Prevalence of Cardiac Sarcoidosis in Middle-Aged Adults Diagnosed with High-Grade Atrioventricular Block.

INTRODUCTION: Atrioventricular block may be idiopathic or a secondary manifestation of an underlying systemic disease. Cardiac sarcoidosis is a significant underlying cause of high-grade atrioventricular block, posing diagnostic challenges and significant clinical implications. This study aimed to assess the prevalence and clinical characteristics of cardiac sarcoidosis among younger patients presenting with unexplained high-grade atrioventricular block. METHODS: We evaluated patients aged between 18 and 65 years presenting with unexplained high-grade atrioventricular block, who were systematically referred for cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, prior to pacemaker implantation. Subjects with suspected cardiac sarcoidosis based on imaging findings were further referred for tissue biopsy. Cardiac sarcoidosis diagnosis was confirmed based on biopsy results. RESULTS: Overall, 30 patients with high-grade atrioventricular block were included in the analysis. The median age was 56.5 years (interquartile range 53-61.75, years). In 37%, cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, were suggestive of cardiac sarcoidosis, and in 33% cardiac sarcoidosis was confirmed by tissue biopsy. Compared with idiopathic high-grade atrioventricular block patients, all cardiac sarcoidosis patients were males (100% vs 60%, P = .029), were more likely to present with heart failure symptoms (50% vs 10%, P = .047), had thicker inter-ventricular septum on echocardiography (12.2 ± 2.7 mm vs 9.45 ± 1.6 mm, P = .002), and were more likely to present with right ventricular dysfunction (33% vs 10%, P = .047). CONCLUSIONS: Cardiac sarcoidosis was confirmed in one-third of patients ≤ 65 years, who presented with unexplained high-grade atrioventricular block. Cardiac sarcoidosis should be highly suspected in such patients, particularly in males who present with heart failure symptoms or exhibit thicker inter-ventricular septum and right ventricular dysfunction on echocardiography.

Significance of Anteroseptal Late Gadolinium Enhancement Among Patients With Acute Myocarditis.

Anteroseptal location of late gadolinium enhancement (LGE) in patients with acute myocarditis (AM) detected by cardiovascular magnetic resonance may indicate an independent marker of unfavorable outcomes according to recent data. We aimed to evaluate the clinical characteristics, management, and inhospital outcomes in patients with AM with positive LGE based on its presence in the anteroseptal location. We analyzed data from 262 consecutive patients hospitalized with a diagnosis of AM with positive LGE within 5 days of hospitalization (n = 425). Patients were divided into 2 groups: those with anteroseptal LGE (n = 25, 9.5%) and those with non-anteroseptal LGE (n = 237, 90.5%). Except for age that was higher in patients with anteroseptal LGE, the demographic and clinical characteristics did not differ significantly between both groups including past medical history, clinical presentation, electrocardiogram parameters, and lab values. Moreover, patients with anteroseptal LGE were more likely to present with reduced left ventricular ejection fraction and to receive congestive heart failure treatments. Although univariate analysis showed that patients with anteroseptal LGE were more likely to have inhospital major adverse cardiac events (28% vs 9%, p = 0.003), there was no difference inhospital outcomes on multivariable analysis between both groups (hazard ratio, 1.17 [95% confidence interval, 0.32 to 4.22], p = 0.81). A higher left ventricular ejection fraction in either echocardiography or cardiovascular magnetic resonance corresponded to better inhospital outcomes regardless of the presence or absence of anteroseptal LGE. In conclusion, the presence of anteroseptal LGE did not confer additional prognostic value for inhospital outcomes.

Impaired tolerance to the autoantigen LL-37 in acute coronary syndrome.

Background: LL-37 is the only member of the cathelicidin family of antimicrobial peptides in humans and is an autoantigen in several autoimmune diseases and in acute coronary syndrome (ACS). In this report, we profiled the specific T cell response to the autoimmune self-antigen LL-37 and investigated the factors modulating the response in peripheral blood mononuclear cells (PBMCs) of healthy subjects and ACS patients. Methods and results: The activation induced marker (AIM) assay demonstrated differential T cell profiles characterized by the persistence of CD134 and CD137, markers that impair tolerance and promote immune effector and memory response, in ACS compared to Controls. Specifically, CD8+CD69+CD137+ T cells were significantly increased by LL-37 stimulation in ACS PBMCs. T effector cell response to LL-37 were either HLA dependent or independent as determined by blocking with monoclonal antibody to either Class-I HLA or Class-II HLA. Blocking of immune checkpoints PD-1 and CTLA-4 demonstrated the control of self-reactive T cell response to LL-37 was modulated predominantly by CTLA-4. Platelets from healthy controls down-modulated CD8+CD69+CD137+ T cell response to LL-37 in autologous PBMCs. CD8+CD69+CD137+ T cell AIM profile negatively correlated with platelet count in ACS patients. Conclusions: Our report demonstrates that the immune response to the autoantigen LL-37 in ACS patients is characterized specifically by CD8+CD69+CD137+ T cell AIM profile with persistent T cell activation and the generation of immunologic memory. The results provide potentially novel insight into mechanistic pathways of antigen-specific immune signaling in ACS.

The burden of heart failure in cardiac intensive care unit: a prospective 7 years analysis.

AIMS: The profiles of patients at cardiac intensive care units (CICU) have evolved towards a patient population with an increasing number of co-morbid medical conditions and acute heart failure (HF). The current study was designed to illustrate the burden of HF patients admitted to CICU, and evaluate patient characteristics, in-hospital course and outcomes of CICU patients with HF compared with patients with acute coronary syndrome (ACS). METHODS AND RESULTS: A prospective study including all consecutive patients admitted to the CICU at a tertiary medical centre between 2014 and 2020. The main outcome was a direct comparison between HF and ACS patients in processes of care, resource use, and outcomes during CICU hospitalization. A secondary analysis compared ischaemic versus non-ischaemic HF aetiology. Adjusted analysis evaluated parameters associated with prolonged hospitalization. The cohort included 7674 patients with a total annual CICU admissions of 1028-1145 patients. HF diagnosis patients represented 13-18% of the annual CICU admissions and were significantly older with higher incidence of multiple co-morbidities compared with patients with ACS. HF patients also required more intensive therapies and demonstrated higher incidence of acute complications as compared with ACS patients. Length of stay at the CICU was significantly longer among HF patients compared with patients with ACS (either STEMI or NSTEMI) (6.2 ± 4.3 vs. 4.1 ± 2.5 vs. 3.5 ± 2.1, respectively, P < 0.001). HF patients represented a disproportionately higher amount of total CICU patient days during the study period, as the total length of hospitalization of HF patients was 44-56% out of the total cumulative days in CICU of patients with ACS every year. In hospital mortality rates were also significantly higher among patients with HF compared with STEMI or NSTEMI (4.2% vs. 3.1% vs. 0.7%, respectively, P < 0.001). Despite several differences in baseline characteristics between patients with ischaemic versus non-ischaemic HF, which can be attributed mainly to disease aetiology, hospitalization length and outcomes were similar among the groups regardless of HF aetiology. In multivariable analysis for the risk of prolonged hospitalization in the CICU adjusted to potential significant co-morbidities associated with poor outcomes, HF was found to be an independent and significant parameter associated with the risk of prolonged hospitalization with an OR of 3.5 (95% CI 2.9-4.1, P < 0.001). CONCLUSIONS: Patients with HF in CICU have higher severity of illness with a prolonged and complicated hospital course, all of which can substantially increase the burden on clinical resources.

Elevated Native T1 Values in the Remote Myocardium Supplied by Obstructive Non-Infarct Related Coronary Arteries in Post-STEMI Cardiac Magnetic Resonance.

INTRODUCTION: Native T1 mapping values are elevated in acutely injured myocardium. We sought to study whether native T1 values, in the non-infarct related myocardial territories, might differ when supplied by obstructive or nonobstructive coronary arteries. METHODS: Consecutive patients (N = 60, mean age 59 years) with the first STEMI following primary percutaneous coronary intervention, underwent cardiac magnetic resonance within 5 ± 2 days. A retrospective review of coronary angiography reports classified coronary arteries as infarct-related coronary artery (IRA) and non-IRA. Obstructive coronary artery disease (CAD) was defined as stenosis ≥50%. Native T1 values were presented using a 16-segment AHA model according to the three main coronary territories: left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA). RESULTS: The cutoff native T1 value for predicting obstructive non-IRA LAD was 1,309 msec with a sensitivity and specificity of 67% and 82%, respectively (AUC 0.76, 95% CI: 0.57-0.95, p = 0.04). The cutoff native T1 value for predicting obstructive non-IRA RCA was 1,302 msec with a sensitivity and specificity of 83% and 55%, respectively (AUC 0.7, 95% CI: 0.52-0.87, p = 0.05). Logistic regression model adjusted for age and infarct size demonstrated that native T1 was an independent predictor for the obstructive non-IRA LAD (OR 4.65; 1.32-26.96, p = 0.05) and RCA (OR 3.70; 1.44-16.35, p = 0.03). CONCLUSION: Elevated native T1 values are independent predictors of obstructive non-IRA in STEMI patients. These results suggest the presence of concomitant remote myocardial impairment in the non-infarct territories with obstructive CAD.

Clinical predictors of left ventricular thrombus after myocardial infarction as detected by magnetic resonance imaging.

Background: The diagnosis of a left ventricular (LV) thrombus in patients with ST-segment elevation myocardial infarction (STEMI) remains challenging. The aim of the current study is to characterize clinical predictors for LV thrombus formation, as detected by cardiac magnetic resonance imaging (CMRI). Methods: We retrospectively evaluated 337 consecutive STEMI patients. All patients underwent transthoracic echocardiography (TTE) and CMRI during their index hospitalization. We developed a novel risk stratification model (ThrombScore) to identify patients at risk of developing an LV thrombus. Results: CMRI revealed the presence of LV thrombus in 34 patients (10%), of whom 33 (97%) had experienced an anterior wall myocardial infarction (MI), and the majority (77%) had at least mildly reduced left ventricular ejection fraction (LVEF < 45%). The sensitivity for thrombus formation of the first and second TTE was 5.9% and 59%, respectively. Multivariate logistic regression model revealed that elevated C-reactive protein levels, lack of ST-segment elevation (STe) resolution, elevated creatine phosphokinase levels, and STe in anterior ECG leads are robust independent predictors for developing an LV thrombus. These variables were incorporated to construct the ThrombScore: a simple six-point risk model. The odds ratio for developing thrombus per one-point increase in the score was 3.2 (95% CI 2.1-5.01; p < 0.001). The discrimination analysis of the model revealed a c-statistic of 0.86 for thrombus development. The model identified three distinct categories (I, II, and III) with corresponding thrombus incidences of 0%, 1.6%, and 27.6%, respectively. Conclusion: ThrombScore is a simple and practical clinical model for risk stratification of thrombus formation in patients with STEMI.

The Impact of Novel Anti-Diabetic Medications on CV Outcomes: A New Therapeutic Horizon for Diabetic and Non-Diabetic Cardiac Patients.

It is estimated that in the past two decades the number of patients diagnosed with diabetes mellites (DM) has doubled. Despite significant progress in the treatment of cardiovascular disease (CVD), including novel anti-platelet agents, effective lipid-lowering medications, and advanced revascularization techniques, patients with DM still are least twice as likely to die of cardiovascular causes compared with their non-diabetic counterparts, and current guidelines define patients with DM at the highest risk for atherosclerotic cardiovascular disease and major adverse cardiovascular events (MACE). Over the last few years, there has been a breakthrough in anti-diabetic therapeutics, as two novel anti-diabetic classes have demonstrated cardiovascular benefit with consistently reduced MACE, and for some agents, also improvement in heart failure status as well as reduced cardiovascular and all-cause mortality. These include the sodium-glucose cotransporter-2 inhibitors and the glucagon-like peptide-1 receptor agonists. The benefits of these medications are thought to be derived not only from their anti-diabetic effect but also from additional mechanisms. The purpose of this review is to provide the everyday clinician a detailed review of the various agents within each class with regard to their specific characteristics and the effects on MACE and cardiovascular outcomes.

Low ALT levels are associated with poor outcomes in acute coronary syndrome patients in the intensive cardiac care unit.

BACKGROUND: Frailty is an underrecognized and important entity that bears worse prognosis. Although low serum alanine aminotransferase (ALT) can serve as a novel marker of frailty, its use was never assessed in acute coronary syndrome (ACS) patients. METHODS: A retrospective analysis of hospitalized ACS patients in the intensive cardiac care unit (ICCU)between 1/5/2011 and 1/12/2020 at a single tertiary medical center. RESULTS: The study included 3956 patients after excluding patients with ALT >40 IU/L, cirrhosis, and missing data, followed for a medianduration of 47 months (IQR 20-77).Patients were stratified into two groups based on their first ALT measurement within the index hospitalization: low-normal ALT group (ALT ≤10 IU/L) vs. high-normal ALT group (ALT >10 IU/L). Patients with ALT≤10 IU/L were older (mean age 71 years vs. 65 years, p<0.001), presented more frequently with non-ST elevation myocardial infarction (66.4% vs. 53.2%, p< 0.001), had higher rates of comorbiditiesat baseline, and had a lower Norton score upon admission. Hospitalization length was longer in the low-normal ALT group (p< 0.001). Although the in-hospital mortality rate was similar between the groups (0.9% vs. 0.7%, p = 0.99), long-termmortality was significantly higher in the low-normal ALT group (22.7% vs. 7.9%, p< 0.001). In a multivariate regression model ALT ≤10 IU/l was associated with increased mortality (HR 2.1, 95% CI 1.46-3). CONCLUSIONS: Lower serum ALT is associated with worse outcomes in ACS patients admitted to the ICCU.

PESI score for predicting clinical outcomes in PE patients with right ventricular involvement.

Pulmonary embolism (PE) patients with right ventricular (RV) involvement are a heterogenous group who mandate further risk stratification. Our objective was to evaluate the efficacy of the PE severity index (PESI) for predicting adverse clinical outcomes among PE patients with RV involvement. Consecutive normotensive PE patients with RV involvement were allocated according to admission PESI score (PESI ≤ III vs. PESI ≥ IV). The primary outcome included hemodynamic instability and in-hospital mortality. Secondary outcomes included each component of the primary outcome as well as mechanical ventilation, thrombolytic therapy, acute kidney injury, and major bleeding. Multivariable logistic regression model was performed to assess the independent association between the PESI score and primary outcome. C-Statistic was used to compare the PESI with the BOVA score. A total of 253 patients were evaluated: 95 (38%) with a PESI ≥ IV. Of them, 82 (32%) patients were classified as intermediate-low risk and 171 (68%) as intermediate-high risk. Fifty (20%) patients had at least 1 adverse event. Multivariate analysis demonstrated the PESI to be an independent predictor for the primary outcome (HR 4.81, CI 95%, 1.15-20.09, p = 0.031), which was increased with a concomitant increase of the PESI score (PESI I 4.2%, PESI II 3.4%, PESI III 12%, PESI IV 16.3%, PESI V 23.1%, p for trend < 0.001). C-Statistic analysis for the PESI score yielded an AUC-0.746 (0.637-0.854), p = 0.001, compared to the BOVA score: AUC-0.679 (0.584-0.775), p = 0.011. PESI score was found to predict adverse outcomes among normotensive PE patients with RV involvement.

Left ventricular global longitudinal strain in identifying subclinical myocardial dysfunction among patients hospitalized with COVID-19.

BACKGROUND: The incidence of acute cardiac injury in COVID-19 patients is very often subclinical and can be detected by cardiac magnetic resonance imaging. The aim of this study was to assess if subclinical myocardial dysfunction could be identified using left ventricular global longitudinal strain (LV-GLS) in patients hospitalized with COVID-19. METHODS: We performed a search of COVID-19 patients admitted to our institution from January 1st, 2020 to June 8th, 2020, which revealed 589 patients (mean age = 66 ± 18, male = 56%). All available 60 transthoracic echocardiograms (TTE) were reviewed and off-line assessment of LV-GLS was performed in 40 studies that had sufficient quality images and the views required to calculate LV-GLS. We also analyzed electrocardiograms and laboratory findings including inflammatory markers, Troponin-I, and B-type natriuretic peptide (BNP). RESULTS: Of 589 patients admitted with COVID-19 during our study period, 60 (10.1%) underwent TTE during hospitalization. Findings consistent with overt myocardial involvement included reduced ejection fraction (23%), wall motion abnormalities (22%), low stroke volume (82%) and increased LV wall thickness (45%). LV-GLS analysis was available for 40 patients and was abnormal in 32 patients (80%). All patients with LV dysfunction had elevated cardiac enzymes and positive inflammatory biomarkers. CONCLUSIONS: Subclinical myocardial dysfunction as measured via reduced LV-GLS is frequent, occurring in 80% of patients hospitalized with COVID-19, while prevalent LV function parameters such as reduced EF and wall motion abnormalities were less frequent findings. The mechanism of cardiac injury in COVID-19 infection is the subject of ongoing research.

The Role of T Cells Reactive to the Cathelicidin Antimicrobial Peptide LL-37 in Acute Coronary Syndrome and Plaque Calcification.

The human cationic anti-microbial peptide LL-37 is a T cell self-antigen in patients with psoriasis, who have increased risk of cardiovascular events. However, the role of LL-37 as a T cell self-antigen in the context of atherosclerosis remains unclear. The objective of this study was to test for the presence of T cells reactive to LL-37 in patients with acute coronary syndrome (ACS). Furthermore, the role of T cells reactive to LL-37 in atherosclerosis was assessed using apoE-/- mice immunized with the LL-37 mouse ortholog, mCRAMP. Peripheral blood mononuclear cells (PBMCs) from patients with ACS were stimulated with LL-37. PBMCs from stable coronary artery disease (CAD) patients or self-reported subjects served as controls. T cell memory responses were analyzed with flow cytometry. Stimulation of PBMCs with LL-37 reduced CD8+ effector T cell responses in controls and patients with stable CAD but not in ACS and was associated with reduced programmed cell death protein 1 (PDCD1) mRNA expression. For the mouse studies, donor apoE-/- mice were immunized with mCRAMP or adjuvant as controls, then T cells were isolated and adoptively transferred into recipient apoE-/- mice fed a Western diet. Recipient mice were euthanized after 5 weeks. Whole aortas and hearts were collected for analysis of atherosclerotic plaques. Spleens were collected for flow cytometric and mRNA expression analysis. Adoptive transfer experiments in apoE-/- mice showed a 28% reduction in aortic plaque area in mCRAMP T cell recipient mice (P < 0.05). Fifty six percent of adjuvant T cell recipient mice showed calcification in atherosclerotic plaques, compared to none in the mCRAMP T cell recipient mice (Fisher's exact test P = 0.003). Recipients of T cells from mice immunized with mCRAMP had increased IL-10 and IFN-γ expression in CD8+ T cells compared to controls. In conclusion, the persistence of CD8+ effector T cell response in PBMCs from patients with ACS stimulated with LL-37 suggests that LL-37-reactive T cells may be involved in the acute event. Furthermore, studies in apoE-/- mice suggest that T cells reactive to mCRAMP are functionally active in atherosclerosis and may be involved in modulating plaque calcification.

Significance of Syncope at Presentation among Patients With Pulmonary Emboli.

Patients with intermediate-risk pulmonary emboli (PE) present a challenging clinical problem. Although syncope has been suggested as a marker for adverse outcomes in these patients, data remain scarce. We aimed to investigate the clinical outcomes of intermediate risk PE patients presenting with syncope. We performed a retrospective cohort study comprised of consecutive, normotensive, PE patients, with evidence of right ventricular involvement. The primary outcome of major adverse clinical events included either one or a combination of mechanical ventilation, hemodynamic instability and need for inotropic support, reperfusion therapy, and in-hospital mortality. Secondary outcomes included each of the above individual components including major bleeding and renal failure. Overall, 212 patients were evaluated, 40 (19%) presented with syncope, and had a higher prevalence of major adverse clinical events (29% vs 9.4%, p = 0.003), as well as each of the individual secondary end points: mechanical ventilation (10% vs 1.8%, p = 0.026), hemodynamic instability (18% vs 2.9%, p = 0.02), increased need of inotropic support (10% vs 0.6%, p = 0.005), and bleeding (15% vs 2.4%, p = 0.004). The prevalence of in-hospital mortality was very low (0.5%) with no significant difference between those with and without syncope. There was no significant difference in the need for reperfusion therapy. Upon multivariable analysis, syncope was found to be an independent predictor of adverse clinical outcomes (odds ratio 3.8, confidence interval 1.48 to 9.76, p = 0.005). In conclusion, in intermediate-risk PE patients with right ventricular involvement, the presence of syncope is associated with a more complicated in-hospital course.

Epidemiology Characteristics and Outcome of Patients With Clinically Diagnosed Acute Myocarditis.

BACKGROUND: There are controversial data regarding the outcome and management of patients hospitalized with clinically diagnosed acute myocarditis. METHODS: We retrospectively evaluated data of 322 consecutive patients admitted to the Sheba Medical Center with clinically suspected acute myocarditis from January 2005 to December 2017. Patients were subdivided into 2 groups based on their left ventricular ejection fraction (LVEF) at presentation: 1) patients with an LVEF <50% (n = 60) and 2) patients with an LVEF ≥50% (n = 260). We aimed to evaluate the clinical characteristics, management, and in-hospital outcome as well as short-term and 1-year outcome of patients admitted with acute myocarditis. RESULTS: The mean age of the study population was 37 ± 14 years, most of them (84%) males. Although chest pain was the main complaint in 89% of the patients at presentation, only 35% had typical pericardial pain. Patients with a LVEF <50% were more likely to demonstrate ST depression or T wave inversion on their electrocardiogram (ECG) at presentation (33% vs 18%, P = 0.007), and have higher levels of admission and peak troponin compared to those with LVEF ≥50%,(12.7 µ/L ± 15 µ/L vs 5.5 µ/L ± 9.2 µ/L, P = 0.001 for admission troponin, 18.8 µ/L ± 19.9 µ/L vs 8.4 µ/L ± 11.6 µ/L, P <0.001, for peak troponin). Univariate analysis showed that patients with an LVEF <50% were more likely to suffer from adverse cardiovascular events, defined as a composite of the following: 1) acute decompensated congestive heart failure; 2) ventricular arrhythmias; and 3) in-hospital mortality, compared to those with an LVEF ≥50% (15 [25%] vs10 [4%], P <0.001). Consistently, multivariable analysis showed that patients with an LVEF <50% had a 4-fold increased risk of adverse cardiovascular events compared to those patients with an LVEF ≥50% (heart rate [HR] = 4.30; 95% confidence interval [CI] 1.59-11.49; P <0.001). CONCLUSIONS: Patients with clinical acute myocarditis seem to have an overall good prognosis. Although patients with an LVEF <50% are at a higher risk of in-hospital adverse events compared to those with an LVEF ≥50%, this propensity is not reflected during 1-year of follow-up.

Death with an implantable cardioverter-defibrillator: a MADIT-II substudy.

AIMS: There are limited data regarding factors that identify implantable cardioverter-defibrillator (ICD) patients who will experience either ventricular tachyarrhythmic (VTA) or non-arrhythmic (NA) mortality, and the commonly used clinical classification of sudden cardiac death (SCD) vs. non-sudden cardiac death (NSCD) may not be accurate enough. We aimed to correlate clinical adjudication of mortality events to device interrogation data and to identify risk factors for VTA mortality in Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II). METHODS AND RESULTS: Of the 746 patients who received an ICD in MADIT-II, 44 died from cardiac causes and had available interrogation data at the time of death. Sudden cardiac death vs. NSCD was defined by an adjudication committee. Ventricular tachyarrhythmic and NA arrhythmic deaths were categorized by the presence or absence of ventricular tachycardia or fibrillation (VT/VF) during the terminal event. Mode of death was found to be inaccurate when validated by device interrogation for VTA events: 50% patients adjudicated as SCD did not have a VTA event at the time of death; and 25% of adjudicated NSCD were found to have VT/VF during the mortality event. Multivariate analysis showed that factors independently associated with VTA mortality included: VT/VF >72 h prior to the mortality event [hazard ratio (HR) 8.0; P < 0.001], hospitalization for heart failure (HR 6.7; P = 0.001), and a history of hypertension (HR 4; P = 0.04). CONCLUSION: Current classification of SCD vs. NSCD fails to identify VTA events at the time of death in a significant proportion of patients, and simple clinical parameters can be used to identify ICD recipients with increased risk for VTA mortality.

Intermediate-risk pulmonary embolism: Aiming to improve patient stratification.

BACKGROUND: Intermediate-risk pulmonary embolism (PE) patients present a therapeutic dilemma. While some are at risk for developing adverse events, possibly requiring escalation therapy, most will have a benign course. Our aim was to define predictors which will identify those patients who will not deteriorate despite the presence of RV involvement. METHODS: We evaluated 179 consecutive intermediate-risk PE patients (47% males; mean age: 66 ±â€¯16 years), allocating them to those who did and did not need escalation therapy and evaluating the predictors for deterioration. We then formulated a score to distinguish between those who would not require escalation therapy. RESULTS: Twenty-six patients (15%) required escalation therapy which was associated with significantly more episodes of syncope (42% vs. 15%, p = 0.001), higher D-Dimer levels (10,810 ±â€¯19,147 vs. 3816 ±â€¯6255, p < 0.001), echocardiographic evidence of severe right ventricular (RV) dysfunction (42% vs. 19%, p < 0.01), or a higher RV/left ventricular (LV) diameter ratio on computed tomography (CT) (1.9 ±â€¯0.6 vs. 1.46 ±â€¯0.5, p < 0.001). On multivariate analysis the presence of syncope (HR 2.8 CI 1.1-7.1) and severe RV dysfunction on echocardiography (HR 3.5 CI 1.4-9.3) were found to be independent predictors for escalation therapy. A combined score of 1 was associated with only a 1.9% risk for escalation, while a maximum score of 4 was associated with a 57% risk for escalation therapy (P for trend<0.001). CONCLUSIONS: A small but significant number of intermediate-risk PE patients required escalation therapy. A combined score comprising clinical, imaging, and laboratory parameters might aid in further risk stratification, identifying those intermediate risk PE patients with a more benign clinical course.

Mitral Annulus Calcium Score.

BACKGROUND: The risk of conduction system abnormalities (CSA) after transcatheter aortic valve implantation remains high. We aimed to evaluate the impact of mitral annular calcium (MAC) score on the development of CSA after transcatheter aortic valve implantation. METHODS: Consecutive patients (n=168), with severe AoV stenosis, without prior CSA, underwent computed tomography transcatheter AoV implantation followed by device implantation; CoreValve (n=72) and SAPIEN (n=96). MAC, AoV, and left ventricular outflow tract calcium (Ca++) scores were quantitated from noncontrast ECG-gated computed tomography using Agatston method. The primary end point was a combination of complete left bundle branch block or high-degree atrioventricular block. Logistic regression was used to analyze the predictive value of Ca++ scores of different locations. RESULTS: The primary end point was documented in 62% of the fourth quartile MAC score (>2700) patients as compared with 31% of the first quartile (<140); P=0.03. Logistic regression analysis documented MAC score as an independent predictor either of primary end point as a continuous variable (odds ratio: 1.02, 95% [CI]: 1.00 - 1.03, p = 0.021) or as quartile cutoffs, whereas Q4 was a strong and independent predictor (odds ratio: 3.69, 95% [CI]: 1.37 - 9.95, p = 0.010). CONCLUSIONS: MAC score was found to be an independent predictor of CSA in patients undergoing transcatheter aortic valve implantation without preexisting CSA. Therefore, the current study suggests that patients with high MAC score category (fourth MAC score quartile) should be considered at high risk for CSA, warranting closer monitoring. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02023060.

Long-Term Outcomes of Iliofemoral Artery Stents after Transfemoral Aortic Valve Replacement.

PURPOSE: To report long-term results of iliofemoral stent placement after transcatheter aortic valve replacement (TAVR). MATERIALS AND METHODS: TAVR access-related complications treated with iliofemoral stent placement were recorded in 56 patients (mean age, 81 years; range; 53-93 years; 48% male) of 648 patients who underwent TAVR at a single center. Fifty-six patients treated with stent placement (40 patients with stent grafts and 16 patients with bare metal stents) underwent clinical and ultrasonographic follow-up after a mean of 676 days (range, 60-1840 days). RESULTS: During follow-up, none of the 56 patients who had stent placement underwent a vascular reintervention of the affected limb, and none suffered from limb claudication. No decrease was observed in ankle-brachial index (ABI) values to an abnormal value, except in 1 patient (mean preprocedural and postprocedural ABI of 1.2 ± 0.14, range, 0.97-1.4 and 1.19 ± 0.24, range, 0.65-1.54, respectively). Arterial duplex assessment showed normal stent flow velocity (mean, 168.7 ± 63.2 cm/sec; range, 80-345 cm/sec) in all but 1 patient. CONCLUSION: Iliofemoral stent implantation is a safe and efficacious treatment for vascular access site and access-related complications during transfemoral TAVR.

Effect of Chewing vs Swallowing Ticagrelor on Platelet Inhibition in Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial.

Importance: Dual anti-platelet therapy represents standard care for treating patients with ST-segment elevation myocardial infarction (STEMI). Ticagrelor is a direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Objective: To evaluate whether chewing a loading dose (LD) of ticagrelor, 180 mg, vs traditional oral administration of an equal dose enhances platelet inhibition at 30 minutes and 1 hour after LD administration in patients with STEMI. Design, Setting, and Participants: A randomized clinical trial was conducted in adults aged 30 to 87 years from May to October 2016 in a large tertiary care center. Analyses were intention-to-treat. Interventions: Fifty patients with STEMI were randomized to either chewing an LD of ticagrelor, 180 mg, or standard oral administration of an equal dose. Main Outcomes and Measures: P2Y12 reaction units were evaluated using VerifyNow (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD. Results: Baseline characteristics were similar in both groups. The mean (SD) of P2Y12 reaction units in the chewing group compared with the standard group at baseline, 30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44) (95% CI, -16.77 to 27.73; P = .26), 168 (78) vs 230 (69) (95% CI, -103.77 to -19.75; P = .003), 106 (90) vs 181 (89) (95% CI, -125.15 to -26.29; P = .005), and 43 (41) vs 51 (61) (95% CI, -36.34 to 21.14; P = .30), respectively. Platelet reactivity in the chewing group was significantly reduced by 24% at 30 minutes after LD (95% CI, 19.75 to 103.77; P = .001). The relative inhibition of platelet aggregation in the chewing vs the standard group were 51% vs 10% (95% CI, 13.69 to 67.67; P = .005) at 1 hour and 81% vs 76% (95% CI, -12.32 to 16.79; P = .24) at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at 30 days was low (4%) and occurred in 1 patient in each group (95% CI, 0.06 to 16.93; P > .99). Conclusions and Relevance: Chewing an LD of ticagrelor, 180 mg, in patients with STEMI is feasible and facilitates better early platelet inhibition compared with a standard oral LD. Larger studies are warranted to see if our preliminary findings translate into clinical outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT02725099.

Quality of life and long-term mortality in patients with advanced chronic heart failure treated with intermittent low-dose intravenous inotropes in an outpatient setting.

AIMS: There are limited data on the effect of low-dose, intermittent inotropic therapy in an outpatient setting on the quality of life (QOL) in patients with advanced refractory heart failure (HF) symptoms. We aimed to analyse the effect of this treatment modality on QOL and subsequent survival. METHODS AND RESULTS: The study population comprised 287 consecutive patients with advanced refractory HF symptoms who were treated with low-dose, intravenous intermittent inotropic therapy in the HF Day Care Service at Sheba Medical Centre between September 2000 and September 2012. All patients completed a baseline Minnesota Living with Heart Failure Questionnaire (MLWHFQ), and 137 (48%) completed a 1 year follow-up questionnaire. MLWHFQ scores' means ranged from 0 (better QOL) to 5 (worse QOL). Mean age was 68 ± 12, 86% were men, 77% had ischaemic cardiomyopathy, and the mean left ventricle ejection fraction (LVEF) was 26% ± 13. The mean baseline MLWHFQ score was 3.1 (±1), while the mean at 1 year of treatment was of 2.7 (±1.1), indicating an overall improvement in QOL associated with intermittent low-dose inotrope therapy (p < 0.01). Multivariate analysis showed that younger age, non-ischaemic cardiomyopathy, and worse renal function were independently associated with improvement in QOL at 1 year. Improvement in QOL was not associated with a significant survival benefit during subsequent follow-up. CONCLUSIONS: In patients with advanced refractory HF symptoms, treatment with low-dose, intermittent intravenous inotropes in an outpatient setting is associated with significant improvement in QOL. However, improvement in QOL in this population does not appear to affect subsequent long-term survival.

Cardiac rehabilitation following an acute coronary syndrome: Trends in referral, predictors and mortality outcome in a multicenter national registry between years 2006-2013: Report from the Working Group on Cardiac Rehabilitation, the Israeli Heart Society.

Background Utilization of cardiac rehabilitation is suboptimal. The aim of the study was to assess referral trends over the past decade, to identify predictors for referral to a cardiac rehabilitation program, and to evaluate the association with one-year mortality in a large national registry of acute coronary syndrome patients. Design and methods Data were extracted from the Acute Coronary Syndrome Israeli Survey national surveys between 2006-2013. A total of 6551 patients discharged with a diagnosis of acute coronary syndrome were included. Results Referral to cardiac rehabilitation following an acute coronary syndrome increased from 38% in 2006 to 57% in 2013 ( p for trend < 0.001). Multivariate modeling identified the following independent predictors for non-referral: 2006 survey, older age, female sex, past stroke, heart or renal failure, prior myocardial infarction, minority group, and lack of in-hospital cardiac rehabilitation center (all p < 0.01). Kaplan-Meier survival analyses showed one-year survival rates of 97% vs 92% in patients referred for cardiac rehabilitation as compared to those not referred (log-rank p < 0.01). Multivariate analysis showed that referral for cardiac rehabilitation was associated with a 27% mortality risk reduction at one-year follow-up ( p = 0.03). Consistently, a 32% lower one-year mortality risk was evident in a propensity score matched group of 3340 patients (95% confidence interval 0.48-0.95, p = 0.02). Conclusions Over the past decade there was a significant increase in cardiac rehabilitation referral following an acute coronary syndrome. However, cardiac rehabilitation is still under-utilized in important high-risk subsets of this population. Patients referred to cardiac rehabilitation have a lower adjusted mortality risk.