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.

The impact of diabetes mellitus on the clinical phenotype of hypertrophic cardiomyopathy.

AIMS: Diabetes mellitus (DM) aggravates the clinical features of ischaemic and hypertensive heart diseases and worsens the prognosis of heart failure patients. Hypertrophic cardiomyopathy (HCM) and diabetes coexist fairly frequently in elderly patients but the impact of DM on the clinical phenotype of HCM is yet unknown. We sought to describe if predominant features of heart failure in DM patients exist independently in HCM. METHODS AND RESULTS: We reviewed clinical characteristics of 937 patients, age ≥40, diagnosed with HCM, from two tertiary medical centres in Spain and Israel. A propensity score matched cohort of 294 patients was also analysed. Our cohort comprised 102 HCM patients with diabetes (8.7%). Patients with DM were older at diagnosis {median 56 [interquartile range (IQR) 47-67] vs. 53 (IQR 43-63), P = 0.02} and had a higher prevalence of comorbidities. Hypertrophic cardiomyopathy patients with DM had a higher prevalence of diastolic dysfunction, pulmonary hypertension, significant mitral regurgitation, and pacemaker implantation. Hypertrophic cardiomyopathy patients with DM had a higher New York Heart Association (NYHA) class (P < 0.001) and lower exercise capacity [7.0 METS (IQR 5.0-10.0) vs. 9.0 METS (IQR 6.6-11.0), P = 0.002]. These findings were independent of age, gender, country of origin, hypertension, and coronary artery disease. Patients with diabetes had a significantly higher 15-year mortality (22% vs. 15%, P = 0.03), with no differences in sudden cardiac death, appropriate implanted cardioverter-defibrillator therapy, or heart transplantation. CONCLUSION: Hypertrophic cardiomyopathy patients with diabetes are older and have a higher cardiovascular risk profile. They have a lower functional capacity and more heart failure symptoms due to diastolic dysfunction.

Electrophysiological abnormalities in induced pluripotent stem cell-derived cardiomyocytes generated from Duchenne muscular dystrophy patients.

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle degenerative disease, caused by mutations in the dystrophin gene and resulting in death because of respiratory or cardiac failure. To investigate the cardiac cellular manifestation of DMD, we generated induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes (iPSC-CMs) from two DMD patients: a male and female manifesting heterozygous carrier. Dystrophin mRNA and protein expression were analysed by qRT-PCR, RNAseq, Western blot and immunofluorescence staining. For comprehensive electrophysiological analysis, current and voltage clamp were used to record transmembrane action potentials and ion currents, respectively. Microelectrode array was used to record extracellular electrograms. X-inactive specific transcript (XIST) and dystrophin expression analyses revealed that female iPSCs underwent X chromosome reactivation (XCR) or erosion of X chromosome inactivation, which was maintained in female iPSC-CMs displaying mixed X chromosome expression of wild type (WT) and mutated alleles. Both DMD female and male iPSC-CMs presented low spontaneous firing rate, arrhythmias and prolonged action potential duration. DMD female iPSC-CMs displayed increased beat rate variability (BRV). DMD male iPSC-CMs manifested decreased If density, and DMD female and male iPSC-CMs showed increased ICa,L density. Our findings demonstrate cellular mechanisms underlying electrophysiological abnormalities and cardiac arrhythmias in DMD.

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.

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.

High tacrolimus trough level variability is associated with rejections after heart transplant.

Tacrolimus, the major immunosuppressant after heart transplant (HTx) therapy, is a narrow therapeutic index drug. Hence, achieving stable therapeutic steady state plasma concentrations is essential to ensure efficacy while avoiding toxicity. Whether high variability in steady state concentrations is associated with poor outcomes is unknown. We investigated the association between tacrolimus trough level variability during the first year post-HTx and outcomes during and beyond the first postoperative year. Overall, 72 patients were analyzed for mortality, of whom 65 and 61 were available for rejection analysis during and beyond the first year post-HTx, respectively. Patients were divided into high (median >28.8%) and low tacrolimus level variability (<28.8%) groups. Mean tacrolimus levels did not differ between the groups (12.7 ± 3.4 ng/mL vs 12.8 ± 2.4 ng/mL, P = .930). Patients in the high variability group exhibited higher long-term rejection rate (median total rejection score: 0.33 vs 0, P = .04) with no difference in rejection scores within the first year post-HTx. Multivariate analysis showed that high tacrolimus trough level variability was associated with >8-fold increased risk for any rejection beyond the first year post-HTx (P = .011). Mortality was associated only with cardiovascular complications (P = .018), with no effect of tacrolimus through level variability.

Donor-recipient ethnic mismatching impacts short- and long-term results of heart transplantation.

BACKGROUND: The impact of donor-recipient ethnic matching on heart transplantation (HT) has been poorly studied with inconclusive results. We aimed to investigate the impact of ethnic matching on HT outcomes in Israeli multiethnic patients. METHODS: The study comprised 168 patients who underwent HT from 1990-2017. Patients and their donors were ethnically categorized to Jews and Arabs. Primary end points were all-cause in-hospital and late mortality; secondary end points included primary graft dysfunction (PGD), rejections, and vasculopathy. RESULTS: Donor-recipient ethnic matching was found in 111 patients, while 57 were ethnically mismatched. Baseline characteristics were similar in both groups. Ethnic mismatching was associated with >7-fold (P = 0.018) increased risk for in-hospital mortality and >8-fold (P < 0.001) increased risk for PGD. Kaplan-Meier survival analysis showed that overall survival at 10 years was significantly higher among matched patients (73% vs 43%, log-rank P < 0.001). Multivariate analysis showed that ethnic mismatching was associated with an approximately fourfold higher risk for death (P < 0.01). These findings were validated by propensity score analysis. The ethnic mismatched group experienced significantly higher rejection rates compared with the matched group with lower survival free of rejections (log-rank P = 0.029). No differences in vasculopathy were found. CONCLUSIONS: Donor-recipient ethnic mismatch is an important independent predictor of early- and long-term outcomes following HT, and is associated with increased risk for PGD, rejections, and mortality. These findings will help to design tailored treatment protocols leading to improved outcomes after HT.

Sub-acute vs. Late-onset Presentation of Oncotherapy Related Cardiotoxicity: Predictors of Cardiac Function Recovery and Long-Term Outcome.

BACKGROUND: Cardiac damage caused by oncological therapy may manifest early or many years after the exposure. OBJECTIVES: To determine the differences between sub-acute and late-onset cardiotoxicity in left ventricular ejection fraction (LVEF) recovery as well as long-term prognosis. METHODS: We studied 91 patients diagnosed with impaired systolic function and previous exposure to oncological therapy. The study population was divided according to sub-acute (from 2 weeks to ≤ 1 year) and late-onset (> 1 year) presentation cardiotoxicity. Recovery of LVEF of at least 50% was defined as the primary end point and total mortality was the secondary end point. RESULTS: Fifty-three (58%) patients were classified as sub-acute, while 38 (42%) were defined as late-onset cardiotoxicity. Baseline clinical characteristics were similar in the two groups. The mean LVEF at presentation was significantly lower among patients in the late-onset vs. sub-acute group (28% vs. 37%, respectively, P < 0.001). Independent predictors of LVEF recovery were trastuzumab therapy and a higher baseline LVEF. Although long-term mortality rates were similar in the groups with sub-acute and late-onset cardiotoxicity, improvement of LVEF was independently associated with reduced mortality. CONCLUSIONS: Our findings suggest that early detection and treatment of oncological cardiotoxicity play an important role in LVEF recovery and long-term prognosis.

Trends and Outcomes in Heart Transplantation over the Past Three Decades: A Single Tertiary Center Experience in Israel.

BACKGROUND: Heart transplantation (HT) is the treatment of choice for patients with end-stage heart failure. The HT unit at the Sheba Medical Center is the largest of its kind in Israel. OBJECTIVES: To evaluate the experience of HT at a single center, assess trends over 3 decades, and correlate with worldwide data. METHODS: Between 1990 and 2017, we reviewed all 285  adult HT patients. Patients were grouped by year of HT: 1990-1999 (decade 1), 2000-2009 (decade 2), and 2010-2017 (decade 3). RESULTS: The percentage of women undergoing HT has increased and etiology has shifted from ischemic to non-ischemic cardiomyopathy (10% vs. 25%, P = 0.033; 70% vs. 40% ischemic, for decades 1 vs. 3, respectively). Implantation of left ventricular assist device as a bridge to HT has increased. Metabolic profile has improved over the years with lower low-density lipoprotein, diabetes, and hypertension after HT (101 mg/dl, 27%, and 41% at decade 3, respectively). There has been a prominent change in immunosuppressive treatments, currently more than 90% are treated with tacrolimus, compared with 2.7% and 30.9% in decades 1 and 2, respectively (P < 0.001). Cardiac allograft vasculopathy (CAV) rates have declined significantly (47% vs. 17.5% for decades 1 and 2, P < 0.001) as have the combined endpoint of CAV/death. Similarly, the current incidence of acute rejections is significantly lower. CONCLUSIONS: Our analysis of over 25 years of a single-center experience with HT shows encouraging improved results, which are in line with worldwide standards and experience.

Disease management in the treatment of patients with chronic heart failure who have universal access to health care: a randomized controlled trial.

BACKGROUND: The efficacy of disease management programs in improving the outcome of heart failure patients remains uncertain and may vary across health systems. This study explores whether a countrywide disease management program is superior to usual care in reducing adverse health outcomes and improving well-being among community-dwelling adult patients with moderate-to-severe chronic heart failure who have universal access to advanced health-care services and technologies. METHODS: In this multicenter open-label trial, 1,360 patients recruited after hospitalization for heart failure exacerbation (38%) or from the community (62%) were randomly assigned to either disease management or usual care. Disease management, delivered by multi-disciplinary teams, included coordination of care, patient education, monitoring disease symptoms and patient adherence to medication regimen, titration of drug therapy, and home tele-monitoring of body weight, blood pressure and heart rate. Patients assigned to usual care were treated by primary care practitioners and consultant cardiologists. The primary composite endpoint was the time elapsed till first hospital admission for heart failure exacerbation or death from any cause. Secondary endpoints included the number of all hospital admissions, health-related quality of life and depression during follow-up. Intention-to-treat comparisons between treatments were adjusted for baseline patient data and study center. RESULTS: During the follow-up, 388 (56.9%) patients assigned to disease management and 387 (57.1%) assigned to usual care had a primary endpoint event. The median (range) time elapsed until the primary endpoint event or end of study was 2.0 (0-5.0) years among patients assigned to disease management, and 1.8 (0-5.0) years among patients assigned to usual care (adjusted hazard ratio, 0.908; 95% confidence interval, 0.788 to 1.047). Hospital admissions were mostly (70%) unrelated to heart failure. Patients assigned to disease management had a better health-related quality of life and a lower depression score during follow-up. CONCLUSIONS: This comprehensive disease management intervention was not superior to usual care with respect to the primary composite endpoint, but it improved health-related quality of life and depression. A disease-centered approach may not suffice to make a significant impact on hospital admissions and mortality in patients with chronic heart failure who have universal access to health care. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00533013 . Trial registration date: 9 August 2007. Initial protocol release date: 20 September 2007.

Feelings of indebtedness and guilt toward donor and immunosuppressive medication adherence among heart transplant (HTx) patients, as assessed in a cross-sectional study with the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS).

BACKGROUND: Nonadherence (NA) to immunosuppressive (IS) medications after organ transplant is a major risk factor for transplant failure, morbidity, and treatment costs. This study examined the association between feelings of indebtedness and guilt toward the donor, and IS medication adherence among HTx patients. METHODS: In this cross-sectional, descriptive, correlational study, a convenience sample of 102 HTx patients, from the outpatient facility of a tertiary medical center in Israel, completed the BAASIS, a validated instrument for assessing adherence, and reported their feelings of indebtedness and guilt toward the donor. RESULTS: Missing a dose or skipping two or more doses, taking medication >2 hours before or after the recommended dosing time, altering the prescribed amount, or completely stopping the IS treatment in the last 4 weeks, characterized 64 patients (64%). The highest score received the item "timing nonadherence," characterizing 58 patients (56.9%). Age, waiting time, and time since transplant, guilt feelings, and indebtedness to donor explained 17% (R2 =.17) of the variance in adherence (χ2(5) =13.22, P=.021), with age, time since transplant, and guilt feelings significantly explaining adherence. CONCLUSION: Physicians and nurses should inquire about the presence of guilt feelings, as they might be associated with NA to medications after HTx.

Risk of early, intermediate, and late rejection following heart transplantation: Trends over the past 25 years and relation to changes in medical management. Tertiary center experience: The Sheba Heart Transplantation Registry.

AIM: To explore the trends in the risk for rejection following heart transplantation (HT) over the past 25 years, and their relation to changes in medical management. METHODS: The study population comprised 216 HT patients. Rejection periods were defined as follows: 0-3 months (early), 3-12 months (intermediate), and 12+ months (late). HT era was dichotomized as follows: 1991-1999 (remote era) and 2000-2016 (recent era). Medication combination was categorized as newer (TAC, MMF, and everolimus) vs older therapies (AZA, CSA). RESULTS: Multivariate analysis showed that patients who underwent HT during the recent era experienced a significant reduction in the risk for major rejection. These findings were consistent for early (OR = 0.44 [95% CI 0.22-0.88]), intermediate (OR = 0.02 [95% CI 0.003-0.11]), and late rejections (OR = 0.18 [95% CI 0.05-0.52]). Using the year of HT as a continuous measure showed that each 1-year increment was independently associated with a significant reduction in the risk for early, intermediate, and late rejections (5%, 21%, 18%, respectively). In contrast, the risk reduction associated with newer types of immunosuppressive therapies was not statistically significant after adjustment for the treatment period. CONCLUSIONS: Major rejection rates following HT have significantly declined over the past 2 decades even after adjustment for changes in immunosuppressive therapies, suggesting that other factors may also play a role in the improved outcomes of HT recipients.

Early aspirin initiation following heart transplantation is associated with reduced risk of allograft vasculopathy during long-term follow-up.

AIM: Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality after heart transplantation (HT). Enhanced platelet reactivity is a contributing factor. We aimed to investigate the association between early initiation of aspirin therapy post-HT and the 15-year risk of the development of CAV. METHODS: We studied 206 patients who underwent HT between 1991 and 2016. Multivariate Cox proportional hazards regression modeling was employed to evaluate the association between early aspirin initiation and the long-term risk of CAV. RESULTS: Ninety-seven patients (47%) received aspirin therapy. At 15 years of follow-up, the rate of CAV was lowered by sixfold in patients treated with aspirin compared with the non-treated patients: 7% vs 37% (log-rank P-value<.001). The corresponding rates of the combined end-point of CAV or death were also lower in patients treated with aspirin, compared with the non-treated patients: 42% vs 78% (log-rank P < .001). Consistently, multivariate analysis showed that early aspirin therapy was associated with a significant 84% (P < .001) reduction in CAV risk, and with a corresponding 68% (P < .0001) reduction in the risk of the combined end-point of CAV or death. We further validated these results using a propensity score-adjusted Cox model. CONCLUSIONS: Early aspirin initiation is independently associated with a significant reduction in the risk of CAV.

Prevalence and clinical predictors of reverse remodeling in patients with dilated cardiomyopathy.

BACKGROUND: Contemporary therapiesimprove prognosis and may restore left ventricular (LV) sizeand function. OBJECTIVES: To examine the prevalence, clinical features and therapies associated with reverse remodeling (RR) in dilated cardiomyopathy (DCM). METHODS: The study group comprised 188 DCM patients who had undergone two echo examinations at least 6 months apart. RR was defined as increased LV ejection fraction (LVEF) by > or = 10% concomitant with > or = 10% decreased LV end-diastolic dimension. RESULTS: RR occurred in 50 patients (26%) and was associated with significantly reduced end-systolic dimension, left atrial size, grade of mitral regurgitation, and pulmonary artery pressure. NYHA class improved in the SRR group. RR was less common in familial DCM and a long-standing disease and was more prevalent in patients with prior exposure to chemotherapy. Recent-onset disease, Iower initial LVEF and normal electrocardiogram were identified as independent predictors of RR. Beta-blocker dose wasrelated to improved LVEF but not to RR. Over a mean follow-up of 23 months, 16 patients (12%) from the 'no-RR' group died or underwent heart transplantation compared to none from the RR group (P < 0.01). CONCLUSIONS: Contemporary therapies led to an an improvement in the condition of a considerable number of DCM patients. A period of close observation while optimizing medical therapy should be considered before deciding on invasive procedures.

Merits and pitfalls of genetic testing in a hypertrophic cardiomyopathy clinic.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM. OBJECTIVES: To analyze the impact of genetic diagnosis on the clinical management of HCM. METHODS: Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation. RESULTS: Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation. CONCLUSIONS: Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determines the indication for genetic testing and interpretation of the results.

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.

Peritoneal dialysis in patients with refractory congestive heart failure: potential prognostic factors.

BACKGROUND: Peritoneal dialysis (PD) is increasingly used for long-term management of refractory congestive heart failure (CHF). In this study, we investigated the outcome of patients with refractory CHF treated with PD, aiming to identify potential prognostic factors for long term-survival. METHODS: This was a prospective observational study over a period of 42 months which included 37 refractory CHF patients. RESULTS: Median survival on PD was 14 months (1-41 months). Long survivors had serum sodium >132 mEq/l (p < 0.001), serum albumin >3.2 g/dl (p < 0.001) and hospitalization rate <2 days per month a year before starting the treatment (p = 0.008). Patients in the lowest survival quartile had lower serum albumin (2.8 vs. 3.5 g/dl in longer survivors, p = 0.003) and serum sodium (126 vs. 137 mEq/l, p < 0.0001), higher serum leukocyte count (7,500 vs. 6,800/µl in long survivors, p = 0.033), higher glomerular filtration rate (39.4 vs. 29.9 ml/min/1.73 m(2), p = 0.035), had more hospitalization before starting the treatment (3.4 vs. 1.9 days per month, p = 0.003) and lower estimated left ventricular mass index (113 vs. 137 g/m(2), p = 0.035). Long-term survivors demonstrated significant improvement in the New York Heart Association functional class by a median of one class, reduced hospitalization rate by 55% and decrease in dependence on intravenous diuretics and vasoactive medications (73% drop in CHF day care visits during the first year of treatment). CONCLUSIONS: Survival of patients with refractory CHF treated with PD is highly variable. Serum sodium, serum albumin and hospitalization rate are important prognostic factors for long-term survival. Long survivors demonstrated improved functional status, reduced hospitalization and mortality rates.

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.

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.