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1. Background Catheter ablation is a common treatment for atrial fibrillation (AF). Atrial-oesophageal fistula (AOF) is a rare yet fatal complication of catheter ablation. Chest computed tomography (CT) is the diagnostic modality of choice but may be undiagnostic in up to 24% of cases. 2. Case Summary We present the case of a 61-year-old male who presented with pleuritic chest pain, hypotension, fever, and coffee-ground emesis twenty days after cryoablation for AF. His chest CT was undiagnostic. AOF was diagnosed by injecting agitated saline into the nasogastric tube during a transthoracic echocardiogram (TTE) that showed bubbles in the left atrium and ventricle. 3. Discussion In the case presented, as often happens, the diagnosis of AOF was delayed for several days, during which the patient presented with septic shock and concomitant multiorgan failure. The high mortality rate associated with AOF is partially attributable to delayed diagnosis. As prompt surgical intervention offers the best chance of survival, a high level of suspicion is of the utmost importance. We suggest contrast-enhanced TTE as a potential diagnostic tool when a rapid and definitive diagnosis is crucial and CT is inconclusive. Since this procedure is not without risk, proper risk consideration and management are necessary.

Background: Previous studies described a higher prevalence of cardiovascular comorbidities during the winter season. Data regarding seasonal association of atrioventricular (AV) block are scarce. Methods: A retrospective cohort analysis of all patients admitted to a tertiary medical center with AV block requiring a permanent pacemaker (PPM) implantation between 2006-2017 was performed. In a time-series analysis, the seasonal incidence of PPM implementations due to AV block was assessed and adjusted for meteorological factors. The association between the weekly incidence of PPM implantations and the weekly rates of influenza as reported by the Israel Center of Disease Control (ICDC) were also assessed. Result: The study population included 759 patients. Mean age was 76.1 years and 55% were males. Most of the patients (34.1%) were admitted in the winter season. In multivariate analysis, there was a significantly higher incidence of PPM implantations among men during the winter season as compared to the fall season (Adjusted IRR [Incidence Rate-Ratio] 1.40, 95% CI 1.05;1.88; pConclusion: In the present analysis the incidence of PPM implantations due to AV block was higher among men during the winter season and correlated with high influenza illness rates. Further prospective and larger studies are required to assess these findings.

Aims To evaluate the benefit of speckle tracking radial strain imaging (STRSI)-guided left ventricular (LV) lead (LVL) positioning in cardiac resynchronization therapy (CRT) in patients (pts) with ischaemic cardiomyopathy with CRT indication. Methods and results We conducted a prospective randomized controlled trial. Patients were enrolled in nine centres with 2:1 randomization into two groups (guided vs. control). Patients underwent STRSI to identify the optimal LV position from six LV segments at midventricular level. Implantation via STRSI was attempted for recommended segment in the guided group only. Follow-up included echocardiography (6 months) and clinical evaluation (6 and 12 months). The primary endpoint was comparison % reduction in LV end-systolic volume at 6 months with baseline. Secondary endpoints included hospitalizations for heart failure and death, and improvement in additional echocardiographic measurements and quality of life score. A total of 172 patients (115 guided vs. 57 control) were enrolled. In the guided group, 60% of the implanted LV leads were adjudicated to be successfully located at the recommended segment, whereas in the control group 44% reached the best STRSI determined segment. There was no difference between the groups in any of the primary or secondary endpoints at 6 and 12 months. Conclusion Our findings suggest that echo-guided implantation of an LV lead using STRSI does not improve the clinical or echocardiographic response compared with conventional implantation.

Management of patients with a single CHA2DS2-VASc score risk factor is controversial. We attempt to identify the “truly low risk” AF patients who will not benefit from oral anticoagulation (OAC) treatment. Retrospective cohort analysis, all incident non-valvular AF (NVAF) cases between 2004 and 2015, and age 21 and older, with up to one thromboembolic risk factor besides sex (CHA2DS2-VASc score of up to 1 for men and up to 2 for women). A “low risk” score was created for these patients using a logistic regression model on the incidence of stroke within 30–2500 days following the NVAF diagnosis. We identified 15,621 patients. Average age was 53.7 ± 12.3 years, 56.6% male. Mean follow-up was 5.5 years. Significant predictors of ischemic stroke were age 65–74 and diabetes (2 points each), hypertension, vascular disease, and chronic kidney disease stage 2–3 (1 point each). Stroke incidence ranged from 0.8% for score 0 and up to 3.4% for scores ≤ 2. Odds ratio for stroke among patient group with a score ≤ 2 was 4.3 (2.9–6.6) compared with score 0. Our risk score’s area-under-the-curve (AUC) for prediction of stroke was 0.68 (0.65–0.71), compared with 0.60 (0.57–0.62) for the CHAD2S2-VASc score, within this low-risk group. Patients considered at low or intermediate risk using traditional risk stratification schemes, with ≥ 2 points using this proposed low-risk index (65–74 years old, diabetics or a combination of chronic renal failure and an additional risk factor), had an overall stroke risk that may justify anticoagulation therapy.

A 13-year-old boy was hospitalized after a syncopal episode that occurred during exercise. He suddenly felt chest tightness, sweating and palpitations, followed by a transient loss of conciseness. Upon emergency medical team arrival, he was awake and oriented. Baseline ECG showed sinus rhythm at a rate of 98 bpm, with narrow QRS, and no signs of long QT, Brugada, or pre-excitation. Physical examination, blood tests, 24 hours Holter monitoring, transthoracic echocardiography and stress test were all within normal limits. Eight days later he experienced a second episode of palpitations while walking to school. ECG revealed regular wide complex tachycardia (WCT) at a rate of 200 bpm, with LBBB morphology that terminated with Adenosine (Figure 1). The clinical tachycardia was easily induced by programmed electrical stimulation (Figure 2A). Diagnostic electrophysiological maneuver (Figure 2B) was followed by successful ablation, during which a unique phenomenon was noted (Figure 3). What is the diagnosis of the tachycardia and what are the unique findings noted during and after ablation?

Purpose Previous studies have demonstrated differences in atrial fibrillation (AF) detection based on data from hospital sources without data from outpatient sources. We investigated the detection of documented diagnoses of non-valvular AF in a large Israeli health-care organization using electronic health record data from multiple sources. Patients and methods This was an open-chart validation study. Three distinct algorithms for identifying AF in electronic health records, differing in the source of their International Classification of Diseases, Ninth Revision code and use of the associated free text, were defined. Algorithm 1 incorporated inpatient data with outpatient data and the associated free text. Algorithm 2 incorporated inpatient and outpatient data regardless of the free text associated with AF diagnosis. Algorithm 3 used only inpatient data source. These algorithms were compared to a gold standard and their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. To establish the gold standard (documentation of arrhythmia based on electrocardiography interpretation or a cardiologist's written diagnosis), 200 patients at highest risk for having non-valvular AF were randomly selected for open-chart validation by two physicians. Results The algorithm that included hospital settings, outpatient settings, and incorporated associated free text in the outpatient records had the optimal balance between all validation measures, with a high level of sensitivity (85.4%), specificity (95.0%), PPV (81.4%), and NPV (96.2%). The alternative algorithm that combined inpatient and outpatient data without free text also performed better than the algorithm that included only hospital data (82.9%, 95.0%, 81.0%, and 95.6%, compared to 70.7%, 96.9%, 85.3%, and 92.8%, sensitivity, specificity, PPV, and NPV, respectively). Conclusion In this study, involving a comprehensive data collection from inpatient and outpatient sources, incorporating outpatient data with inpatient data improved the diagnosis of non-valvular AF compared to inpatient data alone.

Introduction: Atrial fibrillation (AF) and chronic kidney disease (CKD) are both associated with increased risk of stroke, and CKD carries a higher bleeding risk. Oral anticoagulation (OAC) treatment is used to reduce the risk of stroke in patients with nonvalvular AF (NVAF); however, the risk versus benefit of OAC for advanced CKD is continuously debated. We aim to assess the management and outcomes of NVAF patients with impaired renal function within a population-based cohort. Methods: We conducted a retrospective observational cohort study using ICD-9 healthcare coding. Patients with incident NVAF between 2004 and 2015 were identified stratified by CKD stage. We compared treatment strategies and estimated risks of stroke, death, or any major bleeding based on CKD stages and OAC treatment. Results: We identified 85,116 patients with incident NVAF. Patients with impaired renal function were older and had more comorbidities. OAC was most common among stage 2 CKD patients (49%) and least in stages 4–5 CKD patients (27.6%). Higher CKD stages were associated with worse outcomes. Stroke rates increased from 1.04 events per 100 person-years (PY) in stage 1 CKD to 3.72 in stages 4–5 CKD. Mortality increased from 3.42 to 32.95 events/100 PY, and bleeding rates increased from 0.89 to 4.91 events/100 PY. OAC was associated with reduced stroke and intracranial bleeding risk regardless of CKD stage, and with a reduced mortality risk in stages 1–3 CKD. Conclusion: Among NVAF patients, advanced renal failure is associated with higher risk of stroke, death, and bleeding. OAC was associated with reduced stroke and intracranial bleeding risk, and with improved survival in stages 1–3 CKD.

ObjectiveAtrial fibrillation (AF) screening by age achieves a low yield and misses younger individuals. We aimed to develop an algorithm in nationwide routinely collected primary care data to predict the risk of incident AF within 6 months (Future Innovations in Novel Detection of Atrial Fibrillation (FIND-AF)).MethodsWe used primary care electronic health record data from individuals aged ≥30 years without known AF in the UK Clinical Practice Research Datalink-GOLD dataset between 2 January 1998 and 30 November 2018, randomly divided into training (80%) and testing (20%) datasets. We trained a random forest classifier using age, sex, ethnicity and comorbidities. Prediction performance was evaluated in the testing dataset with internal bootstrap validation with 200 samples, and compared against the CHA2DS2-VASc (Congestive heart failure, Hypertension, Age >75 (2 points), Stroke/transient ischaemic attack/thromboembolism (2 points), Vascular disease, Age 65–74, Sex category) and C2HEST (Coronary artery disease/Chronic obstructive pulmonary disease (1 point each), Hypertension, Elderly (age ≥75, 2 points), Systolic heart failure, Thyroid disease (hyperthyroidism)) scores. Cox proportional hazard models with competing risk of death were fit for incident longer-term AF between higher and lower FIND-AF-predicted risk.ResultsOf 2 081 139 individuals in the cohort, 7386 developed AF within 6 months. FIND-AF could be applied to all records. In the testing dataset (n=416 228), discrimination performance was strongest for FIND-AF (area under the receiver operating characteristic curve 0.824, 95% CI 0.814 to 0.834) compared with CHA2DS2-VASc (0.784, 0.773 to 0.794) and C2HEST (0.757, 0.744 to 0.770), and robust by sex and ethnic group. The higher predicted risk cohort, compared with lower predicted risk, had a 20-fold higher 6-month incidence rate for AF and higher long-term hazard for AF (HR 8.75, 95% CI 8.44 to 9.06).ConclusionsFIND-AF, a machine learning algorithm applicable at scale in routinely collected primary care data, identifies people at higher risk of short-term AF.

Background A high percentage of SARS-CoV-2 patients suffer from comorbidities and there is increasing evidence that previous cardiac disease contributes to poor outcome in these patients (1,2). There is a paucity of information regarding the implications of the disease in patients with cardiac implantable electronic devices (CIEDs). Due to the increasing use of CIEDs in the management of arrhythmias and heart failure, determining the association between CIEDs and the severity of this disease is essential. Aim To obtain an adequate understanding regarding the association between cardiac devices and severity of COVID-19 infection in order to achieve optimum management of these patients. Methods All clinical and demographic parameters were collected retrospectively from a cohort of patients who underwent implantation of CIED in our Medical Center, Israel. We included 42 patients who tested positive for SARS-CoV-2, between January and December of 2020. Propensity score matching based on age and gender and adjusted Kaplan Meier curve of mortality were performed in order to evaluate the clinical outcome of patients with CIEDs and SARS- CoV-2 infection in comparison to the control group. Results The mean age of patients was 72.9 years, compose of 50% male and 50% female in both groups. In the group of patients with CIEDs, 11 (26.1%) patients had implantable defibrillator, and 31 (73.8%) had pacemaker. Univariate analysis revealed that patients with CIEDs suffered more from heart failure, coronary artery disease and atrial fibrillation, as well as hypertension, diabetes, and chronic kidney disease. Four patients (9.5%) with cardiac devices were hospitalized in the ICU due to critical illness, as compared to 1 (0.6%) patient in the control group (p=0.005). Moreover, 10 patients in the cardiac devices group (23.8%) died of SARS-CoV-2 infection, versus 25 (14.9%) in the control group. Conclusions CIEDs are a marker of poor outcome in patients with SARS-CoV-2 infection. Patients with CIEDs suffer from increased comorbidities in comparison with age and gender matched population and therefore should be managed with the utmost caution. Funding Acknowledgement Type of funding sources: None. KM curve of all-cause mortality

Diabetes mellitus (DM) is associated with an increased risk of complications in atrial fibrillation (AF). This study aimed to assess the incidence and risks of ischemic stroke and mortality according to baseline HbA1c levels in patients with DM and AF. We conducted a cohort study using Clalit Health Services electronic medical records. The study population included all Clalit Health Services members aged ≥25 years, with the first diagnosis of AF between January 1, 2010, and December 31, 2016, who had a diagnosis of DM. The risk of stroke and all-cause death were compared according to HbA1c levels at the time of AF diagnosis:7.0%, between 7% and 9%, and ≥9%. A total of 44,451 patients with DM and AF were identified. The median age was 75 years (interquartile 65 to 83), and 52.5% were women. During a mean follow-up of 38 months, higher levels of HbA1c were associated with an increased risk of stroke with a dose-dependent response when compared with patients with HbA1c7% (Adjusted hazard ratio [aHR] =1.30 [95% confidence interval 1.10 to 2.05] for levels between 7% and 9% and 1.60 (95% confidence interval 1.25 to 2.03) for HbA1c9%, even after adjusting for CHA

We discuss an unusual case of a patient who initially presented with apparent commotio cordis but returned several months later with spontaneous wide complex tachycardia. This case highlights the importance of investigation of survivors of commotio cordis, especially if atypical, to determine if there is underlying cardiac disease. (Level of Difficulty: Beginner.), Graphical abstract, We discuss an unusual case of a patient who initially presented with apparent commotio cordis but returned several months later with recurrent wide…

Several stroke risk stratification scores have been developed to guide clinical decision-making in patients with nonvalvular atrial fibrillation (AF). The aim of this study was to compare the performance of the CHADS2, CHA2DS2-VASc and R2CHADS2 risk scores to predict stroke. This retrospective cohort study was based on electronic medical records from Clalit Health Services (CHS), the largest payer provider healthcare organization in Israel. Data of CHS members with AF diagnosis between 2004 and 2015 were extracted. Demographic and co-morbidity data were used to calculate the 3 risk scores, and the performance of the scores to predict stroke were compared using area under the curve and net reclassification index. Of the 89,213 CHS members with AF, 52.3% were women and median age was 76 years. The proportions of patients at high risk were 66.2%, 86.7%, and 71.1% in the CHADS2, CHA2DS2-VASc, and R2CHADS2, respectively, with stroke incidence rates of 2.91, 2.35, and 2.80 per 100 person-years, respectively. Area under the curves for stroke prediction were 0.61 for both CHADS2 and CHA2DS2-VASc and 0.59 for R2CHADS2. Net reclassification index analysis demonstrated a net improvement of 0.089 in the index when CHA2DS2-VASc was compared with CHADS2 and a net reduction of 0.083 when R2CHADS2 was compared with CHADS2. In conclusion, current stroke stratification scores have comparable but limited ability to predict stroke in patients with AF. Stroke prevention strategies may vary depending on the applied stratification. There is a need for a better stroke risk stratification score for patients with AF.

Oral anticoagulation (OAC) is effective in stroke prevention in elderly patients with nonvalvular atrial fibrillation (AF), but older patients are also at higher risk of bleeding.We aimed to examine whether OAC has net clinical benefit (NCB) in elderly patients with AF.This is a retrospective cohort study of patients with AF, aged 75 years and older, who were diagnosed from January 1, 2013, through December 31, 2015. Incidences of stroke and intracranial hemorrhage (ICH) were estimated as the number of events per 100 person-years. The NCBs were estimated with respect to time in therapeutic range (TTR) (60% or ≥60%) and treatment type (warfarin and low or high dose of direct oral anticoagulants [DOACs]).We included 11,760 patients, of whom 4982 (42.4%) were treated with OACs: 2042 (17.4%) with warfarin and 2940 (25.0%) with DOACs. Among patients treated with warfarin, those who achieved TTR ≥ 60% had a lower incidence of stroke (2.54 per 100 person-years vs 5.21 per 100 person-years; P = .01) but without a statistically significant lower incidence of ICH (0.68 per 100 person-years vs 1.10 per 100 person-years; P = .45) and a higher NCB (9.78 vs 6.52) than did those with TTR60%. Among patients treated with DOACs, patients treated with the high dose had a statistically significant similar incidence of stroke (8.40 per 100 person-years vs 9.81 per 100 person-years; P = .67), a statistically significant lower incidence of ICH (0.33 per 100 person-years vs 1.20 per 100 person-years; P = .02), and a higher NCB (4.42 vs 1.78) than did patients treated with the low dose.A large proportion of elderly patients are not treated with OACs. We found that the NCB of OAC in the elderly is positive, with the highest benefit in elderly patients treated with warfarin who achieved TTR ≥ 60% or high dose of DOACs.

Background Brugada syndrome (BrS) is an inherited disorder associated with increased risk of ventricular arrhythmias and sudden cardiac death. The most common genetic alteration is a loss of function mutation of SCN5A gene. Several mutations in SCN5A gene were found to be associated with an overlap phenotype of both BrS and long QT3 (LQT3) syndrome. Case summary We report of a 29-year-old man with familial LQT3 syndrome that was diagnosed at age 6 during evaluation of syncope. He has been treated for several years with Flecainide. Now presented with recurrent episodes of syncope. Electrocardiogram (ECG) upon admission was notable for Brugada type 1 pattern that was attenuated after Flecainide was discontinued. Genetic analysis revealed SCN5A 1790D>G mutation that is associated with overlap of LQT3 and BrS. Due to recurrent syncope and difficult management of both LQT3 and BrS, an implantable cardioverter-defibrillator was implanted together with beta-blockers treatment. The patient was discharged home with no evidence of Brugada type 1 pattern on his ECG. He had no further syncope or arrhythmias during 6 months of follow-up. Discussion There are few reports describing the phenotypic overlap between LQT3 and BrS. Despite the confirmed genetic link between both syndromes, their management strategy is controversial. In particularly, the treatment with sodium channel blockers for LQT3 syndrome may increase the risk for arrhythmias in patients with coexisting BrS. The present case demonstrates the link between LQT3 and BrS and the difficult dilemma in the management of these patients.

Management of patients with a single CHARetrospective cohort analysis, all incident non-valvular AF (NVAF) cases between 2004 and 2015, and age 21 and older, with up to one thromboembolic risk factor besides sex (CHAWe identified 15,621 patients. Average age was 53.7 ± 12.3 years, 56.6% male. Mean follow-up was 5.5 years. Significant predictors of ischemic stroke were age 65-74 and diabetes (2 points each), hypertension, vascular disease, and chronic kidney disease stage 2-3 (1 point each). Stroke incidence ranged from 0.8% for score 0 and up to 3.4% for scores ≤ 2. Odds ratio for stroke among patient group with a score ≤ 2 was 4.3 (2.9-6.6) compared with score 0. Our risk score's area-under-the-curve (AUC) for prediction of stroke was 0.68 (0.65-0.71), compared with 0.60 (0.57-0.62) for the CHADPatients considered at low or intermediate risk using traditional risk stratification schemes, with ≥ 2 points using this proposed low-risk index (65-74 years old, diabetics or a combination of chronic renal failure and an additional risk factor), had an overall stroke risk that may justify anticoagulation therapy.

Background Diabetes mellitus (DM) increases the risk of embolism in nonvalvular atrial fibrillation (NVAF). The association between pre-diabetes and risk of ischemic stroke has not been studied separately in this population. Objectives The purpose of this study was to evaluate whether pre-diabetes is associated with increased risk of stroke and death in patients with NVAF. Methods We conducted a historical cohort study using the Clalit Health Services electronic medical records. The study population included all members aged ≥25 years, with a first diagnosis of NVAF between January 1, 2010, and December 31, 2016. We compared 3 groups of individuals: those with pre-diabetes, those with diabetes, and normoglycemic patients. Results A total of 44,451 cases were identified. The median age was 75 years, and 52.5% were women. During a mean follow-up of 38 months, the incidence rates of stroke (per 100 person-years) were: 1.14 in normoglycemic individuals, 1.40 in those with pre-diabetes, and 2.15 in those with diabetes. In both univariate and multivariate analyses, pre-diabetes was associated with an increased risk of stroke compared with normoglycemic persons (adjusted hazard ratio [adjHR]: 1.19; 95% confidence interval [CI]: 1.01 to 1.4) even after adjustment for CHA2DS2-Vasc risk factors and use of anticoagulants, while diabetes conferred an even higher risk (vs. normoglycemia (adjHR: 1.56; 95% CI: 1.37 to 1.79). The risk for mortality was higher for individuals with diabetes (adjHR: 1.47; 95% CI: 1.41 to 1.54) but not for those with pre-diabetes (adjHR: 0.98; 95% CI: 0.92 to 1.03). Conclusions In this cohort of patients with incident NVAF, pre-diabetes was associated with an increased risk of stroke even after accounting for other recognized risk factors.

Funding Acknowledgements Pfizer Israel Background Diabetes mellitus (DM) is associated with increased risk of embolic complications in non-valvular atrial fibrillation (NVAF). Whether the risk of stroke in AF patients remains the same among the wide spectrum of disease is yet to be determined. Aim Among individuals with AF and DM, to assess the incidence rates and risk of ischemic stroke and mortality by baseline HbA1C levels. Methods We conducted a prospective, historical cohort study using the Clalit Health Services (CHS) electronic medical records database. The study population included all CHS members ≥ 21 years old, with a first diagnosis of NVAF between January 1, 2010 to December 31, 2016 and a minimal follow-up period of 1 year. Among those patients identified as diabetics, we compared three groups of patients according to HBA1C levels at the time of AF diagnosis: Results A total of 44,451 cases were identified. The median age was 75 years (IQR 65-83) and 52.5% were women. During a mean follow up of 38 months, the incidence of stroke per 100 person-years in the three study groups was: 1.9 in patients with HBA1C 9%. In both univariate and multivariate analyses, higher levels of HBA1C were associated with an increased risk of stroke compared with a dose-dependent response when compared to individuals with HBA1C 9% group after adjusted analysis {aHR = 1.17 (1.07- 1.28)} Conclusion: In this observational cohort of patients with incident newly diagnosed nonvalvular atrial fibrillation, HBA1C levels were associated with an increased risk of stroke in a dose-dependent manner even after accounting for other recognized risk factors for stroke in this population. Abstract Figure. Kaplan-Meier for stroke-free survival

Funding Acknowledgements Pfizer pharmaceutical corporation Background Diabetes is a known risk factor for thromboembolic events in patients with non-valvular atrial fibrillation (NVAF). Whether patients on insulin therapy are at an increased risk for stroke compered to patients treated solely by oral antidiabetic medications is not yet established. Aim To assess the risk of ischemic stroke and mortality in patients with NVAF and diabetes mellitus (DM) treated by insulin vs. oral antidiabetic treatment. Methods A prospective, historical cohort study based on the Clalit Health Services (CHS) electronic medical records database, including all individuals age ≥ 21 years with a first diagnosis of NVAF between January 2010 to December 2016 and a minimal follow-up period of 1 year. Patients were divided into two groups based on their diabetes therapy regiment (insulin vs. oral antidiabetic medications). Results Overall study population included 12,231 patients with AF and DM, of them 3510 (28.7%) had an insulin-requiring diabetes. The median age was 72.4 years (IQR 65-80) in the insulin- treated group and 75.2 (IQR 68-83) in the orally treated group, with a slight majority of women in both groups, 51.6% and 53.5% respectively. Patients in the insulin group had significantly higher co-morbidity rates including hypertension (HTN) (93.6% vs. 91.2%; p Conclusion In this cohort of patients with newly diagnosed NVAF and DM, patients on insulin are at increased risk of all cause mortality and a have a trend of increased risk of stroke after accounting for other recognized risk factors for stroke and mortality in this population.

Funding Acknowledgements None Background Patients with preserved LVEF and atrioventricular block (AVB) who are anticipated for high-burden of right ventricular (RV) pacing possess a risk to develop pacing induced cardiomyopathy (PICM). Aims To evaluate the incidence and outcomes of RV-PICM in this patient"s population. Methods 1013 patients with AVB underwent first time pacemaker (PM) implantation between 2002 and 2016. A total of 203 patients with normal LVEF were included. Follow-up echocardiography was examined for a decrease in LVEF > 10%. Alternative causes for cardiomyopathy were excluded. Patient"s characteristics, mortality and hospitalizations for heart failure (HF) were compared between the PICM and non-PICM groups. Results 51 patients (25%) developed PICM, with 22 patients (11%) showing LVEF Conclusions The incidence of PICM in patients with normal LVEF and AVB is alarmingly high. PICM in patients with a previously normal LVEF is associated with unfavorable outcomes. Table 1 Characteristics Cohort without PICM (152) n (%) Cohort with PICM (51) n(%) p Age mean ± SD 74.6 ± 10.5 71 ± 13 0.04 Gender (male) 80 (52.6) 29 (56.9) 0.6 Pacing modeDDDVDDVVI 108 (71.1) 38 (25) 6 (3.9) 34 (66.7) 15 (29.4) 2(3.9) 0.83 Hypertension 112 (73.7) 36 (70.6) 0.67 PVD 16 (10.5) 5 (8.9) 0.88 CAD 36 (23.7) 19 (37.3) 0.01 CVA / TIA 17 (11.2) 7 (13.7) 0.63 Atrial fibrillation / flutter 18 (11.8) 9 (17.6) 0.29 COPD 15 (9.9) 2 (3.9) 0.25 Diabetes Mellitus 56 (36.8) 27 (52.9) 0.04 Chronic Kidney Disease 27 (17.9) 14 (27.5) 0.14 Statins 65 (43) 30(60) 0.04 ACE inhibitors / ARBs 52 (34.4) 18 (36) 0.84 Beta Blockers 42 (28) 10 (20) 0.26 LVEDD mm 45.13 ± 5.53 48.46 ± 5.97 Abstract Figure. HF and Mortality outcomes

Funding Acknowledgements Pfizer Israel Background Diabetes mellitus is a well-established independent risk factor for embolic complications in patients with non-valvular atrial fibrillation (NVAF). The association between prediabetes and risk of ischemic stroke, however, has not been studied separately in patients with NVAF. Purpose To evaluate whether pre-diabetes is associated with increased risk of stroke and death in patients with NVAF Methods We conducted a prospective, historical cohort study using the Clalit Health Services (CHS) electronic medical records database. The study population included all CHS members ≥ 21 years old, with a first diagnosis of NVAF between January 1 2010 to December 31 2016 and a minimal follow-up period of 1 year. We compared three groups of patients: prediabetes, those with established DM, and normoglycemic individuals Results A total of 44,451 cases were identified. The median age was 75 years and 52.5% were women. During a mean follow up of 38 months, the incidence of stroke per 100 person-years in the three study groups was: 1.14 in non-diabetics, 1.40 in pre-diabetics and 2.15 in diabetics. In both univariate and multivariate analyses, pre-diabetes was associated with an increased risk of stroke compared with non-diabetics (Adjusted Hazard Ratio (HR) = 1.19 {95% CI 1.01-1.4}) even after adjusting for CHA2DS2-VASC individual risk factors and use of oral anti-coagulants while diabetes conferred an even higher risk (vs non-diabetics { HR = 1.56, 95% CI ;1.37 - 1.79}). The risk for mortality was higher for diabetics (HR =1.47, 95% CI ;1.41, 1.54}) but not for pre-diabetics (HR = 0.98 ,CI 95%; 0.92 - 1.03). Conclusion: In this observational cohort of patients with incident newly diagnosed patients with NVAF, pre-diabetes was associated with an increased risk of stroke even after accounting for other recognized risk factors. Abstract Figure. Kaplan-Meier for stroke-free survival

Funding Acknowledgements pfizer Background Diabetes mellitus (DM) is associated with increased risk of embolic complications in non-valvular atrial fibrillation (NVAF). Chronic kidney disease (CKD) has been shown in some studies to increase the risk of stroke. This finding is not consistent among all studies. Therefore the relationship between kidney function, diabetes and stroke risk is complex and warrants further investigation. Purpose To assess the incidence rates and risk of ischemic stroke and mortality by baseline Estimated Glomerular Filtration Rate (eGFR) levels among individuals with AF and DM. Methods A prospective, historical cohort study using our electronic medical records database. The study population included all members 21 years old, with a first diagnosis of NVAF between January 1, 2010 to December 31, 2016 and a minimal follow-up period of 1 year. Among those patients identified as diabetics, we compared three groups of patients according to eGFR levels at the time of AF diagnosis: eGFR ≥ 60, between 30-60 and ≤ 30 or chronic dialysis or kidney transplant. Results A total of 17,567 cases were included in the final analysis, of them, 11013 (62.7%) had eGFR ≥ 60, 4930 (28%) with eGFR between 30-60 and 1624 (9.24%) with eGFR ≤30 . The median age was 75 years (IQR 65-83) with a majority of females in all groups, 52.5%, 51.2% and 55.5% respectively. The incidence of stroke per 100 person-years in the three study groups was: 1.88 in patients with eGFR ≥ 60, 2.69 in patients with eGFR between 30-60 and 3.34 in those with eGFR ≤ 30 . Impaired renal function was associated with increased risk of stroke in univariate analysis, but not found in the adjusted model (Adjusted Hazard Ratio (AHR) = 1.04 {95% 0.89-1.23} for eGFR 30-60 and 1.16 {95% CI 0.88-1.51} for eGFR ≤ 30 compared to GFR ≥ 60). incidence of mortality per 100 person-years was 10.78 in patients with eGFR ≥ 60, 21.49 in patients with eGFR 30-60 and 41.55 in those with eGFR ≤ 30. In both univariate and multivariate analyses, decreased levels of eGFR were associated with increased mortality risk compared to subjects with normal renal function (AHR 1.22 {95%CI 1.14-1.27} and AHR 2.09 {95%CI 1.95-2.24} for eGFR between 30-60 and for eGFR ≤ 30, respectively). Conclusion In this observational prospective cohort of patients with newly diagnosed NVAF, impaired renal function was not found to be associated with increased risk of stroke. Lower eGFR levels were associated with an increased mortality risk.

Patients with preserved left ventricular (LV) ejection function (EF) and atrioventricular block (AVB) who are anticipated for high-burden of right ventricular (RV) pacing possess a risk to develop pacing-induced cardiomyopathy (PIC) and adverse clinical outcomes. Hence, the aim of the study is to evaluate the incidence, predictors, and clinical outcomes of RV PIC in patients with preserved LVEF, AVB, and high-burden of RV pacing. One thousand and thirteen patients with second or third-degree AVB underwent first time pacemaker implantation between January 2002 and August 2016. A total of 203 patients with a newly implanted pacemaker, normal baseline LVEF, and high burden of RV pacing were included in the present study. Follow-up echocardiography was examined for a new decrease in LVEF of 10% or higher. Alternative causes for cardiomyopathy were ruled out. Patient characteristics, echocardiographic measurements, device clinic data, mortality, and hospitalizations for heart failure were collected and compared between the PIC and the non-PIC groups. Fifty-one patients (25%) developed LV dysfunction with 22 patients (11%), showing LVEF40%. During a mean follow-up of 49.2 months, the risk of heart failure hospitalization or all-cause mortality was significantly higher in the PIC group versus non-PIC group (35.3% vs 19.1%, p = 0.009). In conclusion the incidence of PIC in patients with normal LVEF and AVB, who are anticipated for high-burden of RV pacing is high. PIC in patients with a previously normal LV function is associated with unfavorable long-term clinical outcomes, including higher rates of heart failure hospitalizations and all-cause mortality.

This chapter will discuss differences in response to cardiac resynchronization therapy (CRT) between men and women. This chapter will specifically address data derived from registries, metaanalyses, and observational studies that compared clinical and echocardiographic data. Data will be given as to differences in response to CRT between men and women as measured by echocardiographic parameters of reverse cardiac remodeling. In addition, we will address differences in clinical response and mortality between men and women as well as the difference between men and women in regard to QRS duration above which a favorable response is seen.

The standard approach for urgent trans-venous temporary cardiac pacemaker (TVTP) implantation is fluoroscopy guidance. The delay in activation of the fluoroscopy-room and the transfer of unstable patients may be life-threatening. Echocardiography-guided TP implantation may increase the safety of the patients by obviating the need for in-hospital transfer. We examined the feasibility and safety of echocardiography-guided vs. fluoroscopy-guided TVTP implantation. From January 2015 to September 2017 data for consecutive patients who needed emergent TVTP implantation were retrospectively reviewed. Ultrasound-guided TVTP protocol that was introduced in our center in January 2015 involved ultrasound guidance for both central venous access and pacing lead positioning. Access sites included femoral, subclavian, or jugular veins. Electrodes were placed in the right ventricular apex by means of echocardiographic monitoring in intensive care unit or by fluoroscopic guidance. Endpoints were achievement of successful ventricular pacing and procedural complications. Sixty-six patients (17 echocardiography-guided and 49 fluoroscopy-guided) were included. There were no differences in pacing threshold between the echocardiography-guided group and the fluoroscopy-guided group (0.75 ± 0.58 mA vs. 0.57 ± 0.35 mA, p = 0.24). The access site for implantation was femoral vein in 27% for the fluoroscopy-guided vs. none for the echocardiography-guided approach (p = 0.015). One hematoma and one related infection occurred in the fluoroscopy-guided group. The need for electrode repositioning was observed in 1 patient in each group. There were no procedural-related deaths in either group. Echocardiography-guided temporary cardiac pacing is a feasible and safe alternative to fluoroscopy-guided approach and significantly lowers the need for in-hospital transfer.

Objectives This study sought to identify the differences in stroke, mortality, and bleeding between men and women with atrial fibrillation (AF). Background There are inconsistent data regarding the thromboembolic risk difference between men and women with AF. The authors assessed the risk of stroke, death, and bleeding in men and women with incident AF. Methods The authors employed a prospective historical cohort using an electronic database from a large health maintenance organization. All members with incident AF between 2004 and 2015 were included. Primary endpoints were ischemic stroke, death, and major bleeding. Results The authors identified 89,213 members with incident nonvalvular atrial fibrillation (NVAF), 52.3% of whom were women. Women were older, with a higher prevalence of hypertension, whereas more men had diabetes, heart failure, and ischemic heart disease than the women did. Ischemic stroke occurred in 6.4% of the patients: 7.0% of women and 5.8% of men. Sex did not affect adjusted stroke risk (hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.77 to 1.06; p = 0.22). However, women 75 years of age and older were at an increased risk (HR: 1.25; 95% CI: 1.17 to 1.34). Mortality rates were higher among women (33.5% vs. 32%; p Conclusions Men and women with AF had a similar risk of ischemic stroke, except for women 75 years of age or older, who had a higher risk. Our findings support using a similar anticoagulation strategy for prevention of stroke in men and women with a similar number of risk factors.

Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure (HF); however, a third of patients are non-responders. The development of quadripolar left ventricular (LV) lead was shown, mainly in single manufactures’ registry, to improve LV remodeling and overall mortality. However, limited reports exist on the impact of quadripolar LV leads on HF hospitalization rates in real-life cohorts. We evaluated the clinical outcomes associated with quadripolar LV leads in a large nation-wide registry including all patients implanted with a cardiac resynchronization therapy with defibrillator (CRT-D). Between July 2010 and October 2016, 2913 consecutive patients were implanted with a CRT-D and all were prospectively enrolled in the Israeli ICD Registry. Quadripolar LV leads were implanted in 973 (33.4%) patients during this period, and their clinical outcomes were compared to CRT-D recipients implanted with a bipolar LV lead. Primary endpoint was HF hospitalization rate. Quadripolar leads were implanted more in patients with non-ischemic cardiomyopathy and for primary prevention indication and less in post-infarction patients and for secondary prevention of sudden death. Longer QRS duration was observed with quadripolar leads (147 ± 23 vs 143 ± 25; p

Introduction Oral anticoagulation (OAC) therapy reduces the risk of ischemic stroke in patients with atrial fibrillation (AF) while increasing the risk of bleeding. Recently, non-vitamin K antagonist oral anticoagulants (NOACs) have become available with lower rates of intracranial bleeding, and some of them have presented a reduced risk of major bleeding. The purpose of this study is to evaluate the change in purchasing patterns of OACs (both warfarin and NOACs) over time in patients with AF according to stroke and bleeding risk, in the first 3 months after diagnosis. Methods and results We conducted a historical cohort study using the Clalit Health Services electronic medical records database. The study population included all members aged ≥21 years, with a new diagnosis of nonvalvular AF between 2008 and 2015. A total of 58 385 cases were identified. The mean age was 73.1 (±14.1) years, and 52.3% of the patients were women. The median CHA2 DS2 -VASc score was 4 (interquartile range, 3-5). OACs were purchased by 19 705 patients (33.8%) within the first 3 months of first diagnosis of AF, with patients at higher embolic risk as stratified by the CHA2 DS2 -VASc score and having higher purchasing rates (37.1%). Between 2008 and 2010, 29% of patients purchased a vitamin K antagonist, the only available OAC at the time. OAC purchasing increased to 41.4% between 2014 and 2015, with half of the patients purchasing an NOAC. Conclusion In this real-world, population-based cohort study of patients with newly diagnosed AF, we found a lower than expected rate of OAC prescription within 3 months of diagnosis but an encouraging increase in OAC purchasing over time. The use of NOACs has risen exponentially within just a few years, accounting for a greater pool of patients with being prescribed an OAC.

Objective To compare the clinical outcomes of a single- versus dual-chamber ICD for primary prevention of sudden cardiac death in a large, national ICD registry. Methods Data were collected from the prospective Israeli ICD Registry. Baseline characteristics and clinical outcomes including mortality, admissions for heart failure (HF), and ICD therapy were compared between the two groups. Results A total of 1,125 subjects, 37% with a single-chamber and 63% with a dual-chamber ICD, constructed the baseline cohort. Approximately 80% had ischemic heart disease (IHD). Mean follow-up was 22 months, mean ejection fraction was 30%, and mean QRS width was 103 milliseconds in both groups. During follow-up, there were no significant differences in the rate of mortality, admissions for HF, appropriate or inappropriate therapy, or in time to any of the clinical outcomes. Using multivariate analysis, single-chamber ICD was not associated with increased risk of death or admission for HF. In a subgroup of patients with IHD, single-chamber ICD was associated with a higher rate of inappropriate therapy. Conclusions In this large retrospective population-based cohort, dual-chamber ICD showed no benefit in reducing the incidence of death or HF admissions, whereas in a subgroup of patients with IHD, single-chamber ICD was associated with increased inappropriate therapy. Further prospective studies are necessary to assess the benefit of dual-chamber ICD in reducing the rate of inappropriate therapy.

Sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is caused by ventricular tachyarrhythmia that can be effectively treated by implantable cardioverter defibrillator (ICD) therapy. We report of a 28-year-old man with HCM and a dual chamber ICD, originally implanted for primary prevention of SCD, (programmed to AAI(R)-DDD(R); managed ventricular pacing (MVP) mode, Medtronic Inc. St Paul, MN USA). He presented with recurrent ICD shocks due to ventricular fibrillation (VF) despite antiarrhythmic therapy. Careful assessment of the stored electrograms demonstrated a repetitive pattern of VF initiation following short-long-short sequences. Initially, activation of ventricular rate stabilization (VRS) algorithm failed to prevent recurrent VF. Ultimately, deactivation of MVP and reprogramming the device to DDD mode with VRS on, resulted in arrhythmia suppression and avoidance of ICD shocks. Physicians should be aware that although VRS function is available in MVP mode, it does not function in the AAI mode during MVP; in order to effectively treat short-long-short sequence induced ventricular arrhythmia by device programming.

Swallow induced syncope is a rare clinical condition which is thought to result from an abnormal vagal reflex leading to bradycardia and cerebral hypoperfusion. It mostly occurs in patients with organic or functional disorders of the esophagus, and often requires permanent pacemaker implantation, along with treatment of the underlying esophageal pathology. In the following case, we report of a 71-year-old male with achalasia post per oral endoscopic myectomy, who presented with syncope and documented AV-block while eating solid food. In addition, long sinus pauses were noted during carotid sinus massage, suggesting that the two distinct entities may be associated, and further supporting the mechanism of neurally mediated syncope in the pathophysiology of swallow-induced syncope.

Introduction Life expectancy of less than 1 year is usually a contraindication for implantable cardioverter defibrillator (ICD) implantation. The aim was to identify patients at risk of death during the first year after implantation. Methods and results Data were derived from a prospective Israeli ICD Registry. Two groups of patients were compared, those who died and those who were alive 1 year after ICD implantation. Factors associated with 1-year mortality were identified on a derivation cohort. A risk score was established and validated. A total of 2617 patients have completed 1 year of follow-up after ICD or cardiac resynchronization therapy defibrillator (CRT-D) implantation. Age greater than 75 years (hazard ratio [HR], 2.7; 95% confidence interval [95% CI], 1.6 to 4.4), atrial fibrillation (AF; HR, 1.9; 95% CI, 1.12 to 3.17), chronic lung disease (HR, 2.0; 95% CI, 1.1 to 3.76), anemia (HR, 2.3; 95% CI, 1.3 to 3.93) and chronic renal failure (CRF; HR, 3.4; 95% CI, 1.74 to 6.6) were independent risk factors for 1-year mortality. We propose a simple AAACC ("triple A double C") score for prediction of 1-year mortality after ICD implantation: Age greater than 75 years (3 points(pts)), anemia (2 pts), AF (1 pt), CRF (3 pts) and chronic lung disease (1 pt). Mortality risk increased with rising number of points (from 1% with 0 pts to 12.5% with >4 pts). The risk score was evaluated with receiver operating characteristic curve and the area under the curve of the validation curve is 0.71 (95% CI, 0.66 to 0.76). Conclusions Age greater than 75, AF, chronic lung disease, anemia, and CRF were independent risk factors for 1-year mortality. AAACC risk score identifies patients at high risk of death during 1 year after ICD implantation.

The new oral anticoagulants (NOACs) reduce stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), but dabigatran may increase risk of coronary ischemic events for unclear reasons. Thus, this study assessed the effects of dabigatran and rivaroxaban on platelet reactivity and inflammatory markers in patients with non-valvular AF. Patients with non-valvular AF planned to begin treatment with NOACs were included. Seventeen patients were prescribed dabigatran and ten rivaroxaban. Platelet function (as assessed by multiple-electrode aggregometry, Impact-R shear-induced platelet deposition, P-selectin expression and plasma RANTES levels) and high-sensitivity C-reactive protein (hs-CRP) were measured at enrollment (prior to initiation of NOAC treatment) and at least 7 days into treatment with either dabigratran or rivaroxaban. Seventeen patients treated with dabigatran (mean age 69 ± 7 years, 35 % women, mean CHADS2 score 2.6 ± 1.2), and ten patients treated with rivaroxaban (mean age 73 ± 9 years, 20 % women, mean CHADS2 score 2.7 ± 1.6) completed the study. In both groups, there were no significant differences in platelet reactivity between the baseline and on-anticoagulant treatment time-points, as measured by each of the platelet-specific assays. There was a trend towards increased platelet reactivity in response to arachidonic acid from baseline to on-treatment in both groups, probably as a result of aspirin discontinuation in 33 % of patients. No significant differences were noted between baseline and on-treatment in hs-CRP in both anticoagulant groups. Treatment with dabigatran and rivaroxaban does not appear to be associated with changes in markers of platelet reactivity or systemic inflammation.

High-grade atrioventricular block (HAVB) is a frequent complication of acute myocardial infarction (AMI) and is associated with increased morbidity and mortality. We aimed to evaluate the incidence, predictors, and prognostic significance of HAVB in a contemporary cohort of patients with AMI, in the recent era of early reperfusion. Patients with acute coronary syndromes (n=11,487) during the years 2000-2010 were included. Patients were divided into two groups: with HAVB (n=308, 2.7%) and without HAVB (n=11,179, 97.3%). The incidence of HAVB decreased from 4.2% in 2000 to 2.1% in 2010 (p for trend

Renal Function and Outcomes After Defibrillator Implantation Background Implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) reduce mortality in patients with heart failure (HF) and left ventricular dysfunction. However, their efficacy in patients with chronic kidney disease (CKD) is controversial. Objective We examined the association between renal dysfunction and clinical outcomes in patients undergoing ICD and CRT defibrillator (CRTD) implantation. Methods Data were collected from the Israeli ICD registry. Estimated glomerular filtration rate (eGFR) at implantation was assessed using the modification of diet in renal disease formula. Primary outcome was all-cause mortality. Secondary outcomes included the composite endpoints of death or HF and death or ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]); any hospitalizations; first appropriate and inappropriate ICD therapy. Results During the study period (July 2010–November 2012), 2,811 patients were implanted with ICD or CRTD. One-year follow-up data were available for 730 ICD patients and 453 CRTD patients. Patients with eGFR < 30 mL/minute/1.73 m2 (n = 54, 4.6%) were older, had a higher prevalence of diabetes, hypertension, or ischemic heart disease. eGFR

Background Heart failure (HF) carries poor prognosis in coronary artery disease (CAD) patients despite advances in therapy. Inflammation predicts recurrent cardiovascular events in CAD patients. It is unknown whether increased levels of inflammatory markers are associated with incident HF in these patients. Aim The aims of this study were to evaluate the association between inflammatory markers and future HF risk in patients with stable CAD and to explore possible mediation by myocardial infarction (MI). Methods The study comprised 2,945 patients with stable CAD without HF at baseline during a median follow-up of 7.9 years. Inflammatory baseline markers were the basis of this study. Results Heart failure was diagnosed in 508 patients (17.2%). Patients who developed HF were older and had more often previous MI, diabetes, hypertension, and peripheral vascular disease. Baseline levels of C-reactive protein (CRP), fibrinogen, and white blood cells (WBCs) were significantly higher in patients who developed HF compared with those who did not. Age-adjusted incident HF rates were related to elevated baseline inflammatory markers in a dose-response manner. Adjusting for multiple confounders, the HF hazard ratios were 1.38 (95% CI 1.11-1.72), 1.33 (95% CI 1.07-1.66), and 1.36 (95% CI 1.10-1.68) for the third tertiles of CRP, fibrinogen, and WBC levels, respectively. Hazard ratio for the fifth quintile of a combined "inflammation score" was 1.83 (95% CI 1.40-2.39). Mediation by MI preceding the HF onset during follow-up accounted for 10.4%, 10.8%, and 8.6% of the association of subsequent HF with CRP, fibrinogen, and WBC, respectively. Conclusions Increased levels of CRP, fibrinogen, and WBC are independently related to the incidence of HF in patients with stable CAD.

Elderly patients are underrepresented in clinical trials of device therapy.To provide real-world data regarding outcomes associated with device-based therapy in a large cohort of elderly patients enrolled in the Israeli ICD Registry.Between July 2010 and June 2012, a total of 2807 consecutive patients undergoing implanted cardioverter-defibrillator/cardiac resynchronization therapy-defibrillator (ICD/CRT-D) implantation were prospectively enrolled in the Israeli ICD Registry. For the present analysis, patients were categorized into 3 age groups: ≤60 years (n = 1378 [49%]), 61-75 years (n = 863 [31%]), and75 years (n = 566 [20%]).Elderly patients (75 years of age) had more comorbid conditions and were more likely to undergo CRT-D implantation (all P.01). However, the rate of device-related complications associated with surgical reinterventions at 1 year was3% regardless of age (P = .70 for the comparison among the 3 age groups). Multivariate analysis showed that the risk of heart failure or death and of appropriate ICD therapy for ventricular arrhythmias was significantly increased with increasing age among patients who received an ICD. In contrast, the age-related increase in the risk of all end points was attenuated among patients who received CRT-D devices (all P values for age-by-device-type interactions are.05).In a real-world scenario, elderly patients (75 years of age) comprise approximately 20% of the ICD/CRT-D recipients and experience a device reintervention rate similar to that of their younger counterparts. Our data suggest that the association between advanced age and adverse clinical outcomes is attenuated in elderly patients implanted with CRT-D devices.