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BACKGROUND There are sparse clinical data on the procedural trends, outcomes and readmission rates following FDA approval and expansion of Transcatheter mitral valve repair/MitraClip® . Whether a complex new technology can be disseminated safely and quickly is controversial. METHODS The study cohort was derived from the National Readmission Data (NRD) 2013-14. MitraClip® was identified using appropriate International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. The primary outcome was a composite of in-hospital mortality + procedural complications. Secondary outcome included 30-day readmissions. Hierarchical two level logistic models were used to evaluate study outcomes. RESULTS Our analysis included 2003 MitraClip® procedures. Overall in-hospital mortality was 3.9%. As expected, there was a significant increase in procedural volume post-FDA approval. Importantly, a corresponding downward trend in mortality and procedural complications was observed. Significant predictors of in-hospital mortality and procedural complications included the use of vasopressors (P

Robots are electromechanical machines that can be used to perform repetitive or dangerous tasks in place of humans. Although robots are now widely used in industrial mass production, it was not until the mid‐1990s that robots were first introduced to clinical medicine. Medical robots are gaining

This study hypothesized that left ventricular (LV) ejection fraction (EF) and global longitudinal strain (GLS) derived from 3-dimensional echocardiographic (3DE) images would better predict mortality than those obtained by 2-dimensional echocardiographic (2DE) measurements, and that 3DE-based LV shape analysis may have added prognostic value.Previous studies have shown that both LVEF and GLS derived from 2DE images predict mortality. Recently, 3DE measurements of these parameters were found to be more accurate and reproducible because of independence of imaging plane and geometric assumptions. Also, 3DE analysis offers an opportunity to accurately quantify LV shape.We retrospectively studied 416 inpatients (60 ± 18 years of age) referred for transthoracic echocardiography between 2006 and 2010, who had good-quality 2DE and 3DE images were available. Mortality data through 2016 were collected. Both 2DE and 3DE images were analyzed to measure LVEF and GLS. Additionally, 3DE-derived LV endocardial surface information was analyzed to obtain global shape indices (sphericity and conicity) and regional curvature (anterior, septal, inferior, lateral walls). Cardiovascular (CV) mortality risks related to these indices were determined using Cox regression.Of the 416 patients, 208 (50%) died, including 114 (27%) CV-related deaths over a mean follow-up period of 5 ± 3 years. Cox regression revealed that age and body surface area, all 4 LV function indices (2D EF, 3D EF, 2D GLS, 3D GLS), and regional shape indices (septal and inferior wall curvatures) were independently associated with increased risk of CV mortality. GLS was the strongest prognosticator of CV mortality, superior to EF for both 2DE and 3DE analyses, and 2D EF was the weakest among the 4 functional indices. A 1% decrease in GLS magnitude was associated with an 11.3% increase in CV mortality risk.GLS predicts mortality better than EF by both 3DE and 2DE analysis, whereas 3D EF is a better predictor than 2D EF. Also, LV shape indices provide additional risk assessment.

The aim of this study was to report the use trends and immediate and long-term outcomes of a large cohort of patients who underwent redo surgery or transcatheter repair of paravalvular leaks (PVLs) at a tertiary referral center.Percutaneous treatment of mitral PVL has emerged as an alternative to surgical treatment in high-risk surgical candidates. There are limited data on the utilization trends, safety, and efficacy of both procedures in the management of mitral PVL.Patients who underwent treatment of mitral PVL at the Mayo Clinic between January 1995 and December 2015 were enrolled. Utilization trends, procedural details, technical success, and in-hospital and long-term outcomes were assessed.Three hundred eighty-one patients underwent percutaneous (n = 195) or surgical (n = 186) treatment of mitral PVLs. The mean age was 66 ± 12 years, and 37% of patients had bioprosthetic valves. Technical success was higher in the surgical group (95.5% vs. 70.1%; p 0.001). In-hospital major adverse events were more common after surgery (22.5% vs. 7.7%; p 0.001). In-hospital death occurred in 3.1% and 8.6% of patients undergoing percutaneous and surgical treatment, respectively (p = 0.027). However, in a multivariate logistic regression analysis, only active endocarditis, chronic renal failure, and severe mitral annular calcifications were significant predictors of in-hospital mortality. Reintervention rates were similar (11.3% vs. 17.2% in the percutaneous and surgical groups, respectively; p = 0.10), with the majority of reinterventions in the percutaneous group occurring early because of residual leak or persistent hemolysis. After risk adjustment, there was no significant difference in long-term survival between patients who underwent surgical versus transcatheter treatment of PVLs.In contemporary practice, patients with symptomatic mitral PVLs are best treated with an integrated team approach incorporating both surgical and percutaneous techniques. Patient selection and timing of intervention are critical to achieve optimal results.

Background— Data on the clinical use of left atrial (LA) hemodynamic monitoring during MitraClip procedure are limited. This study evaluated the association between intraprocedural changes in LA pressure after MitraClip and improvement in exercise capacity as documented by 6-minute walk test (6MWT). Methods and Results— Study population included 50 patients who underwent MitraClip at the Mayo Clinic (Rochester, MN), between June 2014 and July 2016 and completed both baseline and 30-day follow-up 6MWT. Primary outcome for the current analysis was defined as 6MWT improvement above the median. Mean age of the study population was 79±10 years, and 34 (68%) were men. Baseline preprocedural 6MWT distance was 308 m (interquartile range [IQR], 234–394 m). Acute, intraprocedural change in LA pressure after MitraClip was 3 mm Hg (IQR, 1–6 mm Hg), and change in V wave was 11 mm Hg (IQR, 6–19 mm Hg). Median 6MWT improvement was 25 m (IQR, 19–47 m). Univariate analysis showed that patients with ≤ mild postprocedural mitral regurgitation were 4-fold more likely to experience an improvement in 6MWT ( P =0.02). Multivariate model demonstrated that each 5 mm Hg decrease in V wave was associated with 49% increased likelihood for improvement in 6-minute walk ( P =0.04). Similar model with V-wave change as a dichotomous variable showed that patients with a V-wave decrease of ≥11 mm Hg were 3.8× more likely to improve their 6MWT ( P =0.05). Conclusions— Acute changes in LA pressure after MitraClip procedure are associated with clinical improvement as measured by 6MWT. Continuous LA pressure monitoring may be a useful tool for procedural guidance during transcatheter mitral repair.

Aims Heart failure with preserved ejection fraction can lead to pulmonary hypertension. The aim of the present study was to evaluate the role of exercise during right heart catheterization in the unmasking of diastolic dysfunction. Methods and results Between 2004 and 2012, 200 symptomatic patients with exertional dyspnoea, preserved left ventricular systolic function and suspected pulmonary hypertension, underwent right heart catheterization. Included in the study were 63 patients with resting pulmonary arterial wedge pressure (PAWP) ≤15 mmHg. Patients were divided to three tertiles based on their peak exercise PAWP. Mean age was 60 ± 20 years and 29% were males. Mean pulmonary arterial pressure was 31 ± 14 mmHg at rest and 42 ± 18 mmHg upon exercise. Mean change in PAWP between rest and exercise was 0.0 ± 4.3, 4.6 ± 2.4, and 16.6 ± 7.1 mmHg in the lower, middle, and upper tertiles, respectively (P

Cardiac sympathetic denervation is an early nonmotor feature of Parkinson's disease (PD). The aim of the current study was to trace evidence for cardiac dysfunction abnormalities in the premotor phase of PD. We retrospectively reviewed treadmill ergometric tests of a large cohort (n 5 16,841) between 2000 and 2012, that attended the Executive Screening Survey (ESS) at Sheba Medical Center. Heart rate and blood pressure profiles as well as exercise capacity were compared between subjects who later developed PD and age- and sex-matched subjects (ratio 1:2) who did not. We identi- fied 28 subjects (24 males) who developed PD at follow- up. The PD group was older than the group of subjects who did not develop PD on first ergometric test (64.82 6 8.82 vs. 48.91 6 10.60 years, P < 0.001). The time between the first ergometri ct est and motor symptoms onset was 4.64 6 2.86 years. Patients who later devel- oped PD had lower maximal heart rate (P < 0.001) and lower heart rate reserve than healthy controls (P < 0.001); however, compared with age- and sex-matched subjects, subjects who developed PD had similar exercise capacity and heart rate profile during rest, exercise, and recovery, even 1 year before diagnosis. In this study, we did not detect significant signs of sympathetic dysfunction during the premotor phase of PD. V C 2014 International Parkinson and Movement Disorder Society

Smoking is an independent cardiovascular risk factor and correlates with reduced exercise tolerance. However, data on the time dependent effect of smoking cessation on exercise tolerance are limited.We investigated 17,115 men and women who were annually screened at the Institute for Medical Screening of the Chaim Sheba Medical Centre. All subjects had their smoking status documented and performed an exercise stress testing (EST) according to Bruce protocol at each visit. Subjects were divided at baseline into four groups: active smokers (N = 2858), recent quitters (smoking cessation ≤2 years before baseline EST; N = 861), remote quitters (smoking cessation2 years before the baseline EST; N = 3856) and never smokers (N = 9810). Baseline and follow up EST duration were compared among the four groups.Recent quitters demonstrated a 2.4-fold improvement in their EST duration compared with active smokers (improvement of 24 ± 157 vs. 10 ± 157 s, respectively, p = 0.02). Multivariate logistic regression showed that recent quitters were 26% more likely to improve their exercise tolerance compared with active smokers (95% confidence interval (CI) 1.08-1.47, p = 0.003). Assessing smoking status as a time-dependent covariate during four consecutive visits demonstrated that recent quitters were 17% more likely to improve their exercise tolerance compared with active smokers (95% CI 1.02-1.34, p = 0.02), with a less pronounced benefit among remote quitters (hazard ratio = 1.11, 95% CI 1.02-1.21; p = 0.01).Smoking cessation is independently associated with improved exercise tolerance. The benefits of smoking cessation are evident within the first two years of abstinence.

High-density lipoprotein cholesterol (HDL-C) is a strong inverse predictor of cardiovascular events. The aim of the current study was to evaluate the correlation between changes in HDL-C and subsequent cardiovascular events.Study population comprised 13,037 subjects free of cardiovascular disease with a mean follow up of 6 ± 3 years. Low HDL-C was defined as40 mg/dl for men and50mg/dl for women. Participants were divided into three groups based on HDL-C levels at the first and second baseline visits: persistently-low HDL-C (LL); persistently-high HDL-C (HH); and those with high HDL-C in a one visit only: intermittently high HDL-C (LH/HL). The primary endpoint was the first occurrence of a cardiovascular event.A total of 529 (4.1%) incident events occurred during follow-up. HDL-C levels increased significantly between the two landmark visits (47.5 ± 12.6 vs. 48.1 ± 12.2, p0.001). Kaplan-Meier survival analysis showed that the cumulative probability of cardiovascular events at 6 years was highest among subjects in the LL group (7.6%), and similar among LH/HL and HH groups (3.3% and 4%, respectively; log-rank p=0.001). Multivariate Cox regression analysis, with HDL-C as time-dependent covariate, showed that subjects with persistently low HDL-C during follow up experienced a 51% increased cardiovascular risk compared with subjects with persistently high HDL-C (p=0.026). Subjects with intermittently high HDL-C during follow up experienced similar risk to those with persistently high HDL-C (HR=1.02; p=0.89).Variations in HDL-C levels during follow-up are associated with subsequent cardiovascular risk. Patients who retain low HDL-C levels are at the cardiovascular highest risk.

OBJECTIVES: The presence of a coronary chronic total occlusion (CTO) is a common consideration in favour of surgical revascularization. However, studies have shown that not all patients undergoing coronary artery bypass grafting (CABG) have a bypass graft placed on the CTO vessel. The aim of this study was to determine the prevalence of CTO among patients referred for CABG and the significance of incomplete CTO revascularization in these patients. METHODS: The study included 405 consecutive patients undergoing CABG during a 2-year period. Clinical, echocardiographic and angiographic data were collected. Determination of whether or not a CTO was bypassed was made by correlating data from the surgical reports and preprocedural angiograms. The primary end point of this study was 5-year all-cause mortality. RESULTS: Two hundred and twenty-one CTOs were found in 174 patients: 132 patients (76) had 1 CTO; 37 (21) had 2 CTOs and 5 (3) had 3 CTOs. Of the 221 CTOs, 191 (86%) were bypassed. All left anterior descending (LAD) CTOs were grafted; however, 12 of left circumflex and 22% of right coronary artery CTOs did not receive bypass grafts. Incomplete CTO revascularization was associated with older age, more comorbidities, including stroke, renal impairment and lower ejection fraction. However, incomplete CTO revascularization was not associated with increased 5-year mortality. CONCLUSIONS: Coronary CTOs are a common finding in patients referred for bypass surgery. The presence of a CTO is not independently associated with an adverse long-term outcome. While most CTOs are successfully bypassed, failure to revascularize a non-LAD CTO is not associated with adverse long-term outcome.

The Pooled Cohort Equations (PCE) are used for atherosclerotic cardiovascular disease (ASCVD) risk stratification. The purpose of the current study was to evaluate whether cardiorespiratory fitness could be used to improve the accuracy of the risk model. We evaluated 15,596 asymptomatic self

Contemporary heart failure (HF) therapies have not resulted in improved outcomes among patients with HF and preserved left ventricular ejection fraction (LVEF). We sought to evaluate the differential effect of LVEF on long-term mortality after hospitalization for acute decompensated HF in a real-world setting. All-cause mortality at 4 years after hospitalization for HF was assessed by LVEF (categorized as preserved [≥50%], mildly [40% to 49%], moderately [30% to 39%], and severely [30%] reduced) among 1,620 patients enrolled in the Heart Failure Survey in ISrael. Among the study patients, 30% had preserved LVEF and 20%, 25%, and 25%, had mild, moderate, and severe reductions in LVEF, respectively. Multivariate analysis showed that patients with preserved LVEF had a similar risk of long-term mortality as patients with mild or moderate reduction in LVEF (hazard ratio [HR] 0.92 [p = 0.40] and 1.01 [p = 0.90], respectively) while severely reduced LVEF conferred increased increase rate compared with preserved LVEF (HR 1.20, p = 0.04). Interaction term analysis showed that the risk associated with severely reduced LVEF was evident only among patients ≤75 years (HR 1.49, p = 0.003), whereas among older patients, there was no difference in the risk of long-term mortality between those with preserved versus severely reduced LVEF (HR 1.02 [p = 0.86]; p value for age-by-LVEF interaction = 0.03). In conclusion, patients hospitalized for HF who have preserved LVEF experience similar long-term mortality as patients with mild or moderate reductions in LVEF, whereas severely reduced LVEF remains an independent predictor of long-term mortality in this population. The differential effect of LVEF on long-term mortality is significantly attenuated in the older age group.

Attenuated heart rate (HR) response during exercise is associated with adverse cardiovascular outcome. The acceptable value for HR response is 85% of the age-predicted maximal HR (APMHR). This study hypothesized that mild attenuation of HR response during exercise among healthy subjects is associated with increased cardiovascular risk. The study population comprised 10,323 healthy men and women without known cardiovascular disease (CVD) or diabetes mellitus who underwent a yearly screening program and were followed up during a mean period of 4.3 years. Participants were grouped to 3 tertiles based on the percentage of their APMHR reached at the baseline stress test. The primary end point was the occurrence of CVD or cerebrovascular disease. A total of 1,015 incident cases of CVD occurred during follow-up. A multivariate Cox proportional hazards regression model showed that the CVD risk of subjects who reached 60% to 96% of their APMHR was 35% greater compared with those who reached their APMHR (p = 0.001). A subgroup analysis among subjects who reached 85% of their APMHR showed that even mildly attenuated heart response (in the range of 85% to 96% APMHR) was independently associated with 36% increase in CVD risk (p0.001). In conclusion, attenuated HR response during exercise is a powerful and independent predictor of adverse cardiovascular events during long-term follow-up among healthy men and women. The prognostic implications of attenuated HR response in this population are apparent even with a minor decrease of the maximal HR to96% of the APMHR.

Limited information exists on whether changes in medical practices over the study decades have affected the outcomes of acute coronary syndrome (ACS) patients who undergo early coronary artery bypass surgery (CABG) during index hospitalisation.Data on trends for early CABG referral and associated outcomes were obtained among 11,485 ACS patients enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) 2000-2010.Among 11,485 patients, 566 (5%) were referred to early CABG. These patients displayed higher risk characteristics, including Killip classII, anterior myocardial infarction, greater left ventricular dysfunction, and more frequent use of mechanical ventilation and intra-aortic balloon pump (all p0.01). Nevertheless, mortality rates of patients referred to early CABG vs. treated with percutaneous coronary intervention (PCI) or medically, was similar (11.4% vs. 10.2%; log-rank p-value=0.40). There was a significant decline in the referral trend over the study decade (6.7% - 1.7%; p0.001). One year survival was similar between patients referred to early CABG during the late (years: 2006-2010) vs. early (years: 2000-2005) period (85.7% vs. 90%; log-rank p-value=0.15), whereas, among patients who didn't undergo early CABG, and underwent percutaneous coronary intervention (PCI) or medical management only, enrolment during the late periods was associated with a significant survival benefit (91.5% vs. 88.1%; log-rank p-value0.001).Over the study decade there was a significant decline in referral for early CABG, without a difference in the one-year mortality between the early and non-early CABG group.

The aim of this study is to provide a summary of the currently applied aortic paravalvular leak (PVL) closure techniques and describe the procedural and long-term outcomes in a large consecutive cohort of patients.Percutaneous repair has emerged as an effective therapy for patients with PVL. To date, clinical outcome data on percutaneous closure of aortic PVL are limited.All patients who underwent catheter-based treatment of aortic PVL between 2006 and 2015 were identified. Procedural and short-term results were assessed. Patients were contacted for clinical events and symptoms.Eighty-six procedures were performed in 80 patients. The mean age was 68 ± 15 years, and 70% were men. The primary indications for PVL closure were symptoms of heart failure, hemolysis, and both in 83%, 5%, and 12%, respectively. Successful device deployment was accomplished in 94 defects (90%). Reduction in PVL to mild or less was achieved in 62% of patients. In-hospital major adverse events occurred in 8% of procedures. Symptomatic improvement at 30 days was achieved in 64% of patients. Patients who had reduction in the PVL grade to mild or less experienced more improvement in New York Heart Association functional class (from 2.93 ± 0.62 to 1.72 ± 0.73) compared with those with mild or greater residual leak (from 3.03 ± 0.57 to 2.52 ± 0.74) (p 0.001). In patients with severe hemolysis (n = 8), transfusion requirements were eliminated in 7 (88%) after PVL closure. Kaplan-Meier survival analysis showed that the cumulative probability of freedom from repeat surgery at 2 years was 98 ± 2% in patients who had mild or less residual leak compared with 68 ± 10% in patients with higher grades of residual PVL (log-rank p = 0.004).Percutaneous reduction of aortic PVL is associated with durable symptom relief and lower rates of repeat cardiac surgery. The magnitude of benefit is greatest with PVL reduction to a grade of mild or less. Therefore, attempts should be made to reduce PVL as much as possible.

Background Metabolic syndrome and its components are severe global health issues that are increasing in frequency as the prevalence of obesity increases. Various studies have established a correlation between metabolic syndrome and diseases including, diabetes mellitus, non-alcoholic fatty liver disease, cirrhosis, and cardiovascular disease. In recent years, correlations have also been detected between obesity and metabolic syndrome and the prevalence of certain types of cancer. The current study examines whether obesity and metabolic syndrome components are risk factors for cancer among the adult population in Israel. Methods A cohort study analysis was performed of 24,987 initially healthy men and women who underwent yearly medical assessments at the Institute for Medical Screening in the Sheba Medical Center. Data from the Institute for Medical Screening database was correlated with that from the Israel Cancer Center in the Ministry of Health updated to December 2013. The correlation between metabolic syndrome, obesity, and the overall risk of cancer as well as the risks of specific types of cancer were examined. Results Of 20,444 subjects for whom complete data were available, 1535 were diagnosed with cancer during the mean follow-up time of 104.3 months. In a multi-variant analysis, no significant correlation was found between metabolic syndrome or obesity and the incidence of cancer. When the data were stratified by gender and cancer type, however, a significant association between metabolic syndrome and breast cancer in women was observed (P = 0.03, HR = 1.67, 95% CI = 1.05–2.67). Conclusion Metabolic syndrome correlates with higher than expected breast cancer incidence in women.

Men tend to develop cardiovascular disease (CVD) earlier in life than women. Whether this difference is attributable only to gender is a matter of debate. The purpose of this study was to evaluate gender differences in cardiovascular risk in a large cohort of asymptomatic men and women and explore gender-related risk in prespecified risk factor subgroups. We investigated 14,966 asymptomatic men and women free of diabetes, hypertension, or ischemic heart disease who were annually screened. The primary end point of the present study was the occurrence of ischemic or cerebrovascular disease as composite end point. Multivariate Cox proportional hazards regression modeling was used to assess the gender difference regarding CVD and to examine the association between CVD risk factors and gender. Mean age of the study population was 47 ± 10 years and 30% were women. Kaplan-Meier survival analysis showed that at 6.2 ± 3.9 years' follow-up, the rate of CVD events was 6.1% among men compared with 1.8% among women (log-rank p0.001). Consistently, multivariate analysis demonstrated that male gender was independently associated with a significant threefold increased risk for development of CVD events (hazard ratio 3.05, CI 2.25 to 4.14). The CVD risk associated with male gender was consistent in each risk subset analyzed, including older age, low high-density lipoprotein, impaired fasting glucose, and positive family history for ischemic heart disease (all p values for gender-by-risk factor interactions0.05). Higher performance on treadmill test had a protective effect regarding CVD development in both men and women. In conclusions, healthy middle-aged men experienced increased risk for the development of CVD events compared with women independently of traditional CVD risk factors. However, better exercise capacity is associated with a protective effect.

Background Irreversible electroporation (IRE) is a non-thermal cell ablation approach that induces selective damage to cell membranes only. The purpose of the current study was to evaluate and optimize its use for in-vivo myocardial decellularization. Methods Forty-two Sprague-Dawley rats were used to compare myocardial damage of seven different IRE protocols with anterior myocardial infarction damage. An in-vivo open thoracotomy model was used, with two-needle electrodes in the anterior ventricular wall. IRE protocols included different combinations of pulse lengths (70 vs. 100 μseconds), frequency (1, 2, 4 Hz), and number (10 vs. 20 pulses), as well as voltage intensity (50, 250 and 500 Volts). All animals underwent baseline echocardiographic evaluation. Degree of myocardial ablation was determined using repeated echocardiography measurements (days 7 and 28) as well as histologic and morphometric analysis at 28 days. Results All animals survived 28 days of follow-up. Compared with 50V and 250V, electroporation with 500V was associated with significantly increased myocardial scar and reduction in ejection fraction (67.4%±4% at baseline vs. 34.6%±20% at 28 days; p

Restenosis following coronary angioplasty represents a major clinical problem. Irreversible electroporation (IRE) is a nonthermal, nonpharmacological cell ablation method. IRE utilizes a sequence of electrical pulses that produce permanent damage to tissue within a few seconds. The left carotid arteries of eight rats underwent in vivo intimal damage using two Fogarty angioplasty catheters. The procedure was immediately followed by IRE ablation in four rats, while the remaining four were used as the control group. The IRE ablation was performed using a sequence of ten dc pulses of 3800 V/cm, 100 mus each, at a frequency of ten pulses per second, applied across the blood vessel between two parallel electrodes. The electrical conductance of the treated tissue was measured during the electroporation to provide real-time feedback of the process. Left carotid arteries were excised and fixated after a 28-day follow-up period. Neointimal formation was evaluated histologically. The use of IRE was successful in three out of four animals in a way that is consistent with the measurements of blood vessel electrical properties. The integrity of the endothelial layer was recovered in the IRE-treated animals, compared with control. Successful IRE reduced neointima to media ratio (0.57 plusmn 0.4 versus 1.88 plusmn 1.0, P = 0.02). Conclusions: We report for the first time the in vivo results of attenuation of neointimal formation using IRE. Our study shows that IRE might be able to attenuate neointimal formation after angioplasty damage in a rodent model of restenosis. This approach may open new venues in the treatment of coronary artery restenosis after balloon angioplasty.

We present a pilot study on the long term effects of irreversible electroporation (IRE) on a large blood vessel. The study was motivated by the anticipated use of IRE for treatment of cancer tumors abutting large blood vessels. A sequence of 10 direct current IRE pulses of 3800 V/cm, 100μs each, at a frequency of 10 pulses per second, were applied directly to the carotid artery in six rats. Measuring tissue conductivity during the procedure showed, as predicted, an increase in conductivity during the application of the pulse, which suggests that this measurement can be used to control the application of IRE. All the animals survived the procedure and showed no side effects. Histology performed 28 days after the procedure showed that the connective matrix of the blood vessels remained intact and the number of vascular smooth muscle cells (VSMC) in the arterial wall decreased with no evidence of aneurysm, thrombus formation or necrosis. Average VSMC density was significantly lower following IRE ablation compared with control (24 ± 11 vs. 139 ± 14, P

Heart failure (HF) patients have frequent exacerbations leading to high consumption of medical services and recurrent hospitalizations. Different precipitating factors have various effects on long-term survival. We investigated 2212 patients hospitalized with a diagnosis of either acute HF or acute exacerbation of chronic HF. Patients were divided into 2 primary precipitant groups: ischemic (N = 979 [46%]) and nonischemic (N = 1233 [54%]). The primary endpoint was all-cause mortality. Multivariate analysis demonstrated that the presence of a nonischemic precipitant was associated with a favorable in-hospital outcome (OR 0.64; CI 0.43–0.94), but with a significant increase in the risk of 10-year mortality (HR 1.12; CI 1.01–1.21). Consistently, the cumulative probability of 10-year mortality was significantly higher among patients with a nonischemic versus ischemic precipitant (83% vs 90%, respectively; Log-rank P value

Background Diabetes mellitus (DM) and aortic stenosis (AS) are frequent findings in the elderly population. Data regarding the influence of DM on the outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) due to AS are limited. The aim of this study was to examine the impact of DM on TAVR outcomes. Methods We investigated 443 patients with severe AS undergoing TAVR. Subjects were divided into insulin-dependent diabetic mellitus (IDDM) patients (N = 44), non-dependent insulin diabetic mellitus (NIDDM) patients (N = 114) and non-diabetics (N = 285) of whom 31 (74 %), 86 (79 %) and 209 (76 %) respectively had trans-femoral TAVR. Peri-procedural complications and outcomes were recorded according to the Valve Academic Research Consortium-2 criteria. Results Patients with IDDM as well as NIDDM demonstrated similar complication rates compared with non-diabetic patients, except for acute kidney injury (AKI) grade 3 [4 (2 %) and 3 (3 %) vs. 1 (0.4 %) respectively, p = 0.032]. Kaplan–Meier survival analysis showed that DM, regardless of the type of treatment, was not associated with increased 2 years mortality (Log-rank p value 0.44). Multivariate cox regression analysis adjusted for age, gender, coronary artery disease, DM, AKI3, hypertension, chronic renal failure and peripheral vascular disease found that AKI3 was associated with increased risk of 2 years mortality [HR = 7.35, 95 % CI 2.16–25.07, p = 0.001] whereas female gender was found as a protective factor [HR = 0.47, 95 % CI 0.28–0.8, p = 0.005], and DM was not associated with increased risk. Conclusions Following TAVR, DM patients seem to have similar peri-procedural and mid-term outcomes compared with patients without DM, while IDDM patients seem to suffer greater incidence of AKI. Further research in larger cohorts of patients is needed to validate our results. Electronic supplementary material The online version of this article (doi:10.1186/s12933-015-0291-3) contains supplementary material, which is available to authorized users.

Background The aim of the present study was to examine whether exercise blood pressure can be used to predict the development of hypertension in normotensive middle‐aged adults. Methods and Results We investigated 7082 normotensive subjects who were annually screened in a tertiary medical center and completed maximal treadmill exercise tests at each visit. After the initial 3 years, subjects were divided into approximate quartiles according to their average exercise systolic and diastolic blood pressure responses (≤158; 158 to 170; 170 to 183; ≥183 mm Hg for systolic blood pressure and ≤73; 73 to 77; 77 to 82; ≥82 mm Hg for diastolic blood pressure). Mean age of the study population was 48±9 years and 73% were men. Average baseline resting blood pressure was 120/77±12/7 mm Hg. During a follow‐up of 5±3 years, 1036 (14.6%) subjects developed hypertension. The cumulative probability of new‐onset hypertension at 5 years was significantly increased with increasing quartiles of exercise systolic blood pressure (5%, 9%, 17%, and 35%, respectively; P P P Conclusions In normotensive middle‐aged individuals, blood pressure response to exercise is associated with future development of hypertension.

Increased body mass index (BMI) and obesity are associated with increased risk of new-onset atrial fibrillation (AF) among middle-aged adults.The objective of the study is to investigate the association between BMI and the risk for new-onset AF among middle-aged adults.We investigated 18,290 men and women who were annually screened in a tertiary medical center. Participants were divided at baseline into 3 groups: normal weight (BMI ≥18 and25 kg/m(2), n = 7,692), overweight (BMI ≥25 and30 kg/m(2), n = 8,032), and obese (BMI ≥30 kg/m(2), n = 2,566). The primary end point was new-onset AF during follow-up.Mean age of study population was 49 ± 11 years, and 73% were men. A total of 288 incident events (1.6%) occurred during 6 ± 4 years. Kaplan-Meier survival analysis showed that the cumulative probability of AF at 6 years was highest among obese participants, intermediate among overweight participants, and lowest among participants with normal weight (2.1%, 1.7%, and 0.8% respectively, P.001). Multivariable Cox regression analysis showed that overweight and obesity were independently associated with increased AF risk (hazard ratio 1.54 [P = .004] and 2.41 [P.001], respectively). Assessment of BMI change as a time-dependent covariate in the multivariable model showed that each 1 kg/m(2) reduction in BMI during follow-up was associated with a significant 7% reduction in the risk for the occurrence of a first AF event (hazard ratio 0.93, 95% CI 0.88-0.99, P = .019). Consistently, similar analysis showed that each 5-kg weight loss during follow-up was independently associated with a significant 12% reduced risk of new-onset AF (95% CI 0.81-0.98, P = .02).Our findings suggest that overweight and obesity are associated with increased AF risk, whereas weight reduction is independently associated with reduced risk of de novo AF.

The prevalence of thrombophilia and dyslipidemia among young survivors of acute coronary syndrome has not been clearly defined. The purpose of the current study was to investigate the prevalence of multiple markers of thrombophilia and dyslipidemia in a cohort of consecutive young survivors of acute coronary syndrome. The study cohort included 156 consecutive young patients (men45 and women50 years), admitted to the intensive cardiac care unit with newly diagnosed acute coronary syndrome. Analysis included baseline, clinical and epidemiological characteristics, angiographic coronary anatomy, echocardiographic evaluation, extensive lipid and thrombophilia laboratory profiles, and in-hospital and 1-year clinical outcomes for all patients. Acute myocardial infarction was diagnosed in 142 (92 %) patients, of whom 108 (72 %) had ST-segment elevation. Eighteen (12 %) patients had no traditional risk factors. Low levels of high-density lipoprotein (40 mg/dL) were found in 101 (65 %) patients, and 49 (34 %) patients had elevated levels of lipoprotein(a) (Lp(a)) (30 mg/dL). Eighteen (12 %) patients were diagnosed with antiphospholipid antibody syndrome (APS), and 73 (47 %) had at least one laboratory finding consistent with thrombophilia. Patients with APS had significantly higher levels of Lp(a) (46 ± 32 vs. 29 ± 31 mg/dL, p = 0.005). APS is a common prothrombotic state found in young survivors of acute coronary syndrome. Lp(a) levels are elevated among APS patients who present with premature acute coronary syndrome.

Background The introduction of transcatheter aortic valve replacement (TAVR) expanded definitive therapy of aortic stenosis to many high-risk patients, but it has not been fully evaluated in the dialysis population. We aimed to evaluate the current trend and in-hospital outcome of surgical aortic valve replacement (SAVR) and TAVR in the dialysis population. Methods Severe aortic stenosis patients on maintenance dialysis who underwent SAVR or TAVR in the Nationwide Inpatient Sample database from January 1, 2005, through December 31, 2014, were included in our comparative analysis. The trends of SAVR and TAVR were assessed. In-hospital mortality, rates of major adverse events, hospital length of stay, cost of care, and intermediate care facility utilization were compared between the 2 groups using both unadjusted and propensity-matched data. Results Utilization of aortic valve replacement in dialysis patients increased 3-fold; a total of 2531 dialysis patients who underwent either SAVR (n = 2264) or TAVR (n = 267) between 2005 and 2014 were identified. Propensity score matching yielded 197 matched pairs. After matching, a 2-fold increase in in-hospital mortality was found with SAVR compared with TAVR (13.7% vs 6.1%, P = .021). Patients who underwent TAVR had more permanent pacemaker implantation (13.2% vs 5.6%, P = .012) but less blood transfusion (43.7% vs 56.8%, P = .02). Rates of other key morbidities were similar. Hospital length of stay (19 ± 16 vs 11 ± 11 days, P P = .002) were significantly higher with SAVR. Cost of hospitalization was 25% less with TAVR. Conclusion In patients on maintenance dialysis, TAVR is associated with lower hospital mortality, resource utilization, and cost in comparison with SAVR.

e12064 Background: Data on long-term cardiovascular effects and safety of aromatase inhibitors (AI) are limited and conflicting. The purpose of the current study was to evaluate the effect of AI on vascular injury as assessed by peripheral endothelial function among women with breast cancer. Methods: This is an observational, prospective study of 96 postmenopausal women with breast cancer at initiation of treatment, with or without AI. All participants underwent baseline and 6-12 months follow up non-invasive peripheral endothelial function measurement. Reactive hyperemia index (RHI) was measured using the EndoPAT test. The primary endpoint was endothelial function deterioration of at least 20% between baseline and follow-up. Results: Mean age of the study population was 66±7 years. There was no statistical difference in demographic data between the groups. Compared with the control group, more women in the treatment group demonstrated worsening of RHI (53% vs. 42%, p = 0.207) between baseline and 6-12 month follow up measurement. There was no statistical difference between the groups at baseline. When RHI deterioration was evaluated as a dichotomous variable, with a 20% cutoff, women in the AI group demonstrated higher rates of RHI deterioration (28% vs. 8%, p=0.020). The risk of AIs for endothelial dysfunction was correlated with burden of cardiovascular (CV) risk, such that in women with >3 CV risk factors, AIs were associated with increased risk of RHI deterioration (42% vs. 10%, p=0.016), whereas in women with

Background: Rapid ventricular pacing (RVP) is frequently performed during transcatheter aortic valve replacement (TAVR) in order to temporarily reduce cardiac output. The clinical impact of these hypotensive episodes is unknown. Our aim was to assess correlation between RVP, its duration, and

Background: The primary objective of our study was to evaluate real-world outcomes of Transcatheter mitral valve repair (MitraClip) in terms of length of stay (LOS) and cost of care. Methods: The study cohort was derived from the National Readmission Data (NRD) 2013, a subset of the Healthcare Cost

Background: The primary objective of our study was to evaluate real-world outcomes of Transcatheter mitral valve repair (TMVR) (MitraClip) including in-hospital mortality and short-term readmission rates. Methods: The study cohort was derived from the National Readmission Data (NRD) 2013. TMVR was

Increased blood levels of alanine amino transferase (ALT, also known as SGPT; serum glutamic pyruvic transaminase) serve as a marker of liver injury by various mechanisms. Less is known about the clinical implications associated with low-normal ALT levels. Previous studies showed low ALT levels to be associated with poor long-term outcomes among elderlies, serving as a biomarker for increased incidence of frailty and subsequent risk of mortality. However, it has not been determined yet whether low-normal ALT values might be predictive of frailty and mortality in younger, middle-aged adults.We conducted a historical prospective cohort analysis.A total of 23,506 adults with ALT levels within the normal range, at the mean age of 48 ± 11 years, participating in an annual screening program for preventive medicine, were followed-up for a median period of 8.5 years during which 638 died. Low-normal ALT values (serum ALT activity17IU/L) were found to be predictive for increased risk of all-cause mortality (HR=1.6; 95% CI 1.34-1.92; p0.001). Statistically significant correlation was demonstrated even after applying a multifactorial model correction for age, gender, eGFR, low albumin, arterial hypertension, diabetes mellitus and ischemic heart disease.We suggest that low-normal ALT values may serve as an independent predictive marker for increased long-term mortality in middle-aged adults.

Heart failure with preserved ejection fraction can lead to pulmonary hypertension. The aim of the present study was to evaluate the role of exercise during right heart catheterization in the unmasking of diastolic dysfunction.Between 2004 and 2012, 200 symptomatic patients with exertional dyspnoea, preserved left ventricular systolic function and suspected pulmonary hypertension, underwent right heart catheterization. Included in the study were 63 patients with resting pulmonary arterial wedge pressure (PAWP) ≤15 mmHg. Patients were divided to three tertiles based on their peak exercise PAWP. Mean age was 60 ± 20 years and 29% were males. Mean pulmonary arterial pressure was 31 ± 14 mmHg at rest and 42 ± 18 mmHg upon exercise. Mean change in PAWP between rest and exercise was 0.0 ± 4.3, 4.6 ± 2.4, and 16.6 ± 7.1 mmHg in the lower, middle, and upper tertiles, respectively (P 0.001). Higher exercise PAWP tertiles were associated with reduced pulmonary vascular resistance (8.3 ± 6.7, 2.9 ± 2.7, and 5.8 ± 4.6 Woods units, respectively; P = 0.004). A multivariate linear regression model demonstrated that each 5 kg/m(2) increase in body mass index was associated with 2.5 ± 1.0 mmHg increase in exercise PAWP (P = 0.017). A multivariate binary logistic model showed that subjects with borderline PAWP at rest (12-15 mmHg) were 4.5 times more likely to be in the upper tertile of exercise PAWP (P = 0.011).In symptomatic patients with pulmonary hypertension, preserved left ventricular ejection fraction and PAWP ≤15 mmHg, exercise during right heart catheterization may unmask diastolic dysfunction. This is especially true for obese patients and patients with borderline resting PAWP.

The aim of the present study was to evaluate whether assessment of stroke volume index (SVI) can be used to improve risk stratification among patients with low-gradient severe aortic stenosis and preserved ejection fraction (EF). Study population comprised 409 patients with aortic valve area ≤1.00 cm(2), mean gradient40 mm Hg, and a normal EF (≥50%) who were followed up in a tertiary referral center from 2004 to 2012. Echocardiographic parameters and clinical data were collected. Multivariate Cox proportional hazards regression modeling was used to evaluate the association between SVI and the risk of all-cause mortality. Mean age of study patients was 78 ± 11 years, and 42% were men. The mean SVI was 39 ± 7 ml/m(2) (tertile 1 = 32 ± 4 ml/m(2); tertile 2 = 39 ± 1 ml/m(2); tertile 3 = 47 ± 4 ml/m(2)). Multivariate analysis showed that the SVI was the most powerful echocardiographic parameter associated with long-term outcome: each 5 ml/m(2) reduction in SVI was associated with a 20% increase in adjusted mortality risk (p = 0.01). Consistently, Kaplan-Meier analysis showed that the cumulative probability of survival during 3 years of follow-up was 60%, 72%, and 73% among patients in the low-, intermediate-, and high-SVI groups, respectively (p = 0.012). Our findings suggest that in patients with low-gradient severe aortic stenosis and preserved EF, there is a graded inverse relation between SVI and the risk of long-term mortality.

Percutaneous edge-to-edge mitral valve repair using the MitraClip system has evolved as a new tool in the treatment of mitral regurgitation (MR).To present our initial experience with MitraClip implantation in 20 high risk patients at Sheba Medical Center.Twenty high surgical risk patients with symptomatic significant MR underwent MitraClip implantation. Clinical and echocardiographic parameters were recorded at baseline and at follow-up.The patients' mean age was 76 years and 65% were male. Coronary artery disease was present in 85% and 45% ent in had previous bypass surgery. Renal failure was present in 65%, atrial fibrillation in 60%, and 30% had an implantable cardioverter defibrillator/cardiac resynchronization therapy device. Mean left ventricular ejection fraction was 36%. Grade III-IV MR was present in all patients with the vast majority suffering from functional MR secondary to ventricular remodeling. New York Heart Association (NYHA) class was III-IV in 90%. Patients were followed for a mean of 231 days. Acute reduction of MR grade toor = 2 was accomplished in 19 of the 20 patients (95%) with a 30 day mortality of 5%. At follow-up MR was reduced toor = 2 in 64% of patients, and NYHA class improved in 70% of patients. An additional 2 patients (11%) died during follow-up.MitraClip implantation is feasible and safe in high risk highly symptomatic patients with significant MR. Acute and mid-term results are comparable to similar high risk patient cohorts in the literature. Continued surveillance and longer follow-up are needed to elucidate which patients are most likely to benefit from the procedure.

In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood–brain barrier penetration of most therapeutic agents. In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood–brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r2 = 0.99, p < 0.001) and the number of treatment pulses (r2 = 0.94, p < 0.002). Blood–brain barrier disruption depicted 3.2 ± 0.3 times larger volumes than the final permanent damage volumes (p < 0.0001). These results indicate that it may be beneficial to use more than one modality of electroporation when planning a treatment for brain tumors.

Cardiac sympathetic denervation is an early nonmotor feature of Parkinson's disease (PD). The aim of the current study was to trace evidence for cardiac dysfunction abnormalities in the premotor phase of PD. We retrospectively reviewed treadmill ergometric tests of a large cohort (n = 16,841) between 2000 and 2012, that attended the Executive Screening Survey (ESS) at Sheba Medical Center. Heart rate and blood pressure profiles as well as exercise capacity were compared between subjects who later developed PD and age- and sex-matched subjects (ratio 1:2) who did not. We identified 28 subjects (24 males) who developed PD at follow-up. The PD group was older than the group of subjects who did not develop PD on first ergometric test (64.82 ± 8.82 vs. 48.91 ± 10.60 years, P 0.001). The time between the first ergometric test and motor symptoms onset was 4.64 ± 2.86 years. Patients who later developed PD had lower maximal heart rate (P 0.001) and lower heart rate reserve than healthy controls (P 0.001); however, compared with age- and sex-matched subjects, subjects who developed PD had similar exercise capacity and heart rate profile during rest, exercise, and recovery, even 1 year before diagnosis. In this study, we did not detect significant signs of sympathetic dysfunction during the premotor phase of PD.

Clinical thyroid disease is associated with changes in the cardiovascular system, including changes in heart rate during exercise. However, data on the relation between subclinical thyroid disease (SCTD) and heart rate during exercise are limited.We investigated 3799 apparently healthy subjects who were evaluated in the Institute for Preventive Medicine at the Sheba Medical Center. All subjects answered standard health questionnaires; were examined by a physician; completed routine blood tests including thyrotropin, free triiodothyronine, and free thyroxine levels; and underwent a treadmill exercise according to the Bruce protocol. Subjects with known thyroid disease or those who were taking thyroid-related drugs were excluded from the analysis. Heart rate profile was compared between patients with subclinical hypothyroidism (SCHypoT), patients with normal thyroid function, and patients with subclinical hyperthyroidism (SCHyperT) using propensity score matching.Seventy patients had SCHyperT and 273 had SCHypoT. Compared with age- and sex-matched normal subjects, SCHyperT subjects had a higher resting heart rate (83±17 vs. 76±12 beats per minute [bpm], p=0.006), a significantly higher recovery heart rate (94±12 vs. 90±12 bpm, p=0.045), and a significantly lower heart rate reserve (80±20 vs. 87±18 bpm, p=0.006). Subjects with SCHypoT showed a trend toward a lower resting heart rate (75±13 vs. 77±15 bpm, p=0.09) and had a significantly lower recovery heart rate (88±12 vs. 90±13 bpm, p=0.035). There was no significant difference in exercise duration or blood pressure between subjects with SCTD and their matched normal controls.Subjects with SCTD have a significantly different heart rate profile during rest, exercise, and recovery.

Both resting blood pressure (BP) variability and exercise BP previously showed association with incident hypertension. The aim of the present study was to examine whether visit-to-visit variability in exercise systolic blood pressure (SBP) can predict the risk for new-onset hypertension among normotensive adults. We investigated 6546 normotensive men and women who were annually screened in a tertiary medical center and completed treadmill exercise tests at each visit. Based on the initial three baseline annual visits, long-term intervisit variability of exercise SBP among the three tests was measured using standard deviation (SD) and coefficient of variation for each participant. The rate of newly diagnosed hypertension was measured in different variability levels during 6 ± 3 years of follow-up. Multivariate analysis adjusted for various clinical factors, including resting BP, showed that each 5 mm Hg rise in the SD of exercise SBP resulted in a significant 5% increase in the risk for the development of future hypertension (P = .015). Subjects in the upper exercise SBP SD variability tertile had a 28% (P = .007) increased risk for hypertension during follow-up, as compared with those in the lowest tertile. Similar results were achieved for the assessment of coefficient of variation of exercise SBP. In conclusion, visit-to-visit variability in exercise SBP can predict the development of future hypertension among normotensive individuals.

Autonomic dysfunction is associated with the atrial arrhythmogenesis. The purpose of this study was to investigate the association between heart rate reserve (HRR), and new onset atrial fibrillation (AF) among middle-aged adults. We investigated 15,729 apparently healthy self-referred men and women

Studies in different populations with high risk for cardiovascular disease (CVD) have shown an association between serum uric acid (SUA) and CVD. However, only a few studies have demonstrated such an association in healthy populations. The aim of this study was to investigate the association between SUA and CVD in a cohort of men and women without diabetes or CVD. A retrospective study was conducted, with a mean 4.8-year follow-up. The outcome was the occurrence of a cardiovascular event, defined as the diagnosis of ischemic heart disease, acute coronary syndrome, acute myocardial infarction, or ischemic stroke. Mean SUA levels were 6.2 ± 1.1 mg/dl for men (n = 6,580) and 4.4 ± 1.1 mg/dl for women (n = 2,559). For women, the rate of CVD occurrence was 11.6% for the highest quartile of SUA level, compared with 5.0% to 6.5% for the lower 3 quartiles. For men, the rate of CVD occurrence was 14.0% for the highest quartile of SUA level, compared with 10.8% for the lowest quartile. The hazard ratio for CVD, adjusted for age, serum creatinine level, body mass index, systolic blood pressure, low-density lipoprotein cholesterol level, triglyceride level, plasma fasting glucose, physical activity, cardiovascular family history, use of diuretics, and current smoking, was 1.24 (95% confidence interval 1.08 to 1.41) for women and 1.06 (95% confidence interval 1.00 to 1.13) for men (p for interaction = 0.04). In conclusion, the strong association of SUA levels with CVD in women, compared with the much lesser degree in men, highlights the necessity of stratifying by gender in investigations of cardiovascular risk factors and supports exploration of SUA as a marker of CVD risk in healthy populations.

Nonthermal irreversible electroporation (NTIRE) is an emerging tissue ablation modality that may be ideally suited in developing a decellularized tissue graft. NTIRE utilizes short electric pulses that produce nanoscale defects in the cell membrane lipid bilayer. The electric parameters can be chosen in such a way that Joule heating to the tissue is minimized and cell death occurs solely due to loss in cell homeostasis. By coupling NTIRE with the body’s response, the cells can be selectively ablated and removed, leaving behind a tissue scaffold. Here, we introduce two different methods for developing a decellularized arterial scaffold. The first uses an electrode clamp that is applied to the outside of a rodent carotid artery and the second applies an endovascular minimally invasive approach to apply electric fields from the inner surface of the blood vessels. Both methods are first modeled using a transient finite element analysis of electric and thermal fields to ensure that the electric parameters used in this study will result in minimal thermal damage. Experimental work demonstrates that both techniques result in not only a decellularized arterial construct but an endothelial regrowth is evident along the lumen 7 days after treatment, indicating that the extracellular matrix was not damaged by electric and thermal fields and is still able to support cell growth.

Tissue scaffolding is a key component for tissue engineering, and the extracellular matrix (ECM) is nature’s ideal scaffold material. A conceptually different method is reported here for producing tissue scaffolds by decellularization of living tissues using nonthermal irreversible electroporation (NTIRE) pulsed electrical fields to cause nanoscale irreversible damage to the cell membrane in the targeted tissue while sparing the ECM and utilizing the body’s host response for decellularization. This study demonstrates that the method preserves the native tissue ECM and produces a scaffold that is functional and facilitates recellularization. A two-dimensional transient finite element solution of the Laplace and heat conduction equations was used to ensure that the electrical parameters used would not cause any thermal damage to the tissue scaffold. By performing NTIRE in vivo on the carotid artery, it is shown that in 3 days post NTIRE the immune system decellularizes the irreversible electroporated tissue and leaves behind a functional scaffold. In 7 days, there is evidence of endothelial regrowth, indicating that the artery scaffold maintained its function throughout the procedure and normal recellularization is taking place.

Tissue ablation finds an increasing use in modern medicine. Nonthermal irreversible electroporation (NTIRE) is a biophysical phenomenon and an emerging novel tissue ablation modality, in which electric fields are applied in a pulsed mode to produce nanoscale defects to the cell membrane phospholipid bilayer, in such a way that Joule heating is minimized and thermal damage to other molecules in the treated volume is reduced while the cells die. Here we present a two-dimensional transient finite element model to simulate the electric field and thermal damage to the arterial wall due to an endovascular NTIRE novel device. The electric field was used to calculate the Joule heating effect, and a transient solution of the temperature is presented using the Pennes bioheat equation. This is followed by a kinetic model of the thermal damage based on the Arrhenius formulation and calculation of the Henriques and Moritz thermal damage integral. The analysis shows that the endovascular application of 90, 100 μs pulses with a potential difference of 600 V can induce electric fields of 1000 V/cm and above across the entire arterial wall, which are sufficient for irreversible electroporation. The temperature in the arterial wall reached a maximum of 66.7°C with a pulse frequency of 4 Hz. Thermal damage integral showed that this protocol will thermally damage less than 2% of the molecules around the electrodes. In conclusion, endovascular NTIRE is possible. Our study sets the theoretical basis for further preclinical and clinical trials with endovascular NTIRE.