Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel.

BACKGROUND: Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance. METHODS: We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition. We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons. RESULTS: Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal. The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46). As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20). The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637. CONCLUSIONS: The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.

Establishing a New Left Ventricular Assist Device Program: From Concept to Reality.

BACKGROUND: Left ventricular assist devices (LVAD) are a staple element in contemporary treatment of advanced heart failure. LVAD surgeries are mostly done in heart transplantations centers, as a destination therapy or as a bridge to heart transplantation. OBJECTIVES: To describe our step-by-step experience in establishing and implementing a new LVAD program in a non-heart transplant center. To give insight to our short- and long-term results of our first 25 LVAD patients. METHODS: Preliminary steps included identifying the need for a new program and establishing the leading team. Next is defining protocols for pre-operative evaluation, operating room, post-operative management, and outpatient follow-up. The leading team needs to educate other relevant units in the hospital that will be involved in the care of these patients. It is essential to work in collaboration with a heart transplant center from the very beginning. Patient selection is of major importance especially in the early experience. Initially "low risk" patients should be enrolled. RESULTS: We describe our first 25 LVAD patients. Our first five patients all survived beyond 2 years, with no major complications. Overall, there was one operative death due to massive GI bleeding. There were four late deaths due to septic events. CONCLUSIONS: Establishing a new LVAD program can be successful also with small- and medium-size programs. With careful and meticulous planning LVAD implantation can be extended to more centers thus offering an excellent solution for advanced heart failure patients.

Outcomes following transcatheter repair in patients with functional mitral regurgitation not receiving guideline directed medical therapy in Israel.

BACKGROUND: Transcatheter edge to edge repair (TEER) improves prognosis in patients with functional mitral regurgitation (FMR) receiving guideline directed medical therapy (GDMT). Many patients with FMR do not receive GDMT and the utility of TEER in this population remains unclear. METHODS: We retrospectively studied patients undergoing TEER. Clinical, echocardiographic and procedural variables were recorded. GDMT was defined as use of RAAS inhibitors and MRAs unless GFR was under 30 as well as beta blockers. The primary endpoint of the study was one year mortality. RESULTS: 168 patients (mean age 71.3 ± 9.3; 66% males) with FMR who underwent TEER were included of whom 116 (69%) received GDMT at the time of TEER and 52 (31%) did not. There were no significant demographic or clinical differences between the groups. There were no significant differences in procedural success and complications between groups. One year mortality was identical in the two groups (15% vs. 15%; RR 1.06, CI 0.43-2.63, P = 0.90). CONCLUSIONS: Our findings suggest that procedural success and one year mortality following TEER was not significantly different in HFREF patients with FMR with or without GDMT. Larger, prospective studies are necessary to define the benefit of TEER in this population.

The V-LAP System for Remote Left Atrial Pressure Monitoring of Patients With Heart Failure: Remote Left Atrial Pressure Monitoring.

OBJECTIVE: Patients with heart failure (HF) are at an increased risk of hospital admissions. The aim of this report is to describe the feasibility, safety and accuracy of a novel wireless left atrial pressure (LAP) monitoring system in patients with HF. METHODS: The V-LAP Left Atrium Monitoring systEm for Patients With Chronic sysTOlic & Diastolic Congestive heart Failure (VECTOR-HF) study is a prospective, multicenter, single-arm, open-label, first-in human clinical trial to assess the safety, performance and usability of the V-LAP system (Vectorious Medical Technologies) in patients with New York Heart Association class III HF. The device was implanted in the interatrial septum via a percutaneous, trans-septal approach guided by fluoroscopy and echocardiography. Primary endpoints included the successful deployment of the implant, the ability to perform initial pressure measurements and safety outcomes. RESULTS: To date, 24 patients have received implants of the LAP-monitoring device. No device-related complications have occurred. LAP was reported accurately, agreeing well with wedge pressure at 3 months (Lin concordance correlation coefficient = 0.850). After 6 months, New York Heart Association class improved in 40% of the patients (95% CI = 16.4%-63.5%), while the 6-minute walk test distance had not changed significantly (313.9 ± 144.9 vs 232.5 ± 129.9 meters; P = 0.076). CONCLUSION: The V-LAP left atrium monitoring system appears to be safe and accurate.

Effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute myocardial infarction-Results of the Chymase Inhibitor in Adverse Remodeling after Myocardial Infarction (CHIARA MIA) 2 trial.

BACKGROUND: Adverse cardiac remodeling is a major risk factor for the development of post myocardial infarction (MI) heart failure (HF). This study investigates the effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute ST-segment-elevation myocardial infarction (STEMI). METHODS: In this double-blind, randomized, placebo-controlled trial patients with first STEMI were eligible. To preferentially enrich patients at high risk of adverse remodeling, main inclusion criteria were a left-ventricular ejection fraction (LVEF) ≤45% and an infarct size >10% on day 5 to 9 post MI as measured by cardiac MRI. Patients were then randomized to 6 months treatment with either 25 mg fulacimstat (n = 54) or placebo (n = 53) twice daily on top of standard of care starting day 6 to 12 post MI. The changes in LVEF, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume index (LVESVI) from baseline to 6 months were analyzed by a central blinded cardiac MRI core laboratory. RESULTS: Fulacimstat was safe and well tolerated and achieved mean total trough concentrations that were approximately tenfold higher than those predicted to be required for minimal therapeutic activity. Comparable changes in LVEF (fulacimstat: 3.5% ±â€¯5.4%, placebo: 4.0% ±â€¯5.0%, P = .69), LVEDVI (fulacimstat: 7.3 ±â€¯13.3 mL/m2, placebo: 5.1 ±â€¯18.9 mL/m2, P = .54), and LVESVI (fulacimstat: 2.3 ±â€¯11.2 mL/m2, placebo: 0.6 ±â€¯14.8 mL/m2, P = .56) were observed in both treatment arms. CONCLUSION: Fulacimstat was safe and well tolerated in patients with left-ventricular dysfunction (LVD) after first STEMI but had no effect on cardiac remodeling.

The Effect of Mineralocorticoid Receptor Antagonists on Recruitment and Function of Endothelial Progenitor Cells in Patients with Congestive Heart Failure.

BACKGROUND: Circulating endothelial progenitor cells have an important role in the process of vascular repair. Impaired recruitment and function of endothelial progenitor cells is related to the pathophysiology of congestive heart failure. Endothelial progenitor cells have been shown to express the mineralocorticoid receptor. OBJECTIVES: To investigate the effect of mineralocorticoid receptor antagonists on endothelial progenitor cells in patients with heart failure. METHODS: Twenty-four patients with compensated heart failure, who were not under mineralocorticoid receptor antagonist therapy, were recruited. Either eplerenone (n=8) or spironolactone (n=16) therapy was initiated. Circulating endothelial progenitor cell level, identified as the proportion of mononuclear cells expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34, was evaluated by flow cytometry at baseline and after 8 weeks. Following 7 days of culture, colonies were counted by microscopy and MTT assay was performed on randomly selected patients (n=12) to estimate viability. RESULTS: Both median CD34+/VEGFR2+ and median CD133+/VEGFR2+ increased significantly (P = 0.04 and 0.02, respectively). However, the number of colonies and viability of the cells after therapy (as assessed by the MTT assay) was not significantly different compared with the baseline. CONCLUSIONS: These preliminary results suggest that mineralocorticoid receptor blockade may enhance endothelial progenitor cells recruitment in patients with compensated heart failure.

Who should manage patients with chest pain in the emergency room?

A concise management scheme is discussed for the best outcome in patients with chest pain.

Attenuation in peripheral endothelial function after continuous flow left ventricular assist device therapy is associated with cardiovascular adverse events.

BACKGROUND: Patients with heart failure (HF) have abnormal endothelial function. Although use of a continuous flow left ventricular assist device (CF-LVAD) results in significant hemodynamic improvement, the effects on systemic endothelial function are unclear. METHODS AND RESULTS: Eighteen HF patients with CF-LVAD implantation were included in this prospective observational study. We measured reactive hyperemia index (RHI) before and after CF-LVAD implantation to evaluate sequential changes in endothelial function. Patients were followed clinically for the occurrence of adverse cardiovascular events, a composite of death, thrombosis, bleeding, HF, renal failure, and arrhythmia. Preoperative RHI was 1.77±0.39. Early in the postoperative period (7-14 days after operation) RHI significantly decreased to 1.19±0.31 (P<0.001, compared with preoperative RHI). At first and second follow-up (4-6 weeks and 3-7 months after operation) RHI remained lower at 1.48±0.50 (P=0.030) and 1.26±0.37 (P=0.002), respectively, compared with preoperative RHI. The decrease in early postoperative RHI relative to preoperative RHI was significantly associated with adverse cardiovascular events after CF-LVAD (age-adjusted risk ratio for 0.25 decrease in RHI, 1.35; 95% confidence interval: 1.13-1.62, P=0.001). CONCLUSIONS: Peripheral endothelial function had a significant and persistent decline up to 5 months following implantation of CF-LVAD, and this decline was associated with adverse cardiovascular events. These findings may provide insight into some of the vascular complications following CF-LVAD in HF patients.

Hepatic and renal function with successful long-term support on a continuous flow left ventricular assist device.

INTRODUCTION: Data regarding the long-term clinical effects of a continuous flow left ventricular assist device (CF-LVAD) on hepato-renal function is limited. Hence our aim was to assess changes in hepato-renal function over a one-year period in patients supported on a CF-LVAD. METHODS: During the study period 126 patients underwent CF-LVAD implant. Changes in hepato-renal laboratory parameters were studied in 61/126 patients successfully supported on a CF-LVAD for period of one year. A separate cohort of a high-risk group (HCrB) of patients (56/126) with a serum creat>1.9 mg/dL (168 µmol/L) (75th percentile) or a serum bil>1.5 mg/dL (25.65 µmol/L) (75th percentile) was created. Changes in serum creatinine and bilirubin were analysed at regular intervals for this group along with the need for renal replacement therapy. RESULTS: Baseline creatinine and blood urea nitrogen (BUN) for the entire cohort was 1.4[1.2,1.9 mg/dL] [123.7(106,168) µmol/L) and 27[20,39.5 mg/dL] [9.6(7.1,14.1) mmol/L] respectively. After an initial reduction at the end of one month [1(0.8,1.2) mg/dL; 88(70,105) µmol/L] (p<0.0001), a gradual increase was noted over the study period to reach (1.25[1.1,1.5] mg/dL; 106(97.2,132.6) µmol/L] (p=0.0003). The serum bilirubin normalised from a [1(0.7,1.55) mg/dL] [17(18.8,25.7) µmol/L) to 0.9(0.6,1.2)mg/dL [15.4(10.2,20.5) µmol/L] (p=0.0005) and continued to decline over one year. Improvement in the synthetic function of the liver was demonstrated by a rise in the serum albumin levels to reach 4.3[4.1,4.5] [43(41,45) gm/L] at the end of one year (p<0.0001). The baseline serum creatinine and bilirubin for the high-risk cohort (HCrB) was 1.9(1.3,2.4) mg/dL [168(115,212) µmol/L] and 1.7(1.00,2.4) mg/dL [29(17.1,68.4) µmol/L] respectively. The high-risk cohort (HCrB) demonstrated a trend towards higher 30-day mortality (p=0.06). While the need for temporary renal replacement therapy was higher in this cohort (16% vs. 4%; p=0.03), only 3% need it permanently. A significant reduction in creatinine was apparent at the end of one month [1.1(0.8,1.4) mg/dL; 97(70.7,123.7) µmol/L] (p<0.0001) and then remained stable at [1.3(1.1,1.5) mg/dL; 115(97,132.6) µmol/L]. Bilirubin demonstrated a 30% decline over one month and then remained low at [0.7(0.5,0.8) mg/dL; 62(44,70) µmol/L] p=0.0005 compared to the pre-operative baseline. CONCLUSION: Hepato-renal function demonstrates early improvement and then remains stable in the majority of patients on continuous flow left ventricular assist device support for one year. High-risk patients demonstrate a higher 30-day mortality and temporary need for renal replacement therapy. Yet even in this cohort, improvement is present over a period of one year on the device, with a minimal need for permanent haemodialysis.

Incidence and Predictors for Recurrence of Ventricular Arrhythmia Presenting During Acute Myocarditis: A Multicenter Study.

BACKGROUND: Management of acute myocarditis (AM) patients experiencing ventricular arrhythmia (VA) during acute illness is controversial, especially regarding early implantable cardioverter-defibrillator (ICD) implantation. OBJECTIVES: The purpose of this study was to evaluate the prevalence of and find predictors for long-term sustained VA recurrence and overall mortality among AM patients with VA. METHODS: This was a multicenter retrospective analysis of AM patients (verified by cardiac magnetic resonance imaging or myocardial biopsy) with documented VA during the acute illness ("initial VA"). Patients with history of myocardial infarction, heart failure, or VA were excluded. The study endpoint was a composite of sustained VA and overall mortality during follow-up. RESULTS: The study included 69 AM patients with initial VA: sustained monomorphic ventricular tachycardia (MMVT) (n = 25), sustained polymorphic ventricular tachycardia (VT)/ventricular fibrillation (n = 13), and nonsustained VT (n = 31). Age was 44 ± 13 years, and 23 of 69 (33.3%) were women. During median follow-up of 5.5 years, 27 of 69 (39%) patients reached the composite endpoint including sustained VA (n = 24) and death (n = 11). Initial MMVT, predischarge left ventricular dysfunction (left ventricular ejection fraction <50%), and anteroseptal delayed enhancement on cardiac magnetic resonance imaging were significantly associated with the composite endpoint. On multivariable analysis, initial MMVT (HR: 5.17; 95% CI: 1.81-14.6; P = 0.001) and predischarge LV dysfunction (HR: 4.57; 95% CI: 1.83-11.5; P = 0.005) were independently associated with the composite endpoint. Using these 2 predictors, we could delineate subgroups with low (∼4%), medium (∼42%), and high (∼82%) 10-year incidence of composite endpoint. CONCLUSIONS: AM patients presenting with VA have high incidence of sustained VA recurrence and mortality posthospitalization. Initial MMVT and predischarge LV dysfunction are independently associated with VA recurrence and mortality. Implantable cardioverter-defibrillator implantation may be considered in such high-risk patients.

Culprit Lesion Coronary Intervention Before Complete Angiography in ST-Elevation Myocardial Infarction: A Randomized Clinical Trial.

Importance: Rapid reperfusion during primary percutaneous coronary intervention (PCI) is associated with improved outcomes among patients with ST-elevation myocardial infarction (STEMI). Although attempts at reducing the time from STEMI diagnosis to arrival at the catheterization laboratory have been widely investigated, intraprocedural strategies aimed at reducing the time to reperfusion are lacking. Objective: To evaluate the effect of culprit lesion PCI before complete diagnostic coronary angiography (CAG) vs complete CAG followed by culprit lesion PCI on reperfusion times among patients with STEMI. Design, Setting, and Participants: This open-label, prospective, randomized clinical trial was conducted between April 1, 2021, and August 31, 2022, among patients admitted to a tertiary center in Jerusalem, Israel, with a diagnosis of STEMI undergoing primary PCI. All patients were followed up for 1 year. Analysis was on an intention-to-treat basis. Intervention: Patients were randomized in a 1:1 ratio to undergo either culprit lesion PCI before complete CAG or complete CAG followed by culprit lesion PCI. Main Outcomes and Measures: A needle-to-balloon time of 10 minutes or less. Results: A total of 216 patients were randomized, with 184 patients (mean [SD] age, 62.9 [12.2] years; 155 men [84.2%]) included in the final intention-to-treat analysis; 90 patients (48.9%) were randomized to undergo culprit lesion PCI before CAG, and 94 (51.1%) were randomized to undergo to CAG followed by PCI. Patients who underwent culprit lesion PCI before complete CAG had a shorter mean (SD) needle-to-balloon time (11.4 [5.9] vs 17.3 [13.3] minutes; P < .001). The primary outcome of a needle-to-balloon time of 10 minutes or less was achieved for 51.1% of patients (46 of 90) who underwent culprit lesion PCI before CAG and for 19.1% of patients (18 of 94) who underwent complete CAG followed by culprit lesion PCI (odds ratio, 4.4 [95% CI, 2.2-9.1]; P < .001). Rates of adverse events were similar between groups. In a subgroup analysis, the effect of culprit lesion PCI before complete CAG on the primary outcome was consistent. There were no differences in rates of in-hospital, 30-day, and 1-year all-cause mortality. Conclusions and Relevance: In this randomized clinical trial of patients with STEMI, culprit lesion PCI before complete CAG resulted in shorter reperfusion times. Larger trials are needed to validate these results and to evaluate the effect on clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT05415085.

Physician-directed patient self-management in heart failure using left atrial pressure: Interim insights from the VECTOR-HF I and IIa studies.

AIMS: Haemodynamic monitoring using implantable pressure sensors reduces the risk of heart failure (HF) hospitalizations. Patient self-management (PSM) of haemodynamics in HF has the potential to personalize treatment, increase adherence, and reduce the risk of worsening HF, while lowering clinicians' burden. METHODS AND RESULTS: The VECTOR-HF I and IIa studies are prospective, single-arm, open-label clinical trials assessing safety, usability and performance of left atrial pressure (LAP)-guided HF management using PSM in New York Heart Association class II and III HF patients. Physician-prescribed LAP thresholds trigger patient self-adjustment of diuretics. Primary endpoints include the ability to perform LAP measurements and transmit data to the healthcare provider (HCP) interface and the patient guidance application, and safety outcomes. This is an interim analysis of 13 patients using the PSM approach. Over 12 months, no procedure- or device-related major adverse cardiovascular or neurological events were observed, and there were no failures to obtain measurements from the sensor and transmit the data to the HCP interface and the patient guidance application. Patient adherence was 91.4%. Using PSM, annualized HF hospitalization rate significantly decreased compared to a similar period prior to PSM utilization (0 admissions vs. 0.69 admissions over 11.84 months, p = 0.004). At 6 months, 6-min walk test distance and the Kansas City Cardiomyopathy Questionnaire overall summary score demonstrated significant improvement. CONCLUSIONS: Interim findings suggest that PSM using a LAP monitoring system is feasible and safe. PSM is associated with high patient adherence, potentially improving HF patients' functional status, quality of life, and limiting HF hospitalizations.

Sirolimus as primary immunosuppression attenuates allograft vasculopathy with improved late survival and decreased cardiac events after cardiac transplantation.

BACKGROUND: We retrospectively analyzed the potential of sirolimus as a primary immunosuppressant in the long-term attenuation of cardiac allograft vasculopathy progression and the effects on cardiac-related morbidity and mortality. METHODS AND RESULTS: Forty-five cardiac transplant recipients were converted to sirolimus 1.2 years (0.2, 4.0) after transplantation with complete calcineurin inhibitor withdrawal. Fifty-eight control subjects 2.0 years (0.2, 6.5 years) from transplantation were maintained on calcineurin inhibitors. Age, sex, ejection fraction, and time from transplantation to baseline intravascular ultrasound study were not different (P>0.2 for all) between the groups; neither were secondary immunosuppressants and use of steroids. Three-dimensional intravascular ultrasound studies were performed at baseline and 3.1 years (1.3, 4.6 years) later. Plaque index progression (plaque volume/vessel volume) was attenuated in the sirolimus group (0.7±10.5% versus 9.3±10.8%; P=0.0003) owing to reduced plaque volume in patients converted to sirolimus early (<2 years) after transplantation (P=0.05) and improved positive vascular remodeling (P=0.01) in patients analyzed late (>2 years) after transplantation. Outcome analysis in 160 consecutive patients maintained on 1 therapy was performed regardless of performance of intravascular ultrasound examinations. Five-year survival was improved with sirolimus (97.4±1.8% versus 81.8±4.9%; P=0.006), as was freedom from cardiac-related events (93.6±3.2% versus 76.9±5.5%; P=0.002). CONCLUSIONS: Substituting calcineurin inhibitor with sirolimus as primary immunosuppressant attenuates long-term cardiac allograft vasculopathy progression and may improve long-term allograft survival owing to favorable coronary remodeling. Because of the lack of randomization and retrospective nature of our analysis, the differences in outcome should be interpreted cautiously, and prospective clinical trials are required.