The effect of kidney function on guideline-directed medical therapy implementation and prognosis in heart failure with reduced ejection fraction.

BACKGROUND: Kidney dysfunction (KD) is a main limiting factor of applying guideline-directed medical therapy (GDMT) and reaching the recommended target doses (TD) in heart failure (HF) with reduced ejection fraction (HFrEF). HYPOTHESIS: We aimed to assess the success of optimization, long-term applicability, and adherence of neurohormonal antagonist triple therapy (TT:RASi [ACEi/ARB/ARNI] + ßB + MRA) according to the KD after a HF hospitalization and to investigate its impact on prognosis. METHODS: The data of 247 real-world, consecutive patients were analyzed who were hospitalized in 2019-2021 for HFrEF and then were followed-up for 1 year. The application and the ratio of reached TD of TT at hospital discharge and at 1 year were assessed comparing KD categories (eGFR: ≥90, 60-89, 45-59, 30-44, <30 mL/min/1.73 m2 ). Moreover, 1-year all-cause mortality and rehospitalization rates in KD subgroups were investigated. RESULTS: Majority of the patients received TT at hospital discharge (77%) and at 1 year (73%). More severe KD led to a lower application ratio (p < .05) of TT (92%, 88%, 80%, 73%, 31%) at discharge and at 1 year (81%, 76%, 76%, 68%, 40%). Patients with more severe KD were less likely (p < .05) to receive TD of MRA (81%, 68%, 78%, 61%, 52%) at discharge and a RASi (53%, 49%, 45%, 21%, 27%) at 1 year. One-year all-cause mortality (14%, 15%, 16%, 33%, 48%, p < .001), the ratio of all-cause rehospitalizations (30%, 35%, 40%, 43%, 52%, p = .028), and rehospitalizations for HF (8%, 13%, 18%, 20%, 38%, p = .001) were significantly higher in more severe KD categories. CONCLUSIONS: KD unfavorably affects the application of TT in HFrEF, however poorer mortality and rehospitalization rates among them highlight the role of the conscious implementation and up-titration of GDMT.

The Impact of Specialised Heart Failure Outpatient Care on the Long-Term Application of Guideline-Directed Medical Therapy and on Prognosis in Heart Failure with Reduced Ejection Fraction.

(1) Background: Besides the use of guideline-directed medical therapy (GDMT), multidisciplinary heart failure (HF) outpatient care (HFOC) is of strategic importance in HFrEF. (2) Methods: Data from 257 hospitalised HFrEF patients between 2019 and 2021 were retrospectively analysed. Application and target doses of GDMT were compared between HFOC and non-HFOC patients at discharge and at 1 year. 1-year all-cause mortality (ACM) and rehospitalisation (ACH) rates were compared using the Cox proportional hazard model. The effect of HFOC on GDMT and on prognosis after propensity score matching (PSM) of 168 patients and the independent predictors of 1-year ACM and ACH were also evaluated. (3) Results: At 1 year, the application of RASi, MRA and triple therapy (TT: RASi + ßB + MRA) was higher (p < 0.05) in the HFOC group, as was the proportion of target doses of ARNI, ßB, MRA and TT. After PSM, the composite of 1-year ACM or ACH was more favourable with HFOC (propensity-adjusted HR = 0.625, 95% CI = 0.401-0.974, p = 0.038). Independent predictors of 1-year ACM were age, systolic blood pressure, application of TT and HFOC, while 1-year ACH was influenced by the application of TT. (4) Conclusions: HFOC may positively impact GDMT use and prognosis in HFrEF even within the first year of its initiation.

Incidence and predictors of heart failure with improved ejection fraction category in a HFrEF patient population.

AIMS: The aim of the study was to assess the incidence and predictive factors of the development of heart failure with improved ejection fraction (HFimpEF) category during a 1 year follow-up period in a heart failure with reduced ejection fraction (HFrEF) patient population managed in a heart failure outpatient clinic. METHODS AND RESULTS: The study evaluated data from patients enrolled in the Hungarian Heart Failure Registry (HHFR). The incidence and predictive factors of the development of the HFimpEF category after 1 year follow-up were assessed in the group of patients who had HFrEF at baseline. We evaluated the incidence and predictors of the development of HFimpEF after a 1 year follow-up in relation to time since diagnosis of HFrEF in patients diagnosed within 3 months, between 3 months and 1 year, and beyond 1 year. The predictive factors of the development of HFimpEF were analysed using univariate and multivariate logistic regression analysis. Of the 833 HFrEF patients enrolled in the HHFR, the development of HFimpEF was observed in 162 patients (19.5%) during 1 year follow-up. In the whole patient population, independent predictors of the development of HFimpEF were female gender [odds ratio (OR): 1.73; 95% confidence interval (CI): 1.01-2.96; P < 0.05], non-ischaemic aetiology (OR: 1.95; 95% CI: 1.15-3.30; P < 0.05), and left ventricular end-diastolic diameter (LVEDD) <60 mm (OR: 2.04; 95% CI: 1.18-3.51; P < 0.05). The 1 year incidence of HFimpEF decreased in relation to time since diagnosis of HFrEF. The incidence of HFimpEF was 27.1% in patients diagnosed within 3 months, 18.4% in patients diagnosed between 3 months and 1 year, and 12.2% in patients diagnosed beyond 1 year. Non-ischaemic aetiology (OR: 4.76; 95% CI: 1.83-12.4; P < 0.01) and QRS width (OR: 0.81; 95% CI: 0.71-0.94; P < 0.01) for patients diagnosed within 3 months, LVEDD (OR: 0.54; 95% CI: 0.32-0.90; P < 0.05) and left atrial diameter ≤45 mm (OR: 5.44; 95% CI: 1.45-20.4; P < 0.05) for patients diagnosed between 3 months and 1 year, and LVEDD < 67 mm (OR: 2.71; 95% CI: 1.07-6.88; P < 0.05) for patients diagnosed beyond 1 year were found to be independent predictive factors. CONCLUSIONS: In our study, in this HFrEF patient population managed in a heart failure outpatient clinic, the 1 year incidence of HFimpEF was found to be ~20%. The 1 year incidence of HFimpEF decreased in relation to time since diagnosis of HFrEF. The most important predictors of the development of HFimpEF were female sex, non-ischaemic aetiology, narrower QRS width, and smaller diameter of the left ventricle and left atrium.

[The effect of kidney function on the optimization of medical therapy and on mortality in heart failure with reduced ejection fraction]. / A vesefunkció hatása a gyógyszeres terápia optimalizálására és a mortalitásra csökkent ejekciós frakciójú szívelégtelenségben.

INTRODUCTION: Renal dysfunction is a main limiting factor of applying and up-titrating guideline-directed medical therapy (GDMT) among patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVE: Our retrospective monocentric observational study aimed to analyse the application ratio of combined neurohormonal antagonist therapy (RASi: ACEI/ARB/ARNI + ßB + MRA) and 12-month all-cause mortality differences in terms of renal dysfunction among HFrEF patients hospitalized for heart failure. METHOD: We retrospectively analysed the cohort of consecutive HFrEF patients, hospitalized at the Heart Failure Unit of our tertiary cardiological centre in 2019-2021. The application ratio of discharge triple therapy (TT) in five groups established on admission eGFR parameters, representing severity of renal dysfunction (eGFR≥90, eGFR = 60-89, eGFR = 45-59, eGFR = 30-44, eGFR<30 ml/min/1.73 m2) was investigated with chi-square test, while 12-month mortality differences were analysed with Kaplan-Meier method and log-rank test. RESULTS: 257 patients were included. Median eGFR was 57 (39-75) ml/min/1.73 m2, 54% of patients had eGFR<60 ml/min/1.73 m2. The proportion of patients in eGFR≥90, 60-89, 45-59, 30-44, <30 ml/min/1.73 m2 subgroups was 12%, 34%, 18%, 21%, 15%, respectively. 2% of patients were on dialysis. Even though the application rate of TT was notably high (77%) in the total cohort, more severe renal dysfunction led to a significantly lower implementation rate of TT (94%, 86%, 91%, 70%, 34%; p<0.0001): the application rate of RASi (100%, 98%, 96%, 89%, 50%, p<0.0001), ßB (94%, 88%, 96%, 79%, 68%; p = 0.003) and MRA therapy (97%, 99%, 98%, 94%, 82%; p = 0.001) differed significantly. 12-month all-cause mortality was 23% in the whole cohort. Mortality rates were higher in more severe renal dysfunction (3%, 15%, 22%, 31%, 46%; p<0.0001). CONCLUSION: Even though the proportion of patients on TT in the whole cohort was remarkably high, renal dysfunction led to a significantly lower application ratio of TT, associating with worse survival. Our results highlight that despite renal dysfunction the application of HFrEF cornerstone pharmacotherapy is essential. Orv Hetil. 2023; 164(35): 1387-1396.

Long-Term Efficacy and Safety of Left Atrial Appendage Closure Procedures.

The aim of the present single-center, nonrandomized, retrospective study was to assess the safety and long-term efficacy of percutaneous left atrial appendage closure (LAAC) procedures and to compare the different LAAC devices and therapeutic regimes in this respect.Medical data of 136 patients (pts) (mean age, 72.5 ± 7.6 years; score for atrial fibrillation stroke risk estimation [CHA2DS2-VASc], 4.6 ± 1.6; and score for estimation of major bleeding risk for patients on anticoagulant therapy [HAS-BLED], 2.6 ± 0.9) who underwent percutaneous LAAC procedures in Gottsegen National Cardiovascular Center from January 2010 to January 2020 were analyzed.The rates of outpatient cardiac mortality, ischemic brain event, and major bleeding were 3.8, 1, and 1.9/100 pt years, respectively. The rate of successful device deployment was 96.4%. There was one case of procedural mortality (0.7%), one case of device dislocation (0.7%), one case of ischemic stroke (0.7%), and one case of myocardial infarction (0.7%). Two cases of pericardial tamponades (1.5%) and four cases of major femoral complications (3%) occurred. Although the implantation success of different occluder types was similar, significant differences were found concerning procedural characteristics. Patients on single antiplatelet therapy (SAPT) in the first 3 months after the LAAC procedure did not suffer from stroke or embolic events.The present study confirmed the safety and effectivity of percutaneous LAAC. Robust relative stroke risk reduction and less pronounced but significant bleeding risk reduction were observed. Device implantation success was high. The perioperative complication rate was relatively low. The results of long-term observations regarding ischemic events confirmed the safety of using a simplified antithrombotic regime after LAAC in pts with high bleeding risk.

The Optimization of Guideline-Directed Medical Therapy during Hospitalization among Patients with Heart Failure with Reduced Ejection Fraction in Daily Clinical Practice.

INTRODUCTION: Hospitalization due to heart failure (HF) progression is associated with poor prognosis. This highlights the role of the implementation of guideline-directed medical therapy (GDMT) in improving the morbidity and mortality of patients with heart failure with reduced ejection fraction (HFrEF). There are limited data about the intrahospital applicability of GDMT in real-world circumstances. We aimed to assess retrospectively the use of cornerstone GDMT including RASi (ACEI/ARB/ARNI), ßB, MRA, and SGLT2i treatment in a consecutive real-world HFrEF patient population admitted with signs and symptoms of HF to the HF Unit of a Hungarian tertiary cardiac center between 2019 and 2021. The independent predictors of therapy optimization and the applicability of new HFrEF medication (ARNI, SGLT2i, vericiguat) were also investigated. METHODS: Statistical comparison of admission and discharge medication was accomplished with Fisher's exact test. The independent predictors of the introduction of triple therapy (RASi + ßB + MRA) were analyzed using univariate and multivariate logistic regression. The proportion of patients eligible for vericiguat based on the inclusion and exclusion criteria of the VICTORIA trial was also investigated, as well as the number of patients suitable for ARNI and SGLT2i, taking into account the contraindications of application contained in the ESC 2021 HF Guidelines. RESULTS: 238 patients were included. During hospitalization, the use of RASi (69% vs. 89%) (ACEI/ARBs [58% vs. 70%], ARNI [10% vs. 19%]), ßBs (69% vs. 85%), and MRAs (61% vs. 95%) increased significantly (p < 0.05) compared to at admission, and the use of SGLT2i (3% vs. 11%) also rose (p = 0.0005). The application ratio of triple (RASi + ßB + MRA; 43% vs. 77%) and quadruple (RASi + ßB + MRA + SGLT2i; 2% vs. 11%) therapy increased as well (p < 0.0001). The independent predictors of discharge application of triple therapy revealed through multivariate logistic regression analysis were age, duration of hospitalization, eGFR, NTproBNP, and presence of diabetes mellitus. Sixty-eight percent of the cohort would have been suitable for vericiguat, 83% for ARNI, and 84% for SGLT2i. CONCLUSION: High rates of application of disease-modifying drugs are achievable among hospitalized HFrEF patients in severe clinical condition; thus, awareness of the need for their initiation must be raised.

Treatment of three-vessel disease in light of the results of the FAME-3 study / A háromér-betegség kezelése a FAME-3 vizsgálat eredményeinek tükrében

Previous randomized clinical studies have shown the superiority of coronary artery bypass grafting over percutaneous coronary intervention in the treatment of severe multivessel disease mainly because of a reduced need for repeat revascularization but, in some, a mortality benefit and reduced rate of myocardial infarction were shown among those undergoing surgery. The late breaker multicentric, randomized FAME (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation)-3 study, involving 1500 patients, sought to determine whether fractional flow reserve guided percutaneous coronary intervention with implantation of new-generation drug-eluting stents was non -inferior to present-day coronary bypass surgery with respect to the composite of all-cause death, myocardial infarction, stroke and repeat revascularization at one year. The authors who were particularly active in the FAME-3 trial describe the study setting, the characteristics of the patient population, the procedures, and the results. The FAME-3 study failed to show the non-inferiority of percutaneous coronary intervention to bypass surgery in the treatment of three vessel disease using the predetermined margin. The authors present a detailed analysis of the possible reasons and some important secondary results. These include a lack of significant difference between the two arms with respect to `hard end points' and the significantly higher perioperative morbidity of the surgical group. Albeit our clinical practice should be based on the analysis of the primary end point, informing patients and shared decision making must include these secondary results when individual revascularization strategies are planned.

The Genetic Architecture of Hypertrophic Cardiomyopathy in Hungary: Analysis of 242 Patients with a Panel of 98 Genes.

Hypertrophic cardiomyopathy (HCM) is a primary disease of the myocardium most commonly caused by mutations in sarcomeric genes. We aimed to perform a nationwide large-scale genetic analysis of a previously unreported, representative HCM cohort in Hungary. A total of 242 consecutive HCM index patients (127 men, 44 ± 11 years) were studied with next generation sequencing using a custom-designed gene-panel comprising 98 cardiomyopathy-related genes. A total of 90 patients (37%) carried pathogenic/likely pathogenic (P/LP) variants. The percentage of patients with P/LP variants in genes with definitive evidence for HCM association was 93%. Most of the patients with P/LP variants had mutations in MYBPC3 (55 pts, 61%) and in MYH7 (21 pts, 23%). Double P/LP variants were present in four patients (1.7%). P/LP variants in other genes could be detected in ≤3% of patients. Of the patients without P/LP variants, 46 patients (19%) carried a variant of unknown significance. Non-HCM P/LP variants were identified in six patients (2.5%), with two in RAF1 (p.Leu633Val, p.Ser257Leu) and one in DES (p.Arg406Trp), FHL1 (p.Glu96Ter), TTN (p.Lys23480fs), and in the mitochondrial genome (m.3243A>G). Frameshift, nonsense, and splice-variants made up 82% of all P/LP MYBPC3 variants. In all the other genes, missense mutations were the dominant form of variants. The MYBPC3 p.Gln1233Ter, the MYBPC3 p.Pro955ArgfsTer95, and the MYBPC3 p.Ser593ProfsTer11 variants were identified in 12, 7, and 13 patients, respectively. These three variants made up 36% of all patients with identified P/LP variants, raising the possibility of a possible founder effect for these mutations. Similar to other HCM populations, the MYBPC3 and the MYH7 genes seemed to be the most frequently affected genes in Hungarian HCM patients. The high prevalence of three MYBPC3 mutations raises the possibility of a founder effect in our HCM cohort.

Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features.

BACKGROUND: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were available on the genotype, phenotype, and prevalence of Hungarian ATTRv patients. The aim of our study was to assess the prevalence, regional distribution, genotypes, and phenotypes of Hungarian patients with ATTRv. METHODS: With the collaboration of Hungarian regional and university centers, we identified patients diagnosed with ATTRv. We also searched prior publications for case studies of Hungarian ATTRv patients. RESULTS: 40 individuals in 23 families with ATTRv were identified within the borders of Hungary. At the time of the diagnosis, 24 of them were symptomatic. The two most common mutations were ATTRHis88Arg (nine families) and ATTRIle107Val (8 families). ATTRVal30Met was demonstrated in 2 families, and ATTRVal122del, ATTRPhe33Leu, ATTRIle84Ser, and ATTRAsp18Gly in one family each. The median age of the symptomatic patients at the time of clinical diagnosis was 65 years. The most common clinically significant organ involvement was restrictive cardiomyopathy, found in 24 patients. Polyneuropathy was diagnosed in 20 patients. A total of 19 patients showed a mixed phenotype. The leading symptom was heart failure in 8 cases (3 of them had only cardiac symptoms), polyneuropathy in 11 cases (all of them also had cardiac symptoms), and equally severe cardiac and neuropathy symptoms were present in 3 cases. Out of 24 symptomatic patients, 10 received targeted pharmacological therapy. The follow-up period ranged from 1 to 195 months. At the time of the retrospective analysis, 12 patients had already died, and 1 patient underwent heart transplantation. CONCLUSIONS: As TTR genotype influences the phenotype and clinical course of ATTRv, it is important to know the regional data. In Hungary, ATTRHis88Arg and ATTRIle107Val are the most common mutations in ATTRv, both presenting with mixed phenotype, but the median age at the time of the diagnosis is 9 years lower in patients with ATTRHis88Arg than in patients with ATTRIle107Val.

Proportion of Patients Eligible for Cardiac Contractility Modulation: Real-Life Data from a Single-Center Heart Failure Clinic.

INTRODUCTION: Based on recently published randomized controlled trials, cardiac contractility modulation (CCM) seems to be an effective device-based therapeutic option in symptomatic chronic heart failure (HF) (CHF). The aim of the current study was to estimate what proportion of patients with CHF and left ventricular ejection fraction (LVEF) <50% could be eligible for CCM based on the inclusion criteria of the FIX-HF-5C trial. METHODS: Consecutive patients referred and followed up at our HF clinic due to HF with reduced or mid-range LVEF were retrospectively assessed. After a treatment optimization period of 3-6 months, the inclusion criteria of the FIX-HF-5C trial (New York Heart Association (NYHA) class III/IV, 25% ≤ LVEF ≤45%, QRS <130 ms, and sinus rhythm) were applied to determine the number of patients eligible for CCM. RESULTS: Of the 640 patients who were involved, the proportion of highly symptomatic patients in NYHA class III/IV decreased from 77.0% (n = 493) at baseline to 18.6% (n = 119) after the treatment optimization period (p < 0.001). Mean LVEF increased significantly from 29.0 ± 7.9% to 36.3 ± 9.9% (p < 0.001), while the proportion of patients with 25% ≤ LVEF ≤45% increased from 69.7% (n = 446) to 73.3% (n = 469) (p < 0.001). QRS duration was below 130 ms in 63.1% of patients, while 30.0% of patients had persistent or permanent atrial fibrillation. We found that the eligibility criteria for CCM therapy based on the FIX-HF-5C study were fulfilled for 23.0% (n = 147) of patients at baseline and 5.2% (n = 33) after treatment optimization. CONCLUSION: This single-center cohort study showed that 5% of patients with CHF and impaired LVEF immediately after treatment optimization fulfilled the inclusion criteria of the FIX-HF-5C study and would be candidates for CCM.

The impact of serum concentration-guided digoxin therapy on mortality of heart failure patients: A long-term follow-up, propensity-matched cohort study.

BACKGROUND: Recently published studies suggested that digoxin may increase mortality in heart failure with reduced ejection fraction (HFrEF). However, in the vast majority of former trials serum digoxin concentration (SDC) was not measured and therapy was not SDC-guided. AIM: To assess the impact of SDC-guided digoxin therapy on mortality in HFrEF patients. METHODS: Data of 580 HFrEF patients were retrospectively analyzed. In patients on digoxin, SDC was measured every 3 months and digoxin dosage was SDC-guided (target SDC: 0.5-0.9 ng/mL). All-cause mortality of digoxin users and nonusers was compared after propensity score matching (PSM). RESULTS: After 7.1 ± 4.7 years follow-up period (FUP) all-cause mortality of digoxin users (n = 180) was significantly higher than nonusers (n = 297) (propensity-adjusted HR = 1.430; 95% CI = 1.134-1.804; P = .003). Patients having SDC of 0.9 to 1.1 ng/mL (n = 60) or > 1.1 ng/mL (n = 44) at any time during the FUP had an increased risk of all-cause mortality (HR = 1.750; 95% CI = 1.257-2.436, P = .001 and HR = 1.687; 95% CI = 1.153-2.466, P = .007), while patients having a maximal SDC < 0.9 ng/mL (n = 76) had similar mortality risk (HR = 1.139; 95% CI = 0.827-1.570, P = .426), compared to digoxin nonusers. CONCLUSIONS: According to our propensity-matched analysis, SDC-guided digoxin therapy was associated with increased all-cause mortality in optimally treated HFrEF patients, especially with SDC ≥0.9 ng/mL. These results reinforce the expert opinion that digoxin in HFrEF can only be used among carefully selected patients with close SDC monitoring.

Association of Remote Monitoring With Survival in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy: Retrospective Observational Study.

BACKGROUND: Remote monitoring is an established, guideline-recommended technology with unequivocal clinical benefits; however, its ability to improve survival is contradictory. OBJECTIVE: The aim of our study was to investigate the effects of remote monitoring on mortality in an optimally treated heart failure patient population undergoing cardiac resynchronization defibrillator therapy (CRT-D) implantation in a large-volume tertiary referral center. METHODS: The population of this single-center, retrospective, observational study included 231 consecutive patients receiving CRT-D devices in the Medical Centre of the Hungarian Defence Forces (Budapest, Hungary) from January 2011 to June 2016. Clinical outcomes were compared between patients on remote monitoring and conventional follow-up. RESULTS: The mean follow-up time was 28.4 (SD 18.1) months. Patients on remote monitoring were more likely to have atrial fibrillation, received heart failure management at our dedicated heart failure outpatient clinic more often, and have a slightly lower functional capacity. Crude all-cause mortality of remote-monitored patients was significantly lower compared with patients followed conventionally (hazard ratio [HR] 0.368, 95% CI 0.186-0.727, P=.004). The survival benefit remained statistically significant after adjustment for important baseline parameters (adjusted HR 0.361, 95% CI 0.181-0.722, P=.004). CONCLUSIONS: In this single-center, retrospective study of optimally treated heart failure patients undergoing CRT-D implantation, the use of remote monitoring systems was associated with a significantly better survival rate.

Risk of cardiac arrhythmias after electrical accident: a single-center study of 480 patients.

OBJECTIVE: Patients with electrical injury are considered to be at high risk of cardiac arrhythmias. Due to the small number of studies, there is no widely accepted guideline regarding the risk assessment and management of arrhythmic complications after electrical accident (EA). Our retrospective observational study was designed to determine the prevalence of ECG abnormalities and cardiac arrhythmias after EA, to evaluate the predictive value of cardiac biomarkers for this condition and to assess in-hospital and 30-day mortality. METHODS: Consecutive patients presenting after EA at the emergency department of our institution between 2011 and 2016 were involved in the current analysis. ECG abnormalities and arrhythmias were analyzed at admission and during ECG monitoring. Levels of cardiac troponin I, CK and CK-MB were also collected. In-hospital and 30-day mortality data were obtained from hospital records and from the national insurance database. RESULTS: Of the 480 patients included, 184 (38.3%) had suffered a workplace accident. The majority of patients (96.2%) had incurred a low-voltage injury (< 1000 V). One hundred and four (21.7%) patients had a transthoracic electrical injury while 13 (2.7%) patients reported loss of consciousness. The most frequent ECG disorders at admission were sinus bradycardia (< 60 bpm, n = 50, 10.4%) and sinus tachycardia (> 100 bpm, n = 21, 4.4%). Other detected arrhythmias were as follows: newly diagnosed atrial fibrillation (n = 1); frequent multifocal atrial premature complexes (n = 1); sinus arrest with atrial escape rhythm (n = 2); ventricular fibrillation terminated out of hospital (n = 1); ventricular bigeminy (n = 1); and repetitive nonsustained ventricular tachycardia (n = 1). ECG monitoring was performed in 182 (37.9%) patients for 12.7 ± 7.1 h at the ED. Except for one case with regular supraventricular tachycardia terminated via vagal maneuver and one other case with paroxysmal atrial fibrillation, no clinically relevant arrhythmias were detected during the ECG monitoring. Cardiac troponin I was measured in 354 (73.8%) cases at 4.6 ± 4.3 h after the EA and was significantly elevated only in one resuscitated patient. CK elevation was frequent, but CK-MB was under 5% in all patients. Both in-hospital and 30-day mortality were 0%. CONCLUSIONS: Most of cardiac arrhythmias in patients presenting after EA can be diagnosed by an ECG on admission, thus routine ECG monitoring appears to be unnecessary. In our patient cohort cardiac troponin I and CK-MB were not useful in risk assessment after EA. Late-onset malignant arrhythmias were not observed.

Cardiac Index by Transthoracic Echocardiography (CITE) study.

AIMS: Left ventricular ejection fraction (LVEF) is the most frequently used parameter in the assessment of heart failure (HF). Cardiac index (CI) is considered a potential alternative to LVEF despite limited evidence. We aimed to assess and compare the predictive accuracy of LVEF and echocardiographically-assessed CI in HF patients. METHODS AND RESULTS: A single-centre, retrospective cohort study was conducted in patients hospitalized for acute HF from 2010-2016. Cox proportional hazard models including either LVEF or CI were created to predict all cause death, cardiovascular (CV) death, or first HF-readmission. Of 334 patients included in the analysis, 58.7% exhibited HF with reduced LVEF (HFrEF). Left ventricular ejection fraction did not show correlation with any endpoint, while CI was predictive of HF-readmission in the entire cohort. Both the LVEF-based and CI-based models demonstrated moderate discriminative accuracy when predicting all-cause death, CV death, or HF-readmission. Left ventricular ejection fraction proved to be an independent predictor of CV mortality in HFrEF-patients, while CI was predictive of HF-readmission in the non-HFrEF group. CONCLUSIONS: Left ventricular ejection fraction seemed to be associated more closely with disease severity in HFrEF, and CI in the non-HFrEF group, in this real-life cohort of elderly HF patients. The LVEF-based and CI-based predictive models have clinically similar predictive accuracy for mortality and HF-readmission, thus CI may be a potential alternative to LVEF in the assessment of left ventricular function. Cardiac index may be an important new tool in the assessment of HF patients with midrange or preserved LVEF.

Unrecognised cardiovascular disease in type 2 diabetes: is it time to act earlier?

Cardiovascular disease (CVD) is the most significant prognostic factor in individuals with type 2 diabetes (T2D). However, a significant number of individuals may develop CVD that does not present with the classic angina-related or heart failure symptoms. In these cases, CVD may seem to be 'silent' or 'asymptomatic', but may be more accurately characterised as unrecognised diabetic cardiac impairment. An initial step to raise awareness of unrecognised CVD in individuals with T2D would be to reach a consensus regarding the terminology used to describe this phenomenon. By standardising the terminologies, and agreeing on the implementation of an efficient screening program, it is anticipated that patients will receive an earlier diagnosis and appropriate and timely treatment. Given the availability of anti-diabetic medications that have been shown to concomitantly reduce CV risk and mortality, it is imperative to improve early identification and initiate treatment as soon as possible in order to enable as many patients with T2D as possible to benefit.

[Perioperative use of levosimendan in cardiac surgery. Hungarian recommendation]. / A levoszimendán perioperatív alkalmazása a szívsebészetben. Magyar ajánlás.

Low output syndrome significantly increases morbidity and mortality of cardiac surgery and lengthens the durations of intensive care unit and hospital stays. Its treatment by catecholamines can lead to undesirable systemic and cardiac complications. Levosimendan is a calcium sensitiser and adenosine triphosphate (ATP)-sensitive potassium channel (IK,ATP) opener agent. Due to these effects, it improves myocardium performance, does not influence adversely the balance between O2 supply and demand, and possesses cardioprotective and organ protective properties as well. Based on the scientific literature and experts' opinions, a European recommendation was published on the perioperative use of levosimendan in cardiac surgery in 2015. Along this line, and also taking into consideration cardiac surgeon, anaesthesiologist and cardiologist representatives of the seven Hungarian heart centres and the children heart centre, the Hungarian recommendation has been formulated that is based on two pillars: literature evidence and Hungarian expert opinions. The reviewed fields are: coronary and valvular surgery, assist device implantation, heart transplantation both in adult and pediatric cardiologic practice. Orv Hetil. 2018; 159(22): 870-877.

Matrix Metalloproteinase-2 Impairs Homing of Intracoronary Delivered Mesenchymal Stem Cells in a Porcine Reperfused Myocardial Infarction: Comparison With Intramyocardial Cell Delivery.

BACKGROUND: Intracoronary (IC) injection of mesenchymal stem cells (MSCs) results in a prompt decrease of absolute myocardial blood flow (AMF) with late and incomplete recovery of myocardial tissue perfusion. Here, we investigated the effect of decreased AMF on oxidative stress marker matrix metalloproteinase-2 (MMP-2) and its influence on the fate and homing and paracrine character of MSCs after IC or intramyocardial cell delivery in a closed-chest reperfused myocardial infarction (MI) model in pigs. METHODS: Porcine MSCs were transiently transfected with Ad-Luc and Ad-green fluorescent protein (GFP). One week after MI, the GFP-Luc-MSCs were injected either IC (group IC, 11.00 ± 1.07 × 106) or intramyocardially (group IM, 9.88 ± 1.44 × 106). AMF was measured before, immediately after, and 24 h post GFP-Luc-MSC delivery. In vitro bioluminescence signal was used to identify tissue samples containing GFP-Luc-MSCs. Myocardial tissue MMP-2 and CXCR4 receptor expression (index of homing signal) were measured in bioluminescence positive and negative infarcted and border, and non-ischemic myocardial areas 1-day post cell transfer. At 7-day follow-up, myocardial homing (cadherin, CXCR4, and stromal derived factor-1alpha) and angiogenic [fibroblast growth factor 2 (FGF2) and VEGF] were quantified by ELISA of homogenized myocardial tissues from the bioluminescence positive and negative infarcted and border, and non-ischemic myocardium. Biodistribution of the implanted cells was quantified by using Luciferase assay and confirmed by fluorescence immunochemistry. Global left ventricular ejection fraction (LVEF) was measured at baseline and 1-month post cell therapy using magnet resonance image. RESULTS: AMF decreased immediately after IC cell delivery, while no change in tissue perfusion was found in the IM group (42.6 ± 11.7 vs. 56.9 ± 16.7 ml/min, p = 0.018). IC delivery led to a significant increase in myocardial MMP-2 64 kD expression (448 ± 88 vs. 315 ± 54 intensity × mm2, p = 0.021), and decreased expression of CXCR4 (592 ± 50 vs. 714 ± 54 pg/tissue/ml, p = 0.006), with significant exponential decay between MMP-2 and CXCR4 (r = 0.679, p < 0.001). FGF2 and VEGF of the bioluminescence infarcted and border zone of homogenized tissues were significantly elevated in the IM goups as compared to IC group. LVEF increase was significantly higher in IM group (0.8 ± 8.4 vs 5.3 ± 5.2%, p = 0.046) at the 1-month follow up. CONCLUSION: Intracoronary stem cell delivery decreased AMF, with consequent increase in myocardial expression of MMP-2 and reduced CXCR4 expression with lower level of myocardial homing and angiogenic factor release as compared to IM cell delivery.

Characteristics, treatments and 1-year prognosis of hospitalized and ambulatory heart failure patients with chronic obstructive pulmonary disease in the European Society of Cardiology Heart Failure Long-Term Registry.

AIMS: To describe the characteristics and assess the 1-year outcomes of hospitalized (HHF) and chronic (CHF) heart failure patients with chronic obstructive pulmonary disease (COPD) enrolled in a large European registry between May 2011 and April 2013. METHODS AND RESULTS: Overall, 1334/6920 (19.3%) HHF patients and 1322/9409 (14.1%) CHF patients were diagnosed with COPD. In both groups, patients with COPD were older, more frequently men, had a worse clinical presentation and a higher prevalence of co-morbidities. In HHF, the increase in the use of heart failure (HF) medications at hospital discharge was greater in non-COPD than in COPD for angiotensin-converting enzyme inhibitors (+13.7% vs. +7.2%), beta-blockers (+20.6% vs. +11.8%) and mineralocorticoid receptor antagonists (+20.9% vs. +17.3%), thus widening the gap in HF treatment already existing between the two groups at admission. In CHF patients, there was a similar increase in the use of these medications after enrollment visit in the two groups, leaving a significant difference of 8.2% for beta-blockers in favour of non-COPD patients (89.8% vs. 81.6%, P < 0.001). At 1-year follow-up, the hazard ratios for COPD in multivariable analysis confirmed its independent association with hospitalizations both in HHF [all-cause: 1.16 (1.04-1.29), for HF: 1.22 (1.05-1.42)] and CHF patients [all-cause: 1.26 (1.13-1.41), for HF: 1.37 (1.17-1.60)]. The association between COPD and all-cause mortality was not confirmed in both groups after adjustments. CONCLUSIONS: COPD frequently coexists in HHF and CHF, worsens the clinical course of the disease, and significantly impacts its therapeutic management and prognosis. The matter should deserve greater attention from the cardiology community.

Combination of Hydralazine and Isosorbide-Dinitrate in the Treatment of Patients with Heart Failure with Reduced Ejection Fraction.

The use of direct acting vasodilators (the combination of hydralazine and isosorbide dinitrate -Hy+ISDN-) in heart failure with reduced ejection fraction (HFrEF) is supported by evidence, but rarely used.However, treatment with Hy+ISDN is guideline-recommended for HFrEF patients who cannot receive either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers due to intolerance or contraindication, and in self-identified African-American HFrEF patients who are symptomatic despite optimal neurohumoral therapy.The Hy+ISDN combination has arterial and venous vasodilating properties. It can decrease preload and afterload, decrease left ventricular end-diastolic diameter and the volume of mitral regurgitation, reduce left atrial and left ventricular wall tension, decrease pulmonary artery pressure and pulmonary arterial wedge pressure, increase stroke volume, and improve left ventricular ejection fraction, as well as induce left ventricular reverse remodelling. Furthermore, Hy+ISDN combination has antioxidant property, it affects endothelial dysfunction beneficially and improves NO bioavailability. Because of these benefits, this combination can improve the signs and symptoms of heart failure, exercise capacity and quality of life, and, most importantly, reduce morbidity and mortality in well-defined subgroups of HFrEF patients.Accordingly, this therapeutic option can in many cases play an essential role in the treatment of HFrEF.