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.

Sex differences of patients with acute chest pain evaluated through a chest pain unit.

BACKGROUND: Although sex disparities between patients with acute myocardial infarction are well known, the data regarding sex differences among symptomatic patients with acute chest pain (ACP) are limited. METHODS: We retrospectively evaluated the records of 1000 consecutive patients with ACP and hospitalized in a tertiary medical center chest pain unit (CPU). Patients were divided according to sex. The primary outcome was defined as a composite end point of readmission because of chest pain, incidence of acute coronary syndrome, revascularization, and death at 90 days and 1 year. RESULTS: Overall, 673 men and 327 women were included in the current analysis. There was no difference in regard to sex for patients who underwent noninvasive evaluation, (87.8 vs. 87.3%, P  = 0.85, for female vs. male, respectively). Among patients who underwent coronary computed tomography angiography, women were less likely to have significant coronary artery disease (CAD) (4.2 vs. 11.3%, P  = 0.005). Similarly, women had fewer significant findings (4.4 vs. 7.6%, P  = 0.007) on myocardial perfusion imaging. Consequently, fewer women underwent angiography (8 vs. 14%, P  = 0.006) and revascularization (2.8 vs. 7.3%, P  = 0.004). During follow-up, sex was not associated with the development of the primary composite outcome [odds ratio (OR) 0.91, 95% confidence interval (CI) 0.39-2.09, P -value = 0.82 and OR 1.16, 95% CI 0.65-2.06, P -value = 0.59 for 90-day and 1-year follow-up, respectively]. CONCLUSION: Evaluation of patients through a CPU enables comparable noninvasive evaluation, appropriate utilization of invasive assessment with similar outcomes during the short and intermediate follow-up period regardless of patients' sex.

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.

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.

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.

Coronary Artery Bypass Grafting Following Acute Coronary Syndrome: Impact of Gender.

The impact of gender on clinical outcomes after coronary artery bypass grafting (CABG) has generated conflicting results. We investigated the impact of gender, on 30 day mortality, complications and late survival in patients with acute coronary syndrome (ACS) undergoing CABG. The study included 1308 patients enrolled from the biennial Acute Coronary Syndrome Israeli Survey between 2000 and 2016, who were hospitalized for ACS and underwent CABG. Of them, 1045 (80%) were men and 263 (20%) women. While women were older and had more hypertension and hyperlipidemia, they demonstrated less diabetes mellitus, previous ischemic heart disease, smoking, and fewer implicated coronary arteries. Women presented with more atypical symptoms as compared to men (26.3% vs 19.4%, p = 0.017). Overall multivariable-adjusted 30 day mortality was higher in women than in men (OR 2.47 95% CI 1.19-5.1, p = 0.015). Among patients with ST-elevation myocardial infarction (STEMI) or non-STEMI, women had a higher 10 year mortality rate than men (42.5% vs 19.2%, log-rank p < 0.001 and 31.5% vs 20.7%, log-rank, p = 0.012). However, in patients with unstable angina pectoris on admission, these differences were not seen (16.9% vs 13.4%, log-rank p = 0.540). Multivariable analysis demonstrated that female gender was a significant predictor for 10 year mortality (HR 1.39, 95% CI 1.02-1.9, p = 0.038). In a real-life setting, women constitute an independent predictor for short- and long-term mortality following ACS treated by CABG surgery. The reasons for a higher mortality in women should be further investigated as well as specific and/or more intensive therapies after CABG in this high-risk group of patients.

Smidt Heart Institute Takotsubo Registry - Study design and baseline characteristics.

Background: Takotsubo syndrome (TTS) is an acute form of transient systolic heart failure that occurs predominantly among women and in association with emotional or physical stressors. The Smidt Heart Institute Takotsubo Registry aims to establish a database through an online patient-advocate registry for deep phenotyping of this syndrome. Methods: The Takotsubo Registry is a retrospective and prospective observational registry of individuals with a prior history of TTS. Participants are sourced through physician referrals, medical records review, peer- and self-referrals using social media. Research Electronic Data Capture (REDCap) and Mitra® microsamplers are used to collect questionnaire data and blood samples to facilitate completely remote study enrollment and participation for most participants. Results: From January 2019 to May 2021, 125 participants (99% female, mean age: 61.5 ± 9.9 years) enrolled in the registry across 25 US states and 3 international countries, with reported first TTS event a median of 2 years prior to enrollment. Psychosocial characteristics determined by standardized questionnaires at baseline include relatively high anxiety trait (44%), moderate to severe depression severity (19%), moderate to high severity of posttraumatic stress disorder symptoms (58%) and a history of childhood trauma/abuse (50%). Conclusions: The Smidt Heart Institute Takotsubo Registry will contribute to advancing the management of TTS by deep phenotyping to understand its pathophysiology, and identify treatment targets in a participant base for future clinical trials.

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.

Predicted Versus Observed Major Adverse Cardiac Event Risk in Women With Evidence of Ischemia and No Obstructive Coronary Artery Disease: A Report From WISE (Women's Ischemia Syndrome Evaluation).

Background Primary prevention risk scores are commonly used to predict cardiovascular (CVD) outcomes. The applicability of these scores in patients with evidence of myocardial ischemia but no obstructive coronary artery disease is unclear. Methods and Results Among 935 women with signs and symptoms of ischemia enrolled in WISE (Women's Ischemia Syndrome Evaluation), 567 had no obstructive coronary artery disease on angiography. Of these, 433 had had available risk data for 6 commonly used scores: Framingham Risk Score, Reynolds Risk Score, Adult Treatment Panel III, Atherosclerotic Cardiovascular Disease, Systematic Coronary Risk Evaluation, Cardiovascular Risk Score 2. Score-specific CVD rates were assessed. For each score, we evaluated predicted versus observed event rates at 10-year follow-up using c statistic. Recalibration was done for 3 of the 6 scores. The 433 women had a mean age of 56.9±9.4 years, 82.5% were white, 52.7% had hypertension, 43.6% had dyslipidemia, and 16.9% had diabetes mellitus. The observed 10-year score-specific CVD rates varied between 5.54% (Systematic Coronary Risk Evaluation) to 28.87% (Framingham Risk Score), whereas predicted event rates varied from 1.86% (Systematic Coronary Risk Evaluation) to 6.99% (Cardiovascular Risk Score 2). The majority of scores showed moderate discrimination (c statistic 0.53 for Atherosclerotic Cardiovascular Disease and Systematic Coronary Risk Evaluation; 0.78 for Framingham Risk Score) and underestimated risk (statistical discordance -58% for Adult Treatment Panel III; -84% for Atherosclerotic Cardiovascular Disease). Recalibrated Reynolds Risk Score, Atherosclerotic Cardiovascular Disease, and Framingham Risk Score had improved performance, but significant underestimation remained. Conclusions Commonly used CVD risk scores fail to accurately predict CVD rates in women with ischemia and no obstructive coronary artery disease. These results emphasize the need for new risk assessment scores to reliably assess this population.

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.

Sex differences in crude mortality rates and predictive value of intensive care unit-based scores when applied to the cardiac intensive care unit.

BACKGROUND: Limited data exists regarding sex differences in outcome and predictive accuracy of intensive care unit-based scoring systems when applied to cardiac intensive care unit patients. METHODS: We reviewed medical records of patients admitted to cardiac intensive care unit from 1 January 2011-31 December 2016. Sex differences in mortality rates and the performance of intensive care unit-based scoring systems in predicting in-hospital mortality were analyzed. Calibration was assessed by the Hosmer-Lemeshow test and locally weighted scatterplot smoothing curves. Discrimination was assessed using the c statistic and receiver-operating characteristic curve. RESULTS: Among 6963 patients, 2713 (39%) were women. Overall in-hospital and cardiac intensive care unit mortality rates were similar in women and men (9.1% vs 9.4%, p=0.67 and 5.9% vs 6%, p=0.88, respectively) and in age and major diagnosis subgroups. Of the scoring systems, Acute Physiology and Chronic Health Evaluation III and Sequential Organ Failure Assessment had poor calibration (Hosmer-Lemeshow p value <0.001), while Simplified Acute Physiology Score II performed better (Hosmer-Lemeshow p value 0.09), in both women and men. All scores had good discrimination (C statistics >0.8). In the subgroups of acute myocardial infarction and heart failure patients, all scores had good calibration (Hosmer-Lemeshow p>0.001) and discrimination (C statistic >0.8) while in diagnosis subgroups with highest mortality, the calibration varied among scores and by sex, and discrimination was poor. CONCLUSIONS: No sex differences in mortality were seen in cardiac intensive care unit patients. The mortality predictive value of intensive care unit-based scores is limited in both sexes and variable among different subgroups of diagnoses.

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.

Keratin 8 is a potential self-antigen in the coronary artery disease immunopeptidome: A translational approach.

BACKGROUND: Inflammation is an important risk factor in atherosclerosis, the underlying cause of coronary artery disease (CAD). Unresolved inflammation may result in maladaptive immune responses and lead to immune reactivity to self-antigens. We hypothesized that inflammation in CAD patients would manifest in immune reactivity to self-antigens detectable in soluble HLA-I/peptide complexes in the plasma. METHODS: Soluble HLA-I/peptide complexes were immuno-precipitated from plasma of male acute coronary syndrome (ACS) patients or age-matched controls and eluted peptides were subjected to mass spectrometry to generate the immunopeptidome. Self-peptides were ranked according to frequency and signal intensity, then mouse homologs of selected peptides were used to test immunologic recall in spleens of male apoE-/- mice fed either normal chow or high fat diet. The peptide detected with highest frequency in patient plasma samples and provoked T cell responses in mouse studies was selected for use as a self-antigen to stimulate CAD patient peripheral blood mononuclear cells (PBMCs). RESULTS: The immunopeptidome profile identified self-peptides unique to the CAD patients. The mouse homologs tested showed immune responses in apoE-/- mice. Keratin 8 was selected for further study in patient PBMCs which elicited T Effector cell responses in CAD patients compared to controls, associated with reduced PD-1 mRNA expression. CONCLUSION: An immunopeptidomic strategy to search for self-antigens potentially involved in CAD identified Keratin 8. Self-reactive immune response to Keratin 8 may be an important factor in the inflammatory response in CAD.

Early mobility in frail and non-frail older adults admitted to the cardiovascular intensive care unit.

PURPOSE: Little is known about the effects of early mobilization in older adults in the Cardiovascular Intensive Care Unit (CICU). MATERIALS AND METHODS: We reviewed consecutive patients ≥60 years of age admitted to the CICU at an academic tertiary care center from 2016 to 2017. The level of function (LOF) was assessed prehospital, at CICU admission, and at CICU transfer using a graded scale ranging from LOF 1 (bedbound) to 4 (walk > 50 ft). The prehospital frailty status was assessed using Rockwood's Clinical Frailty Scale. We sought to determine whether the mean change of LOF during CICU admission differed based on frailty status. RESULTS: There were 264 patients in the cohort (77.1 ±â€¯9.3 years old; 40% female; 34% frail). Frail patients were more likely to have lower prehospital, CICU admission, day of transfer LOFs (all P < 0.001). The mean LOF improvement during CICU stay was 0.5 ±â€¯0.8 and did not differ based on frailty status. Frailty was not predictive of EM responsiveness in the adjusted analysis. CONCLUSIONS: EM is feasible in older adults admitted to the CICU. Functional status improved in both frail and non-frail older adults during CICU admission. Prospective studies are needed to determine whether frail older adults may benefit from EM.

Immediate response to prasugrel loading in patients with ST-elevation myocardial infarction: Predictors and outcome.

INTRODUCTION: Information regarding immediate response to novel P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) is scarce and has been associated with adequate reperfusion. Recent studies have shown that the onset of anti-platelet effects of novel P2Y12 inhibitors in patients with STEMI might be slower and more variable than in stable coronary syndrome. We aimed to assess the predictors and significance of immediate platelet response to prasugrel loading in STEMI. METHODS: Platelet aggregation (PA) was prospectively evaluated in STEMI patients upon prasugrel loading and at primary percutaneous coronary intervention (PPCI). Early platelet responsiveness was defined as percent reduction of PA from baseline to PPCI, divided by the time lapse from loading to PPCI. High- and low-platelet responsiveness was defined as above and below the median value respectively. RESULTS: Fifty consecutive STEMI patients (age 58±8, 90% male) underwent PPCI with a mean door-to-balloon time of 42±15min. Mean PA upon prasugrel loading and at PPCI was 76±9% and 63±19%, respectively. Older age and prior aspirin use were predictors of low platelet responsiveness to prasugrel [ß=(-0.33), p=0.02 and ß=(-0.28), p=0.04, respectively]. Fast compared with slow responders demonstrated more frequent early ST resolution (93% vs. 72%, p=0.02) and lower peak troponin levels (76±62µg/L vs. 48±28µg/L, p=0.05). CONCLUSIONS: Immediate platelet responsiveness to prasugrel among STEMI patients is highly variable and inversely associated with older age and prior aspirin use. Fast compared with slow responders have improved reperfusion and infarct size markers.

Prior chronic clopidogrel therapy is associated with increased adverse events and early stent thrombosis.

Despite the growing use of clopidogrel, limited data exist regarding the prognostic significance of chronic clopidogrel therapy in patients sustaining acute coronary syndrome (ACS). Our aim was to determine whether patients sustaining ACS while on chronic clopidogrel therapy have a worse prognosis than clopidogrel-naïve patients. A total of 5,386 consecutive ACS patients were prospectively characterised and followed-up for 30 days. Of them, 680 (13%) were treated with clopidogrel prior to the index ACS. Major adverse cardiovascular events (MACE) were defined as death, recurrent ACS, stroke and/or stent thrombosis. Compared with clopidogrel-naïve, chronic clopidogrel-treated patients were older (66 ± 12 vs 63 ± 13, respectively; p<0.01), suffered more from diabetes mellitus, hypertension, dyslipidaemia, prior cardiovascular history, including prior myocardial infarction, revascularisation, coronary artery bypass graft and stroke (p<0.01 for all), and were less likely to present with ST-elevation myocardial infarction (21% vs 45%; respectively; p < 0.001). Prior clopidogrel therapy was associated with a two-fold increase in in-hospital (1.6% vs 0.6%, respectively; p =0.006) as well as 30-day stent thrombosis (2.2% vs 1.0%, respectively; p=0.007). MACE at 30 days was also higher among chronic clopidogrel-treated compared with clopidogrel-naïve patients [12.3% vs 9.4%, respectively; p<0.01]. In multivariate log regression analysis chronic clopidogrel treatment was an independent predictor of stent thrombosis [OR=2.6 (95%CI 1.2-5.6), p=0.001]. Patients sustaining ACS while on chronic clopidogrel treatment are at higher risk for in-hospital and 30-day adverse outcomes, including stent thrombosis.

Early intervention and long-term outcome with cardiac resynchronization therapy in patients without a history of advanced heart failure symptoms.

AIMS: MADIT-CRT showed that cardiac resynchronization therapy with a defibrillator (CRT-D) improves long-term outcomes in currently mildly symptomatic heart failure (HF) patients with LBBB regardless of the presence of prior advanced HF symptoms. We aimed to evaluate the long-term benefit of CRT-D in patients who never experienced advanced HF symptoms prior to device implantation. METHODS AND RESULTS: Interaction term analysis was used to compare the clinical and echocardiographic benefit of CRT-D vs. implantable cardioverter defibrillator (ICD)-only therapy during long-term follow-up (median 5.6 years) between LBBB patients with or without a history of advanced HF [defined as NYHA class ≥ III or past hospitalization for worsening HF >3 months prior to enrolment in MADIT-CRT (n = 529 and 752, respectively)]. Multivariable analysis showed that treatment with CRT-D was associated with a significant reduction in the risk of HF or death during long-term follow-up regardless of the presence of prior advanced HF symptoms [hazard ratio 0.53 (P < 0.001) and 0.47 (P < 0.001) in the respective groups of patients with and without prior advanced HF; interaction P for the difference = 0.58]. Echocardiographic response to CRT at 1 year was also similar between the two groups (P > 0.10 for all comparisons). CONCLUSION: Our findings suggest that treatment with CRT-D is associated with pronounced echocardiographic and long-term clinical benefit in patients with LV dysfunction and LBBB who never experienced advanced HF symptoms. These data further emphasize the benefit of early intervention with CRT in this population.