Machine learning-based detection of sleep-disordered breathing in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is often concomitant with sleep-disordered breathing (SDB), which can cause adverse cardiovascular events. Although an appropriate approach to SDB prevents cardiac remodelling, detection of concomitant SDB in patients with HCM remains suboptimal. Thus, we aimed to develop a machine learning-based discriminant model for SDB in HCM. METHODS: In the present multicentre study, we consecutively registered patients with HCM and performed nocturnal oximetry. The outcome was a high Oxygen Desaturation Index (ODI), defined as 3% ODI >10, which significantly correlated with the presence of moderate or severe SDB. We randomly divided the whole participants into a training set (80%) and a test set (20%). With data from the training set, we developed a random forest discriminant model for high ODI based on clinical parameters. We tested the ability of the discriminant model on the test set and compared it with a previous logistic regression model for distinguishing SDB in patients with HCM. RESULTS: Among 369 patients with HCM, 228 (61.8%) had high ODI. In the test set, the area under the receiver operating characteristic curve of the discriminant model was 0.86 (95% CI 0.77 to 0.94). The sensitivity was 0.91 (95% CI 0.79 to 0.98) and specificity was 0.68 (95% CI 0.48 to 0.84). When the test set was divided into low-probability and high-probability groups, the high-probability group had a higher prevalence of high ODI than the low-probability group (82.4% vs 17.4%, OR 20.9 (95% CI 5.3 to 105.8), Fisher's exact test p<0.001). The discriminant model significantly outperformed the previous logistic regression model (DeLong test p=0.03). CONCLUSIONS: Our study serves as the first to develop a machine learning-based discriminant model for the concomitance of SDB in patients with HCM. The discriminant model may facilitate cost-effective screening tests and treatments for SDB in the population with HCM.

Prediction of cardiac death in patients with hypertrophic cardiomyopathy using plasma adipokine levels.

BACKGROUNDS AND AIMS: Hypertrophic cardiomyopathy (HCM) causes cardiac death through both sudden cardiac death (SCD) and death due to heart failure (HF). Although adipokines lead to adverse cardiac remodeling in HCM, the prognostic value of plasma adipokines in HCM remains unknown. We aimed to predict cardiac death in patients with HCM using plasma adipokines. METHODS AND RESULTS: We performed a multicenter prospective cohort study of patients with HCM. The outcome was cardiac death including heart transplant, death due to HF, and SCD. With data from 1 institution (training set), a prediction model was developed using random forest classification algorithm based on 10 plasma adipokines. The performance of the prediction model adjusted for 8 clinical parameters was examined in samples from another institution (test set). Time-to-event analysis was performed in the test set to compare the rate of outcome events between the low-risk and high-risk groups determined by the prediction model. In total, 389 (267 in the training set; 122 in the test set) patients with HCM were included. During the median follow-up of 2.7 years, 21 patients experienced the outcome event. The area under the covariates-adjusted receiver-operating characteristics curve was 0.89 (95 % confidence interval [CI] 0.71-0.99) in the test set. revealed the high-risk group had a significantly higher risk of cardiac death (hazard ratio 17.8, 95 % CI 2.1-148.3, P = 0.008). CONCLUSION: The present multicenter prospective study demonstrated that a panel of plasma adipokines predicts cardiac death in patients with HCM.

Mitral regurgitation mechanisms related to systolic anterior motion in hypertrophic cardiomyopathy.

Background: Systolic anterior motion (SAM) of the mitral valve can result in mitral regurgitation (MR) and adverse outcomes in patients with obstructive hypertrophic cardiomyopathy (HCM). However, the mechanism and characteristics of MR severity mediated by SAM are unresolved. This study aimed to elucidate the anatomic and hemodynamic associations of MR and the impact of septal myectomy on changes in MR severity in patients with HCM. Methods: We retrospectively reviewed patients who underwent septal myectomy with SAM and interpretable imaging between 2017-2022. Significant MR was defined as moderate or more MR. The mitral valve, papillary muscle, and left ventricular geometry were quantitatively evaluated via echocardiography and cardiac computed tomography. Results: Out of 34 patients, two groups were identified: those with preoperative significant MR (n=16) and those without significant MR (n=18). Patients with significant preoperative MR exhibited worse heart failure symptoms at baseline than those without. Following myectomy, these patients showed higher residual left ventricular outflow tract (LVOT) gradients at rest and with provocative measures than those without preoperative MR. Multivariate regression analysis revealed a significant association between the tenting area and MR severity. Additionally, the chordal cutting procedure alleviated the tenting area [2.1 (1.8-2.6) vs. 1.4 (1.2-1.6) cm2] compared to those without it. Conclusions: Our preliminary data suggested that chordal cutting with septal myectomy was associated with an improvement in the tenting area, contributing to MR severity. This procedure may serve as an effective therapy for patients with SAM and significant MR.

Model for classification of heart failure severity in patients with hypertrophic cardiomyopathy using a deep neural network algorithm with a 12-lead electrocardiogram.

OBJECTIVES: In hypertrophic cardiomyopathy (HCM), specific ECG abnormalities are observed. Therefore, ECG is a valuable screening tool. Although several studies have reported on estimating the risk of developing fatal arrhythmias from ECG findings, the use of ECG to identify the severity of heart failure (HF) by applying deep learning (DL) methods has not been established. METHODS: We assessed whether data-driven machine-learning methods could effectively identify the severity of HF in patients with HCM. A residual neural network-based model was developed using 12-lead ECG data from 218 patients with HCM and 245 patients with non-HCM, categorised them into two (mild-to-moderate and severe) or three (mild, moderate and severe) severities of HF. These severities were defined according to the New York Heart Association functional class and levels of the N-terminal prohormone of brain natriuretic peptide. In addition, the patients were divided into groups according to Kansas City Cardiomyopathy Questionnaire (KCCQ)-12. A transfer learning method was applied to resolve the issue of the low number of target samples. The model was trained in advance using PTB-XL, which is an open ECG dataset. RESULTS: The model trained with our dataset achieved a weighted average F1 score of 0.745 and precision of 0.750 for the mild-to-moderate class samples. Similar results were obtained for grouping based on KCCQ-12. Through data analyses using the Guided Gradient Weighted-Class Activation Map and Integrated Gradients, QRS waves were intensively highlighted among true-positive mild-to-moderate class cases, while the highlighted part was highly variable among true-positive severe class cases. CONCLUSIONS: We developed a model for classifying HF severity in patients with HCM using a deep neural network algorithm with 12-lead ECG data. Our findings suggest that applications of this DL algorithm for using 12-lead ECG data may be useful to classify the HF status in patients with HCM.

Effects of bariatric surgery on cardiovascular-related acute care use in patients with hypertrophic cardiomyopathy.

AIMS: Prior studies have suggested causal relationships between obesity and acute cardiovascular events. It has been also known that the risk of acute cardiovascular events is reduced by bariatric surgery. However, little is known about whether bariatric surgery lowers the risk of acute cardiovascular events in patients with obesity and hypertrophic cardiomyopathy (HCM). In this context, we aimed to investigate whether bariatric surgery is associated with a reduced risk of cardiovascular-related acute care use in patients with HCM. METHODS AND RESULTS: In this population-based study, the bariatric surgery group consisted of patients with HCM who underwent bariatric surgery from January 2004 to December 2014. The control group included those who have obesity and HCM and received non-bariatric elective intra-abdominal surgery during the same period. The outcome was cardiovascular-related acute care use (i.e. emergency department (ED) visits or unplanned hospitalizations for cardiovascular disease) during a 1-year post-surgery period. We used the SPARCS database, a population-based ED and inpatient database in New York State. We constructed logistic regression models with generalized estimating equations to compare the risk of the outcome events during sequential 6-month post-surgery periods. We adjusted for age, sex, number of ED visits and hospitalizations for cardiovascular disease within 2 years before the index surgery, and the Elixhauser co-morbidity measures. We also performed propensity score (PS)-matching and inverse probability treatment weighting analyses using these variables. The analytic cohort consisted of 207 adults with obesity and HCM, including 147 patients who underwent bariatric surgery and 60 in the control group. The risk was not significantly different in the 1-6 months post-surgery period. By contrast, in the 7-12 months post-surgery period, the risk of cardiovascular-related acute care use was significantly lower in the bariatric surgery group (adjusted odds ratio 0.23; 95% CI 0.068-0.71; P = 0.01) compared with the control group. In the PS-matched cohort, there were no significant differences in the baseline characteristics. The PS-matched analysis demonstrated lower risk of the outcome event in the bariatric surgery group in the 7-12 months post-surgery period. The inverse probability treatment weighting analysis replicated the findings. CONCLUSIONS: Bariatric surgery was associated with a lower risk of cardiovascular-related acute care use in the 7-12 months post-surgery period in this population-based study.

Alcohol septal ablation versus surgical septal myectomy of obstructive hypertrophic cardiomyopathy: systematic review and meta-analysis.

OBJECTIVES: To elucidate the optimal septal reduction therapy for obstructive hypertrophic cardiomyopathy, we conducted a meta-analysis comparing alcohol septal ablation (ASA) and septal myectomy. METHODS: MEDLINE, EMBASE and Cochrane CENTRAL were searched to identify studies investigating the outcomes of ASA and septal myectomy in patients with obstructive hypertrophic cardiomyopathy in January 2023. The primary outcome of interest was all-cause mortality in studies with ≥1 year of follow-up. The secondary outcomes of interest comprised left ventricular outflow tract (LVOT) pressure gradient reduction and reoperations of LVOT. A subgroup analysis of all-cause mortality including studies with follow-up ≥5 years was performed. RESULTS: 27 observational studies were included (15 968 patients). Analysis demonstrated similar all-cause mortality [hazard ratio (HR) (95% confidence interval) (CI) 1.24 (0.88-1.76); P = 0.21; I2 = 56%]. In contrast, ASA was associated with less reduction of LVOT pressure gradient and a reoperation rate [weighted mean difference (95% CI) 11.04 mmHg (5.60-16.48); P < 0.01; I2 = 64%, HR (95% CI) 9.14 (6.55-12.75); P < 0.001; I2 = 0%, respectively]. The subgroup analysis with follow-up ≥5 years revealed higher long-term mortality with ASA [HR (95% CI) 1.50 (1.04-2.15); P = 0.03; I2 = 52%]. CONCLUSIONS: Although both septal reduction therapies were associated with similar all-cause mortality, ASA was associated with a higher rate of reoperation and less reduction of LVOT pressure gradient. Furthermore, all-cause mortality with follow-up ≥5 years showed favourable outcomes with septal myectomy, although the result is only hypothesis-generating given a subgroup analysis.

Association of an Increased Abnormal Mitochondria Ratio in Cardiomyocytes with a Prolonged Oxygen Uptake Time Constant during Cardiopulmonary Exercise Testing of Patients with Non-ischemic Cardiomyopathy.

Objective The cardiac function, blood distribution, and oxygen extraction in the muscles as well as the pulmonary function determine the oxygen uptake (VO2) kinetics at the onset of exercise. This factor is called the VO2 time constant, and its prolongation is associated with an unfavorable prognosis for heart failure (HF). The mitochondrial function of skeletal muscle is known to reflect exercise tolerance. Morphological changes and dysfunction in cardiac mitochondria are closely related to HF severity and its prognosis. Although mitochondria play an important role in generating energy in cardiomyocytes, the relationship between cardiac mitochondria and the VO2 time constant has not been elucidated. Methods We calculated the ratio of abnormal cardiac mitochondria in human myocardial biopsy samples using an electron microscope and measured the VO2 time constant during cardiopulmonary exercise testing. The VO2 time constant was normalized by the fat-free mass index (FFMI). Patients Fifteen patients with non-ischemic cardiomyopathy (NICM) were included. Patients were divided into two groups according to their median VO2 time constant/FFMI value. Results Patients with a low VO2 time constant/FFMI value had a lower abnormal mitochondria ratio than those with a high VO2 time constant/FFMI value. A multiple linear regression analysis revealed that the ratio of abnormal cardiac mitochondria was independently associated with a high VO2 time constant/FFMI. Conclusion An increased abnormal cardiac mitochondria ratio might be associated with a high VO2 time constant/FFMI value in patients with NICM.

Safety of a Cardiac Resynchronization Therapy Device Implantation in a Patient with Unstable Heart Failure Who Require Impella-Device Assistance.

Implantation of a cardiac resynchronization therapy (CRT) device is usually scheduled in the compensated phase of heart failure; however, procedural safety may be sometimes disturbed in the decompensated phase. We report a case of a successful semi-urgent implantation of a CRT device temporary assisted with Impella in a patient with the decompensated phase of severe heart failure dependent on inotropic agents and who cannot maintain the supine position. Impella assistance with left ventricular (LV) unloading and maintenance of end-organ perfusion contributed to early recovery from acute heart failure. Furthermore, an acute effect of mechanical resynchronization by biventricular pacing plays an important role in weaning from the mechanical support or inotropic dependence. These mutual effects of mechanical support and CRT might contribute to a decrease in LV end-diastolic pressure and to a remarkable early recovery from a severely decompensated condition.

The association between the clinical severity of heart failure and docosahexaenoic acid accumulation in hypertrophic cardiomyopathy.

OBJECTIVE: Hypertrophic cardiomyopathy (HCM) is a common genetic disease with diverse morphology, symptoms, and prognosis. Hypertrophied myocardium metabolism has not been explored in detail. We assessed the association between myocardium lipid metabolism and clinical severity of heart failure (HF) in HCM using imaging mass spectrometry (IMS). RESULTS: We studied 16 endomyocardial biopsy (EMB) specimens from patients with HCM. Analysis was conducted using desorption electrospray ionization IMS. The samples were assigned into two cohorts according to the period of heart biopsy (cohort 1, n = 9 and cohort 2, n = 7). In each cohort, samples were divided into two groups according to the clinical severity of HF in HCM: clinically severe and clinically mild groups. Signals showing a significant difference between the two groups were analyzed by volcano plot. In cohort 1, the volcano plot identified four signals; the intensity in the clinically severe group was more than twice that of the mild group. Out of the four signals, docosahexaenoic acid (DHA) showed significant differences in intensity between the two groups in cohort 2 (10,575.8 ± 2750.3 vs. 19,839.3 ± 4803.2, P = 0.025). The intensity of DHA was significantly higher in EMB samples from the clinically severe HCM group than in those from the mild group.

NAD+ Levels Are Augmented in Aortic Tissue of ApoE-/- Mice by Dietary Omega-3 Fatty Acids.

BACKGROUND: Maintaining bioenergetic homeostasis provides a means to reduce the risk of cardiovascular events during chronological aging. Nicotinamide adenine dinucleotide (NAD+) acts as a signaling molecule, and its levels were used to govern several biological pathways, for example, promoting angiogenesis by SIRT1 (sirtuin 1)-mediated inhibition of Notch signaling to rejuvenate capillary density of old-aged mice. NAD+ modulation shows promise in the vascular remodeling of endothelial cells. However, NAD+ distribution in atherosclerotic regions remains uncharacterized. Omega-3 polyunsaturated fatty acids consumption, such as docosahexaenoic acid and eicosapentaenoic acid, might increase the abundance of cofactors in blood vessels due to omega-3 polyunsaturated fatty acids metabolism. METHODS: Apolipoprotein E-deficient (ApoE-/-) mice were fed a Western diet, and the omega-3 polyunsaturated fatty acids-treated groups were supplemented with docosahexaenoic acid (1%, w/w) or eicosapentaenoic acid (1%, w/w) for 3 weeks. Desorption electrospray ionization mass spectrometry imaging was exploited to detect exogenous and endogenous NAD+ imaging. RESULTS: NAD+, NADH, NADP+, NADPH, FAD+, FADH, and nicotinic acid adenine dinucleotide of the aortic arches were detected higher in the omega-3 polyunsaturated fatty acids-treated mice than the nontreated control. Comparing the distribution in the outer and inner layers of the arterial walls, only NADPH was detected slightly higher in the outer part in eicosapentaenoic acid-treated mice. CONCLUSIONS: Supplementation of adding docosahexaenoic acid or eicosapentaenoic acid to the Western diet led to a higher NAD+, FAD+, and their metabolites in the aortic arch. Considering the pleiotropic roles of NAD+ in biology, this result serves as a beneficial therapeutic strategy in the animal model counter to pathological conditions.

Association between plasma xanthine oxidoreductase activity and in-hospital outcomes in patients with stable coronary artery disease after percutaneous coronary intervention.

OBJECTIVES: Reactive oxygen species generated by xanthine oxidoreductase (XOR) are associated with the progression of atherosclerosis. However, changes in plasma XOR (pXOR) activity after percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) remains unknown. METHODS: Herein, we compared the change in the pXOR activity in patients undergoing PCI with that in patients undergoing coronary angiography (CAG) and further evaluated the relation between changes in pXOR activity and in-hospital and long-term outcomes of patients undergoing PCI. The pXOR activity of 80 consecutive patients who underwent PCI and 25 patients who underwent CAG during the hospitalization was analyzed daily. The percentage changes from baseline regulated time interval was evaluated. RESULTS: We found that although pXOR activity decreased after PCI, and remained low until discharge, no significant changes were observed in patients undergoing CAG. Furthermore, among the patients undergoing PCI, those who experienced in-hospital adverse events, had a higher percentage of pXOR reduction 3 days after PCI. There was no association between these changes and long-term events. CONCLUSIONS: A significant change in pXOR activity was observed in patients undergoing PCI than in patients undergoing CAG, and there seems to be a correlation between the in-hospital outcomes and the percentage reduction from baseline in pXOR activity.

Hemodynamic change in patients with hypertrophic obstructive cardiomyopathy before and after alcohol septal ablation using 4D flow magnetic resonance imaging: a retrospective observational study.

BACKGROUND: The hemodynamics in the left ventricle (LV) and the ascending aorta (AAO) before and after alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM) is elucidated. Our objective was to evaluate the pattern changes in AAO and intra-LV flow assessed by four-dimensional (4D) flow magnetic resonance imaging (MRI) before and after ASA and to clarify the association between 4D flow MRI-derived hemodynamic characteristics and the peak pressure gradient (PPG) in patients with drug-refractory HOCM. METHODS: In this retrospective observational study, 11 patients with HOCM underwent 4D flow MRI before and a week after ASA. The 4D flow MRI included blood flow visualization and quantification using streamline images. The combined score of vortex and helix in AAO was analyzed. The duration and phase count of the AAO vortex or helix flow and the size of the intra-LV anterior vortex were quantified. The correlation between the changes in hemodynamics and the resting PPG at LV outflow tract was also analyzed. We used the paired t-test for the comparison between before and after ASA and the Pearson's correlation coefficient for the analysis. RESULTS: The combined score for the incidence of vortex and/or helix flow in AAO after ASA was significantly lower than that before ASA (1.45 ± 0.52 vs. 1.09 ± 0.30, p = 0.046). The duration (744 ± 291 ms vs. 467 ± 258 ms, p < 0.001) and phase count (14.8 ± 4.4 phases vs. 10.5 ± 5.8 phases, p < 0.001) of the vortex or helix flow in AAO were significantly decreased after ASA. The LV anterior vortex area after ASA was significantly larger than that before ASA (1628 ± 420 mm2 vs. 2974 ± 539 mm2, p = 0.009). The delta phase count of the AAO vortex or helix before and a week after ASA was significantly correlated with delta PPG before and a week after ASA (R = 0.79, p = 0.004) and with delta PPG before and 6 months after ASA (R = 0.83, p = 0.002). CONCLUSIONS: Lower vortex or helix flow in AAO and larger diastolic vortex flow in LV were observed after ASA, which suggests the possibility to detect the changes of aberrant hemodynamics in HOCM.

Combined ablation for paroxysmal atrial fibrillation and drug-refractory hypertrophic obstructive cardiomyopathy: a case report.

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is sometimes concomitant with atrial fibrillation (AF) and exacerbates heart failure symptoms. Although optimal medication for the reduction of left ventricular outflow tract (LVOT) obstruction and the maintenance of sinus rhythm should be considered, it is difficult to control the symptoms permanently. CASE SUMMARY: A 45-year-old man, diagnosed with HOCM, presented with progressive dyspnoea on exertion, which significantly deteriorated during episodes of paroxysmal AF, despite optimal medical therapy. On echocardiography, we found LVOT obstruction with a peak pressure gradient of 98 mmHg, concomitant with redundant mitral valve leaflets, which caused significant systolic anterior motion (SAM). Since he declined open surgery, we selected a combination of catheter interventions, AF ablation, and alcohol septal ablation (ASA). After the AF ablation, the occurrence of AF significantly decreased, and there was no recurrence after the ASA. By 6 months, the plasma N-terminal pro-B-type natriuretic peptide level had decreased from 1022 to 124 pg/mL, the peak pressure gradient of LVOT decreased from 98 to 12 mmHg, and the left atrium volume decreased from 203 to 178.4 mL. The improvement in the SAM was visualized on echocardiography and was haemodynamically corroborated by the four-dimensional (4D)-flow cardiac magnetic resonance (CMR). DISCUSSION: The treatment of drug-refractory HOCM concomitant with paroxysmal AF needs both septal reduction and the maintenance of sinus rhythm, which can be accomplished through transcatheter interventions. Moreover, the detailed intra-ventricular haemodynamic assessment in HOCM patients can be explored using the 4D-flow CMR.

Impact of reduced-dose prasugrel vs. standard-dose clopidogrel on in-hospital outcomes of percutaneous coronary intervention in 62 737 patients with acute coronary syndromes: a nationwide registry study in Japan.

AIMS: In Japan, reduced-dose prasugrel (loading/maintenance dose, 20/3.75 mg) has been approved for use in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), because of the higher bleeding risk among East Asians. However, its safety in the real-world population has not been investigated. We aimed to evaluate the effectiveness and safety of reduced-dose prasugrel vs. standard-dose clopidogrel in ACS patients undergoing PCI. METHODS AND RESULTS: Acute coronary syndrome patients who underwent PCI in 2016, who were treated with either reduced-dose prasugrel or standard-dose clopidogrel in addition to aspirin, were identified from the nationwide Japanese PCI registry. The primary outcome was in-hospital mortality following PCI. Secondary outcomes included stent thrombosis and bleeding complication after PCI. Among 62 737 ACS patients who underwent PCI at any of 986 participating centres across Japan (clopidogrel 31.9%; prasugrel 68.1%), we identified 12 016 propensity score-matched pairs (24 032 patients; age 69.4 ± 12.2 years; female 24.9%; ST-elevation myocardial infarction 42.3%). Compared with standard-dose clopidogrel, reduced-dose prasugrel was associated with increased risk of bleeding [odds ratio (OR) 1.65, 95% confidence interval (CI) 1.10-2.51; P = 0.016], but both had similar rates of mortality (OR 1.11, 95% CI 0.89-1.38; P = 0.371) and stent thrombosis (OR 1.29, 95% CI 0.73-2.30; P = 0.387) as well as similar falsification endpoints of cardiac tamponade and emergent operation. CONCLUSION: In Japanese ACS patients undergoing PCI, the risk of bleeding is higher when using reduced-dose prasugrel than when using standard-dose clopidogrel, but there is no significant difference in in-hospital mortality and incidence of stent thrombosis between the two antiplatelet regimens.

Prognostic Impact of Previous Hospitalization in Acute Heart Failure Patients.

BACKGROUND: The natural course of heart failure (HF) is typically associated with repeated hospitalizations, and subsequently, patient prognosis deteriorates. However, the precise relationship between repeated admissions for HF and long-term prognosis remains unknown. Methods and Results: We analyzed data from 1,730 consecutive acute HF patients registered in the West Tokyo Heart Failure (WET-HF) registry between June 2005 and April 2014 (median age, 76 years). Patients were divided into 3 groups according to the number of previous HF admissions at the time of the index admission (0, n=876 [55.4%]; 1, n=425 [26.9%]; ≥2, n=279 [17.7%] previous admissions). A history of multiple previous admissions was an independent predictor for all-cause death and HF readmission in reference to a history of a single previous admission (hazard ratio (HR), 1.53; 95% confidence interval (CI) 1.10-2.13; HR, 1.90 95% CI, 1.47-2.44, respectively) or no previous admissions (HR, 1.37, 95% CI, 1.01-1.85; HR, 2.83, 95% CI, 2.19-3.65, respectively). On the other hand, a history of a single previous admission was an independent predictor for HF readmission in reference to a history of no previous admissions (HR, 1.51, 95% CI, 1.18-1.92), but not for all-cause death (HR, 0.89, 95% CI, 0.66-1.20). CONCLUSIONS: Based on a contemporary multicenter HF registry, a history of multiple previous HF admissions was revealed as an independent, strong risk factor of adverse events following the index admission. The number of hospitalizations could be a simple and important surrogate indicating subsequent adverse events in patients with HF.