozin were generally consistent across the range of BMI, absolute risk reduction in obesity-related outcomes including HHF and AF/AFL tended to be larger in obese patients with T2DM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01730534.

Trends in the treatment and survival of heart failure patients: a nationwide population-based study in the Czech Republic.

AIMS: A retrospective nationwide observational analysis of diagnoses, procedures, and treatment reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018. METHODS AND RESULTS: Prevalence of heart failure (HF) patients increased from 176 496 (1679.4 per 100 000 population) in 2012 to 285 745 (2689.0 per 100 000 population) patients in 2018 (mean age 74.4 ± 12.8 years). In the last years, a stable incidence of HF patients was observed (544 per 100 000 population in 2016 vs. 551 per 100 000 population in 2018; P = 0.310). Mortality rate decreased from 20.55% in 2012 to 15.89% in 2018. The number of hospitalized patients remained similar (318.2 per 100 000 population in 2012 vs. 311.8 per 100 000 population in 2018; P = 0.479). The most used drugs were diuretics (173 295; 60.6%) and beta-blockers (178 823; 62.6%), followed by angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (angiotensin-converting enzyme inhibitors 120.581; 42.2%; angiotensin II receptor blockers 47 216; 16.5%). Even though the whole number of implanted devices in HF patients increased steadily (from 25 205 in 2012 to 45 363 in 2018), the prevalence of all devices (pacemakers and defibrillators) in the HF patients remained about the same (14.3% in 2012; 15.9% in 2018). CONCLUSIONS: The study included all patients with HF in the Czech Republic. These are the first nationwide data of HF epidemiology in the Eastern bloc. The incidence of HF remains stable in the last years. Due to aging of the population, the prevalence of HF significantly increased in the last 6 years. Despite a continuous increase in the prevalence of HF and a suboptimal utilization of its pharmacological therapy, mortality decreased, and the number of hospitalized patients remained the same.

Empagliflozin in Heart Failure with a Preserved Ejection Fraction.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. METHODS: In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. RESULTS: Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin. CONCLUSIONS: Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).

Long-Term Ticagrelor in Patients With Prior Coronary Stenting in the PEGASUS-TIMI 54 Trial.

Background Coronary stent type and risk of stent thrombosis remain important factors affecting recommended duration of dual antiplatelet therapy. We investigated the efficacy and safety of long-term ticagrelor in patients with prior coronary stenting enrolled in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial. Methods and Results Patients in PEGASUS-TIMI 54 had a myocardial infarction 1 to 3 year prior and were randomized 1:1:1 to ticagrelor 60 or 90 mg BID or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events). Stent thrombosis was prospectively adjudicated (Academic Research Consortium definition). Baseline characteristics were compared by most recent stent type (bare metal versus drug-eluting stent and first- versus later-generation drug-eluting stent). Treatment arms were compared using Cox proportional hazards models. Of 21 162 patients randomized, 80% (n=16 891) had prior coronary stenting. Following randomization, myocardial infarction was the most frequent ischemic event in patients with prior stenting in the placebo arm, occurring in 5.2% of patients (Type 1: 4.1%), followed by cardiovascular death (2.3%), stroke (1.7%), and stent thrombosis (0.9%). Ticagrelorpooled reduced major adverse cardiovascular events (7.0% versus 8.0%; hazard ratio [HR], 0.85; 95% CI, 0.75-96) regardless of stent type (bare metal stent versus drug-eluting stent: pinteraction=0.767; first versus later generation: pinteraction=0.940). The rate of any stent thrombosis was numerically lower with ticagrelorpooled (0.7% versus 0.9%; HR, 0.73; 95% CI, 0.50-1.05) and Thrombolysis in Myocardial Infarction major bleeding was increased (HR, 2.65; 95% CI, 1.90-3.68). Conclusions Long-term ticagrelor reduces major adverse cardiovascular events in patients with prior myocardial infarction and coronary stenting regardless of stent type, with the benefit driven predominantly by reduction in de novo events. Nonfatal major bleeding is increased with ticagrelor. Registration Information clinicaltrials.gov. Identifier: NCT01225562.

Prognostic value of high-sensitivity cardiac troponin I in heart failure patients with mid-range and reduced ejection fraction.

BACKGROUND: The identification of high-risk heart failure (HF) patients makes it possible to intensify their treatment. Our aim was to determine the prognostic value of a newly developed, high-sensitivity troponin I assay (Atellica®, Siemens Healthcare Diagnostics) for patients with HF with reduced ejection fraction (HFrEF; LVEF < 40%) and HF with mid-range EF (HFmrEF) (LVEF 40%-49%). METHODS AND RESULTS: A total of 520 patients with HFrEF and HFmrEF were enrolled in this study. Two-year all-cause mortality, heart transplantation, and/or left ventricular assist device implantation were defined as the primary endpoints (EP). A logistic regression analysis was used for the identification of predictors and development of multivariable models. The EP occurred in 14% of the patients, and these patients had higher NT-proBNP (1,950 vs. 518 ng/l; p < 0.001) and hs-cTnI (34 vs. 17 ng/l, p < 0.001) levels. C-statistics demonstrated that the optimal cut-off value for the hs-cTnI level was 17 ng/l (AUC 0.658, p < 0.001). Described by the AUC, the discriminatory power of the multivariable model (NYHA > II, NT-proBNP, hs-cTnI and urea) was 0.823 (p < 0.001). Including heart failure hospitalization as the component of the combined secondary endpoint leads to a diminished predictive power of increased hs-cTnI. CONCLUSION: hs-cTnI levels ≥ 17 ng/l represent an independent increased risk of an adverse prognosis for patients with HFrEF and HFmrEF. Determining a patient's hs-cTnI level adds prognostic value to NT-proBNP and clinical parameters.

Vericiguat in patients with heart failure and reduced ejection fraction.

BACKGROUND: The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear. METHODS: In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5 050 patients with chronic heart failure (New York Heart Association class II, III, or IV) and an ejection fraction of less than 45% to receive vericiguat (target dose 10 mg once daily) or placebo, in addition to guideline-based medical therapy.The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure. RESULTS: Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2 526 patients (35.5%) in the vericiguat group and in 972 of 2 524 patients (38.5%) in the placebo group (p = 0.02). A total of 691 patients (27.4%) in the vericiguat group and 747 patients (29.6%) in the placebo group were hospitalized for heart failure. Death from cardiovascular causes occurred in 414 patients (16.4%) in the vericiguat group and in 441 patients (17.5%) in the placebo group. The composite endpoint of death from any cause or hospitalization for heart failure occurred in 957 patients (37.9%) in the vericiguat group and in 1 032 patients (40.9%) in the placebo group (p = 0.02). Symptomatic hypotension occurred in 9.1% of the patients in the vericiguat group and in 7.9% of the patients in the placebo group (p = 0.12), syncope occurred in 4.0% of the patients in the vericiguat group and in 3.5% of the patients in the placebo group (p = 0.30). CONCLUSION: Among patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat than those who received placebo.

Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF.

BACKGROUND: In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (≤35%). OBJECTIVES: The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil. METHODS: Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF. RESULTS: The risk of the PCE in the placebo group was nearly 1.8-fold greater in the lowest EF (≤22%) compared with the highest EF (≥33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (interaction as continuous variable, p = 0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF ≤22% (n = 2,246; hazard ratio: 0.83; 95% confidence interval: 0.73 to 0.95) compared with patients with EF ≥33% (n = 1,750; hazard ratio: 0.99; 95% confidence interval: 0.84 to 1.16; interaction as EF by quartiles, p = 0.013). The absolute reduction in the PCE increased with decreasing EF (EF ≤22%; absolute risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile. CONCLUSIONS: In heart failure patients with reduced EF, omecamtiv mecarbil produced greater therapeutic benefit as baseline EF decreased. These findings are consistent with the drug's mechanism of selectively improving systolic function and presents an important opportunity to improve the outcomes in a group of patients at greatest risk. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).

EMPEROR reduced - empagliflozin in patients with heart failure and reduced ejection fraction.

Type 2 diabetes mellitus (T2DM) is common in patients with chronic heart failure and is associated with high morbidity and mortality. Significant advances have recently occured in the treatment of diabetes mellitus type 2 (T2DM) and cardiovascular diseases. Several new glucose lowering drugs have shown either neutral or positive cardiovascular effect especially on hospitalisations, but also on mortality. Some of these drugs have safety characteristics with strong practical implication in heart failure, for example sodium-glucose co-transporters type 2 inhibitors (SGLT-2). Position paper of the European Society of Cardiology/Heart Failure Association was published in October 2019 and in June 2020. The results of EMPEROR reduced study were presented on European congress in september 2020. In this phase III, placebo-controlled trial, 3730 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less were randomly assigned to receive either empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. Over a median of 16 months, the primary outcome (cardiovascular mortality and hospitalisation for heart failure) occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P.

Long-term exercise effects after cardiac telerehabilitation in patients with coronary artery disease: 1-year follow-up results of the randomized study.

BACKGROUND: Home-based cardiac telerehabilitation (HBCT) is a feasible and effective alternative to traditional center-based cardiac rehabilitation (CBCR). Currently, there are only limited studies focusing on a long-term effect of HBCT, which means it is essential to do more research in this study field. AIM: This study aimed at investigating a 1-year effect of a randomized controlled study using Cardiac Rehabilitation through the Global Position System (CR-GPS) compared to outpatient cardiac rehabilitation. Study focused on cardiorespiratory fitness (CRF) and health-related quality of life (HRQL) in patients with coronary heart disease (CAD). DESIGN: A long-term follow-up of a randomized study. SETTING: Patients were enrolled, and the intervention was performed in an outpatient or home-based model. The results were obtained and evaluated in a hospital. POPULATION: Patients who participated in the CR-GPS study were diagnosed with CAD with low to moderate cardiovascular risk. METHODS: Patients enrolled in the study were eligible participants who had previously completed a 12-week HBCT program using a wrist heart rate (HR) monitor or attended a traditional CBCR. Primary outcome was the change in CRF expressed in peak oxygen uptake (pVO2), and the secondary outcomes were self-reported HRQL, objectively measured anthropometric characteristics, and mortality and hospitalization rates. RESULTS: Forty-four patients (76%) completed the long-term follow-up. The average peak of pVO2 was higher after 1-year follow-up in the telerehabilitation group (HBCT 25.5 mL/kg/min compared to the active control group CBCR 23.6 mL/kg/min P=0.047). No statistically significant difference between the two groups was found after long-term follow-up for the parameter HRQL. For both groups, there was a significant improvement in the range of perceptions of general health. There was no death case and no difference in hospitalization rate between the groups. CONCLUSIONS: This study supports the HBCT model. It has been demonstrated that it induces satisfactory long-term effects in pVO2, exercise performance, and perceived general health in CAD patients with low to moderate cardiovascular risk. CLINICAL REHABILITATION IMPACT: Cardiovascular telerehabilitation using wrist HR monitors is a feasible and effective rehabilitation method that can help patients eliminate barriers that prevent them from using CBCR programs. Especially in the current global situation with the COVID-19 pandemic, this topic is becoming increasingly important.

Kinetics of procalcitonin, C-reactive protein and interleukin-6 in cardiogenic shock - Insights from the CardShock study.

BACKGROUND: Inflammatory responses play an important role in the pathophysiology of cardiogenic shock (CS). The aim of this study was to investigate the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) in CS and to assess their relation to clinical presentation, other biochemical variables, and prognosis. METHODS: Levels of PCT, CRP and IL-6 were analyzed in serial plasma samples (0-120h) from 183 patients in the CardShock study. The study population was dichotomized by PCTmax ≥ and < 0.5 µg/L, and IL-6 and CRPmax above/below median. RESULTS: PCT peaked already at 24 h [median PCTmax 0.71 µg/L (IQR 0.24-3.4)], whereas CRP peaked later between 48 and 72 h [median CRPmax 137 mg/L (59-247)]. PCT levels were significantly higher among non-survivors compared with survivors from 12 h on, as were CRP levels from 24 h on (p < 0.001). PCTmax ≥ 0.5 µg/L (60% of patients) was associated with clinical signs of systemic hypoperfusion, cardiac and renal dysfunction, acidosis, and higher levels of blood lactate, IL-6, growth-differentiation factor 15 (GDF-15), and CRPmax. Similarly, IL-6 > median was associated with clinical signs and biochemical findings of systemic hypoperfusion. PCTmax ≥ 0.5 µg/L and IL-6 > median were associated with increased 90-day mortality (50% vs. 30% and 57% vs. 22%, respectively; p < 0.01 for both), while CRPmax showed no prognostic significance. The association of inflammatory markers with clinical infections was modest. CONCLUSIONS: Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.

Differences in risk profiles and long-term outcomes in acute heart failure patients with preserved and reduced left ventricular ejection fraction in the Czech Republic: The AHEAD registry sub-analysis.

BACKGROUND: The latest European heart failure guidelines define patients as those with reduced (HFrEF), mid-range, and preserved (HFpEF) left ventricular ejection fraction (LVEF; <40%, 40%-49%, and ≥50%, respectively). We investigated the causes of rehospitalizations/deaths in our institution's heart failure patients and focused on differences in the clinical presentation, risk profile, and long-term outcomes between the HFrEF and HFpEF groups in a real-life scenario. METHODS AND RESULTS: We followed 1274 patients discharged from heart failure hospitalization in 2 centres. The mean patient age was 75.9 years, and men and women were represented equally. During the minimal follow-up of 2 years, 57% of patients were hospitalised for any cause, 24.9% for decompensated heart failure, and 43.3% for any cardiovascular cause. A total of 36.1% of patients died, either with prior (11.8%) or without prior (24.3%) heart failure rehospitalization. Heart failure was also the most frequent cause of cardiovascular hospitalization, followed by gastrointestinal problems, infections, and tumours for noncardiovascular hospitalizations. Patients with HFrEF had different baseline characteristics and risk profiles, experienced more hospitalizations for acute heart failure (28.6% vs 20.2%, P=0.012), and had higher cardiovascular mortality (82.4% vs 63.5%, P<0.001) when compared with HFpEF patients. Overall mortality and rehospitalization rates were similar. CONCLUSION: Within 2 years, half of the patients died and/or were hospitalised for acute decompensation of heart failure, and only one-third of the patients survived without any hospitalization. HFrEF and HFpEF patients were confirmed to be different entities with diverse characteristics, risk profiles, and cardiovascular event rates.

Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

BACKGROUND: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS: We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS: During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.).

Baseline characteristics of patients with heart failure with preserved ejection fraction in the EMPEROR-Preserved trial.

AIMS: EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares them with patients enrolled in prior HFpEF trials. METHODS AND RESULTS: EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients [left ventricular ejection fraction (LVEF) >40%] with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of heart failure hospitalization. Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72 ± 9 years, 45% were women. Almost all patients had New York Heart Association class II or III symptoms (99.6%), and 23% had prior heart failure hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41-50%. The mean LVEF (54 ± 9%) was slightly lower while the median NT-proBNP [974 (499-1731) pg/mL] was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists. CONCLUSION: When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of comorbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists at baseline. Results of the EMPEROR-Preserved trial will be available in 2021.