Pericarditis recurrence is associated with milder electrocardiographic, echocardiographic, and laboratory findings.

Recurrent pericarditis (RP) complicates approximately 30% of acute pericarditis (AP) cases. We sought to compare the prevalence and severity of objective findings seen in patients with RP. A retrospective single-center study during 2010-2019, including 765 patients diagnosed with AP. Clinical, electrocardiographic, echocardiographic, and laboratory findings were extracted from the local electronic health records. Recurrence during follow-up was documented in 134 patients (17.5%), with a median time to recurrence of 101 (± 59-251) days. The median age was 60 years (IQR 45-72), 68% were male. Most patients were defined as having idiopathic\viral pericarditis (64%). The clinical manifestation during the recurrent event of pericarditis was less prominent or attenuated when compared to the initial event-ECG signs (ST elevation 12% vs. 26%; p = 0.006, Knuckle sign 13% vs. 33%; p < 0.001, ST larger in lead L2 than L3 4% vs. 19%; p < 0.001), pericardial effusion moderate and above (11% vs. 30%; p = 0.02), and inflammatory markers (mean peak CRP levels 66 mg/l vs. 97 mg/l; p < 0.001). Similar results were seen in the subgroup of patients defined as having idiopathic\viral pericarditis. Up to 20% of patients who did not have ECG signs or a significant pericardial effusion in their 1st event demonstrated these findings during the recurrence, though still to a lesser extent compared with those who had these signs in their 1st event. The objective findings of AP are less pronounced during recurrent events. Future studies should focus on the role of advanced biomarkers and imaging in defining true RP events.

Sex related differences in the characteristics and outcomes of heart failure: A sub analysis of heart failure disease management study.

Aims: This is a sub-analysis of a randomized controlled trial on heart failure (HF) disease management (DM) in which patients with HF (N = 1,360; 27.5% women) were assigned randomly to DM (N = 682) or usual care (UC) (N = 678). Study intervention did not significantly affect the rate of hospital admissions or mortality. This study evaluates sex-related differences in baseline characteristics, clinical manifestations, adherence to treatment and outcomes among the study cohort. Methods: Association between sex and hospital admissions and mortality was tested in multivariable models adjusted for the patients' baseline characteristics. The primary composite outcome of the study included time to first HF hospitalization or all-cause mortality. Secondary composite outcome included number of hospital admissions and days of hospitalization, for HF and all other causes. Results: Compared to males, females recruited in the study were on average 3 years older [median age 72 (62, 78) vs. 75 (65, 82), p = 0.001], with higher prevalence of preserved left ventricular function (LVEF ≥50%) and lower frequency of ischemic heart disease (IHD) (p ≤ 0.001). Females had shorter 6-min walking distance and worse quality of life and depression scores at baseline (p < 0.001). The proportion of patients receiving HF recommended medical treatment was similar among females and males. During a median follow-up of 2.7 years (range: 0-5), there were no significant differences between females and males with respect to the time elapsed until the study primary endpoint and its components in univariate analysis [557 (56.5%) males and 218 (58.3%) females were hospitalized for HF or died for any cause; p > 0.05]. Multivariable analysis showed that females were significantly less likely than males to experience the primary outcome [adjusted hazard ratio (HR) = 0.835, 95% CI: 0.699, 0.998] or to die from any cause [adjusted HR = 0.712; 95%CI: 0.560, 0.901]. The sex-related mortality differences were especially significant among patients with non-preserved EF, with IHD or with recent HF hospitalization. Females also had lower rates of all-cause hospital admissions [adjusted rate ratio = 0.798; 95%CI: 0.705, 0.904] and were more likely to adhere to HF medical therapy compared to males. Conclusion: Females with HF fare better than men. Sex related differences were not explained by baseline and morbidity-related characteristics or adherence to medical treatment.

Contemporary outcome of subsequent pregnancies in patients with previous peripartum cardiomyopathy.

AIMS: To describe the effect of subsequent pregnancies (SSP) on left ventricular (LV) function and outcomes in patients with peripartum cardiomyopathy (PPCM). METHODS: Among146 women with PPCM who were prospectively followed at two medical centres in Israel (2007-2019), 75 SSPs (in 50 women) were identified: 8 miscarriages, 8 terminations, and 59 life birth. RESULTS: Forty-five patients with 59 full-term SSPs [mean age was 32.9 ± 4.1 years, LV ejection fraction (LVEF) 57.7 ± 5.1%] were analysed. Data on LVEF at 1-month post-delivery were available in 46 and at 6 months in 36 SSPs. There was a small decrease in the mean LVEF, mostly at third trimester (57.2 ± 5.6 vs. 54.4. ± 7.3, P < 0.001); and at 1-mont (57.9 ± 5.7% vs. 55.4 ± 6.1%, P = 0.001) and at 6-month post-delivery (57.4 ± 6.1 vs. 55.3 ± 7.9%, P = 0.03). In patients with pre-SSP LV LVEF ≥55%, a mild reduction in the mean group LVEF was seen at 1-month post-delivery (P = 0.009). One patient with pre-SSP LVEF ≥55% developed severe relapse. In patients with pre-SSP LVEF <55%, a mild reduction in LVEF was obtained mostly at third trimester (51.1 ± 5.6 vs 47.0 ± 7.4%, P < 0.001), which persisted at 6 months (P = 0.03). A relapse was observed in three (25%) women with LVEF <55%. There was no maternal mortality, 32 patients delivered by caesarean section, and there were no foetal complications. CONCLUSIONS: Our study indicates a favourable outcome and low likelihood of maternal mortality associated with SSP in women with a history of PPCM and recovered LV systolic function. SSP was associated with a slight reduction in LVEF mostly during the third trimester, which persisted up to 6 months after delivery.

The clinical course of patients with previous acute and recurrent pericarditis receiving the BNT162b2 vaccine.

Background: Vaccines against SARS-COV2 have been crucial in efforts against COVID19, yet there have been reports of pericarditis following vaccination with mRNA-based vaccines. Methods: We questioned consecutive patients with a history of acute pericarditis (AP) evaluated in the pericardial disease clinic during 3-11/2020 in a single tertiary center. Patients with significant myocardial involvement or pericarditis secondary to another systemic disease were excluded. Results: We included 64 patients in the final analysis. Mean age was 53.1 (±18), and 26 (41%) were female. At least 1 recurrence of AP was documented in 47 (73%) cases, 32 (50%) had ≥ 3 recurrences prior to vaccination. AP was considered to be idiopathic\viral in 45 (70%) cases, 20 (31%) cases were post-injury. All patients received at least 2 doses of the vaccine, and 48 patients (75%) received a 3rd dose. Two cases of breakthrough COVID19 infections were documented. Overall, 12 patients (19%) reported any adverse events. Of which, 2 had recurrent pericarditis. There was a trend for a younger age in those patients who had adverse events (median age 45 [IQR 36-61] vs. 60 [38-71], p = 0.08). no other significant difference was seen. Conclusion: In patients with a history of acute\recurrent pericarditis, the use of BNT162b2 was mostly uneventful, but some mild disease recurrences did occur.

The Prognostic Role of Mitral Valve Regurgitation Severity and Left Ventricle Function in Acute Heart Failure.

Aims: Data about the prognostic interplay between mitral regurgitation MR and left ventricular (LV) function in the outcome of patients admitted with acute heart failure (AHF) are scarce. We evaluated the prognostic impact of MR severity and LV function on mortality and on recurrent heart failure hospitalization (re-HFH) in patients admitted with AHF. Methods and Results: In total, 6843 patients admitted with AHF were evaluated: 2521 patients with LV ejection fraction (LVEF) ≤ 40% (reduced LVEF), 1238 of them (51%) having ≥moderate MR; and 4322 with LVEF > 40% (preserved LVEF), 1175 of them (27%) having ≥moderate MR. One-year mortality and re-HFH rates were higher in patients with ≥moderate MR unrelated to the baseline LV function (p = 0.028 and p < 0.001, respectively). After multivariable analysis, only reduced LVEF, and not the severity of MR, predicted mortality risk (HR: 1.31 [95% CI: 1.12−1.53] for patients with reduced LV function and ≤mild MR; HR: 1.44 [95% CI: 1.25−1.67] for patients with reduced LV function and ≥moderate MR); p < 0.001 for both. There was an increased risk for re-HFH in each group (HR: 1.35 [95% CI: 1.17−1.52] for patients with preserved LV function and ≥moderate MR; HR: 1.31 [95% CI: 1.15−1.51] for patients with reduced LV function and mild MR; and HR: 1.65 [95% CI: 1.45−1.88] for patients with reduced LV function and ≥moderate MR); p < 0.001 for all. Conclusions: In patients admitted with AHF, the LV function is the main prognostic determinant for mortality after 1 year. Significant (≥moderate) MR is associated with an increased risk of recurrent hospitalization.

Effect of levosimendan infusion prior to left ventricular assist device implantation on right ventricular failure.

OBJECTIVE: Investigate the safety and efficacy of preoperative levosimendan in patients undergoing left ventricular assist device (LVAD) implantation. METHODS: Consecutive patients who received LVADs (HeartMate-2, 3, HVAD) in a single tertiary medical center (2012-2018). INTERMACS profile 1 patients were excluded. The primary outcome was post-LVAD right ventricular failure (RVF) and inhospital mortality rates. The secondary outcomes included other clinical, echocardiographic and hemodynamic parameters at follow-up. RESULTS: Final cohort consisted of 62 patients (40[65%] in the levosimendan group and 22[35%] in the no-levosimendan group). Post-operative RVF rate and inotrope or ventilation support time were similar in the levosimendan and no-levosimendan groups (7.5% vs. 13.6%; P = 0.43, median of 51 vs. 72 h; P = 0.41 and 24 vs. 27 h; P = 0.19, respectively). Length of hospitalization, both total and in the intensive care unit, was not statistically significant (median days of 13 vs. 16; P = 0.34, and 3 vs. 4; P = 0.44, respectively). Post-operative laboratory and echocardiographic parameters and in-hospital complication rate did not differ between the groups, despite worse baseline clinical parameters in the Levosimendan group. There was no significant difference in the in-hospital and long term mortality rate (2.5% vs. 4.5%; P > 0.999 and 10% vs. 27.3% respectively; P = 0.64). CONCLUSIONS: Levosimendan infusion prior to LVAD implantation was safe and associated with comparable results without significant improved post-operative outcomes, including RVF.

Hypokinetic hypertrophic cardiomyopathy: clinical phenotype, genetics, and prognosis.

AIMS: To describe the phenotype, genetics, and events associated with the development of hypertrophic cardiomyopathy (HCM) with reduced ventricular function (HCMr). Heart failure in HCM is usually associated with preserved ejection fraction, yet some HCM patients develop impaired systolic function that is associated with worse outcomes. METHODS AND RESULTS: Our registry included 1328 HCM patients from two centres in Spain and Israel. Patients with normal baseline ventricular function were matched, and a competing-risk analysis was performed to find factors associated with HCMr development. Patient records were reviewed to recognize clinically significant events that occurred closely before the development of HCMr. Genetic data were collected in patients with HCMr. A composite of all-cause mortality or ventricular assist device (VAD)/heart transplantation was assessed according to ventricular function. Median age was 56, and 34% were female patients. HCMr at evaluation was seen in 37 (2.8%) patients, and 46 (3.5%) developed HCMr during median follow up of 9 years. HCMr was associated with younger age of diagnosis, poor functional class, and ventricular arrhythmia. Atrial fibrillation, pacemaker implantation, and baseline left ventricular ejection fraction (LVEF) of ≤55% were significant predictors of future HCMr development, while LV obstruction predicted a lower risk. Genetic testing performed in 53 HCMr patients, identifying one or more pathogenic variant in 38 (72%): most commonly in myosin binding protein C (n = 20). Six of these patients had an additional pathogenic variant in one of the sarcomere genes. Patients with baseline HCMr had a higher risk (hazard ratio 6.4, 4.1-10.1) for the composite outcome and for the individual components. Patients who developed HCMr in the course of the study had similar mortality but a higher rate of VAD/heart transplantation compared with HCM with normal LVEF. CONCLUSIONS: Hypertrophic cardiomyopathy with reduced ejection fraction is associated with heart failure and poor outcome. Arrhythmia, cardiac surgery, and device implantation were commonly documented prior to HCMr development, suggesting they may be either a trigger or the result of adverse remodelling. Future studies should focus on prediction and prevention of HCMr.

Characterization of heart failure patients with reverse left ventricular remodelling post-angiotensin receptor blockers/neprilysin inhibitors therapy.

AIMS: To assess the effect of angiotensin receptor blockers/neprilysin inhibitors (ARNI) on left ventricular (LV) ejection fraction (LVEF) and LV dimensions in a real-life cohort of heart failure and reduced ejection fraction (HFrEF) patients, while analysing patient characteristics that may predict reverse LV remodelling. METHODS AND RESULTS: The ARNI-treated HFrEF patients followed at a single tertiary medical centre HF-outpatient clinic were included in the study. Clinical and echocardiographic parameters were evaluated prior to ARNI initiation, and while on ARNI therapy, assessing patient characteristics associated with reverse LV remodelling. The cohort included 91 patients (mean age 60.5 years, 90% male) and 47 (52%) patients exhibited ARNI responsiveness, defined as an increase in LVEF during therapy. Overall, LVEF increased by 19% post-ARNI (23.8 to 28.4%, P < 0.001). Subgroup analysis revealed several parameters associated with significant LVEF improvement, including baseline LVEF <30%, non-ischaemic HF aetiology, lack of cardiac resynchronization therapy (CRT), better initial functional class and ARNI initiation within 3 years from HF diagnosis (P ≤ 0.001 for all). Significant reduction in LV dimensions was noted in patients with lower initial LVEF, non-ischaemic HF and no CRT. Further combined subgrouping of the study population demonstrated that patients with both LVEF <30% and a non-ischaemic HF gained most benefit from ARNI with an average of 51% improvement in LVEF (19.9 to 30%, P < 0.001). CONCLUSIONS: The ARNI treatment response is not uniform among HFrEF patient subgroups. More pronounce reverse LV remodelling is associated with early ARNI treatment initiation in the course of HFrEF, and in those with LVEF <30%, non-ischaemic HF and no CRT.

Prevalence and clinical outcomes of dystrophin-associated dilated cardiomyopathy without severe skeletal myopathy.

AIMS: Dilated cardiomyopathy (DCM) associated with dystrophin gene (DMD) mutations in individuals with mild or absent skeletal myopathy is often indistinguishable from other DCM forms. We sought to describe the phenotype and prognosis of DMD associated DCM in DMD mutation carriers without severe skeletal myopathy. METHODS AND RESULTS: At 26 European centres, we retrospectively collected clinical characteristics and outcomes of 223 DMD mutation carriers (83% male, 33 ± 15 years). A total of 112 individuals (52%) had DCM at first evaluation [n = 85; left ventricular ejection fraction (LVEF) 34 ± 11.2%] or developed DCM (n = 27; LVEF 41.3 ± 7.5%) after a median follow-up of 96 months (interquartile range 5-311 months). DCM penetrance was 45% in carriers older than 40 years. DCM appeared earlier in males and was independent of the type of mutation, presence of skeletal myopathy, or elevated serum creatine kinase levels. Major adverse cardiac events (MACE) occurred in 22% individuals with DCM, 18% developed end-stage heart failure and 9% sudden cardiac death or equivalent. Skeletal myopathy was not associated with survival free of MACE in patients with DCM. Decreased LVEF and increased left ventricular end-diastolic diameter at baseline were associated with MACE. Individuals without DCM had favourable prognosis without MACE or death during follow-up. CONCLUSIONS: DMD-associated DCM without severe skeletal myopathy is characterized by incomplete penetrance but high risk of MACE, including progression to end-stage heart failure and ventricular arrhythmias. DCM onset is the major determinant of prognosis with similar survival regardless of the presence of skeletal myopathy.

Early post-stress decrease in cardiac performance by impedance cardiography and its relationship to the severity and extent of ischemia by myocardial perfusion imaging.

BACKGROUND: While single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a well-established noninvasive procedure for the evaluation of patients with coronary artery disease (CAD), it is unable to detect the presence of, or underestimates the extent of CAD in certain patients. We aimed to show that a bio-impedance device can detect early post-stress changes in several hemodynamic parameters, thereby serving as a potential marker for the presence of significant ischemia. METHODS: Prospectively enrolled patients, referred to our Medical Center for clinically-indicated MPI, underwent testing using a Non-Invasive Cardiac System (NICaS) before and immediately after exercise. The differences between rest and stress hemodynamic parameters were compared with the severity and extent of myocardial ischemia by MPI. The study included 198 patients; mean age was 62 years, 26% were women, 54% had hypertension, and 29% diabetes mellitus. Of them, 188 patients had ≤10%, and 10 had > 10% of myocardial ischemia. RESULTS: In the first group, there was a significantly greater increase in post-exercise stroke index, stroke work index, cardiac index and cardiac power index (19.2, 29.1, 90.5 and 107%, respectively) compared with the second group (- 2.7, 3.8, 43.7 and 53.5%, respectively), as well as a significantly greater decrease in total peripheral resistance index (- 38.7% compared with - 16.3%), with corresponding p values of 0.015, 0.017, 0.040, 0.016, and < 0.001, respectively. CONCLUSIONS: Our data suggest that immediate post-stress changes in several hemodynamic parameters, detected by the NICaS, can be used as an important adjunct to SPECT MPI for the early detection of myocardial ischemia.

Sex Differences in Clinical Characteristics and 1- and 10-Year Mortality Among Patients Hospitalized With Acute Heart Failure.

BACKGROUND: The impact of sex on mortality in patients with acute heart failure (AHF) is unresolved. We aimed to investigate the impact of sex on both short- and long-term mortality outcomes after hospitalization for AHF. METHODS: We analyzed data of 2,328 patients with AHF who were enrolled in the multicenter national survey in Israel between March and April 2003 and followed up until December 2014. RESULTS: Women comprised 45% of the study population. In comparison with men, women were older, had higher rates of heart failure with preserved ejection fraction as well as hypertensive heart disease and had a lower rate of coronary artery disease (all P < 0.001). Survival analysis showed that at 1 year the rate of all-cause mortality was 31% among women compared to 28% among men (P = 0.19). At 10-year follow-up mortality rates were significantly higher among women compared to men (87% vs. 83%, P = 0.048). However, this sex association disappeared once multivariable analysis was carried out, (hazard ratio [HR] = 0.93; CI = 0.79-1.09, P = 0.36). Renal dysfunction, older age and severe heart failure were consistent independent predictors of mortality among men and women. Hyponatremia was a prognostic predictor only among men, whereas digoxin use predicted mortality only among women. CONCLUSIONS: There are important differences in the clinical characteristics between women and men hospitalized with AHF. There were no significant differences in both short- and long-term mortality following multivariable analysis. Although, most independent predictors of mortality were consistent among both sexes, few sex-based differences in prognostic predictors were identified.

Reduction in Filamin C transcript is associated with arrhythmogenic cardiomyopathy in Ashkenazi Jews.

BACKGROUND: Filamin C is a cytoskeletal protein expressed in cardiac cells. Nonsense variations in the filamin C gene (FLNC) were associated with dilated and arrhythmogenic cardiomyopathies. METHODS AND RESULTS: We identified an intronic variation in FLNC gene (c.3791-1G > C) in three unrelated Ashkenazi Jewish families with variable expression of arrhythmia and cardiomyopathy. cDNA was prepared from a mutation carrier's cultured skin fibroblasts. Quantitative PCR demonstrated a reduction in total FLNC transcript, and no other FLNC splice variants were found. Single-nucleotide polymorphism (SNP) analysis revealed heterozygous variations in the genomic DNA that were not expressed in the messenger RNA. Immunohistochemical analysis of cardiac sections detected a normal distribution of filamin C protein in the heart ventricles. CONCLUSION: The transcript that included the FLNC variant was degraded. Haploinsufficiency in filamin C underlies arrhythmogenic cardiomyopathy with variable symptoms.

Relation of Low Serum Magnesium to Mortality and Cardiac Allograft Vasculopathy Following Heart Transplantation.

Hypomagnesemia is commonly observed in heart transplant (HT) recipients receiving calcineurin inhibitors. Since low serum magnesium (s-Mg) has been implicated in the progression of atherosclerosis, potentially leading to worsening coronary heart disease, arrhythmias and sudden death, we investigated the association between s-Mg and HT outcomes. Between 2002 and 2017, 150 HT patients assessed for s-Mg were divided into high (≥1.7 mg/dL) and low s-Mg groups according to the median value of all s-Mg levels recorded during the first 3 months post-HT. Endpoints included survival, cardiac allograft vasculopathy (CAV), any-treated rejection (ATR) and NF-MACE. Kaplan-Meier analysis showed that at 15 years after HT, both survival (76 vs 33%, log-rank p = 0.007) and freedom from CAV (75 vs 48%, log-rank p = 0.01) were higher in the high versus low s-Mg group. There were no significant differences in freedom from NF-MACE or ATR. Multivariate analyses consistently demonstrated that low s-Mg was independently associated with a significant 2.6-fold increased risk of mortality and 4-fold increased risk of CAV (95%CI 1.06 to 6.4, p = 0.04; 95%CI 1.12 to 14.42, p = 0.01, respectively). In conclusion, low s-Mg is independently associated with increased mortality and CAV in HT patients. Larger multi-center prospective studies are needed to confirm these findings and to examine the effect of Mg supplementation.

Hypomagnesemia is associated with new-onset diabetes mellitus following heart transplantation.

BACKGROUND: Diabetes mellitus (DM) is a major cause of morbidity and mortality following heart transplantation (HT), with 21% and 35% of survivors being affected within 1 and 5 years following HT, respectively. Magnesium deficiency is common among HT patients treated with calcineurin inhibitors and is a known risk factor for DM in non-HT patients. We therefore investigated the association between serum Mg (s-Mg) levels and new-onset diabetes after transplantation (NODAT). METHODS: Between 2002 and 2017, 102 non-DM HT patients were assessed. In accordance with the mean value of all s-Mg levels recorded during the first year post-HT, patients were divided into high s-Mg (≥ 1.8 mg/dL) and low s-Mg (< 1.8 mg/dL) groups. The endpoint was NODAT, defined according to the diagnostic criteria of the American Diabetes Association. RESULTS: Baseline clinical and demographic characteristics for the high (n = 45) and low s-Mg (n = 57) groups were similar. Kaplan-Meier survival analysis showed that 15-year freedom from NODAT was significantly higher among patients with high vs low s-Mg (85% vs 46% log-rank test, p < 0.001). Consistently, multivariate analysis adjusted for age, gender, immunosuppression therapies, BMI and mean creatinine values in the first year post-HT, showed that low s-Mg was independently associated with a significant > 8-fold increased risk for NODAT (95% CI 2.15-32.63, p = 0.003). Stroke rate was significantly higher in patients with low s-Mg levels vs high s-Mg (14% vs 0, p = 0.025), as well as long term mortality (HR 2.6, 95% CI 1.02-6.77, p = 0.05). CONCLUSIONS: Low s-Mg level post-HT is an independent risk factor for NODAT in HT patients. The implications of interventions, focusing on preventing or correcting low s-Mg, for the risk of NODAT and for clinical outcomes should be evaluated.

Improved long-term outcomes after heart transplantation utilizing donors with a traumatic mode of brain death.

BACKGROUND: The donor's mode of brain death (BD), being associated with impairment of myocardial function and hemodynamic performance, impacts the prognosis of the heart transplantation (HTx) recipient. METHODS: All patients who underwent HTx between 1996 and 2017 were categorized according to donor's BD mechanism: traumatic BD (TBD) versus non-traumatic BD (NTBD). RESULTS: The TBD group included 105 recipients, and the NTBD group, 85 recipients. Kaplan-Meier survival analysis showed that overall survival was significantly higher for recipients of TBD hearts (10-year survival 58.1 vs. 37.6%, p = 0.044). Consistently, multivariate analysis showed that TBD was independently associated with a significant 43% reduction in mortality [95% confidence interval (CI) 0.42-0.75, p = 0.033]. Rejection rate was lower in the TBD group (total rejection score 0.44 ± 0.32 vs. 0.51 ± 0.38, p = 0.04; any rejection score 0.38 ± 0.26 vs. 0.45 ± 0.31, p = 0.030), and freedom from cardiac allograft vasculopathy (CAV) was significantly higher in recipients of traumatic vs. non-traumatic donors (10 years: 82.9 vs. 62.4%, log-rank p-value = 0.024). Multivariate analysis showed a significant 42% reduction in CAV [hazard ratio (HR) = 0.58, 95% CI 0.51-0.85, p = 0.022). CONCLUSION: Mode of brain death significantly impacts HTx outcomes, with TBD being associated with reduced mortality, rejections and CAV.

Efficacy and safety of exercise rehabilitation in patients with hypertrophic cardiomyopathy.

BACKGROUND: While physical rehabilitation has been shown to be beneficial and safe for patients suffering from heart failure, data on rehabilitation for hypertrophic cardiomyopathy (HCM) patients are limited. METHODS: Forty-five HCM patients participated in an exercise rehabilitation program. Exercise capacity was measured in metabolic equivalent of task (METs) units and functional status was defined according to the New York Heart Association (NYHA). Self-reported measurements addressed the quality of life and daily life function. RESULTS: Of the 45 participants, 32 completed at least 3 months of rehabilitation and had data from two sequential exercise tests. A significant increase in exercise capacity (from mean 5.3 to 6.7 METs, p=0.01), was achieved at higher peak heart rates. Eighteen patients (56%) who showed improvement in exercise capacity did not differ in their NYHA class, clinical, electrocardiographic, or echo-Doppler parameters compared to those who did not improve. The benefit from training was associated with a lower exercise capacity at baseline and was most pronounced in those capable of less than 6.8 METs (p=0.008). No significant arrhythmias or adverse events were recorded in HCM patients during participation. In ∼40% of participants, training improved the subjective perception of functional capacity and quality of life; only 4 patients (9%) discontinued their participation due to discomfort during or following training. The improvement in exercise capacity was comparable between HCM and a reference group of dilated cardiomyopathy patients. CONCLUSIONS: Exercise rehabilitation appears to be applicable and safe in HCM. It mainly benefits patients suffering from significant functional limitation. Larger prospective studies are needed to validate these findings and better characterize patients expected to benefit from these programs.

Does donor-recipient age difference matter in outcome of heart transplantation?

OBJECTIVE: Potential interactions between donor-recipient age difference and outcomes after heart transplantation are not well known. We thus aimed to study the impact of donor-recipient age difference on heart transplantation outcomes. METHODS: Between 1995 and 2017, we assessed 234 heart transplantation patients. Based on donor-recipient age difference histogram, we stratified these patients into three groups: older donors (donor-recipient difference > 0; n = 48), younger donors (donor-recipient difference 0 to -20 years; n = 82), and much younger donors (donor-recipient difference <-20 years; n = 104). RESULTS: The baseline metabolic risk profile of the recipients was significantly higher for the much younger donor group compared with the younger and older groups, including hypertension (52% vs 33% vs 25%, P = 0.002), dyslipidemia (51% vs 51% vs 29%, P = 0.027), diabetes (30% vs 16% vs 17%, P = 0.044), and smoking history (53% vs 46% vs 29%, P = 0.024), respectively. There were no significant differences between the groups in long-term survival, cardiac allograft vasculopathy, or rejection-free survival in unadjusted and adjusted analyses. In the much younger donor group, gender matching was associated with a lower incidence of primary graft dysfunction (37% vs 58% P = 0.05). CONCLUSIONS: Donor-recipient age difference does not significantly impact long-term heart transplantation outcomes.

Differences in Mortality of New-Onset (De-Novo) Acute Heart Failure Versus Acute Decompensated Chronic Heart Failure.

Minimal attention has been paid to understanding the implications of the chronicity of heart failure (HF) diagnosis on prognosis of hospitalized patients with acute HF (AHF). We aimed to assess the differences in outcomes between hospitalized patients with AHF that are new-onset (de-novo) AHF and acutely decompensated chronic HF (ADCHF). We analyzed data of 2,328 patients with AHF, who were enrolled in the HF survey in Israel. Patients were classified into de-novo AHF and ADCHF. A total of 721 (31%) patients were classified as de-novo AHF and 1,607 (69%) patients were classified as ADCHF. Patients with de-novo AHF were more likely to be younger, with fewer co-morbidities represented by lower Charlson index, and less likely to have past myocardial infarction as well as coronary revascularization. At 30 days mortality rates were similar in both groups (9% vs 8% in de-novo AHF and ADCHF, respectively). Survival analysis showed that at 1 and 10 years the all-cause mortality rates were significantly higher in patients with ADCHF (33% vs 22% and 90% vs 72%, 1 and 10 years, log-rank p < 0.001, respectively). Consistently, multivariable analysis showed that patients with ADCHF had an independently 58% and 48%, higher mortality risk at 1 and 10 years, respectively, (1-year hazard ratio = 1.58; 95% confidence interval 1.05 to 2.38, p = 0.03; 10-year hazard ratio = 1.48; 95% confidence interval = 1.23 to 2.77; p < 0.001). In conclusion, previous history of HF is an independent predictor of 1-year and 10-year mortality after hospitalization for AHF. Distinction between de-novo AHF and ADCHF may improve our understanding and risk stratification of patients with AHF.

Recurrent acute cellular rejection graded ISHLT 1R early after heart transplantation negatively affects long-term outcomes: The prognostic significance of 1990 ISHLT grades 1B and 2.

PURPOSE: We investigated the implications of early recurrent 1R rejections for long-term outcomes after heart transplantation (HT) and evaluated the prognostic significance of 1990 ISHLT grading 1B/2 versus 1A. METHODS: Data on all patients who underwent HT between 1992 and 2017 were reviewed. Patients with ≥2 endomyocardial biopsies graded 1R in the first 3 months were classified as "recurrent 1R." Those patients were further categorized according to 1A vs. 1B/2. Outcomes (>3 months) were long-term rejections and the combined endpoint of cardiac allograft vasculopathy (CAV) and cardiovascular (CV) mortality. RESULTS: Sixty-nine out of 228 patients were classified as recurrent grade 1R. In the recurrent 1R group, 2R rejection rate was significantly higher (2.6 ±â€¯0.6 vs 1.2 ±â€¯0.4, p = 0.03), while survival free of rejections was lower (5-year: 57.1% vs. 72.3%, p = 0.022). Multivariate analysis showed that early recurrent 1R rejection was associated with a 30% increased risk for subsequent major rejection. Among 28 patients classified as 1B/2 of the recurrent group, rejection scores were higher, while survival free of rejections was lower, compared to 37 patients of the recurrent group classified as 1A (5-year: 57.1% vs. 72.7%, p = 0.013). Kaplan-Meier analysis showed that CAV/CV mortality at 10 years of follow-up was significantly higher among the recurrent 1R group (38% vs. 18% p < 0.05). Multivariate analysis showed that early recurrent 1R rejections were associated with a 2.5-fold increased risk for CAV/CV mortality. CONCLUSION: Early recurrent grade 1R rejections negatively affect long-term outcomes. The adverse outcomes are experienced mainly by 1R patients subcategorized as1B/2 and not 1A.

Ethnic disparity in Israel impacts long-term results after heart transplantation.

BACKGROUND: Ethnicity may affect graft longevity and recipient mortality after heart transplantation (HTx). We hypothesized that differences in ethnic origin between Arabs and Jews undergoing HTx in Israel may contribute to differences in long-term outcomes. METHODS: The study population comprised all 254 patients who underwent HTx between 1991 and 2017 in a tertiary medical center located in the center of Israel. Patients were categorized as either Jews (226 patients, 89%) or Arabs (28 patients, 11%). The primary end point was cardiac allograft vasculopathy (CAV), secondary end points were cardiovascular (CV) mortality and the combined end point of CAV/CV mortality. RESULTS: In comparison with Jews, Arab patients were significantly younger (ave. age 42 vs. 50) and had shorter in-hospital stay (45 vs. 80 days). However, Kaplan-Meier survival analysis showed that at 10 years of follow-up CAV rates were significantly higher among Arabs (58%) compared with Jews (23%; log-rank P = 0.01) for the overall difference during follow-up. Similar results were shown for the separate end point of CV mortality and the combined end point of CAV/CV mortality. Multivariate analysis, which controlled for age, gender, statin treatment, and other potential confounders, showed that Arab recipient ethnic origin was associated with a significant > 2.5-fold (p = 0.01) increase in the risk for CAV; a > 4-fold increase in the risk for CV mortality (p = 0.001); and approximately 4-fold increase in the risk for the combined end point (p = 0.001). These findings were validated by propensity score analysis. CONCLUSIONS: Our data suggest that Arab ethnic origin is associated with a significantly increased risk for CAV and mortality following HTx. Suggested explanations contributing to ethnic disparities in Israel include socioeconomic, environmental and genetic factors. Further studies are required to evaluate whether more aggressive risk factor management in the Israeli Arab population following HTx would reduce CAV and CV mortality in this high-risk population. Increased awareness and early intervention of the Israeli healthcare system and cooperation with the Arab community is of paramount importance.