Faculty Bibliography

BACKGROUND:Atrial fibrillation (AF) is a well-known complication in the setting of ST elevation myocardial infarction (STEMI). Data on the long-term prognostic implications of New-Onset AF (NOAF) complicating STEMI in the era of complete revascularization remains controversial. Our aim therefore was to evaluate the long-term prognosis of prior AF (pAF) and new-onset AF (NOAF) in STEMI patients undergoing percutaneous coronary intervention (PCI). METHODS:We studied 1657 consecutive STEMI patients hospitalized in the cardiac intensive care unit during 2008-2014. We reviewed patient records for the occurrence of pAF and NOAF. NOAF was defined as AF occurring within 30days of the STEMI episode. Patients were followed for a mean period of 3.4±2.1years. RESULTS:Within our cohort 77 (4.6%) patients had pAF and 47 (2.8%) had NOAF. Patients with any AF were older and had a reduced systolic ejection fraction. Thirty-day mortality and all-cause mortality rates were significantly higher in patients with pAF in comparison to those without AF (9.1% vs. 2.2% p<0.001 and 31.2% vs. 9.4%, p<0.001, respectively). NOAF showed a trend for increased all-cause mortality (17% vs. 9.1%, p=0.07) and 30-days mortality (6.4% vs. 2.1%. p=0.09). In a multivariate regression model, pAF but not NOAF was a predictor of mortality throughout the follow-up period (HR 2.02, 95% CI 1.2 to 3.1, p=0.005 and HR 1.1, 95% CI 0.56 to 2.2, p=0.75, respectively). CONCLUSIONS:Prior AF and not new-onset AF is an independent predictor of both short and long term mortality in patients treated with PCI.

Our aim was to evaluate the mortality rate and occurrence of complications in patients aged <75 versus ≥75 years with ST-elevation myocardial infarction (STEMI). We studied 1,657 consecutive patients with STEMI hospitalized in the cardiac intensive care unit during 2008 to 2014. All patients underwent primary percutaneous intervention, of which 292 (18%) were aged ≥75 years. Patient records were evaluated for in-hospital complications, 30-day mortality, and long-term mortality over a mean period of 3.4 ± 2.1 years. Compared with younger patients, patients aged ≥75 years had a significantly higher rate of coronary disease risk factors, prolonged symptom duration (512 ± 640 vs 333 ± 545 minutes, p <0.01) and door-to-balloon time (51.1 ± 24 vs 45.6 ± 38, p = 0.02). Patients aged ≥75 years had more in-hospital noncardiac and cardiac complications, including cardiogenic shock and arrhythmia, and had higher 30-day and long-term mortalities. Cardiogenic shock was associated with increased short- and long-term mortality in the older group but was not incremental over the noncardiogenic shock cohort. In conclusion, in patients aged ≥75 years who underwent primary percutaneous intervention for STEMI, the short- and long-term mortality rate was greater than fourfold higher compared with younger patients.

BACKGROUND:The Norton scale is traditionally used to assess the risk of pressure ulcers. However, recent studies have shown its prognostic utilization in elderly patients with diverse medical conditions. The association between low admission Norton scale scores (ANSS), complications, and mortality in elderly patients following trans-catheter aortic valve implantation (TAVI) has never been studied. We aimed to determine if low ANSS (≤16) is associated with complications and 30-day and 1-year mortality in elderly patients undergoing TAVI. METHODS:The medical charts of elderly (≥70 years) TAVI patients at the Tel-Aviv Medical Center, a tertiary medical center, were studied for the following measurements: ANSS, demographics, co-morbidities, complications during hospitalization, and 30-day and 1-year mortality. Complications included: an atrio-ventricular block, stroke, and vascular complications. RESULTS:The cohort included 302 elderly patients: 179 (59.3%) were women; the mean age was 83.3±5.1 years. Following TAVI, 112 (37.1%) patients had complications other than pressure ulcers, 10 (3.3%) patients died within 30 days, and 42 (13.9%) patients died within one year. Overall, 36 (11.9%) patients had low ANSS. 1-year mortality rates were almost three times higher in patients with low ANSS relative to patients with high ANSS (27.8% vs. 12.0%; the relative risk 1.1; p=0.018). A stepwise logistic regression analysis showed that ANSS was independently inversely associated with 1-year mortality (p=0.018). Complications and 30-day mortality rates were similar in both groups. CONCLUSIONS:Low ANSS are associated with 1-year mortality after TAVI. The Norton scale may therefore be used as an additional tool for elderly patient selection before TAVI.

Patients with previous coronary artery bypass grafting (CABG) are considered to be at increased perioperative risk for a redo cardiac operation. In the era of transcatheter aortic valve implantation (TAVI), these patients constitute a considerable portion of those with severe aortic stenosis referred for TAVI. We evaluated the impact of previous CABG on transfemoral TAVI outcomes. Patients with severe symptomatic aortic stenosis (n = 515) who underwent transfemoral TAVI were divided according to the presence of history of CABG. Patients with previous valvular surgery were excluded (n = 12). TAVI clinical end points and adverse events were considered according to the Valve Academic Research Consortium 2 definitions. Survival was estimated using Cox regression models at the enter mode with the dependent variable defined as all-cause mortality. Of the total 503 patients who underwent TAVI, 91 (18.1%) had previous CABG. At baseline, patients with previous CABG were younger (80.8 vs 83.1 years, p <0.001), mostly men (85% vs 35%, p <0.001), had more cardiac and vascular co-morbidities, higher mean logistic EuroSCORE (32.8 vs 22; p <0.001), lower ejection fraction (53% vs 56%, p <0.001), and lower AV gradients and larger valve area. At a mean follow-up of 636 days, the overall Valve Academic Research Consortium 2-adjudicated end points did not differ. No differences in mortality were observed at 30 days, 6 months, and 1 year after TAVI (hazard ratio 1.34, p = 0.55, Cox regression). We conclude that patients with previous CABG who underwent TAVI do not have increased risk of periprocedural complications or mortality, although having distinct clinical features compared with the total TAVI population.

Soft tissue filler products have become very popular in recent years, with ever-increasing medical and aesthetic indications. While generally considered safe, the number of reported complications with tissue fillers is growing. Nevertheless, there is no specific animal model that is considered as the gold standard for assessing safety or efficacy of tissue fillers, and there are very little data on interspecies differences in reaction to these products. Here, we report on interspecies differences in reaction to a subcutaneous injectable co-polyester, composed of castor oil and citric acid. Comparison of the histopathological local tissue changes following 1-month postimplantation, indicated that in rats the reaction consisted of cavities, surrounded by relatively thin fibrotic enveloping capsule. In contrast, an unexpected severe inflammatory granulomatous reaction was noticed in Sinclair minipigs. To our knowledge, this is the first report on significant interspecies differences in sensitivity to tissue fillers. It emphasizes the importance of using the appropriate animal model for performing preclinical biocompatibility assays for biodegradable polymers, tissue fillers, and implanted medical devices in general. It also makes the Sinclair minipig subject for scrutiny as an animal model in future biocompatibility studies.

Transcatheter aortic valve implantation (TAVI) is considered a suitable treatment for patients with severe symptomatic aortic stenosis and high operative risk. Our aim was to evaluate the effect of preprocedural and new-onset atrial fibrillation (NOAF) on mortality and stroke in patients who underwent TAVI. We performed a single-center study of 380 consecutive patients enrolled to a TAVI registry. NOAF was defined as postprocedural atrial fibrillation (AF) occurring within 30 days after the procedure. Patients were followed up for a mean of 528 ± 364 days. During follow-up, 19 (5%) new episodes of stroke occurred, of whom 6 and 18 cases occurred within 30 days and 1 year, respectively. Overall mortality during the follow-up was 68 (20%), of those 12 and 58 patients died within 30 days and 1 year, respectively. NOAF occurred in 31 (8.2%) patients and was not associated with higher stroke or mortality rates at 30 days or 1 year of follow-up. Notably, compared with patients without previous AF, patients with previous AF at baseline had increased rates of stroke and mortality at 1-year follow-up (2.1% vs 9.6%, p = 0.01, and 8.2% vs 34.9%, p <0.01; respectively). In multivariate analysis, AF at baseline but not NOAF was a significant predictor of mortality throughout the follow-up period (HR 2.2, 95% confidence interval 1.3 to 3.8, p = 0.003, and HR 1.5, 95% confidence interval 0.5 to 4.1, p = 0.390, respectively). In conclusion, previous AF at baseline but not NOAF significantly increases stroke and mortality rates after TAVI. The inclusion of AF into future TAVI risk stratification scores should be strongly considered.

BACKGROUND:Two important causes of sudden death during endurance races are arrhythmic death and heat stroke. However, "arrhythmic death" has caught practically all the attention of the medical community whereas the importance of heat stroke is less appreciated. OBJECTIVES/OBJECTIVE:The study sought to determine what percentage of life-threatening events during endurance races are due to heat stroke or cardiac causes. METHODS:This retrospective study examined all the long distance popular races that took place in Tel Aviv from March 2007 to November 2013. The number of athletes at risk was known. The number of athletes developing serious sport-related events and requiring hospitalization was known. Life-threatening events were those requiring mechanical ventilation and hospitalization in intensive care units. RESULTS:Overall, 137,580 runners participated in long distance races during the study period. There were only 2 serious cardiac events (1 myocardial infarction and 1 hypotensive supraventricular tachyarrhythmia), neither of which were fatal or life threatening. In contrast, there were 21 serious cases of heat stroke, including 2 that were fatal and 12 that were life threatening. One of the heat stroke fatalities presented with cardiac arrest without previous warning. CONCLUSIONS:In our cohort of athletes participating in endurance sports, for every serious cardiac adverse event, there were 10 serious events related to heat stroke. One of the heat stroke-related fatalities presented with unheralded cardiac arrest. Our results put in a different perspective the ongoing debate about the role of pre-participation electrocardiographic screening for the prevention of sudden death in athletes.

Cell replacement strategies are promising interventions aiming to improve myocardial performance. Yet, the electrophysiological impact of these approaches has not been elucidated. We assessed the electrophysiological consequences of grafting of two candidate cell types, that is, skeletal myoblasts and human embryonic stem cell-derived cardiomyocytes (hESC-CMs). The fluorescently labeled (DiO) candidate cells were grafted into the rat's left ventricular myocardium. Two weeks later, optical mapping was performed using the Langendorff-perfused rat heart preparation. Images were obtained with appropriate filters to delineate the heart's anatomy, to identify the DiO-labeled cells, and to associate this information with the voltage-mapping data (using the voltage-sensitive dye PGH-I). Histological examination revealed the lack of gap junctions between grafted skeletal myotubes and host cardiomyocytes. In contrast, positive Cx43 immunostaining was observed between donor and host cardiomyocytes in the hESC-CMs-transplanted hearts. Optical mapping demonstrated either normal conduction (four of six) or minimal conduction slowing (two of six) at the hESC-CMs engraftment sites. In contrast, marked slowing of conduction or conduction block was seen (seven of eight) at the myoblast transplantation sites. Ventricular arrhythmias could not be induced in the hESC-CM hearts following programmed electrical stimulation but were inducible in 50% of the myoblast-engrafted hearts. In summary, a unique method for assessment of the electrophysiological impact of myocardial cell therapy is presented. Our results demonstrate the ability of hESC-CMs to functionally integrate with host tissue. In contrast, transplantation of cells that do not form gap junctions (skeletal myoblats) led to localized conduction disturbances and to the generation of a proarrhythmogenic substrate.