Publications by authors named "Jindrich Spinar"

159 Publications

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

PLoS One 2021 30;16(7):e0255271. Epub 2021 Jul 30.

Department of Internal Medicine and Cardiology, University Hospital Brno, Brno, Czech Republic.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255271PLOS
July 2021

Vericiguat in patients with heart failure and reduced ejection fraction.

Vnitr Lek 2021 ;67(3):180-182

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.
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June 2021

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

J Am Coll Cardiol 2021 Jul 17;78(2):97-108. Epub 2021 May 17.

Cytokinetics, Inc., South San Francisco, California, USA.

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).
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http://dx.doi.org/10.1016/j.jacc.2021.04.065DOI Listing
July 2021

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

Vnitr Lek 2021 ;67(1):43-47

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.
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March 2021

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

Eur J Phys Rehabil Med 2021 Feb 23. Epub 2021 Feb 23.

First Department of Internal Medicine, Cardioangiology, Institutions shared with St. Anne's Faculty Hospital, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

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 homebased 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: 44 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.
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http://dx.doi.org/10.23736/S1973-9087.21.06653-3DOI Listing
February 2021

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

Eur J Heart Fail 2020 12;22(12):2383-2392

University of Medicine and Pharmacy Carol Davila, University and Emergency Hospital, Bucharest, Romania.

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.
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http://dx.doi.org/10.1002/ejhf.2064DOI Listing
December 2020

Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

N Engl J Med 2021 01 13;384(2):105-116. Epub 2020 Nov 13.

From the Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California, San Francisco, San Francisco (J.R.T.), Amgen, Thousand Oaks (L.S., J.C.L., N.H., S.A.A., C.E.K.), and Cytokinetics, South San Francisco (F.I.M.) - all in California; Estudios Clínicos Latino América, Rosario, Argentina (R.D.); the Division of Cardiology, Duke University School of Medicine and Duke Clinical Research Institute, Durham (G.M.F.), and the University of North Carolina, Chapel Hill (K.F.A.) - both in North Carolina; the British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and the Robertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing (J.G.F.C.), University of Glasgow, Glasgow, and the National Heart and Lung Institute, Imperial College, London (J.G.F.C.) - both in the United Kingdom; Cardiology, ASST Spedali Civili, Department of Medical and Surgical Specialties, Radiologic Sciences, and Public Health, University of Brescia, Brescia, Italy (M.M.); the Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (S.D.S.); the University of Minnesota, Minneapolis (I.A.); Instituto Nacional de Cardiología, Mexico City (A.A.-M.); the Department of Cardiology, Herlev and Gentofte Hospital, and the Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (T.B.-S.); Saarland University, Universitätsklinikum des Saarlandes, Homburg, Germany (M.B.); Medical University of Vienna, Vienna (D.B.); Pontificia Universidad Católica de Chile, Santiago (R.C.); Complexo Hospitalario Universitario A Coruña, Centro de Investigación Biomédica en Red, Enfermedades Cardiovasculares, Instituto de Investigación Biomédica de A Coruña, Universidade da Coruña, A Coruña, Spain (M.G.C.-L.); the Departments of Cardiology and Health, Medicine and Caring Sciences, Linkoping University, Linkoping, Sweden (U.D.); Fundación Cardiovascular de Colombia, Floridablanca, Colombia (L.E.E.); University of Utah, Salt Lake City (J.C.F.); National and Kapodistrian University of Athens, Attikon University Hospital, Athens (G.F.); Hospital S. Francisco Xavier, Centro Hospitalar Lisboa Ocidental, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal (C.F.); Commenius University, Bratislava, Slovakia (E.G.); the Department of Cardiology, Queen Giovanna University Hospital and Medical University, Sofia, Bulgaria (A.R.G.); Libin Cardiovascular Institute and Cumming School of Medicine, University of Calgary, Calgary, AB (J.G.H.), and Montreal Heart Institute and Université de Montréal, Montreal (E.O.) - both in Canada; the Heart and Vascular Institute, Henry Ford Hospital, Detroit (D.E.L.); the National Clinical Research Center for Cardiovascular Diseases, National Health Commission Key Laboratory of Clinical Research for Cardiovascular Medications, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.L.); Middlemore Hospital, Otahuhu, Auckland, New Zealand (M.L.); St. Vincent's Hospital Sydney, Darlinghurst, NSW, Australia (P.M.); University Clinic of Lomonosov, Moscow State University, Moscow (V.M.); Saitama Citizens Medical Center, Saitama, Japan (S.M.); Institute of Cardiology, Kyiv, Ukraine (A.P.); Wroclaw Medical University, Wroclaw, Poland (P.P.); Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo (F.J.A.R.); Vilnius University, Vilnius, Lithuania (P.S.); the University of Cape Town, Cape Town, South Africa (K.S.); the Internal Cardiology Department, St. Ann Hospital and Masaryk University Brno, Brno, Czech Republic (J.S.); the Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (T.M.S.); St. John of God Hospital, Budapest, Hungary (J.T.); AZ Sint-Lucas, Ghent, Belgium (H.V.); the University of Medicine and Pharmacy Carol Davila, University and Emergency Hospital, Bucharest, Romania (D.V.); the University of Groningen, Groningen, the Netherlands (A.A.V.); Dokuz Eylul University, Izmir, Turkey (M.B.Y.); and Université de Lorraine, INSERM Investigation Network Initiative Cardiovascular and Renal Clinical Trialists, Centre Hospitalier Régional Universitaire de Nancy, Nancy (F.Z.), and Servier, Suresnes (C.V.) - both in France.

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.).
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http://dx.doi.org/10.1056/NEJMoa2025797DOI Listing
January 2021

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.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2021 Mar 1;165(1):34-42. Epub 2020 Oct 1.

Department of Cardiology, University Hospital Brno, Czech Republic.

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.
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http://dx.doi.org/10.5507/bp.2020.038DOI Listing
March 2021

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction: GALACTIC-HF baseline characteristics and comparison with contemporary clinical trials.

Eur J Heart Fail 2020 11 27;22(11):2160-2171. Epub 2020 Oct 27.

Institute of Cardiology, Kyiv, Ukraine.

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials.

Methods And Results: Adults with established HFrEF, New York Heart Association (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non-white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N-terminal pro-B-type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC-HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594).

Conclusions: GALACTIC-HF enrolled a well-treated, high-risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation.
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http://dx.doi.org/10.1002/ejhf.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756903PMC
November 2020

Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure.

N Engl J Med 2020 10 28;383(15):1413-1424. Epub 2020 Aug 28.

From Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas (M.P.); Imperial College (M.P.) and the Department of Medical Statistics, London School of Hygiene and Tropical Medicine (S.J.P.), London, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow (N.S.), and the Department of Cardiovascular Sciences, University of Leicester and National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester (I.S.) - all in the United Kingdom; the Department of Cardiology and Berlin Institute of Health Center for Regenerative Therapies, German Center for Cardiovascular Research Partner Site Berlin, Charité Universitätsmedizin, Berlin (S.D.A.), Boehringer Ingelheim International, Ingelheim (M. Brueckmann, W.J.), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim (M. Brueckmann), Boehringer Ingelheim Pharma, Biberach (C.Z.), Klinik für Innere Medizin III, Saarland University, Homburg-Saar (M. Böhm), and the Department of Medicine, University Hospital of Würzburg, Würzburg (C.W.) - all in Germany; the Department of Medicine, University of Mississippi School of Medicine, Jackson (J.B.); National and Kapodistrian University of Athens School of Medicine, Athens University Hospital Attikon, Athens (G.F.); Washington DC Veterans Affairs Medical Center, Washington DC (P.C.); the Division of Cardiology, Harvard Medical School and Massachusetts General Hospital, Boston (J.J.); the Division of Cardiac Surgery, St. Michael's Hospital, University of Toronto, Toronto (S.V.), Boehringer Ingelheim Canada, Burlington, ON (K.K.), and the Division of Cardiology, McGill University and Health Centre, Montreal (N.G.) - all in Canada; the Department of Cardiovascular Medicine, Kyushu University, Higashi-ku, Fukuoka, Japan (H.T.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (J. Schnee, D.C.); Heart Institute, São Paulo University Medical School, São Paulo (E.B.); the Department of Medicine, Seoul National University, Seoul, South Korea (D.-J.C.); the Department of Cardiology, Max Super Speciality Hospital, Saket, New Delhi, India (V.C.); the Department of Clinical Cardiology, National Institute of Cardiology, Mexico City (E.C.); the Department of Cardiology, University Hospital Gasthuisberg of Leuven, Leuven, Belgium (S.J.); Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.Z.); the Cardiology Department, University Hospital, Santiago de Compostela, Spain (J.R.G.J.); the Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles (S.K.); Maastricht Heart and Vascular Center, Maastricht, the Netherlands (H.P.B.-L.R.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Victorian Heart Institute and Monash University, Melbourne, VIC, Australia (S.J.N.); Fleni Institute and Hospital El Cruce-Nestor Kirchner, Buenos Aires (S.P.); the Department of Medicine, Wayne State and Central Michigan Universities, Detroit (I.P.); the Center for Heart Diseases, Wrocław Medical University, Wrocław, Poland (P.P.); the Cardiovascular Department, Papa Giovanni XXIII Hospital, Bergamo (M.S.), and the Department of Clinical and Experimental Medicine, University of Pisa, Pisa (S.T.) - both in Italy; the Department of Cardiology, University Hospital Jean Minjoz, Besançon (M.-F.S.), and Université de Lorraine, INSERM Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists, Centre Hospitalier Régional Universitaire, Nancy (F.Z.) - both in France; and Internal Cardiology, University Hospital Brno, Brno, Czech Republic (J. Spinar).

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes. More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction.

Methods: In this double-blind trial, we randomly assigned 3730 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure.

Results: During a median of 16 months, a primary outcome event 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 for cardiovascular death or hospitalization for heart failure, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P<0.001). The effect of empagliflozin on the primary outcome was consistent in patients regardless of the presence or absence of diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.70; 95% CI, 0.58 to 0.85; P<0.001). The annual rate of decline in the estimated glomerular filtration rate was slower in the empagliflozin group than in the placebo group (-0.55 vs. -2.28 ml per minute per 1.73 m of body-surface area per year, P<0.001), and empagliflozin-treated patients had a lower risk of serious renal outcomes. Uncomplicated genital tract infection was reported more frequently with empagliflozin.

Conclusions: Among patients receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Reduced ClinicalTrials.gov number, NCT03057977.).
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http://dx.doi.org/10.1056/NEJMoa2022190DOI Listing
October 2020

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

Int J Cardiol 2021 01 22;322:191-196. Epub 2020 Aug 22.

Emergency Medicine, University of Helsinki and Department of Emergency Medicine and Services, Helsinki University Hospital, Helsinki, Finland.

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 PCT ≥ and < 0.5 μg/L, and IL-6 and CRP above/below median.

Results: PCT peaked already at 24 h [median PCT 0.71 μg/L (IQR 0.24-3.4)], whereas CRP peaked later between 48 and 72 h [median CRP 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). PCT ≥ 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 CRP. Similarly, IL-6 > median was associated with clinical signs and biochemical findings of systemic hypoperfusion. PCT ≥ 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 CRP 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.
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http://dx.doi.org/10.1016/j.ijcard.2020.08.069DOI Listing
January 2021

Delayed-type Hypersensitivity to Metals in Newly Diagnosed Patients with Nonischemic Dilated Cardiomyopathy.

Cardiovasc Toxicol 2020 12;20(6):571-580

Department of Internal Medicine and Cardiology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

The causes of nonischemic dilated cardiomyopathy are classified as genetic or nongenetic, but environmental factors such as metal pollutants may interact with genetic susceptibility. The presence of metal particles has been detected in the myocardium, including in those patients with dilated cardiomyopathy. It is also known that hypersensitivity reactions can induce inflammation in tissue. The present study aimed to verify if metal-induced delayed-type hypersensitivity is present in patients with nonischemic dilated cardiomyopathy. The patient group consisted of 30 patients with newly diagnosed dilated cardiomyopathy; the control group comprised 41 healthy subjects. All patients and control subjects provided blood samples for lymphocyte transformation testing (MELISA®) to assess possible hypersensitivity to seven common metals. Specific exposure to metals was based on interview data. Results showed that exposure to cadmium and lead (p = 0.0002), aluminum (p = 0.0006), nickel (p = 0.0012), and chromium (p = 0.0065) was more often reported by patients than controls. The patients also had significantly more frequent hypersensitivity reactions to mercury (26.7% vs. 7.3%, p = 0.014624), nickel (40% vs. 12.2%, p = 0.02341), and silver (20% vs. 4.8%, p = 0.025468) than the control group. Patients with dilated cardiomyopathy had greater exposure to certain metals compared with healthy controls. Hypersensitivity to metals was more frequent in patients with dilated cardiomyopathy, suggesting a possible association that warrants further investigation.
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http://dx.doi.org/10.1007/s12012-020-09582-6DOI Listing
December 2020

Heart rate as an independent predictor of long term mortality of acute heart failure patients in sinus rhythm according to their ejection fraction: data from the AHEAD registry.

Eur J Intern Med 2020 08 18;78:88-94. Epub 2020 Apr 18.

Department of Cardiology, University Hospital Brno, Brno, Czech Republic; Medical Faculty, Masaryk University, Brno, Czech Republic; Department of Cardiology, Na Homolce Hospital, Prague, Czech Republic. Electronic address:

Background: Heart rate (HR) at admission in patients with acute heart failure (AHF) has been shown to be an important risk marker of in-hospital mortality. However, its relation with mid and long-term prognosis as well as the impact of Ejection Fraction (EF) is unknown. Our objective was to study the relationship between long-term survival and HR at admission depending on EF in a cohort of patients hospitalized for AHF.

Methods: We analyzed the data of 2335 patients in sinus rhythm hospitalized for AHF from AHEAD registry. Patients with cardiogenic shock and AHF from surgical or non-cardiac etiology were excluded.

Results: Survival rates at 6 and 12 months were 84.8% and 78% respectively. Increased age, decreased diastolic BP, lack of PCI during hospitalization, increased creatinine level and increased HR (with different cut-offs according to EF categories) were found as predictors whatever the EF at 6 and 12 months. Optimal prognostic cut-offs of heart rate were identified for Heart Failure with reduced EF at 100 bpm, for Heart Failure with mid-range EF at 90 bpm and for Heart Failure with preserved EF at 80 bpm for both 6 and 12 months.

Conclusion: Our study suggests that HR at admission appears to be an independent prognostic parameter in AHF patients in sinus rhythm irrespective of EF and can be used to classify patients according to the severity of the disease.
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http://dx.doi.org/10.1016/j.ejim.2020.04.022DOI Listing
August 2020

Benefits and effectiveness of using a wrist heart rate monitor as a telerehabilitation device in cardiac patients: A randomized controlled trial.

Medicine (Baltimore) 2020 Mar;99(11):e19556

Department of Cardiology and Internal Medicine, University Hospital Brno.

Background: Telerehabilitation in cardiology has the potential to become the alternative to regular outpatient cardiac rehabilitation. Our study focuses on the wrist heart rate monitor as a telerehabilitation device, defines detected limitations, and compares results between home-based and regular outpatient rehabilitation methods, related to physical fitness, quality of life, and training adherence. The study design was a randomized controlled trial.

Methods: Eligible 56 cardiac rehabilitation patients were randomized into a 12-week regular outpatient training group (ROT) and interventional home-based telerehabilitation group (ITG). For both groups, the intensity of the training was prescribed to be performed at 70% to 80% of heart rate reserve for 60 minutes, 3 times a week. The ITG patients started their training with a wrist heart rate monitor in their home environment. These patients received feedback once a week, reflecting data uploaded on the internet application. The ROT patients performed their exercise under the direct supervision of a physical specialist in a regular outpatient clinic. Physical fitness and health-related quality of life were assessed at baseline and after 12 weeks. Training adherence in both groups was determined and compared.

Results: Fifty-one patients comleted the intervention (91%); no serious adverse events were recorded. Physical fitness expressed as peak oxygen uptake showed significant improvement (P < .001) in ROT group from 23.4 ± 3.3 to 25.9 ± 4.1 mL/kg/min and (P < .01) in ITG group from 23.7 ± 4.1 to 26.5 ± 5.7 mL/kg/min without significant between-group differences after 12 weeks of intervention. The training adherence between groups was similar.

Conclusion: Our study shows that telerehabilitation via wrist heart rate monitor could become an alternative kind of cardiac rehabilitation which deserves attention and further analyzing.
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http://dx.doi.org/10.1097/MD.0000000000019556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440288PMC
March 2020

Activation of the Nitric Oxide Pathway and Acute Myocardial Infarction Complicated by Acute Kidney Injury.

Cardiorenal Med 2020 20;10(2):85-96. Epub 2020 Jan 20.

Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.

Background/aims: The pathophysiology of acute kidney injury (AKI) in ST-elevation myocardial infarction (STEMI) patients remains poorly explored. The involvement of the nitric oxide (NO) pathway has been demonstrated in experimental ischemic AKI. The aim of this study was to assess the predictive value of circulating biomarkers of the NO pathway for AKI in STEMI patients.

Methods: Four hundred and twenty-seven STEMI patients treated with primary percutaneous coronary intervention were included. The primary end point was AKI. Biomarkers of the NO pathway (plasma superoxide dismutase [SOD], uric acid, nitrite/nitrate [NOx], neopterin) as well as cardiac biomarkers (B-type natriuretic peptide [BNP] and troponin) were sampled 12 h after admission. The predictive value of circulating biomarkers was evaluated in addition to the multivariate clinical model.

Results: AKI developed in 8.9% of patients. The 3-month mortality was significantly higher in patients with AKI (34.2 vs. 4.1%; p < 0.001). SOD, uric acid, NOx, neopterin, BNP and troponin were significantly associated with the development of AKI (area under curve [AUC]-receiver operating curve [ROC] ranging between 0.70 and 0.81). In multivariate analysis cardiogenic shock, neopterin, NOx and troponin were independent predictors of AKI. AUC-ROC of the association of multibiomarkers and clinical model was 0.90 and outperformed the predictive value of the clinical model alone. OR of NOx ≥45 µmol/L was 8.0 (95% CI 3.1-20.6) for AKI.

Conclusion: Biomarkers of the NO pathway are associated with the development of AKI in STEMI patients. These results provide insights into the pathophysiology of AKI and may serve at developing preventing strategies for AKI targeting this pathway.
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http://dx.doi.org/10.1159/000503718DOI Listing
June 2021

Innovations in pharmacological treatment of heart failure.

Vnitr Lek 2019 ;65(10):611-619

The main goal of the heart failure treatment is the decrease of mortality and morbidity, especially improvement of quality of life and decrease of hospitalisations. ACE inhibitors are the cornerstone of the treatment, MRA should be added to ACEI. Angiotensin receptor blockers (ARB) are indicated in the case of ACE inhibitors intolerance. Betablockers in maximal tolerated doses should be added to the renin angiotensin blockade. Diuretics are given to the symptoms relieve - dyspnoe or oedema. Digoxin is indicated in selected patients. There are 3 new promising groups of drugs: (1) Angiotensin Receptor-Neprilysin Inhibitor - ARNI - Sacubitril/Valsartan can replace the ACEI according to the results of the PARADIGM-HF trial. (2) Sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with diabetes mellitus. (3) A hughe clinical research is done with omecamtiv mecarbil and others perspective drugs.
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January 2020

Long-term ticagrelor for secondary prevention in patients with prior myocardial infarction and no history of coronary stenting: insights from PEGASUS-TIMI 54.

Eur Heart J 2020 05;41(17):1625-1632

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.

Aims: PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup.

Methods And Results: This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1-3 years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15-1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68-0.99) and with prior stenting (HR 0.85, 95% CI 0.75-0.96; P for interaction = 0.76).

Conclusion: Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting.

Clinicaltrials.gov Identifier: NCT01225562.
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http://dx.doi.org/10.1093/eurheartj/ehz821DOI Listing
May 2020

Effects of Serelaxin in Patients with Acute Heart Failure.

N Engl J Med 2019 08;381(8):716-726

From Cardiology, Department of Medical and Surgical Specialties, Radiologic Sciences, and Public Health, University of Brescia, Brescia (M.M.), Centro Cardiologico Universitario di Ferrara, University of Ferrara, Ferrara (R.F.), and Maria Cecilia Hospital, GVM Care and Research, Cotignola (R.F.) - all in Italy; the Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California, San Francisco, San Francisco (J.R.T.), and the Division of Cardiology, University of California, San Diego, La Jolla (B.H.G.) - all in California; Momentum Research (G.C., B.A.D.) and the Division of Cardiology, Duke University School of Medicine (G.M.F.), Durham, and the University of North Carolina, Chapel Hill (K.F.A.) - all in North Carolina; the School of Medicine, University of Cyprus, Nicosia, Cyprus (G.F.); the School of Medicine, National and Kapodistrian University of Athens, Athens (G.F.); the Department of Emergency Medicine, Indiana University School of Medicine, and the Regenstrief Institute, Indianapolis (P.S.P.); the Department of Heart Diseases, Medical University, Military Hospital, Wrocław (P.P.), and Instytut Kardiologii, Warsaw (J.S.) - both in Poland; University of Groningen, Groningen, the Netherlands (A.A.V.); the Department of Internal Medicine and Cardiology, German Center for Cardiovascular Research partner site Berlin (S.D.A., B.P.), and Berlin Institute of Health Center for Regenerative Therapies (S.D.A.), Charité Universitätsmedizin Berlin-Campus Virchow Klinikum, Berlin, and Saarland University, Universitätsklinikum des Saarlandes Homburg, Homburg (M.B.) - all in Germany; the Coronary Care and Emergency Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City (A.A.-M.); Hospital Clínico de la Fuerza Aérea de Chile, Las Condes, Chile (P.A.); the Heart Transplantation Department, Heart Institute (InCor), University of São Paulo, and Hospital Israelita Albert Einstein, São Paulo (F.B.); Sanatorio de la Trinidad Mitre, Buenos Aires (G.B.); the Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow (J.G.F.C.), National Heart and Lung Institute, Imperial College, London (J.G.F.C.), and the Department of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester (I.S.) - all in the United Kingdom; Cardiology Department, Hôpital Lariboisière and Université de Paris, Paris (A.C.-S.); Complejo Hospitalario Universitario A Coruña, Universidade da Coruña, Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, La Coruña, Spain (M.G.C.-L.); Carol Davila University of Medicine and Pharmacy, Bucharest, Romania (M.D.); Heart Failure and Heart Transplant Clinic, Fundación Cardiovascular de Colombia, Floridablanca, Colombia (L.E.E.); Heart Institute, Kaplan Medical Center, Rehovot, Hebrew University, Jerusalem (S.G.); National Cardiovascular Institute, Bratislava, Slovakia (E.G.); Medical University of Sofia, Tzaritza Ioanna University Hospital, Sofia, Bulgaria (A.G.); the Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen (L.K.); Internal Medicine-Cardiology, Internal Medicine Department, Hospital Nacional Arzobispo Loayza, Lima, Peru (J.L.-O.); Wayne State University School of Medicine and Cardiovascular Research Institute, Detroit (P.D.L.); the School of Medicine and Medical Sciences and St. Vincent's University Hospital, University College Dublin, Dublin (K.M.); the Department of Internal Medicine, University of Witwatersrand, Johannesburg (P.M.); Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); the Department of Cardiology and Cardiovascular Research Institute Basel, University Hospital Basel, University of Basel (C.M.), and Novartis Pharma (T.H., T.S., P.S., C.G.), Basel, Switzerland; CINTESIS, Porto University Medical School, São João Medical Center, Porto, Portugal (J.S.-C.); University Hospital Brno and Medical Faculty Masaryk University, Brno, Czech Republic (J.Š.); University Hasselt, Hasselt, Belgium (W.V.M.); the Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria (D.L.); the Institute of Medical Sciences, Uppsala University, Uppsala University Hospital, Uppsala, Sweden (G.W.); Dokuz Eylül University, Faculty of Medicine, Department of Cardiology, Izmir, Turkey (M.B.Y.); and Novartis Pharmaceuticals, East Hanover, NJ (N.H., T.H., T.A.H., S.V.S.).

Background: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure.

Methods: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days.

Results: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups.

Conclusions: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).
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http://dx.doi.org/10.1056/NEJMoa1801291DOI Listing
August 2019

Role of Metoprolol Succinate in the Treatment of Heart Failure and Atrial Fibrillation: A Systematic Review.

Am J Ther 2020 Mar/Apr;27(2):e183-e193

Department of Cardiology and Electrotherapy, Medical University of Gdansk, Gdansk, Poland.

Background: Beta-blockers are one of the most important classes of cardiovascular agents and have been considered a cornerstone therapy in heart diseases, such as heart failure (HF) and atrial fibrillation (AF). Among different beta-blockers, metoprolol is a selective beta1-adrenergic antagonist, which has been extensively used since the 1970s.

Areas Of Uncertainty: Although current guidelines include recommendations for the use of controlled-release metoprolol succinate in specific HF and AF indications, and despite extensive clinical experience with metoprolol, comparative evidence on the use of metoprolol succinate compared with other beta-blockers in these indications is limited.

Data Sources: We systematically reviewed the data from head-to-head studies directly comparing this compound with other beta-blockers in the treatment of HF or AF. Only clinical trials and observational studies were considered; no other limits were applied. The quality and relevance of retrieved articles were reviewed.

Results: A total of 18 articles of the 353 articles identified were selected for inclusion; 12 HF articles and 6 for AF. Additional references were identified from the bibliographies of retrieved articles. The studies show that oral prophylaxis with an appropriate dose of metoprolol may reduce new incidents of AF in high-risk patients. Furthermore, metoprolol succinate is associated with significant mortality and morbidity benefits in the treatment of HF.

Conclusions: Despite the introduction of newer beta-blockers with differing clinical characteristics since its introduction, metoprolol succinate remains a useful drug in both HF and AF.
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http://dx.doi.org/10.1097/MJT.0000000000001043DOI Listing
November 2020

Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54.

Eur Heart J Cardiovasc Pharmacother 2019 10;5(4):200-206

Harvard Medical School, TIMI Study Group, Boston, MA, USA.

Aims: In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.

Methods And Results: Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P = 0.58).

Conclusion: In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population.

Clinical Trial Registration: http://www.clinicaltrials.gov NCT01225562.
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http://dx.doi.org/10.1093/ehjcvp/pvz020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749839PMC
October 2019

Hyperuricemia treatment in acute heart failure patients does not improve their long-term prognosis: A propensity score matched analysis from the AHEAD registry.

Clin Cardiol 2019 Aug 29;42(8):720-727. Epub 2019 May 29.

Second Department of Internal Medicine, Department of Cardiology and Angiology, First Faculty of Medicine of the Charles University, Prague, and General University Hospital in Prague, Czech Republic.

Background: Hyperuricemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients.

Methods: The prospective acute heart failure registry (AHEAD) was used to select 3160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricemia was defined as UA ≥500 μmoL/L and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricemia, with treated hyperuricemia, and with untreated hyperuricemia at discharge. Two- and five-year all-cause mortality were defined as endpoints. Patients without hyperuricemia, unlike those with hyperuricemia, had a higher left ventricular ejection fraction, a better renal function, and higher hemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or beta-blockers.

Results: In a primary analysis, the patients without hyperuricemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricemia had a similar 5-year survival rate as those with untreated hyperuricemia (42.0% vs 39.7%, P = 0.362) whereas those with treated hyperuricemia had a poorer prognosis (32.4% survival rate, P = 0.006 vs non-hyperuricemia group and P = 0.073 vs untreated group).

Conclusion: Hyperuricemia was associated with an unfavorable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients.
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http://dx.doi.org/10.1002/clc.23197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6671780PMC
August 2019

Hypoalbuminemia is a frequent marker of increased mortality in cardiogenic shock.

PLoS One 2019 16;14(5):e0217006. Epub 2019 May 16.

Cardiology, University of Helsinki and Department of Cardiology, Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland.

Introduction: The prevalence of hypoalbuminemia, early changes of plasma albumin (P-Alb) levels, and their effects on mortality in cardiogenic shock are unknown.

Materials And Methods: P-Alb was measured from serial blood samples in 178 patients from a prospective multinational study on cardiogenic shock. The association of hypoalbuminemia with clinical characteristics and course of hospital stay including treatment and procedures was assessed. The primary outcome was all-cause 90-day mortality.

Results: Hypoalbuminemia (P-Alb < 34g/L) was very frequent (75%) at baseline in patients with cardiogenic shock. Patients with hypoalbuminemia had higher mortality than patients with normal albumin levels (48% vs. 23%, p = 0.004). Odds ratio for death at 90 days was 2.4 [95% CI 1.5-4.1] per 10 g/L decrease in baseline P-Alb. The association with increased mortality remained independent in regression models adjusted for clinical risk scores developed for cardiogenic shock (CardShock score adjusted odds ratio 2.0 [95% CI 1.1-3.8], IABP-SHOCK II score adjusted odds ratio 2.5 [95%CI 1.2-5.0]) and variables associated with hypoalbuminemia at baseline (adjusted odds ratio 2.9 [95%CI 1.2-7.1]). In serial measurements, albumin levels decreased at a similar rate between 0h and 72h in both survivors and nonsurvivors (ΔP-Alb -4.6 g/L vs. 5.4 g/L, p = 0.5). While the decrease was higher for patients with normal P-Alb at baseline (p<0.001 compared to patients with hypoalbuminemia at baseline), the rate of albumin decrease was not associated with outcome.

Conclusions: Hypoalbuminemia was a frequent finding early in cardiogenic shock, and P-Alb levels decreased during hospital stay. Low P-Alb at baseline was associated with mortality independently of other previously described risk factors. Thus, plasma albumin measurement should be part of the initial evaluation in patients with cardiogenic shock.

Trial Registration: NCT01374867 at ClinicalTrials.gov.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217006PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522037PMC
February 2020

Serum Lactate and A Relative Change in Lactate as Predictors of Mortality in Patients With Cardiogenic Shock - Results from the Cardshock Study.

Shock 2020 01;53(1):43-49

Department of Cardiology, University Hospital Copenhagen, Rigshospitalet, Denmark.

Introduction: Cardiogenic shock complicating acute myocardial infarction has a very high mortality. Our present study focuses on serial measurement of lactate during admission due to cardiogenic shock and the prognostic effect of lactate and a relative change in lactate in patients after admission and the institution of intensive care treatment.

Methods And Results: This is a secondary analysis of the CardShock study. Data on lactate at baseline were available on 217 of 219 patients.In the study population, the median baseline lactate was 2.8 mmol/L (min-max range, 0.5-23.1 mmol/L).At admission, lactate was predictive of 30-day mortality with an adjusted Hazard ratio (HR) of 1.20 mmol/L (95% confidence interval, CI 1.14-1.27). Within the first 24 h of admission, baseline lactate remained predictive of 30-day mortality. Lactate at 6 h had a HR of 1.14 (95% CI 1.06-1.24) and corresponding values at 12 and 24 h had a HR of 1.10 (1.04-1.17), and of HR 1.19 (95% CI 1.07-1.32), respectively. A 50% reduction in lactate within 6 h resulted in a HR of 0.82 (95% CI 0.72-0.94). Corresponding hazard ratios at 12 and 24 h, were 0.87 (95% CI 0.76-0.98) and 0.74 (95% CI 0.60-0.91), respectively.

Conclusion: The main findings of the present study are that baseline lactate is a powerful predictor of 30-day mortality, lactate at 6, 12, and 24 h after admission are predictors of 30-day mortality, and a relative change in lactate is a significant predictor of survival within the first 24 h after instituting intensive care treatment adding information beyond the information from baseline values.
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http://dx.doi.org/10.1097/SHK.0000000000001353DOI Listing
January 2020

Prognostic value of NT-proBNP added to clinical parameters to predict two-year prognosis of chronic heart failure patients with mid-range and reduced ejection fraction - A report from FAR NHL prospective registry.

PLoS One 2019 26;14(3):e0214363. Epub 2019 Mar 26.

Department of Cardiology, University Hospital Brno, Brno, Czech Republic.

Background: According to guidelines, the prognosis of patients with chronic heart failure can be predicted by determining the levels of natriuretic peptides, the NYHA classification and comorbidities. The aim our work was to develop a prognostic score in chronic heart failure patients that would take account of patients' comorbidities, NYHA and NT-proBNP levels.

Methods And Results: A total of 1,088 patients with chronic heart failure with reduced ejection fraction (HFrEF) (LVEF<40%) and mid-range EF (HFmrEF) (LVEF 40-49%) were enrolled consecutively. Two-year all-cause mortality, heart transplantation and/or LVAD implantation were defined as the primary endpoint (EP). The occurrence of EP was 14.9% and grew with higher NYHA, namely 4.9% (NYHA I), 11.4% (NYHA II) and 27.8% (NYHA III-IV) (p<0.001). The occurrence of EP was 3%, 10% and 15-37% in patients with NT-proBNP levels ≤125 ng/L, 126-1000 ng/L and >1000 ng/L respectively. Discrimination abilities of NYHA and NT-proBNP were AUC 0.670 (p<0.001) and AUC 0.722 (p<0.001) respectively. The predictive value of the developed clinical model, which took account of older age, advanced heart failure (NYHA III+IV), anaemia, hyponatraemia, hyperuricaemia and being on a higher dose of furosemide (>40 mg daily) (AUC 0.773; p<0.001) was increased by adding the NT-proBNP level (AUC 0.790).

Conclusion: The use of prediction models in patients with chronic heart failure, namely those taking account of natriuretic peptides, should become a standard in routine clinical practice. It might contribute to a better identification of a high-risk group of patients in which more intense treatment needs to be considered, such as heart transplantation or LVAD implantation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214363PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435170PMC
December 2019

Prescription and dosage of RAAS inhibitors in patients with chronic heart failure in the FAR NHL registry.

Vnitr Lek Winter 2019;65(1):13-14

Background: Congestive heart failure with reduced ejection fraction is a common clinical condition with a serious prognosis. Treatment focuses on improving the symptoms and preventing the progression of the disease. First-line therapy include angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs).

Methods: These data come from the FAR NHL registry (FARmacology and NeuroHumoraL activation). This is a multicenter database of patients with stable systolic heart failure (EF < 50 %) collected between November 2014 and November 2015.

Results: A population of 1 100 patients was evaluated, the mean age was 65 years, 80.8 % were male. The etiology of heart failure was ischemic heart disease (49.7 %), dilated cardiomyopathy (41.7 %) and other (8.6 %). The total prescription of ACEI/ARB was 88.4 %, the most commonly prescribed ACEI were ramipril and perindopril, ARB was losartan. The prescription of ACEI/ARBs decreased with the severity of the disease according to NYHA classification (all 88.4 %, NYHA I 95.2 %, NYHA II 89.0 %, NYHA III-IV 83.5 %, p < 0.001). 129 subjects (11.6 %) were not treated by ACEI/ARBs at all. The target dose of ACEI/ARB, as it is recommended in the ESC Guidelines, was admissioned to only 13.5 % of patients. The dose was decreasing with the severity of disease evaluated by NYHA, NT-proBNP value, systolic blood pressure and renal functions.

Conclusions: These data show the tendency of pharmacological prescription of RAAS blockers (including doses), which reflects not only the severity of heart failure but also renal functions and blood pressure and points to possible reserves in up-titration of the target dose. Key words: angiotensin-converting enzyme inhibitors - angiotensin receptor blockers - FAR NHL - heart failure - pharmacotherapy - registry - target dose.
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July 2019

Current Use and Impact on 30-Day Mortality of Pulmonary Artery Catheter in Cardiogenic Shock Patients: Results From the CardShock Study.

J Intensive Care Med 2020 Dec 7;35(12):1426-1433. Epub 2019 Feb 7.

Critical Care Department, Hospital Sant Joan Despi Moisès Broggi, Consorci Sanitari Integral, University of Barcelona, Barcelona, Spain.

Background: Cardiogenic shock (CS) is the most life-threatening manifestation of acute heart failure. Its complexity and high in-hospital mortality may justify the need for invasive monitoring with a pulmonary artery catheter (PAC).

Methods: Patients with CS included in the CardShock Study, an observational, prospective, multicenter, European registry, were analyzed, aiming to describe the real-world use of PAC, evaluate its impact on 30-day mortality, and the ability of different hemodynamic parameters to predict outcomes.

Results: Pulmonary artery catheter was used in 82 (37.4%) of the 219 patients. Cardiogenic shock patients who managed with a PAC received more frequently treatment with inotropes and vasopressors, mechanical ventilation, renal replacement therapy, and mechanical assist devices ( < .01). Overall 30-day mortality was 36.5%. Pulmonary artery catheter use did not affect mortality even after propensity score matching analysis (hazard ratio = 1.17 [0.59-2.32], = .66). Cardiac index, cardiac power index (CPI), and stroke volume index (SVI) showed the highest areas under the curve for 30-day mortality (ranging from 0.752-0.803) and allowed for a significant net reclassification improvement of 0.467 (0.083-1.180), 0.700 (0.185-1.282), 0.683 (0.168-1.141), respectively, when added to the CardShock risk score.

Conclusions: In our contemporary cohort of CS, over one-third of patients were managed with a PAC. Pulmonary artery catheter use was associated with a more aggressive treatment strategy. Nevertheless, PAC use was not associated with 30-day mortality. Cardiac index, CPI, and SVI were the strongest 30-day mortality predictors on top of the previously validated CardShock risk score.
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http://dx.doi.org/10.1177/0885066619828959DOI Listing
December 2020

Renal Functions and Prognosis Stratification in Chronic Heart Failure Patients and the Importance of Neutrophil Gelatinase-Associated Lipocalin.

Kidney Blood Press Res 2018 7;43(6):1865-1877. Epub 2018 Dec 7.

Department of Internal Cardiology Medicine, Faculty Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Background/aims: The rate of incidence and prevalence of acute kidney injury is increasing due to an increased number of patients with heart failure. Therefore it is very pertinent to early detect the level of renal injuries and to make necessary heart failure predictions. Thus the aim of this study is to determine renal functions and prognosis stratification in chronic heart failure patients and importance of Neutrophil Gelatinase-Associated Lipocalin (NGAL), an early diagnostic marker of acute kidney injury, as well as stratification of cardiovascular risk in heart failure patients.

Methods: Data including age, gender, comorbidities and medical history of outpatients and hospitalized patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry comprising three Cardiological Centers in the Czech Republic were collected between 1st October 2014 and 30th November 2015. One-year follow-up data were collected in November 2016 in such a way that all patients had at least one-year data from the time of recruitment, but up to two years to the time of follow-up. One-year data were used for the whole set of patients while data up to 24 months were used with Kaplan-Meier's survival curves to analyse the patients' survival data. Blood samples were collected from the patients and basic parameters were evaluated in order to analyse Neutrophil gelatinase-associated lipocalin (NGAL) and plasma levels of N-terminal pro-brain natriuretic peptide (NT-ProBNP) using Lipocalin-2/NGAL Human ELISA kit (Bio Vendor, Czechia) and the Cobas E411 NT-proBNP Immunoassay kit (Roche Diagnostics, Indianapolis, IN, USA) respectively. Statistical analysis was further carried out to explain the level of significance of the evaluated parameters using Spearman Correlation, Mann Whitney or Kruskal-Wallis test and log-rank test.

Results: Out of 547 patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry with available data on hospitalizations, mortality, biomarkers and one-year follow-up that were recorded, there were 439 males (80.3%) with a median age of 66 years. At least one-month stable patients with left ventricle ejection fraction (LV EF) under 50% were recorded. The etiology of heart failure was ischemic heart disease in 54%, dilated cardiomyopathy in 40% and others in 6%. 69% patients were in New York Heart Association functional class II. There were 76 events (13.9%; all-cause mortality, acute heart failure hospitalization, left ventricle assist device implantation and orthotopic heart transplant) in the first 365 days of follow-up. The area under the receiver operating characteristic curve was higher for NT-proBNP (0.77) than the creatinine (0.57), NGAL (0.55) or creatinine clearance (0.54). In multivariable analyses, NT-proBNP (P= 0.001) and NGAL (P = 0.004) were significant predictors of events. Subjects with NT-proBNP and NGAL above the cut off value (NT-proBNP 1,121 pg/ml, NGAL 80 ng/ml) survived without any event in 55.7%, subjects with NT-proBNP and NGAL under the cut off value survived without any event in 90.5%, after two years (P = 0.001).

Conclusion: The findings of the study showed that NGAL associated with NT-proBNP was a stronger predictor of the primary endpoint than NGAL or NT-proBNP alone. The level of NGAL was rising in hypertension, ischemia, anemia, hypoalbuminemia, diabetes or arrhythmias.
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http://dx.doi.org/10.1159/000495819DOI Listing
February 2019

Arrhythmias and conductance disturbances and heart failure.

Vnitr Lek Fall 2018;64(9):874-877

Arrhythmias and conductance disturbances and heart failure have a close relation. Arrhythmias are serious complication, but also etiology of heart failure. So it is not clear, what is the cause and what is a consequence. Atrial fibrillation is a frequent cause, ventricular arrhythmias a frequent consequence and ventricular fibrillation a frequent cause of death in patients with heart failure. Overview are about frequent arrhythmias as well as their therapy with regard to left ventricular dysfunction. Key words: arrhythmias - heart failure.
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April 2019

Comorbidities in heart failure.

Vnitr Lek Fall 2018;64(9):867-873

Comorbidities are important parts of care in patients with heart failure. Comorbidities, as well as their treatments, directly influence the course of heart failure. We present the most comorbidities a their therapy with regard to left ventricular dysfunction. Key words: comorbidities - heart failure.
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April 2019

The heart transplantation.

Vnitr Lek Fall 2018;64(9):860-866

The article reviews history, indication and follow-up after heart transplantation, including the mechanical assist devices. Various complications of posttransplant follow-up are mentioned, e.g. rejection, infection, vasculopathy, meta-bolic disorders, hypertension or malignities. Pharmacotherapy used for immunosuppression is discussed. Heart transplantation improves the prognosis of patients with previous heart failure and also their quality of life. Key words: heart transplantation - immunosuppression - mechanical assist devices - rejection - terminal heart failure.
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April 2019
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