Short- and long-term outcomes of patients with active cancer presenting with an acute coronary syndrome.

BACKGROUND: Management of cancer patients presenting with an acute coronary syndrome (ACS) may be challenging. In this study, we sought to examine whether and how a concomitant diagnosis of active cancer affects patients' management and outcomes following an event of ACS. METHODS: We used a retrospective cohort data analysis of patients from the Acute Coronary Syndrome Israeli Survey (ACSIS) carried out between the years 2016-2021 to compare patients with and without a concomitant diagnosis of active cancer. RESULTS: Of 4913 patients who presented with an ACS, 90 (1.8%) patients had a concomitant active cancer. Cancer patients were older, with a higher prevalence of hypertension and chronic renal failure. The rate of ST-elevation myocardial infarction (STEMI) was similar (40%) between both groups. Cancer patients were less likely to undergo coronary angiography during hospitalization; but once it was performed, the rate of percutaneous coronary intervention was similar. The presence of cancer during an ACS was associated with an increased short- and long-term mortality. In a multivariate analysis, the risk for 1-year mortality remained significantly higher in cancer patient (HR 2.72, 95% CI 1.74-4.24, p < 0.001), and was most prominent in patients presenting with STEMI (HR 5.00, 95% CI 2.40-10.39, p < 0.001). Short- and long-term death rates were also higher in cancer patients after a propensity score matching and adjustment for comorbidities other than cancer. CONCLUSION: Despite significant advances in oncologic and cardiac care, the presence of active cancer in patients with an ACS is still associated with significantly increased risk for 1-year mortality.

Sixth monovalent XBB.1.5 vaccine elicits robust immune response against emerging SARS-CoV-2 variants in heart transplant recipients.

Continued circulation of severe acute respiratory syndrome coronavirus 2 has driven the selection of variants with improved ability to escape preexisting vaccine-induced responses, posing a persistent threat to heart transplant recipients (HTRs). The immunogenicity and safety of the updated XBB.1.5-containing monovalent vaccines are unknown. We prospectively enrolled 52 HTRs who had previously received a 5-dose ancestral-derived monovalent and bivalent messenger RNA (mRNA) vaccination schedule to receive the monovalent XBB.1.5 vaccine. Immunogenicity was evaluated using live virus microneutralization assays. The XBB.1.5 monovalent vaccine elicited potent and diverse neutralizing responses and broadened the reactivity spectrum to encompass newer strains, with the highest increase in neutralization activity being more pronounced against XBB.1.5 (15.8-fold) and JN.1 (13.3-fold) than against BA.5 (6.7-fold) and wild-type (4-fold). Notably, XBB.1.5 and JN.1 were resistant to neutralization by prevaccination sera. There were no safety concerns. Our findings support the updating of coronavirus disease 2019 vaccines to match antigenically divergent variants and exclude ancestral spike-antigen to protect HTRs.

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.

Sex differences in ventricular arrhythmia, atrial fibrillation and atrioventricular block complicating acute myocardial infarction.

Background: Acute myocardial infarction (AMI) complicated by tachyarrhythmias or high-grade atrioventricular block (HAVB) may lead to increased mortality. Purpose: To evaluate the sex differences in patients with AMI complicated by tachyarrhythmias and HAVB and their associated outcomes. Materials and methods: We analyzed the incidence rates of arrhythmias following AMI from the Acute Coronary Syndrome Israeli Survey database from 2000 to 2018. We assessed the differences in arrhythmias incidence and the associated mortality risk between men and women. Results: This cohort of 14,280 consecutive patients included 3,159 (22.1%) women and 11,121 (77.9%) men. Women were less likely to experience early ventricular tachyarrhythmia (VTA), (1.6% vs. 2.3%, p = 0.034), but had similar rates of late VTA (2.3% vs. 2.2%, p = 0.62). Women were more likely to experience atrial fibrillation (AF) (8.6% vs. 5.0%, p < 0.001) and HAVB (3.7% vs. 2.3%, p < 0.001). The risk of early VTAs was similar in men and women [adjusted Odds Ratio (aOR) = 0.76, p = 0.09], but women had a higher risk of AF (aOR = 1.27, p = 0.004) and HAVB (aOR = 1.30, p = 0.03). Early [adjusted hazard ratio (aHR) = 2.84, p < 0.001] and late VTA (aHR =- 4.59, p < 0.001), AF (aHR = 1.52, p < 0.001) and HAVB (aHR = 2.83, p < 0.001) were associated with increased 30-day mortality. Only late VTA (aHR = 2.14, p < 0.001) and AF (aHR = 1.44, p = 0.002) remained significant in the post 30 days period. Conclusions: During AMI women experienced more AF and HAVB but fewer early VTAs than men. Early and late VTAs, AF, and HAVB were associated with increased 30-day mortality. Only late VTA and AF were associated with increased post-30-day mortality.

BNT162b2-vaccine-induced neutralization responses are immune correlates of clinical protection against SARS-CoV-2 in heart transplant recipients.

BACKGROUND: Defining immune correlates of protection against COVID-19 is pivotal for optimizing the use of COVID-19 vaccines, predicting the impact of novel variants on clinical outcomes, and advancing the development of immunotherapies and next-generation vaccines. We aimed to identify vaccine-induced immune correlates of protection against COVID-19-related hospitalizations in a highly vaccinated heart transplant (HT) cohort. METHODS: In a case-control study of HT recipients vaccinated with the BNT162b2 vaccine, patients were prospectively assessed for vaccine-induced neutralization of the wild-type virus, and the Delta and Omicron BA.1, BA.2, BA.4, and BA.5 variants. Comparative analyses with controls were conducted to identify correlates of protection against COVID-19 hospitalization. ROC analyses were performed. Primary outcomes were COVID-19 hospitalizations and severity of SARS-CoV-2 breakthrough infection. RESULTS: The study cohort comprised 59 HT recipients aged 58 (49,65) years with breakthrough infections after three or four monovalent BNT162b2 doses; 41 (69.5%) were men. Thirty-six (61%) patients with COVID-19 were hospitalized; most cases were non-severe (58, 98%). For hospitalized (vs. non-hospitalized) COVID-19 patients, vaccine-induced neutralization titers were significantly lower against all SARS-CoV-2 variants (p < .005). Vaccine-induced neutralization of the wild-type virus and delta and omicron BA.1, BA.2, BA.4, and BA.5 variants was associated with a reduced risk for COVID-19-related hospitalization. The optimal neutralization titer thresholds that were predictive of COVID-19 hospitalizations were 96 (wild-type), 48 (delta), 12 (BA.1), 96 (BA.2), 96 (BA.4), and 48 (BA.5). CONCLUSIONS: BNT162b2-vaccine-induced neutralization responses are immune correlates of protection and confer clinical protection against COVID-19 hospitalizations.

Heart Failure Therapies following Acute Coronary Syndromes with Reduced Ejection Fraction: Data from the ACSIS Survey.

BACKGROUND: Guideline-directed medical therapies for heart failure (HF) may benefit patients with reduced left ventricular ejection fraction (LVEF) following acute coronary syndromes (ACS). Few real-world data are available regarding the early implementation of HF therapies in patients with ACS and reduced LVEF. METHODS: Data collected from the 2021 nationwide, prospective ACS Israeli Survey (ACSIS). Drug classes included: (a) angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitors (ARNI); (b) beta-blockers; (c) mineralocorticoid receptor antagonist (MRA) and (d) sodium-glucose cotransporter-2 inhibitors (SGLT2I). The utilization of HF therapies at discharge or 90 days following ACS was analyzed in relation to LVEF [reduced ≤40% (n = 406) or mildly-reduced 41-49% (n = 255)] and short-term adverse outcomes. RESULTS: History of HF, anterior wall myocardial infarction and Killip class II-IV (32% vs. 14% p < 0.001) were more prevalent in those with reduced compared to mildly-reduced LVEF. ACEI/ARB/ARNI and beta-blockers were used by the majority of patients in both LVEF groups, though ARNI was prescribed to only 3.9% (LVEF ≤ 40%). MRA was used by 42.9% and 12.2% of patients with LVEF ≤40% and 41-49%, respectively, and SGLT2I in about a quarter of both LVEF groups. Overall, ≥3 HF drug classes were documented in 44% of the patients. A trend towards higher rates of 90-day HF rehospitalizations, recurrent ACS or all-cause death was noted in those with reduced (7.6%) vs. mildly-reduced (3.7%) LVEF, p = 0.084. No association was observed between the number of HF drug classes or the use of ARNI and/or SGLT2I with adverse clinical outcomes. CONCLUSIONS: In current clinical practice, the majority of patients with reduced and mildly-reduced LVEF are treated by ACEI/ARB and beta-blockers early following ACS, whereas MRA is underutilized and the adoption of SGLT2I and ARNI is low. A greater number of therapeutic classes was not associated with reduced short-term rehospitalizations or mortality.

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.

Fifth bivalent omicron BA.4/BA.5 vaccination neutralization of SARS-CoV-2 in heart transplant recipients.

In 2022, the antigenically divergent SARS-CoV-2 omicron variants (BA.1, BA.2, BA.4, BA.5) outcompeted previous variants and continued to cause substantial numbers of illnesses and deaths. We evaluated the safety and immunogenicity of the bivalent original/omicron BA.4/BA.5 Pfizer/BioNTech vaccine administered as a fifth dose to heart transplant recipients (HTxRs). We compared neutralization (using live virus assays) of SARS-CoV-2-infected cells in serum samples from HTxRs who had previously received 4 doses of the monovalent BNT162b2 vaccine with samples from HTxRs with breakthrough infection after 4 monovalent BNT162b2 doses. The fifth vaccination induced high neutralization efficiency against the wild-type virus and omicron BA.1, BA.2, BA.4, and BA.5 variants, with significantly higher neutralization efficiency being induced in HTxRs with breakthrough infection than in those without. Neutralizing titers in those with breakthrough infection were sustained above the level induced by the fifth dose in the uninfected. We conclude that the fifth bivalent vaccine is immunogenic, including to variants, with higher vaccine immunogenicity conferred by breakthrough infection. Nevertheless, the clinical protection conferred by the fifth dose is yet to be determined. The sustained neutralization responses in those with breakthrough infection support the notion of delaying booster in those with natural breakthrough infection.

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 obesity paradox in patients with acute coronary syndromes over 2 decades - the ACSIS registry 2000-2018.

BACKGROUND: Obesity is a worldwide epidemic which is associated with major cardiovascular (CV) risk factors. Nevertheless, substantial distant data, mostly published more than a decade ago, have demonstrated an obesity paradox, where obese patients generally have a better short- and long-term prognosis than do their leaner counterparts with the same CV profile. Nonetheless, it is not fully elucidated whether the obesity paradox is still relevant in the contemporary cardiology era among patients with acute coronary syndrome (ACS). We aimed to examine temporal trends in the clinical outcomes of ACS patients by their BMI status. METHODS: Data from the ACSIS registry including all patients with calculated BMI data between the years 2002-2018. Patients were stratified by BMI groups to underweight, normal, overweight and obese. Clinical endpoints included 30d major cardiovascular events (MACE), and 1-year mortality. Temporal trends were examined in the late (2010-2018) vs. the early period (2002-2008). Multivariable models examined factors associated with clinical outcomes by BMI status. RESULTS: Among the 13,816 patients from the ACSIS registry with available BMI data, 104 were underweight, 3921 were normal weight, 6224 were overweight and 3567 were obese. 1-year mortality was highest among underweight patients (24.8%), as compared to normal weight patients (10.7%) and lowest among overweight and obese patients (7.1% and 7.5% respectively; p for trend <0.001). 30-day MACE rates followed a similar pattern (24.3% for underweight, 13.6% for normal weight, 11.6% for overweight, and 11.7% for obese; p for trend<0.001). Comparing the 2 time-periods, 30-day MACE was significantly lower in the late period in all BMI groups, but unchanged in patients who were underweight. Similarly, 1-year mortality has decreased in normal weight and obese patients but remained similarly high in underweight patients. CONCLUSIONS: In ACS patients, during 2-decades, 30-day MACE and 1-year mortality were lower among overweight and obese patients compared to underweight and even normal weight patients. Temporal trends revealed that 30-day MACE and 1-year mortality have decreased among all BMI groups other than the underweight ACS patients, among whom the adverse CV rates were consistently high. Our findings suggest that the obesity paradox is still relevant in ACS patients in the current cardiology era.

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.

Outcomes among patients admitted for non-ST-segment myocardial infarction in the pre-pandemic and pandemic COVID-19 era: Israel Nationwide study.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic in 2019, several countries have reported a substantial drop in the number of patients admitted with non-ST-segment myocardial infarction (NSTEMI). OBJECTIVE: We aimed to evaluate the changes in admissions, in-hospital management and outcomes of patients with NSTEMI in the COVID-19 era in a nationwide survey. METHOD: A prospective, multicenter, observational, nationwide study involving 13 medical centers across Israel aimed to evaluate consecutive patients with NSTEMI admitted to intensive cardiac care units over an 8-week period during the COVID-19 outbreak and to compare them with NSTEMI patients admitted at the same period 2 years earlier (control period). RESULTS: There were 624 (43%) NSTEMI patients, of whom 349 (56%) were hospitalized during the COVID-19 era and 275 (44%) during the control period. There were no significant differences in age, gender and other baseline characteristics between the two study periods. During the COVID-19 era, more patients arrived at the hospital via an emergency medical system compared with the control period (P = 0.05). Time from symptom onset to hospital admission was longer in the COVID-19 era as compared with the control period [11.5 h (interquartile range, IQR, 2.5-46.7) vs. 2.9 h (IQR 1.7-6.8), respectively, P < 0.001]. Nevertheless, the time from hospital admission to reperfusion was similar in both groups. The rate of coronary angiography was also similar in both groups. The in-hospital mortality rate was similar in both the COVID-19 era and the control period groups (2.3% vs. 4.7%, respectively, P = 0.149) as was the 30-day mortality rate (3.7% vs. 5.1%, respectively, P = 0.238). CONCLUSION: In contrast to previous reports, admission rates of NSTEMI were similar in this nationwide survey during the COVID-19 era. With longer time from symptoms to admission, but with the same time from hospital admission to reperfusion therapy and with similar in-hospital and 30-day mortality rates. Even in times of crisis, adherence of medical systems to clinical practice guidelines ensures the preservation of good clinical outcomes.

Peripheral artery disease, abnormal ankle-brachial index, and prognosis in patients with acute coronary syndrome.

Objectives: Ankle-brachial index (ABI) is an independent prognostic marker of cardiovascular events among patients with coronary artery disease (CAD). We aimed to investigate the outcome of patients hospitalized with acute coronary syndrome (ACS) and abnormal ABI. Approach and results: ABI was prospectively measured in 1,047 patients hospitalized due to ACS, who were stratified into three groups, namely, those with clinical peripheral artery disease (PAD) (N = 132), those without clinical PAD but with abnormal (< 0.9) ABI (subclinical PAD; N = 148), and those without clinical PAD with normal ABI (no PAD; N = 767). Patients were prospectively followed for 30-day major adverse cardiovascular event (MACE) and 1-year all-cause mortality. The mean age was 64 years. There was a significant gradual increase throughout the three groups in age, i.e., the incidence of prior stroke, diabetes mellitus, and hypertension (p for trend = 0.001 for all). The in-hospital course showed a gradual rise in the incidence of complications with an increase in heart failure [2.5, 6.1, and 9.2%, (p for trend = 0.001)] and acute kidney injury [2, 4.1, and 11.5%, (p for trend = 0.001)]. At day 30, there was a stepwise increase in MACE, such that patients without PAD had the lowest rate, followed by subclinical and clinical PADs (3.5, 6.8, and 8.1%, respectively, p for trend = 0.009). Similarly, there was a significant increase in 1-year mortality from 3.4% in patients without PAD, through 6.8% in those with subclinical PAD, to 15.2% in those with clinical PAD (p for trend = 0.001). Conclusion: Subclinical PAD is associated with poor outcomes in patients with ACS, suggesting that routine ABI screening could carry important prognostic significance in these patients regardless of PAD symptoms.

Peripheral Arterial Disease in Patients With Acute Coronary Syndrome: Results From a Large Real-World Registry.

BACKGROUND: Limited data exist regarding the significance of peripheral arterial disease (PAD) in patients with acute coronary syndrome (ACS). METHODS: We evaluated 16,922 consecutive ACS patients who were prospectively included in a national ACS registry. The co-primary endpoint included 30 days major adverse cardiovascular event (MACE) (re-infarction, stroke, and/or cardiovascular death) and 1-year mortality. RESULTS: PAD patients were older (70±11 vs 63±13; p<0.01), male predominance (80% vs 77%; p=0.01), and more likely to sustain prior cardiovascular events. PAD patients were less likely to undergo coronary angiography (69% vs 83%; p<0.001) and revascularisation (80% vs 86%; p<0.001). Patients with PAD were more likely to sustain 30-day MACE (22% vs 14%; p<0.001) and mortality (10% vs 4.4%; p<0.001), as well as re-hospitalisation (23% vs 19%; p=0.001). After adjusting for potential confounders, PAD remained an independent predictor of 30-day MACE (odds ratio [OR], 1.6 [95% confidence interval (CI), 1.24-2.06]). Patients with compared to those without PAD had 2.5 times higher 1-year mortality rate (22% vs 9%; p<0.001). Co-existence of PAD remained an independent predictor of 1-year mortality after adjustment for potential confounders by multivariable regression analysis (OR, 1.62; 95% CI, 1.4-1.9). PAD was associated with a significant higher 1-year mortality rate across numerous sub-groups of patients including type of myocardial infarction (ST-elevation myocardial infarction vs non-ST-elevation myocardial infarction), and whether the patient underwent revascularisation. CONCLUSIONS: Acute coronary syndrome with concomitant PAD represents a high-risk subgroup that warrants special attention and a more tailored approach.

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.

Management and outcomes over time of acute coronary syndrome patients at particularly high cardiovascular risk : the ACSIS registry-based retrospective study.

OBJECTIVE: Some patients following acute coronary syndrome (ACS) are at particularly increased risk for recurrent cardiovascular events. We aimed to examine temporal trends in the management and outcomes across the spectrum of these particularly high-risk patients. DESIGN AND SETTING: A retrospective study based on the ACS Israeli survey (ACSIS) registry, a multicentre prospective national registry, taking place biennially in 25 cardiology departments in Israel. Temporal trends were examined in the early (2002-2008) and late (2010-2018) time periods. PARTICIPANTS: Consecutive patients with ACS enrolled in the ACSIS registry were stratified according to the Thrombolysis in Myocardial Infarction Risk Score for secondary prevention (TRS2°P) to high (TRS2°p=3), very high (TRS2°p=4) or extremely high risk (TRS2°p=5-9). Patients with TRS2°p<3 were excluded. From the initial 15 196 patients enrolled, 5359 patients were eventually included.Clinical outcome measures included 30-day major adverse cardiovascular events (MACE) and 1-year mortality. RESULTS: Among 5359 patients (50% high risk, 30% very high risk and 20% extremely high risk), those with a higher risk were older, had more comorbidities, presented more with non-ST elevation myocardial infarction, and were treated less often with guideline-recommended pharmacotherapy and percutaneous coronary intervention. Over time, treatment has improved in all risk strata, and the rate of 30-day MACE has significantly decreased in all risk groups (from 21% to 10%, from 22% to 15%, and from 26% to 16%, in high, very high and extremely high-risk groups, respectively, p<0.001 for each). However, 1-year mortality decreased only among high and very high-risk patients, and not among extremely high-risk patients in whom 1-year mortality rates remained very high (28.7% vs 28.9%, p=1). CONCLUSION: Within a particularly high-risk cohort of patients with ACS, treatment has significantly progressed over almost 2 decades. While short-term outcomes have improved in all risk groups, 1-year mortality has remained unchanged in extremely high-risk patients with ACS.

Immediate and early percutaneous coronary intervention in very high-risk and high-risk non-ST segment elevation myocardial infarction patients.

BACKGROUND: The European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (non-ST-segment elevation myocardial infarction [NSTEMI]) has recommended immediate (<2 h) percutaneous coronary intervention (PCI) in very-high risk patients and early (<24 h) PCI in high-risk patients. HYPOTHESIS: To examine the ESC NSTEMI guidelines adherence in a nationwide survey in Israel using the Acute Coronary Syndrome Israeli Survey (ACSIS). We hypothesized that adherence to the guidlines' recommnded PCI timing in NSTEMI pateints will be inadequate, partly due to the inconsistent evidence regarding its effect on clinical outcomes. METHODS: All NSTEMI patients who underwent PCI during the ACSIS surveys in 2016 and 2018 were included in the analysis. RESULTS: Out of 1793 NSTEMI patients, 1643 (92%) patients underwent PCI, and door to balloon time was documented in 1078 of them. One hundred and fifty-six (14.5%) patients and 922 (85.5%) patients were defined as very high-risk and high-risk NSTEMI patients, respectively. Of the very high-risk NSTEMI patients, only 10 (6.4%) underwent immediate coronary angiography, and 50 (32.1%) underwent early coronary angiography. Acute heart failure 139 (89.1%) was the main reason for including NSTEMI patients in the very high-risk category. Of the high-risk patients, early coronary angiography was performed in only 405 (43.9%) patients. Patients in whom coronary angiography was postponed were older and had more comorbidities. CONCLUSIONS: Despite guidelines recommendations for immediate and early PCI in very high-risk and high-risk NSTEMI patients, respectively, most patients do not undergo immediate or early PCI according to contemporary guidelines. Further studies are needed to better understand the reasons for guidelines' nonadherence in those high-risk patients.

Pericardial Involvement in ST-Segment Elevation Myocardial Infarction as Detected by Cardiac MRI.

Background: Post myocardial infarction pericarditis is considered relatively rare in the current reperfusion era. The true incidence of pericardial involvement may be underestimated since the diagnosis is usually based on clinical and echocardiographic parameters. Objectives: This study aims to document the incidence, extent, and prognostic implication of pericardial involvement in ST-segment elevation myocardial infarction (PISTEMI) using cardiac MRI (CMR). Methods: One hundred and eighty-seven consecutive ST-segment elevation myocardial infarction patients underwent CMR on day 5 ± 1 following admission, including steady-state free precession (SSFP) and late Gadolinium enhancement (LGE) sequences. Late Gadolinium enhancement and microvascular obstruction (MVO) were quantified as a percentage of left ventricular (LV) mass. Late Gadolinium enhancement was graded for transmurality according to the 17 AHA left ventricle (LV) segment model (LGE score). Late pericardial enhancement (LPE), the CMR evidence of pericardial involvement, was defined as enhanced pericardium in the LGE series and was retrospectively recorded as present or absent according to the 17 AHA segments. Late pericardial enhancement was evaluated adjacent to the LV, the right ventricle, and both atria. Clinical, laboratory, angiographic, and echocardiographic data were collected. Clinical follow-up for major adverse cardiac events (MACE) was documented and correlated with CMR indices, including LGE, MVO, and LPE. Results: Late pericardial enhancement (LPE+) was documented in 77.5% of the study cohort. A strong association was found between LPE and the degree and extent of myocardial injury (LGE, MVO). Both LGE and MVO were significantly correlated with increased MACE on follow-up. On the contrary, LPE presence, either adjacent to the LV or the other cardiac chambers, was associated with a lower MACE rate in a median of 3 years of follow-up HR 0.39, 95% CI (0.21-0.7), p = 0.002, and HR 0.48, 95% CI (0.26-0.9), p = 0.02, respectively. Conclusions: Prognostic implication of pericardial involvement in ST-segment elevation myocardial infarction was documented by CMR in 77.5% of our STEMI cohort. Late pericardial enhancement presence correlated significantly with the extent and severity of the myocardial damage. Unexpectedly, it was associated with a considerably lower MACE rate in the follow-up period.

Systolic Time Intervals for Diagnosis of Severe Aortic Stenosis.

BACKGROUND: Estimated frequency of aortic stenosis (AS) in those over 75 years of age is 3.4%. Symptomatic patients with severe AS have increased morbidity and mortality and aortic valve replacement should be offered to improve life expectancy and quality of life. OBJECTIVES: To identify whether systolic time intervals can identify severe AS. METHODS: The study comprised 200 patients (mean age 79 years, 55% men). Patients were equally divided into normal, mild, moderate, or severe AS. All patients had normal ejection fraction. Acceleration time (AT) was defined as the time from the beginning of systolic flow to maximal velocity; ejection time (ET) was the time from onset to end of systolic flow. The relation of AT/ET was calculated. Death or aortic valve intervention were documented. AT increased linearly with the severity of AS, similar to ET and AT/ET ratio (P for trend < 0.05 for all). Receiver-operator characteristic curve analysis demonstrated that AT can identify severe AS with a cutoff ≥ 108 msec with 100% sensitivity and 98% specificity, while a cutoff of 0.34 when using AT/ET ratio can identify severe AS with 96% sensitivity and 94% specificity. Multivariate analysis adjusting to sex, stroke volume index, heart rate, and body mass index showed similar results. Kaplan-Meier curve for AT ≥ 108 and AT/ET ≥ 0.34 predicted death or aortic valve intervention in a 3-year follow-up. CONCLUSIONS: Acceleration time and AT/ET ratio are reliable measurements for identifying patients with severe AS. Furthermore, AT and AT/ET were able to predict aortic valve replacement or death.