Transcatheter Left Atrial Appendage Occlusion: A Multi-Center Real Life Experience.

(1) Background: left atrial appendage occlusion (LAAO) is considered an effective and relatively safe treatment for the prevention of thromboembolic events in patients with atrial fibrillation and a contra-indication for anticoagulation. We present a large multicenter real-world experience of transcatheter LAAO implementation in patients with atrial fibrillation who cannot be treated with chronic anti-coagulation; (2) Methods: included were atrial fibrillation patients who underwent transcatheter LAAO between 1 January 2016 and 30 June 2021. The study was conducted using the electronic health record database of Clalit Health Services (CHS). The primary outcomes included hemorrhagic and ischemic stroke following LAAO; (3) Results: included were 389 atrial fibrillation patients. During a median follow-up of 2.1 years, 13% patients had ischemic cerebrovascular accident (CVA), and 4.4% patients had hemorrhagic CVA. While the risk of ischemic stroke increased gradually over time, the risk of hemorrhagic CVA was highest during the first 3 months following the procedure. Moreover, previous ischemic stroke was the only significant predictor for both hemorrhagic and ischemic stroke following LAAO; (4) Conclusions: while the annual performance rate of transcatheter LAAO has increased significantly over the past years, post procedural long-term prognosis remains poor with a substantial risk of both thrombotic and bleeding events.

Comparison of Transcatheter Aortic Valve Implantation Devices in Aortic Stenosis: A Network Meta-Analysis of 42,105 Patients.

Background: In recent years, trans-catheter aortic valve implantation (TAVI) has emerged as an excellent alternative to surgical aortic valve replacement (SAVR). Currently, there are several approved devices on the market, yet comparisons among them are scarce. We aimed to compare the various devices via a network meta-analysis. Methods: We performed a network meta-analysis including randomized controlled trials (RCTs) and propensity-matched studies that provide comparisons of either a single TAVI with SAVR or two different TAVI devices and report clinical outcomes. Results: We included 12 RCT and 13 propensity-matched studies comprising 42,105 patients, among whom 27,134 underwent TAVI using various valve systems (Sapien & Sapien XT, Sapien 3, Corvalve, Evolut & Evolut Pro, Acurate Neo, Portico). The mean follow-up time was 23.4 months. Sapien 3 was superior over SAVR in the reduction of all-cause mortality (OR = 0.53; 95%CrI 0.31-0.91), while no significant difference existed between other devices and SAVR. Aortic regurgitation was more frequent among TAVI devices compared to SAVR. There was no significant difference between the various THVs and SAVR in cardiovascular mortality, myocardial infarction, NYHA class III-IV, and endocarditis. Conclusions: Newer generation TAVI devices, especially Sapien 3 and Evolut R/Pro are associated with improved outcomes compared to SAVR and other devices of the older generation.

CHA2DS2-VASc Score, Mortality and Acute Myocardial Infarction in Patients With Nonvalvular Atrial Fibrillation.

Patients with atrial fibrillation (AF) are at increased cardiovascular risk. The CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, previous stroke, vascular disease, age 65 to 74 years, female gender) has been used to predict thromboembolic risk in patients with nonvalvular AF. We aimed to evaluate the association between the CHA2DS2-VASc score and the risk of acute myocardial infarction (AMI) and all-cause mortality in patients with AF treated with direct oral anticoagulants (DOACs). The study was based on the Clalit Health Services database. Included were 21,129 patients with nonvalvular AF treated with DOACs. Patients were stratified into four groups according to the CHA2DS2-VASc score.1-9 The primary end point was the occurrence of AMI and all-cause mortality. During 21,129 patient-years, there were 1,253 incidents (5.9%) of AMI. A higher CHA2DS2-VASc score was associated with a significantly increased risk of AMI (7.8, 14.9, 23.9, and 35.3 cases per 1,000 person-years, for patients with CHA2DS2-VASc score of 1 to 2, 3 to 4, 5 to 6, and 7 to 9, respectively, p <0.001). Each 1-point increase in the CHA2DS2-VASc score was associated with a 27% increased risk of AMI. A higher CHA2DS2-VASc score was also associated with a significantly increased ll-cause mortality rate (21.7, 60.2, 103.9, 162.6 cases per 1,000 person-years, for patients with CHA2DS2-VASc score of 1 to 2, 3 to 4, 5 to 6, 7 to 9, respectively, p <0.001). All associations remained statistically significant after a multivariate analysis. In conclusion, among patients with nonvalvular AF treated with DOACs, the CHA2DS2-VASc score was associated with increased risk of AMI and all-cause mortality.

Renal function and outcome of patients with non-valvular atrial fibrillation.

AIMS: Atrial fibrillation and renal dysfunction are associated with increased cardiovascular risk. We examined the association between renal function and incident ischaemic stroke or myocardial infarction in patients with atrial fibrillation treated with direct oral anticoagulants (DOACs). METHODS AND RESULTS: This study was conducted using a large health record database. Included were 19 713 patients with first time diagnosis of non-valvular atrial fibrillation treated with DOACs between 2010 and 2018. Patients were categorized into four groups according to the estimated glomerular filtration rate (eGFR) (<30, 30-59, 60-89, and ≥90 mL/min/1.73 m2). Ischaemic stroke and acute myocardial infarction rates were compared between the groups. During 55 086 person-years of follow-up, there were 2295 (11.6%) cases of ischaemic stroke and 1158 (5.9%) cases of acute myocardial infarction. There was a significant inverse association between eGFR and the risk of myocardial infarction. A multivariate analysis using the group with eGFR ≥90 mL/min/1.73 m2 as a reference demonstrated an increased risk of myocardial infarction with lower eGFR [hazard ratio (HR) = 1.2 95% confidence interval (CI) 0.9-1.4, HR = 1.4, 95% CI 1.2-1.7, and HR = 2.5, 95% CI 1.8-3.4 for patients with eGFR 60-89, 30-59, and <30 mL/min/1.73 m2, respectively, P < 0.001]. Each 10 mL decrease in eGFR was associated with an 8% increase in the risk of myocardial infarction. There was no association between eGFR and the risk of ischaemic stroke (HR = 0.9 95% CI 0.8-1.1, HR = 0.93, 95% CI 0.8-1.1, and HR = 1.1, 95% CI 0.8-1.4 for patients with eGFR 60-89, 30-59, and <30 mL/min/1.73 m2, respectively, P = 0.325). CONCLUSIONS: Renal dysfunction is associated with an increased risk of myocardial infarction but not of ischaemic stroke among patients with atrial fibrillation treated with DOACs.

Incidence, characteristics and outcomes in very young patients with ST segment elevation myocardial infarction.

OBJECTIVE: ST-segment elevation acute myocardial infarction (STEMI) in very young adults is uncommon. Many studies have focused on the cutoff of 45-50 years old to define young patients with STEMI leaving limited data on the group of very young patients aged less than 35 years old. We investigated the incidence of STEMI in different subgroups of young patients and focused on the characteristics, possible pathogenesis and outcomes in very young patients aged less than 35 years old. METHODS: We retrospectively studied 792 STEMI patients aged less than 55 years who underwent successful primary PCI. We categorized patients as very young if they were or less 35 years old and as young if they were between 36 and 55 years old. Baseline characteristics, angiographic findings, as well as short- and long-term outcomes were compared between the two groups. RESULTS: There were 46 (6%) very young patients (age ≤ 35 years) and 748 (94%) young patients (36 < age ≤ 55 years). Very young patients had fewer atherosclerotic risk factors than young patients, but there was no difference in short- or long-term outcomes. Overt hypercoagulable state was evident serologically (antiphospholipid antibodies) in 2/7 (29%) of screened patients and clinically (left ventricular thrombus or acute coronary thrombosis without an atherosclerotic plaque) in 6/46 patients (13%). CONCLUSION: Very young patients with STEMI constitute a distinct subset of young patients with fewer atherosclerotic risk factors yet comparable outcomes. More efforts should be made screening for serologic and clinical evidence of hypercoagulability in this group of patients.

Grapefruit juice prolongs the QT interval of healthy volunteers and patients with long QT syndrome.

BACKGROUND: The list of medications linked to drug-induced long QT syndrome (LQTS) is diverse. It is possible that food products too have QT-prolonging potential. OBJECTIVE: We tested the effects of grapefruit juice on the QT interval with the methodology used by the pharmaceutical industry to test new drugs. METHODS: This was an open-label, randomized, crossover study with blinded outcome evaluation, a thorough QT study of grapefruit juice performed according to the Guidelines for the Clinical Evaluation of QT/QTc for Non-antiarrhythmic Drugs. Thirty healthy volunteers and 10 patients with congenital LQTS were studied. Healthy volunteers drank 2 L of grapefruit juice (in divided doses), or received 400 mg oral moxifloxacin, in a randomized crossover study. Patients with LQTS were tested with only grapefruit. Repeated baseline, off-drug, and on-drug (grapefruit or moxifloxacin) electrocardiograms were scanned and coded. QT measurements were done with electronic calipers. RESULTS: In comparison to off-drug electrocardiograms, grapefruit juice led to significant rate-corrected QT (QTc) prolongation. The absolute net QTc prolongation from grapefruit was 14.0 ms (95% confidence interval 6.2-21.7 ms; P < .001). The QT-prolonging effects of grapefruit in healthy volunteers were comparable with those of moxifloxacin. The QT-prolonging effects of grapefruit juice were greater in female patients and particularly marked in patients with LQTS (net QTc prolongation 21.8 ms; 95% confidence interval 3.4-35.3 ms; P = .034). CONCLUSION: Grapefruit juice, at doses tested, prolongs the QT interval. The effect is significant in healthy volunteers, greater in female patients, and more so in patients with LQTS.

Clinical Outcome of Isolated Tricuspid Regurgitation in Patients with Preserved Left Ventricular Ejection Fraction and Pulmonary Hypertension.

BACKGROUND: The outcome of tricuspid regurgitation (TR) remains unclear because of heterogeneity of etiology and the contradictory results of outcome studies. The aim of this study was to evaluate the clinical outcomes of TR in patients with pulmonary hypertension (PH) and normal left systolic function, stratified to patients with post- or precapillary PH. METHODS: In patients with no left valvar disease (isolated) functional TR, preserved left systolic function (ejection fraction ≥ 50%), and PH (systolic pulmonary pressure > 50 mm Hg), TR was assessed both qualitatively (grade) and semiquantitatively using the vena contracta method, and retrospective analysis of long-term outcomes was conducted. Patients with severe comorbid diseases were excluded. RESULTS: The study included 245 patients (age 80.5 years, 37% men, ejection fraction 57%, all with pulmonary systolic pressure > 50 mm Hg). At least moderate to severe TR was diagnosed in 178 patients, and their outcomes were compared with those of 67 patients with the same characteristics and less than mild TR. At least moderate to severe TR was associated with lower survival, independent of all characteristics, right ventricular size or function, comorbidity, or pulmonary pressure (P = .03 for grade and P = .02 for vena contracta). Cox proportional-hazard analysis with interaction terms for TR severity and etiology of PH (post- vs precapillary) showed that the etiology of PH did not affect the association of TR with outcome (P = .90 for the interaction term). CONCLUSIONS: At least moderate to severe isolated TR is independently associated with excess mortality in patients with preserved systolic function and PH, warranting heightened attention to diagnosis and grading. This is irrespective of etiology (pre- or postcapillary) of PH. Semiquantitative assessment of TR by vena contracta is an independent associate of outcome, superior to standard qualitative assessment.

Down-Regulation of Cardiac Erythropoietin Receptor and its Downstream Activated Signal Transducer Phospho-STAT-5 in a Rat Model of Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is often accompanied by impairment of cardiac function that may lead to major cardiac events. Erythropoietin (EPO), a kidney-produced protein, was shown to be beneficial to heart function. It was suggested that reduced EPO secretion in CKD may play a role in the initiation of heart damage. OBJECTIVES: To investigate molecular changes in the EPO/ erythropoietin receptor (EPO-R) axis in rat cardiomyocytes using a rat model for CKD. METHODS: We established a rat model for CKD by kidney resection. Cardiac tissue sections were stained with Masson's trichrome to assess interstitial fibrosis indicating cardiac damage. To evaluate changes in the EPO/EPO-R signaling cascade in the myocardium we measured cardiac EPO and EPO-R as well as the phosphorylation levels of STAT-5, a downstream element in this cascade. RESULTS: At 11 weeks after resection, animals presented severe renal failure reflected by reduced creatinine clearance, elevated blood urea nitrogen and presence of anemia. Histological analysis revealed enhanced fibrosis in cardiac sections of CKD animals compared to the sham controls. Parallel to these changes, we found that although cardiac EPO levels were similar in both groups, the expression of EPO-R and the activated form of its downstream protein STAT-5 were significantly lower in CKD animals. CONCLUSIONS: CKD results in molecular changes in the EPO/EPO-R axis. These changes may play a role in early cardiac damage observed in the cardiorenal syndrome.

Cardiac Hypertrophy and Cardiac Cell Death in Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a prevalent clinical condition affecting 15% of the general population. Cardiorenal syndrome (CRS) type 4 is characterized by an underlying CKD condition leading to impairment of cardiac function and increased risk for major cardiovascular events. To date, the mechanisms leading from CKD to CRS are not completely understood. In particular, it is unclear whether the pathological changes that occur in the heart in the setting of CKD involve enhanced cell death of cardiac cells. OBJECTIVES: To assess whether CKD may mediate loss of cardiac cells by apoptosis. METHODS: We established rat models for CKD, acute myocardial infarction (acute MI), left ventricular dysfunction (LVD), and sham. We measured the cardiac-to-body weight as well as kidney-to-body weight ratios to validate that renal and cardiac hypertrophy occur as part of disease progression to CRS. Cardiac cells were then isolated and the percent of cell death was determined by flow cytometry following staining with annexin-FITC and propidium iodide. In addition, the levels of caspase-3-dependent apoptosis were determined by Western blot analysis using an anti-cleaved caspase-3 antibody. RESULTS: CKD, as well as acute MI and LVD, resulted in significant cardiac hypertrophy. Nevertheless, unlike the increased levels of cell death observed in the acute MI group, in the CKD group, cardiac hypertrophy was not associated with induction of cell death of cardiac cells. Caspase-3 activity was even slightly reduced compared to sham-operated controls. CONCLUSIONS: Our data show that while CKD induces pathological changes in the heart, it does not induce cardiac cell death.