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Objective To assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch. Summary background data The aortic arch remains the most challenging part of the aorta for both open and endovascular repair. Transcatheter aortic arch repair has the potential to significantly reduce surgical risks. Methods Patients underwent transcatheter aortic arch repair with a single branch, two stent graft system, implanted over a through-and-through guidewire from the brachiocephalic trunk, to the descending aorta with an ascending aorta stent graft. The ascending aorta stent graft is deployed into a designated docking sleeve to connect the two stent grafts and isolate the aortic arch pathology. Proximal landing zone in all cases was in Zone 0. Anatomical inclusion criteria included adequate landing zone in the ascending aorta, brachiocephalic trunk and descending thoracic aorta. Preparatory debranching procedure was performed in all patients with carotid - carotid crossover bypass and left carotid to left subclavian bypass, or parallel graft from descending aorta to left subclavian artery. Safety and performance were evaluated through one year. Survival analysis used the Kaplan-Meier method. Results Twenty-eight patients, 79% males, with a mean age of 72.2 ± 6.2 years were treated with 100% procedural success. Isolated aortic arch aneurysm was the principle pathology in 17 (60.7%) of patients while chronic aortic dissection was the principle pathology in 6 (21.4%) of patients. The remaining 5(17.8%) had combined or other pathologies. At one month, the vascular pathology was excluded in 25 of 26 alive patients (96.1%). The 30 days mortality rate was 7.1%, stroke rate was 3.6% (all non-disabling) and combined mortality/stroke rate was 10.7%. One year mortality was 10.7%, without device or aneurysm related death. Two patients (7.1%) reported stroke or transient ischemic attack at one year that recovered completely. One year combined mortality/stroke rate was 17.8%. There were three patients (10.7%) that had device related unplanned reinterventions through one year. Conclusions The NEXUS Aortic Arch Stent Graft System, a novel single branch, two stent graft system used for endovascular aortic arch repair that requires landing in the ascending aorta, demonstrates a high success rate with excellent one year safety and performance.

Background: The association between Body Mass Index (BMI) and clinical outcomes following sepsis continues to be debated. We aimed to investigate the relationship between BMI and in-hospital clinical course and mortality in patients hospitalized with bacteremic sepsis using real-world data. Methods: A sampled cohort of patients hospitalized with bacteremic sepsis between October 2015 and December 2016 was identified in the National Inpatient Sample (NIS) database. In-hospital mortality and length of stay were defined as the relevant outcomes. Patients were divided into 6 BMI (kg/m2) subgroups; (1) underweight ≤ 19, (2) normal-weight 20–25, (3) over-weight 26–30, (4) obese I 31–35, (5) obese II 36–39, and (6) obese stage III ≥ 40. A multivariable logistic regression model was used to find predictors of mortality, and a linear regression model was used to find predictors of an extended length of stay (LOS). Results: An estimated total of 90,760 hospitalizations for bacteremic sepsis across the U.S. were analyzed. The data showed a reverse-J-shaped relationship between BMI and study population outcomes, with the underweight patients (BMI ≤ 19 kg/m2) suffering from higher mortality and longer LOS as did the normal-weight patients (BMI 20–25 kg/m2) when compared to the higher BMI groups. The seemingly protective effect of a higher BMI diminished in the highest BMI group (BMI ≥ 40 kg/m2). In the multivariable regression model, BMI subgroups of ≤19 kg/m2 and ≥40 kg/m2 were found to be independent predictors of mortality. Conclusions: A reverse-J-shaped relationship between BMI and mortality was documented, confirming the “obesity paradox” in the real-world setting in patients hospitalized for sepsis and bacteremia.

Background Transcatheter edge-to-edge repair (TEER) repair is a minimally invasive procedure used for patients with severe mitral regurgitation (MR). Cardioversion is indicated for haemodynamically unstable patients with narrow complex tachycardia and is generally considered safe post-mitral clip. We present a patient who underwent cardioversion post-TEER with a single leaflet detachment (SLD). Case summary An 86-year-old female with severe MR underwent TEER with a MitraClip that reduced MR severity to mild. During the procedure, the patient experienced tachycardia, and cardioversion was performed successfully. However, immediately after the cardioversion, the operators noticed recurrent severe MR with a posterior leaflet clip detachment. Deployment of a new clip adjacent to the detached one was obtained. Discussion Transcatheter edge-to-edge repair is a well-established method for treating severe MR in patients who are not suitable for surgical intervention. However, complications can arise during or after the procedure, such as clip detachment as in this case. Several mechanisms can explain SLD. We presumed that in the current case, immediately after cardioversion, there was an acute (post-pause) increase in left ventricle end-diastolic volume and thus in the left ventricle systolic volume with more vigorous contraction, possibly pulling apart the leaflets and detaching the freshly applied TEER device. This is the first report of SLD related to electrical cardioversion after TEER. Even though electrical cardioversion is considered safe, SLD can occur in this setting.

Background: Tricuspid regurgitation (TR) is a common finding which appears to be associated with a worse prognosis. There are conflicting data regarding the prognostic impact of mild TR. We examined the clinical characteristics and echocardiographic properties of subjects with TR and its impact on clinical outcome with particular emphasis on subjects with mild TR. Methods: Consecutive echocardiography examinations during 5 years were evaluated for TR severity and outcome including mortality and cardiovascular hospitalizations. Results: The study included 21,429 subjects; 45% of the subjects had mild TR, 15% had moderate TR and 6.5% had severe TR. Primary organic TR was evident in 7% of the subjects, a percentage that increased with increasing TR severity. TR severity was incrementally associated with older subjects with an increasing number of comorbidities and echocardiographic abnormalities. 29% of the subjects died at a median follow-up duration of 8.7 years. Increasing severity of TR was independently and incrementally associated with mortality. Subjects with mild TR had a 25% increased mortality rate compared to subjects with minimal TR (HR 1.25, 95% CI 1.12-1.39, P

Background: Cardiogenic shock (CS) continues to be a severe and fatal complication of acute coronary syndrome (ACS). CS patients have a high mortality rate despite significant progress in primary reperfusion, the management of heart failure and the expansion of mechanical circulatory support strategies. The present study addressed the clinical characteristics, management, and outcomes of ACS patients complicated with CS. Methods: We performed an observational study, using the 2000–2013 Acute Coronary Syndrome Israeli Surveys (ACSIS) database and identified hospitalizations of ACS patients complicated with CS. Patients’ demographics and clinical characteristics, complications and outcomes were evaluated. We assessed the outcomes of ACS patients with CS at arrival (on the day of admission) compared with ACS patients who arrived without CS and developed CS during hospitalization. Results: The cohort included 13,434 patients with ACS diagnoses during the study period. Of these, 4.2% were complicated with CS; 224 patients were admitted with both ACS and CS; while 341 ACS patients developed CS only during the hospitalization period. The latter patients had significantly higher rates of MACEs compared with the group of ACS patients who presented with CS at arrival (73% vs. 51%; p < 0.0001). Similarly, the rates of in-hospital mortality (55% vs. 36%; p < 0.0001), 30-day mortality (64% vs. 50%; p = 0.0013) and 1-year mortality (73% vs. 59%; p = 0.0016) were higher in ACS patients who developed CS during hospitalization vs. ACS patients with CS at admission. There was a significant decrease in 1-year mortality trends during the 13 years of this study presented in ACS patients from both groups. Conclusions: Patients who developed CS during hospitalization had higher mortality and MACE rates compared with those who presented with CS at arrival. Further studies should focus on this subgroup of high-risk patients.

AimsSeveral procedural and electrocardiogram (ECG) parameters have been associated with the occurrence of high-degree atrioventricular block (AVB) requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR). We hereunder sought to assess if the baseline R-wave amplitude in V1 ECG lead of patients with normal QRS duration undergoing TAVR is associated with a higher patient’s risk for developing high-degree AVB following left bundle branch block (LBBB).Methods and resultsIn this retrospective single-centre study in 720 consecutive patients who underwent TAVR, 141 (19.6%) patients with normal QRS duration developed a new LBBB after TAVR. The 24 (17%) patients who underwent PPI for reasons other than high-degree AVB were excluded from further analysis. In the remaining 117 study patients, 14 (12%) developed high-degree AVB requiring PPI (Group 1) while the remaining 103 (88%) patients did not (Group 2). There were no significant differences in baseline demographic or procedural characteristics nor in PR interval, QRS duration, and QRS axis between these two groups. The incidence of left anterior hemiblock was higher in Group 1 (3 of 14, 21.4%) than that in Group 2 (9 of 103, 8.7%), but the difference was not statistically significant (P = 0.156). The R-wave amplitude in V1 was smaller in Group 1 than that in Group 2 (0.029 ± 0.04 mV vs. 0.11 ± 0.14 mV, P = 0.0316). In the receiver-operating characteristics analysis, the cutoff for R-wave amplitude pre-TAVR was 0.03 mV, area under the curve = 0.7219 (P = 0.0002).ConclusionThe R-wave amplitude in lead V1 during baseline ECG in patients with normal QRS duration may predict the occurrence of high-degree AVB following new LBBB after TAVR.

Aims Current guidelines recommend anticoagulation with a vitamin K antagonist to treat left ventricular (LV) thrombus after myocardial infarction (MI). Data on the use of direct oral anticoagulants (DOACs) in this setting are limited. The aim of the study was to assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI. Methods and results We conducted a prospective, randomized, multicentre open-label clinical trial including patients with LV thrombus detected by 2D transthoracic echocardiography 1–14 days after acute MI. Thirty-five patients were enrolled in three medical centres; 17 patients were randomized to warfarin and 18 patients to apixaban. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation. Secondary outcomes were major bleeding, stroke or systemic embolism, re-hospitalization, and all-cause mortality. Mean LV thrombus size at enrolment was 18.5 mm × 12.3 mm in the warfarin group and 19.9 mm × 12.4 mm in the apixaban group (P = NS). Thirty-two patients completed 3 months follow-up. In the warfarin group, two patients withdrew, and in the apixaban group one patient died. Thrombus completely resolved in 14 of 15 patients in the warfarin group and in 16 of 17 patients in the apixaban group (P = NS and P = 0.026 for non-inferiority). Two patients had major bleeding in the warfarin group, while no major bleeding events were recorded in the apixaban group. There was one stroke in the warfarin group and one death in the apixaban group. Conclusion Our results suggest that apixaban is non-inferior to warfarin for treatment of patients with LV thrombus after acute MI with a 20% non-inferiority margin.

Patients with rapidly deteriorating clinical status due to severe aortic stenosis are often referred for expedited transcatheter aortic valve replacement (TAVR). Data regarding the outcome of such interventions is limited. We aimed to evaluate the outcome of patients undergoing expedited TAVR.Data were derived from the Israeli Multicenter Registry.Subjects were divided into two groups based on procedure urgency: patients who were electively hospitalized for the procedure (N = 3140) and those who had an expedited TAVR (N = 142). Procedural and periprocedural complication rates were significantly higher among patients with an expedited indication for TAVR compared to those having an elective procedure: valve malposition 4.6% versus 0.6% (p lt; 0.001), procedural cardiopulmonary resuscitation 4.3% versus 1.0% (p = 0.007), postprocedure myocardial infarction 2.0% versus 0.4% (p = 0.002), and stage 3 acute kidney injury 3.0% versus 1.1%, (p lt; 0.001). Patients with expedited indication for TAVR had significantly higher in hospital mortality (5.6% vs. 1.4%, p = 0.003). Kaplan-Meier's survival analysis showed that patients undergoing expedited TAVR had higher 3-year mortality rates compared to patients undergoing an elective TAVR procedure (p lt; 0.001). Multivariate analysis found that patients with expedited indication had fourfolds increased risk of in-hospital mortality (odds ratio: 4.07, p = 0.001), and nearly twofolds increased risk of mortality at 3-year (hazard ratio: 1.69, p = 0.001) compared to those having an elective procedure.Patients with expedited indications for TAVR suffer from poor short- and long-term outcomes. It is important to characterize and identify these patients before the deterioration to perform TAVR in a fast-track pathway to minimize their procedural risk.

Oren Yagel,* Naseem Shadafny,* Ran Eliaz, Gil Dagan, David Leibowitz, Ilgar Tahiroglu, David Planer, Offer Amir, Gabby Elbaz Greener,* Ronny Alcalai* Department of Cardiology, Hadassah Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel*These authors contributed equally to this workCorrespondence: Gabby Elbaz GreenerHadassah Medical Center, Cardiology Division, Room Number 114, Jerusalem, IsraelTel +972(2)6776564Fax +972(2)6411028Email Gabby@hadassah.org.ilBackground: Acute coronary syndrome (ACS) at a young age is uncommon. Limited data regarding the long-term follow-up and prognosis in this population are available. Our objectives were to evaluate the long-term clinical outcomes of patients presenting with ACS at a young age and to assess factors that predict long-term prognosis.Methods: A retrospective analysis of consecutive young patients (male below 40 and female below 50 years old) that were admitted with ACS and underwent percutaneous coronary intervention (PCI) between the years 1997 and 2009. Demographics, clinical characteristics, and clinical outcomes including major cardiovascular (CV) events and mortality were analyzed. Multivariable cox proportional hazard model was performed to identify predictors of long-term prognosis.Results: One-hundred sixty-five patients were included with a mean follow-up of 9.1± 4.6 years. Most patients were men (88%), and mean age (years) was 36.8± 4.2. During follow-up, 15 (9.1%) died, 98 (59.4%) patients had at least one major CV event, 22 (13.3%) patients had more than two CV events, and the mean number of recurrent CV events was 1.4± 1.48 events per patient. In multivariate analysis, the strongest predictors of major CV events and/or mortality were coronary intervention without stent insertion (HR1.77; 95% CI 1.09– 2.9), LAD artery involvement (HR 1.59; 95% CI 1.04– 2.44) and hypertension (HR 1.6; 95% CI 1.0– 2.6).Conclusion: Patients with ACS in young age are at high risk for major CV and/or mortality in long-term follow-up with a high rate of recurrent CV events. Close follow-up and risk factor management for secondary prevention have a major role, particularly in this population.Keywords: acute coronary syndrome, ACS, NSTEMI, STEMI, young population, outcomes

This study sought to identify risk factors for permanent pacemaker implantation (PPMI) after Transcatheter aortic valve implantation (TAVI) and explain their trends over the last decade. TAVI is performed nowadays for severe aortic stenosis in more patients with lower surgical risk. While most TAVI complications have been reduced, PPMI remains common. In this observational, retrospective cohort analysis, 338 TAVI patients treated between 2008 and 2017 were reviewed. Risk factors were compared between the early (2008–2013) and late years (2014–2017), and a multivariable logistic regression model was used. A decreasing trend in PPMI over time was observed (p for trend = 0.008), as was a lower rate of PPMI in the late period (19.3% vs. 31.7%, p = 0.009). Three variables were identified as independent risk factors for PPMI that also decreased significantly in the late period: valve implantation depth ≥ 8 mm (OR = 4.3, 95% CI 2.3–8.2, p

Objectives This study sought to report short-term results of safety, performance, and efficacy of the Mistral device first-in-human study in patients suffering from severe functional tricuspid insufficiency. Background Patients who suffer from severe tricuspid regurgitation (TR) and who are at high surgical risk have no standard care therapy. Therefore, minimally invasive and safer methods are sought. The Mistral device is an investigational spiral-shaped device intended for percutaneous transcatheter repair. The Mistral device approximates the tricuspid leaflets by grasping together the chordae tendineae of the tricuspid valve. Methods Seven patients (4 women; mean age 73.14 ± 7.4 years) with severe (n = 5) and massive (n = 2) symptomatic TR and high surgical risk underwent Mistral tricuspid repair under transesophageal echocardiography guidance. Results Mistral was successfully implanted in all cases with a single device deployed in 6 patients, with 2 devices deployed in 1 patient. No procedural or 30-day adverse events occurred. TR was reduced by at least 1 grade in all patients. Effective regurgitant orifice area was reduced from median 0.52 cm2 (interquartile range [IQR]: 0.40 to 0.60 cm2) at baseline to 0.15 cm2 (IQR: 0.14 to 0.21 cm2) at 30 days post-procedure (p Conclusions Tricuspid valve repair with the Mistral device appears safe and leads to 30-day reduction of tricuspid insufficiency and improvement of right ventricular function and exercise capacity.

OBJECTIVES Endovascular aortic arch stent grafting with branched devices has shown initial promising results. The aim of this prospective, multicentre study was to evaluate 3-year outcomes of aortic arch stent grafting with NEXUS® Aortic Arch Stent Graft System (Nexus), a single-branch, bi-modular, off-the-shelf aortic arch stent graft system in high-risk patients. METHODS Patients treated with Nexus, either under the feasibility clinical study or as compassionate use procedures in 5 centres, were included in this study. The primary end point was overall survival. The secondary end points included the incidence of procedure-related unplanned intervention, stroke, paraplegia and endoleak. Clinical and radiologic follow-up was performed at each study site at 30 days, 6 months and on a yearly basis thereafter up to 3 years postoperatively. RESULTS We analysed data from a total of 28 patients. The overall median follow-up was 1132 (interquartile range: 809–1537). There were no device or procedure-related deaths between 1 and 3 years. Overall survival at 1 and 3 years was 89% and 71%, respectively. The cumulative incidence of unplanned reintervention at 1 and 3 years was 11% and 29%, respectively. There were no reports of stroke, paraplegia, aneurysm rupture, myocardial infarction or new aortic valve insufficiency. In this study’s 1–3 year follow-up period, 1 type Ib (4%), 1 type II (4%) and 2 type III (8%; between Nexus’ distal end and Thoracic endovascular aortic repair (TEVAR) extensions) endoleak were detected. CONCLUSIONS Endovascular aortic arch exclusion with the single-branch, off-the-shelf Nexus system provides promising clinical and radiologic results at 3-year follow-up in a high-risk patient cohort.

Gabby Elbaz-Greener,1,&ast; Guy Rozen,2– 4,&ast; Shemy Carasso,5,6 Fabio Kusniec,5,6 Ibrahim Marai,5,6 Maneesh Sud,7 Bradley Strauss,7 Frank W Smart,8 David Planer,1 Offer Amir1,5,6 1Department of Cardiology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; 2Cardiology Division, Hillel Yaffe Medical Center, Hadera, Israel; 3The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel; 4Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 5Division of Cardiovascular Medicine, Baruch Padeh Medical Center, Poriya, Israel; 6The Azrieli Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel; 7Schulich Heart Centre, Division of Cardiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; 8LSU School of Medicine, New Orleans, LA, USA&ast;These authors contributed equally to this workCorrespondence: Gabby Elbaz-GreenerDepartment of Cardiology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Room Number 114, Jerusalem, IsraelTel +972(2)6776564Fax +972(2)6411028Email Gabbyelbaz@yahoo.comBackground: The association between body mass index (BMI) and clinical outcomes following an acute myocardial infarction (AMI) remains controversial. Our objective was to investigate the relationship between BMI and AMI presentation, in-hospital clinical course and mortality in the contemporary era of AMI management.Methods: Patients, hospitalized for an AMI between October 2015 and December 2016, were identified in the National Inpatient Sample (NIS) database. Socio-demographic and clinical data, including BMI, were collected and outcomes, including length of stay and mortality, were analyzed. Patients were divided into 6 BMI (kg/m2) subgroups; under-weight (≤ 19), normal-weight (20– 25), over-weight (26– 30), obese I (31– 35), obese II (36– 39) and extremely obese (≥ 40). Multivariable logistic regression model was used to identify predictors of in-hospital mortality. Linear regression model was used to identify predictors of length of stay (LOS).Results: An estimated total of 125,405 hospitalizations for an AMI across the US were analyzed. Compared to the other BMI subgroups, the under-weight, normal-weight and extremely obese groups presented with a non-ST segment elevation AMI (NSTEMI) more frequently and were less likely to undergo coronary revascularization. The data show a J-shaped relationship between BMI and study outcomes with lower mortality in patients with BMI over 25 compared to normal- and low-weight patients. In the multivariate regression model, BMI group was found to be an independent predictor of mortality.Conclusion: J-shaped relationship between BMI and mortality was documented in patients hospitalized for an AMI in the recent years. These findings confirm that the “obesity paradox” persists during the contemporary era of an AMI management.Keywords: body mass index, BMI, acute myocardial infarction, obesity paradox

Background: The role of the MitraClip implantation in treatment of critically ill patients with heart failure and severe functional mitral regurgitation is undetermined.Methods: We screened...

Purpose Primary sarcoma of the heart is a rare but devastating tumor. Median survival with conventional treatment is 8-12 months. When resection is not feasible, patients often succumb to heart failure secondary to obstruction of blood flow, valve dysfunction, chamber compression or conduction abnormalities. Palliative treatment options include systemic chemotherapy and external beam irradiation. We herein describe a novel technique using endovascular brachytherapy, aiming at reducing tumor mass, alleviating right ventricular pressure overload and at the same time keeping the option of R0 resection viable. Material and methods A 35-year-old man was diagnosed with a non-resectable high-grade intimal sarcoma of the right ventricle (RV), main pulmonary artery (PA) and right PA. After three cycles of doxorubicin and ifosfamide, the patient's symptoms of right heart failure worsened. Imaging documented tumor progression and supra-systemic pulmonary artery pressure. Through a trans-femoral venous access, a brachytherapy sleeve was placed in the RV and main and right PA. A dose of 20 Gy was delivered over a period of ten minutes. Results The patient had an uneventful course and was discharged home 24 hours after the procedure. Ten months after brachytherapy, repeat imaging demonstrated a significant reduction in tumor volume and an increase in pulmonary artery cross-sectional area with a marked reduction of pulmonary artery pressure, leading to a complete resolution of heart failure symptoms. Conclusions Endovascular brachytherapy is a novel, safe and effective therapeutic modality for non-resectable primary cardiac sarcomas either for palliation of obstruction, or tumor mass reduction to allow complete resection.

Venous thromboembolism (VTE), the combined syndromes of deep vein thrombosis (DVT) and pulmonary embolism (PE), is currently the third most frequent acute cardiovascular syndrome globally behind myocardial infarction and stroke. PE carries substantial mortality. In the past decade we have seen a remarkable improvement in new diagnostic tools as well as advances in therapeutic options to manage patients with PE. Still, even with recently updated society guidelines, the management of intermediate and high-risk PE requires clinician expertise and judgment. To aid health care providers caring for patients with acute PE, we have developed a novel, comprehensive yet straightforward, pathway for the management of patients with PE. We believe this pathway can be used in many health care systems around the globe. Our pathway for the diagnosis and management of PE is divided into three steps: the diagnosis of PE, the acute management of patients with PE, and recommendations for chronic management. The pathway requires classification of the PE by the risk of mortality and thus leads to the appropriate intensity of initial care, intervention and monitoring. The Pulmonary Embolism Response Team (PERT) is a multispecialty team designed to guide the decision-making for the individual patient with intermediate-high or high-risk PE. The PERT team brings together specialists from different disciplines. The team convenes in real time via a platform such as WhatsApp or texts messages to communicate clinical data, discuss the options and provide consensus for a course of management. The success of this pathway to manage PE depends heavily on developing a collaborative group of specialists dedicated to provide care at each stage to patients with PE.

Carcinoid heart disease (CHD) is a paraneoplastic cardiac manifestation occurring in patients with carcinoid syndrome (CS) and advanced neuroendocrine malignancy. In about 20-40% of patients with CS, chronic exposure to tumor-released circulating vasoactive peptides typically results in right-sided valvular fibrosis leading to valve dysfunction and right heart failure. CHD remains a significant cause of morbidity and mortality. The management of patients with CHD is complex, as both the systemic malignant disease and the heart involvement have to be addressed. Early diagnosis and timely surgical intervention in selected patients are of utmost importance and offer a survival benefit. In patients with advanced carcinoid heart disease, valve replacement surgery is the most effective option to alleviate cardiac symptoms and contribute to survival outcomes. A collaboration of a multidisciplinary team in centers with experience is required to provide optimal patient management. Here, we review the current literature regarding CHD presentation, pathophysiology, diagnostic tools, and available treatment strategies.

Background There is a lack of data to support the optimal management of high-risk patients with acute severe mitral regurgitation (MR). The role of the MitraClip implantation in treatment of acute severe mitral regurgitation (MR) is undetermined. Methods We screened all patients who underwent MitraClip implantation at the Hadassah Medical Center between October 2015 and December 2019. We evaluated immediate, 30-day and 1-year outcomes after the procedure. We evaluated patients with severe MR due to ruptured cord because of degenerative disease and acute-on-chronic functional MR due to ischemic (after a recent myocardial infarction (MI)) or non-ischemic etiology (secondary to decompensated HF). Results From a cohort of 151 patients, who underwent MitraClip implantation in our center, we identified 35 patients (23.2%) with acute severe mitral regurgitation (4+) and decompensated refractory heart failure. Patients' mean age was 74.15 years, 66.9% - were males. One, 2, or 3 clips were implanted. Reduction of MR from 4+ to 1+ was achieved in 34 patients (66.7%). Twenty-eight patients (80%) had acute-on-chronic severe MR and refractory heart failure including 6 cases after recent MI, other 7 patients presented with heart failure and acute severe MR secondary to ruptured cord due to degenerative disease. After MitraClip implantation, reduction of MR severity was achieved in all patients. Seven patients were withdrawn from intravenous therapy and intra-aortic balloon pump 2–3 days after the procedure. Four patients died during hospitalization, three of them due to sepsis. 30-day follow-up showed improvement of NYHA functional class and a tendency toward improvement in left ventricle systolic function with signs of reverse remodeling. Nevertheless, we observed high 30-day and 1-year mortality rate (11.4 and 23.8% respectively). Conclusions MitraClip therapy could be an alternative option for treatment of patients with acute and acute-on-chronic severe MR of ischemic and non-ischemic etiology. Funding Acknowledgement Type of funding source: None

Up to 10% of non-ST-segment elevation myocardial infarction (NSTEMI) patients require coronary artery bypass graft (CABG) surgery during their hospitalization. Contemporary, real-world, data regarding CABG utilization and safety in NSTEMI patients are lacking. Our objectives were to investigate the contemporary trends in utilization and outcomes of CABG in patients admitted for NSTEMI. Using the 2003 to 2015 National Inpatient Sample data, we identified hospitalizations for NSTEMI, during which a CABG was performed. Patients' sociodemographic and clinical characteristics, incidence of surgical complications, length of stay, and mortality were analyzed. Multivariate analyses were performed to identify predictors of in-hospital complications and mortality. An estimated total of 440,371 CABG surgeries, during a hospitalization for NSTEMI, were analyzed. The utilization of CABG was steady over the years. The data show increasing prevalence of individual co-morbidities as well as cases with Deyo Co-morbidity Index ≥2 (p

Detection of cardiomyocyte death is crucial for the diagnosis and treatment of heart disease. Here we use comparative methylome analysis to identify genomic loci that are unmethylated specifically in cardiomyocytes, and develop these as biomarkers to quantify cardiomyocyte DNA in circulating cell-free DNA (cfDNA) derived from dying cells. Plasma of healthy individuals contains essentially no cardiomyocyte cfDNA, consistent with minimal cardiac turnover. Patients with acute ST-elevation myocardial infarction show a robust cardiac cfDNA signal that correlates with levels of troponin and creatine phosphokinase (CPK), including the expected elevation-decay dynamics following coronary angioplasty. Patients with sepsis have high cardiac cfDNA concentrations that strongly predict mortality, suggesting a major role of cardiomyocyte death in mortality from sepsis. A cfDNA biomarker for cardiomyocyte death may find utility in diagnosis and monitoring of cardiac pathologies and in the study of normal human cardiac physiology and development., The detection of cardiomyocyte death is a critical aspect in the diagnosis and monitoring of heart diseases. Here the authors show that cardiomyocyte-specific methylation patterns of circulating cell-free DNA may serve as a biomarker of cardiac cell death in infarcted and septic patients.

Objectives The study sought to examine the effect of coronary artery disease (CAD) on mortality in patients undergoing transcatheter aortic valve replacement (TAVR). Background CAD is common in the TAVR population. However, there are conflicting data on the prognostic significance of CAD and its treatment in this population. Methods The authors analyzed 1,270 consecutive patients with severe aortic stenosis (AS) undergoing TAVR at 3 Israeli centers. They investigated the association of CAD severity (no CAD, nonsevere CAD [i.e., SYNTAX score (SS) 22]) and revascularization completeness (“reasonable” incomplete revascularization [ICR] [i.e., residual SS 8]) with all-cause mortality following TAVR using a Cox proportional hazards ratio model adjusted for multiple prognostic variables. Results Of the 1,270 patients, 817 (64%) had no CAD, 331 (26%) had nonsevere CAD, and 122 (10%) had severe CAD. Over a median follow-up of 1.9 years, 311 (24.5%) patients died. Mortality was higher in the severe CAD and the ICR groups, but not in the nonsevere CAD or “reasonable” ICR groups, versus no CAD. After multivariate adjustment, both severe CAD (hazard ratio: 2.091; p = 0.017) and ICR (hazard ratio: 1.720; p = 0.031) were associated with increased mortality. Conclusions Only severe CAD was associated with increased mortality post-TAVR. More complete revascularization pre-TAVR may attenuate the association of severe CAD and mortality.

Pacing Dependency Following TAVIBackground Conduction disorders requiring permanent pacemaker (PPM) implantation are a known complication of transcatheter aortic valve implantation (TAVI). Indications for permanent pacing in this setting are still controversial. The study aim was to characterize the natural history of conduction disorders related to TAVI, and to identify predictors for long-term pacing dependency. Methods Consecutive patients who underwent TAVI were included in this prospective observational study. The conduction system was investigated by reviewing 12-lead ECGs during hospitalization and up to 1-year follow-up and by analyzing pacemaker interrogation data. Multivariate analysis was performed in order to identify independent predictors for pacemaker dependency. Results Of 110 patients included in the analysis, 38 (34.5%) underwent PPM implantation. Of those, 26 (68.4%) had a long-term pacing dependency (required PPM), while 12 (31.6%) did not (not-required PPM). Logistic regression revealed that baseline RBBB (P = 0.01, OR = 18.0), baseline PR interval (P = 0.019, OR = 1.14), post-TAVI PR interval and the change in PR interval from baseline (P < 0.001 for both, OR = 1.17 for each 10 milliseconds increment) were independent predictors for long-term pacing dependency. A PR interval increment of greater than 28 milliseconds had the best accuracy in predicting pacemaker dependency. Conclusions Increased pre- and postprocedural PR intervals and pre-existing RBBB are reliable predictors for long-term PPM dependency, while left bundle branch block or QRS width are misleading factors. Our study suggests that the decision for implanting PPM after TAVI should be based mostly on the prolongation of the PR interval.

Peripheral arterial disease (PAD), caused by atherosclerotic processes, is allied with an increased risk of ischemic events, limb loss, and death. Recently, the use of a solid-state laser at 355 nm within a hybrid catheter was suggested for that purpose. In this work, short nanosecond pulses of a solid-state laser at 355 nm delivered through a hybrid catheter, composed of optical fibers and a blunt mechanical blade, are used to conduct a pre-clinical study and two clinical cases. The pre-clinical study consisted of an atherosclerotic calcified cadaveric leg and a porcine in vivo trial within the iliac artery, respectively. The clinical cases include chronic total occlusions with a calcified lesion. The occluded cadaveric leg is recanalized successfully and no evidence of thermal necrosis is indicated in the histopathology analysis of the porcine study. No arterial wall damage is demonstrated on the animals' treated arteries and no significant impact on blood count and biochemistry analysis is noted in the animal trial. Successful recanalization of the occluded arteries followed by balloon angioplasty is obtained in both clinical cases. Our work constitutes a proof of concept for using a solid-state pulsed laser at 355 nm in atherectomy.

Genomic DNA is packed by histone proteins that carry a multitude of post-translational modifications that reflect cellular transcriptional state. Cell-free DNA (cfDNA) is derived from fragmented chromatin in dying cells, and as such it retains the histones markings present in the cells of origin. Here, we pioneer chromatin immunoprecipitation followed by sequencing of cell-free nucleosomes (cfChIP-seq) carrying active chromatin marks. Our results show that cfChIP-seq provides multidimensional epigenetic information that recapitulates the epigenetic and transcriptional landscape in the cells of origin. We applied cfChIP-seq to 268 samples including samples from patients with heart and liver pathologies, and 135 samples from 56 metastatic CRC patients. We show that cfChIP-seq can detect pathology-related transcriptional changes at the site of the disease, beyond the information on tissue of origin. In CRC patients we detect clinically-relevant, and patient-specific information, including transcriptionally active HER2 amplifications. cfChIP-seq provides genome-wide information and requires low sequencing depth. Altogether, we establish cell-free chromatin immunoprecipitation as an exciting modality with potential for diagnosis and interrogation of physiological and pathological processes using a simple blood test.One Sentence SummaryChIP-seq of plasma-circulating nucleosomes (cfChIP-seq) from a simple blood test provides detailed information about gene expression programs in human organs, and cancer.

We evaluated temporal trends in gender-related differences in patients who underwent transcatheter aortic valve implantation (TAVI) for severe symptomatic aortic stenosis from a multicenter TAVI registry during the years 2008 to 2016. Our final cohort included 1,159 males and 1,370 females, with a median follow-up of 2.3 (IQR 1.2, 4.4) years. For temporal trends analysis, the entire population was divided according to period of procedure: 2008 to 2012 and 2013 to 2016. During the 2008 to 2012 period, the rates of in-hospital aortic paravalvular leak, myocardial infarction, pacemaker implantation, and stroke were higher among men than women, but became comparable between the gender during the 2013 to 2016 period. Multivariate analysis demonstrated that female patients who underwent TAVI between the years 2008 and 2012 had a 26% lower risk of death compared with male patients (p = 0.004), but there were no gender-related differences in mortality risk between the years 2013 and 2016 (hazard ratio 1.07, p = 0.6; gender-by-year of procedure, p = 0.027 for interaction). In conclusion, the favorable long-term prognosis described in female patients during the earlier TAVI period seemed to diminish with contemporary TAVI. This might be attributed to current technological advances and improved valve sizing, with a more significant benefit in favor of male patients.

The latest results of the measurement of the Higgs boson decaying into two photons with the full 2016 data will be presented. The analysis is performed using the dataset recorded by the CMS experiment at the LHC from pp collisions at centre-of-mass energies of 13 TeV corresponding to an integrated luminosity of 35.9 fb$^{-1}$.

Objective The objective of this study was to report the 1-year follow-up study results of the new Horizon stent graft (Endospan, Herzliya, Israel) from two different prospective consecutive trials. The Horizon abdominal aortic aneurysm stent graft system is a 14F profile system requiring only a single access site. It consists of three modules, introduced separately: base limb (iliac to iliac limb); distal aortic limb; and proximal aortic limb with a bare suprarenal crown and active fixation. Methods Data from the first in man (FIM) clinical study with 10 patients enrolled and the pivotal study with 30 patients were analyzed. Outcomes measured were freedom from major adverse events (MAEs) including all-cause mortality, myocardial infarction, renal failure, respiratory failure, paraplegia, stroke, bowel ischemia, and procedural blood loss ≥1000 mL. Performance end points included successful delivery and deployment of the device, freedom from aneurysm growth ≥5 mm, type I or type III endoleak, stent graft occlusion, conversion to open surgery, rupture, and stent graft migration. Results In the FIM study, one conversion to open surgery with >1000 mL of blood loss was registered perioperatively. In the pivotal study, no perioperative MAE was registered. Overall, at 1-year follow-up, two deaths and one aneurysm growth unrelated to endoleak were registered. Conclusions The results of both the FIM and pivotal studies demonstrated that 39 of 40 procedures were successful for delivery and deployment of the Horizon stent graft. No MAE was registered during the follow-up. The primary safety and performance end points were met in both studies.