Higher Rates Of Major Adverse Cardiovascular Events Research Articles

(294) Revisiting Risk of Testosterone Therapy: Assessing the Impact of Supratherapeutic Levels on MACE and Mortality

Abstract Introduction The benefits and risks of testosterone therapy (TT) have been a subject of long-standing debate. The recent TRAVERSE trial demonstrated that men who received TT did not show an increased risk of major adverse cardiovascular events (MACE) or mortality. However, it is essential to note that the median post-treatment testosterone levels were found to be less than 400ng/dL. Therefore, our investigation aims to assess whether supra-therapeutic T levels (>1000ng/dL) are associated with an elevated risk of MACE and/or mortality. Objective To use data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to determine whether supratherapeutic testosterone levels (> 1000 ng/dL) are associated with higher rates of all-cause mortality or MACE. Additionally, to determine whether there was a higher rate of MACE among patients who died. Methods We collected data from the NHANES 2011-2016 Continuous Files and linked them to the National Death Index (NDI) through 2019. The NHANES is a national survey run by the Center for Disease Control that assesses the health status of United States residents by sampling of populations across the country. The survey collects socio-demographic data, lab values, dietary health, clinical variables and body measurements. NDI is a centralized database of United States death record information on file in state vital statistics offices. We included male participants aged 18 years and older with data on total testosterone and who were eligible for mortality data. We compared participants with testosterone > 1000 ng/dL against those with <1000 ng/dL, with the assumption that those > 1000 ng/dL had supratherapeutic levels of testosterone from testosterone therapy. Our primary outcome was mortality, with secondary outcomes of mortality due to MACE. We additionally analyzed association with MACE as the primary cause of mortality among participants who had died. MACE was determined by those who were categorized as dying of “diseases of the heart” or “cerebrovascular diseases.” We used binary logistic regression and controlled for age, race, body mass index, and history of myocardial infarction. Statistical significance was assessed at p<0.05. All analyses were performed on STATA MP 17. Results We identified 7,790 males aged 18 or older with mortality data. Of those, 7,715 had testosterone <1000 and 75 men had testosterone > 1000. Among all patients in our cohort, 643 died of all causes, and 199 died of MACE. In the multivariable logistic regression adjusted for potentially confounding variables, we found testosterone >1000 was associated with all-cause mortality (OR 2.59, 95% CI 1.29-5.20, p=0.007). There was no association with mortality from MACE in either all participants (OR 0.60, 95% CI 0.08-4.45, p=0.615) or among those who died (OR 0.28, 95% CI 0.03-2.17, p=0.221). Conclusions Supratherapeutic levels of testosterone are associated with all-cause mortality by 2019 in NHANES participants from 2011-2016. There were no associations with MACE in this population, although overall numbers of death from MACE were low in this data set. Future studies should examine longitudinal data across a greater duration and consider non-fatal MACE events in men who achieve supra-therapeutic levels on TT. Disclosure No.

Recovery of left ventricular ejection fraction in Takotsubo Syndrome

Abstract Introduction Takotsubo Syndrome (TTS) is a condition of transient left ventricular dysfunction that is typically triggered by emotional or physical stress. Left ventricular ejection fraction (LVEF) recovery in TTS occurs over a wide-range interval, varying from days to weeks. Purpose Our purpose was to access the prognostic impact of delayed recovery of LVEF in patients with TTS. Methods We performed a retrospective analysis of patients admitted in a single centre between 2008 and 2022 with the diagnosis of TTS, with a LVEF <50% at admission. Patients were divided into two groups: Group A- patients with the recovery of ejection fraction during hospitalization (LV EF ≥ 50% at the pre-discharge echocardiogram) and Group B- patients that had a delay in recovery, with LV EF <50% at the pre-discharge echocardiogram. Major adverse cardiovascular events (MACCE) included heart failure hospitalization, cardiovascular mortality, stroke and TTS recurrence. Results We included 63 pts, 88,9% females, mean age of 69,38 ±12,5 years. Group A included 27 pts, with a median LV EF of 37% (IQR 33-41) and group B included 36 pts with a median LV EF of 36% (IQR 33-38,8), with no statistically significant difference between the two groups (p= 0,347). The median pre-discharge LV EF was 60,0% (IQR 56-65,6) in group A and 42,0% (IQR 37-47) in group B (p<0,005). The hospitalization length (HL)was similar between the two groups (mean HL of 7,9 ±7,8 in group A versus 8,1 ±8,4 days in group B, p= 0,93). The two groups were similar in terms of basal characteristics, with more prevalence of psychiatric disease in group A (13,9% vs 33,3%, p= 0,066). We found no statistically differences in clinical presentation and evolution during hospitalization (Killip class, cardiogenic shock, ventricular arrhythmias) and in the rates of concomitant coronary artery disease (14,8% group A versus 26,5% group B, p= 0,270). Also, the in-hospital medication and at discharge (Angiotensin-converting enzyme inhibitors, beta blockers, spironolactone and aspirin) were identical between the two groups. There was a tendency for more prescription of anticoagulants at discharge in group B (45,7% versus 22,2%, p = 0,055). During a median follow-up of 41,0 months (IQR 14,0-54,5), group B had a higher rate of MACCE (34,4% versus 20,0%, log rank p= 0,033). In a multivariate analysis, after adjusting for possible confounders, delayed recovery of LV EF was an independent predictor of MACCE with a HR 6,1 (95% CI: 1,50-24,9, p= 0,012) (Fig.1). Conclusions In this population, delayed recovery of LV EF in TTS was an independent predictor of major adverse cardiovascular events. These findings suggest that this population should be targeted in clinical trials to investigate possible interventions and these patients should have a closer follow-up.

Abstract 13233: Disparities in Speed of Diagnosis of Hypertrophic Cardiomyopathy in the United States

Background: Hypertrophic cardiomyopathy (HCM) is a cardiac disease that can be genetic in cause. Early diagnosis, risk stratification, and pharmacological management can reduce the disease burden, yet several studies have highlighted disparities in early diagnosis by gender and race. Goals: This study compares age, severity at diagnosis, and time-to-diagnosis, by gender, race, and county-level poverty rate in a nationally representative population of over 65-year-olds. Methods: We used Medicare claims data from 2016-2020 to construct a sample who had at least two HCM claims and continuous enrollment for at least 2 years prior to their first HCM claim. We measured age and severity of heart disease at diagnosis, as well as time from the first observed indication of heart disease to HCM diagnosis. Results: We identified 48,857 patients with an HCM diagnosis in the study period, of which 60% were women and 81% were Non-Hispanic White. Comparing relative rates, Black and Hispanic patients at the time of HCM diagnosis had a 16% higher prior rate of heart failure (HF), and a 11% higher rate of prior major adverse cardiovascular events (MACE). In addition, in Black HCM patients, the share of atrial and non-atrial arrhythmias that were clinically diagnosed before HCM diagnosis was 28% lower than among White patients (p<0.001). Importantly our multi-attribute approach highlighted the composite roles of race and county-level poverty: at the time of HCM diagnosis, Black men in the poorest quartile of counties had a 26% higher rate of HF, 22% higher rate of MACE and a 53% lower rate of clinically diagnosed arrhythmia (all p<0.001) than White men in the wealthiest quartile of counties. Additionally, the median time from the first indication of heart disease until the diagnosis of HCM in Black and Hispanic patients from the poorest quartile of counties was 347 days longer than for Non-Hispanic White patients from the wealthiest quartile of counties (p<0.001). Conclusions: This study shows evidence of disparities in diagnosis of older patients with HCM in the United States, particularly in terms of race and county-level poverty. New approaches are needed to address these disparities and improve access to care for patients in underserved and vulnerable communities.

Neutrophil-Enriched Biomarkers and Long-Term Prognosis in Acute Coronary Syndrome: a Systematic Review and Meta-analysis.

Activated neutrophils release a range of inflammatory products that represent potential biomarkers, and there is interest in the prognostic value of these in acute coronary syndrome (ACS) patients. We conducted a systematic review to examine neutrophil-enriched biomarkers and the occurrence of major adverse cardiovascular events (MACE) in patients with ACS. We identified twenty-seven studies including 17,831 patients with ACS. The most studied biomarkers were neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO). Meta-analyses showed that elevated NGAL was associated with higher MACE rates (unadjusted risk ratio (RR) 1.52, 95% CI 1.12-2.06, p = 0.006) as were elevated MPO levels (unadjusted RR 1.61, 95% CI 1.22-2.13, p = 0.01). There was limited data suggesting that increased levels of calprotectin, proteinase-3 and double-stranded DNA were also associated with MACE. These results suggest that higher levels of neutrophil-enriched biomarkers may be predictive of MACE in patients with ACS, although higher-quality studies are needed to confirm these observations.

Using cardiovascular risk indices to predict mortality in Covid-19 patients with acute respiratory distress syndrome: a cross sectional study

Covid-19 patients who require admission to an intensive care unit (ICU) have a higher risk of mortality. Several risk factors for severe Covid-19 infection have been identified, including cardiovascular risk factors. Therefore, the aim was to investigate the association between cardiovascular (CV) risk and major adverse cardiovascular events (MACE) and mortality of Covid-19 ARDS patients admitted to an ICU. A prospective cross-sectional study was conducted in a university hospital in Graz, Austria. Covid-19 patients who were admitted to an ICU with a paO2/fiO2 ratio < 300 were included in this study. Standard lipid profile was measured at ICU admission to determine CV risk. 31 patients with a mean age of 68 years were recruited, CV risk was stratified using Framingham-, Procam- and Charlson Comorbidity Index (CCI) score. A total of 10 (32.3%) patients died within 30 days, 8 patients (25.8%) suffered from MACE during ICU stay. CV risk represented by Framingham-, Procam- or CCI score was not associated with higher rates of MACE. Nevertheless, higher CV risk represented by Procam score was significantly associated with 30- day mortality (13.1 vs. 6.8, p = 0.034). These findings suggest that the Procam score might be useful to estimate the prognosis of Covid-19 ARDS patients.

Colchicine Use and Major Adverse Cardiovascular Events in Male Patients with Gout and Established Coronary Artery Disease: A Veterans Affairs Nested Retrospective Cohort Study

Background: Despite colchicine’s proven efficacy in the non-gout population, the effects of colchicine on the risk of major adverse cardiovascular events (MACE) among high-risk patients with gout remain to be determined. The purpose of this study is to evaluate the association between colchicine use and MACE in gout patients with preexisting coronary artery disease (CAD). Methods: This retrospective cohort study followed patients with gout and established CAD within the VA New York Harbor Healthcare System who did or did not use colchicine regularly (&gt;30 continuous days prescription with at least 1 refill). The primary outcome was first MACE, defined as a composite of non-fatal myocardial infarction, coronary artery bypass graft, non-fatal stroke, and all-cause mortality. Part I of the primary analysis compared MACE between colchicine users and nonusers. Part II of the study compared MACE within the colchicine-use group, divided into quartiles based on consistency of colchicine use (i.e., percentage of time on colchicine). Results: Among 1638 patients with gout, 355 had established CAD (239 colchicine users and 116 nonusers). In this cohort, the odds of MACE were similar between any colchicine use compared to nonuse (OR 1.14; 95% CI (0.59–2.20)); however, colchicine users overall had a higher baseline cardiovascular risk profile than nonusers, suggesting that colchicine may have served to equilibrate risk between the two groups. Moreover, patients in the highest continuous colchicine-use quartile (&gt;70% of observation period on colchicine) demonstrated lower odds of MACE compared to those in the lowest three quartiles (OR 0.35; 95% CI (0.13–0.93)), with no difference in baseline risk. Additionally, colchicine users had a numerically lower rate of MACE during periods of active use compared with periods of lapse. Kaplan–Meier analysis revealed a difference in cumulative MACE over time, favoring the subgroup with the most consistent colchicine use (plog-rank = 0.01). Conclusions: Despite higher CV risk, gout patients with CAD receiving colchicine had no higher rates of MACE than those not receiving colchicine. Among all patients with gout and CAD treated with colchicine, those with the most consistent colchicine use had lower odds of MACE, and event rates were lower during active use. Colchicine protection against cardiovascular events may require maintenance of colchicine bloodstream levels.

Abstract 15606: Diabetes is Associated With Increased Risk of Major Adverse Cardiovascular Events in Patients Covid-19: A Retrospective U.S. Multicenter Cohort Study

Introduction: Diabetes mellitus (DM) increases the risk of adverse outcomes in patients with COVID-19. Whether this is driven by a higher rate of thrombotic complications or cardiovascular events in patients with COVID-19 has rarely been explored. Methods: We analyzed a retrospective cohort of 6920 consecutive patients ≥ 18 years old with confirmed SARS-COV-2 polymerase chain reaction testing from March 2020 to April 2020 using a US multicenter registry. Main outcomes of interest were 30-day of adjudicated major adverse cardiovascular events (MACE), major arterial and venous thromboembolic (VTE) events, and symptomatic VTE. MACE included VTE, catheter related thrombosis, myocardial infarction, stroke, major adverse limb events, heart failure hospitalization, atrial fibrillation (AF), and myocarditis. Results: Of 1252 patients with DM, 49.4% were women, 50.9% were non-white, and 26.2% were Latinx. Mean BMI of patients with and without DM was similar (34.2 vs 33.4 kg/m2, p =0.91). Compared with patients without DM, those with DM were older (50.3±15.4 years. vs 39.6±19.7, p &lt;0.001), had higher rates of hypertension, AF, hospitalization (76.4% vs 23.1%, 5.0% vs 1.0% and 60.8% vs 28.4%, p &lt;0.001, respectively). Thirty days after COVID diagnosis, patients with DM had a higher rate of MACE (12.7% vs 3.9%, p &lt;0.001), major arterial or venous thromboembolism (8.5% vs 3.1%, p &lt;0.001), symptomatic VTE (6.5% vs 4.7%, p &lt;0.001 ), and death (11.9% vs 4.7%, p &lt;0.001) compared with patients without DM (Panel A). After adjusting for age, gender, hypertension, COVID-19 admission, peripheral artery disease, and coronary artery disease, patients with DM had increased risk of MACE (aOR 1.39 95% CI 1.09-1.78), but not of major adverse arterial or VTE events (aOR 1.24 95% CI 0.93-1.65), symptomatic VTE (aOR 1.34 95% CI 0.98-1.86), or death (aOR 1.13 95% CI 0.87-1.47) (Panel B). Conclusions: In patients with COVID-19, DM is independently associated with increased risk of MACE.

Outcomes After Tricuspid Valve Operations in Patients With Drug-Use Infective Endocarditis

The increase of intravenous drug use has led to an increase in right-sided infective endocarditis and its complications including septic pulmonary embolism. The objective of this study was to compare the outcomes of tricuspid valve (TV) operations in patients with drug-use infective endocarditis (DU-IE) complicated by septic pulmonary emboli (PE). Hospitalizations for DU-IE complicated by septic PE were identified from the National Inpatient Sample from 2002 to 2019. Outcomes of patients who underwent TV operations were compared with medical management. The primary outcome was the incidence of major adverse cardiovascular events (MACEs), defined as in-hospital mortality, myocardial infarction, stroke, cardiogenic shock, or cardiac arrest. An inverse probability of treatment weighted analysis was utilized to adjust for the differences between the cohorts. A total of 9,029 cases of DU-IE with septic PE were identified (mean age 33.6years), of which 818 patients (9.1%) underwent TV operation. Surgery was associated with a higher rate of MACE (14.5% vs 10.8%, p <0.01), driven by a higher rate of cardiogenic shock (6.1% vs 1.2%, p <0.01) but a lower rate of mortality (2.7% vs 5.7%, p <0.01). Moreover, TV operation was associated with an increased need for permanent pacemakers, blood transfusions, and a higher risk of acute kidney injury. In the inverse probability treatment weighting analysis, TV operation was associated with an increased risk for MACE driven by a higher rate of cardiogenic shock and cardiac arrest, but a lower rate of mortality when compared with medical therapy alone. In conclusion, TV operations in patients with DU-IE complicated by septic PE are associated with an increased risk for MACE but a decreased risk of mortality. Although surgical management may be beneficial in some patients, alternative options such as percutaneous debulking should be considered given the higher risk.

Coronary calcification is independently associated with major adverse cardiovascular events in men with recurrent prostate cancer while aortic calcification is not

Abstract Background Cardiovascular disease is an important cause of morbidity and mortality in men with prostate cancer. Coronary and aortic calcification have been associated with major adverse cardiovascular events (MACE) in the general population, and are readily seen on staging cancer positron emission tomography (PET)/computed tomography (CT) scans. The utility of vascular calcification on non-gated CT for cardiovascular risk assessment in men with prostate cancer is not known. Purpose We determined the association between coronary and aortic calcification on non-gated CT imaging and MACE in men with prostate cancer. Methods We studied 354 men who underwent indium-111 capromab pendetide PET/CT for recurrent prostate cancer at our institution between 2012–2016. Clinical data were obtained from the medical record. Coronary and aortic calcification were qualitatively assessed using a standardized scoring system. The primary outcome of MACE included myocardial infarction, stroke, coronary and/or peripheral revascularization, heart failure hospitalization, and all-cause mortality. Results Over 5 years of follow-up, 63 patients (18%) met the primary outcome. Vascular calcification was common in this cohort (median 68 years of age), with 214 patients (60%) having coronary calcification and 296 patients (84%) having aortic calcification. Older patients had greater coronary and aortic calcification, and also higher rate of MACE. In adjusted models for age and diabetes, coronary calcification was associated with higher rate of MACE (hazard ratio [HR] 2.1, interquartile range [IQR] 1.1–4.0, p=0.02) while aortic calcification was not (HR 2.7, IQR 0.8–9.0, p=0.12). Undifferentiated vascular calcification was not associated with MACE (p=0.24). Conclusions Coronary calcification on non-gated CT scan is independently associated with MACE in men with recurrent prostate cancer while aortic calcification is not. The presence of coronary calcification should be included in staging PET/CT reports, and this information should prompt implementation of cardiovascular risk modification strategies. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): This study was supported by the Mentors in Medicine Program, Department of Internal Medicine, Washington University School of Medicine.

Clinical and angiographic outcomes following percutaneous treatment of non-occlusive vs. chronically total occluded coronary lesions

Abstract Background Recent advancements in recanalization techniques, introduction of dedicated equipment and elaboration of systematic algorithmic approaches have significantly improved procedural success of coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) procedures. However, despite their undisputable merits in terms of procedural success, direct comparisons of mid-term clinical and angiographic outcomes following CTO and non-CTO-PCI are missing. Purpose The aim of this study was to assess the clinical and angiographic outcomes of patients undergoing successful CTO-PCI as compared to a propensity matched cohort of patients undergoing PCI of non-occlusive coronary lesions. Methods All consecutive patients undergoing successful CTO recanalization procedures at our center between 2015 and 2018 were included (N=453; 472 lesions). For matching purposes, all patients undergoing non-CTO-PCI present in our database were included (N=14733; 23458 lesions). A 1-to-1 nearest neighbour matching using baseline clinical and angiographic variables was performed to identify one patient undergoing non-CTO-PCI (N=453; 472 vessels) for each patient undergoing CTO-PCI (N=453; 472 vessels). Surveillance angiography was scheduled at 6–9 months and clinical follow-up was performed up to 12 months. The primary clinical endpoint of interest was the incidence of major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI) and target lesion revascularization (TLR). The secondary angiographic endpoint was in-segment binary restenosis. Results Patients undergoing CTO-PCI displayed a tendency towards higher degrees of binary restenosis at surveillance angiography as compared to those undergoing non-CTO-PCI (CTO vs. non-CTO: 30.5% vs. 24.0%; P=0.058), despite not meeting statistical significance. Of note, the incidence of occlusive restenosis was low and comparable between groups (2.2% vs. 1.4%; P=0.603). At 12 months follow-up, MACE occurred in 83 patients (19.7%) in the CTO-PCI and 59 patients (14.1%) in the non-CTO-PCI group (hazard ratio [HR] = 1.44; 95% confidence interval [CI]: 1.03–2.01; P=0.033). TLR rates were significantly higher following CTO- as compared to non-CTO-PCI (17.2% vs. 10.3%; HR=1.72 [1.18–2.51], P=0.005). The incidence of all-cause death (2.6% vs. 3.3%; P=0.548) and MI (0.5% vs. 1.4%; P=0.177) was not significantly different between the groups. Conclusion In this large, propensity-matched comparison of clinical and angiographic outcomes following CTO- vs. non-CTO-PCI, we found CTO-PCI to be associated with a higher MACE rate at 12 months, primarily driven by significantly higher TLR rates. The incidence of occlusive restenosis was low and comparable between groups. Funding Acknowledgement Type of funding sources: None.

The prognostic value of global myocardium strain by CMR-feature tracking in immune checkpoint inhibitor-associated myocarditis.

Immune checkpoint inhibitor (ICI)-associated myocarditis is a potentially fatal complication. Sparse published researches evaluated the prognostic value of cardiovascular magnetic resonance feature tracking (CMR-FT) for ICI-associated myocarditis. In the single-center retrospective study, 52 patients with ICI-associated myocarditis and CMR were included from August 2018 to July 2021. The ICI-associated myocarditis was diagnosed by using the clinical criteria of the European Society of Cardiology guidelines. Major adverse cardiovascular events (MACE) were comprised of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. During a median follow-up of 171 days, 14 (27%) patients developed MACE. For patients with MACE, the global circumferential strain (GCS), global radial strain (GRS), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF) were significantly worse and native T1 values and late gadolinium enhancement (LGE) extent were significantly increased, compared with patients without MACE (p < 0.05). The GLS remained the independent factor associated with a higher risk of MACE (hazard ratio (HR): 2.115; 95% confidence interval (CI): 1.379-3.246; p = 0.001) when adjusting for LVEF, LGE extent, age, sex, body mass index, steroid treatment, and prior cardiotoxic chemotherapy or radiation. After adjustment for LVEF, the GLS remained the independent risk factor associated with a higher rate of MACE among patients with a preserved LVEF (HR: 1.358; 95% CI: 1.007-1.830; p = 0.045). GLS could provide independent prognostic value over GCS, GRS, traditional CMR features, and clinical features in patients with ICI-associated myocarditis. • The global circumferential strain (GCS), global radial strain (GRS), and global longitudinal strain (GLS) by cardiovascular magnetic resonance feature tracking were significantly impaired in patients with an immune checkpoint inhibitor (ICI)-associated myocarditis. • GLS was still significantly impaired in patients with preserved left ventricular ejection fraction. • The worse GLS was an independent risk factor over GCS, GRS, traditional CMR features, and clinical features for predicting major adverse cardiovascular events in patients with ICI-associated myocarditis.

Real-world clinical outcomes of left main percutaneous coronary intervention in diabetic patients at a long-term follow-up

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Coronary artery disease in diabetic patients has more aggressivity and tends to be a more complex disease characterized by small, diffuse, calcified, multivessel involvement that it presents higher in-stent restenosis rates after percutaneous coronary intervention (PCI). Besides, left main coronary artery (LMCA) disease has poor prognosis and it usually associates more severe lesions in other coronary arteries. Currently, the PCI in LMCA disease in these patients is controversial. Purpose The main objective of this study was to evaluate the efficacy and safety of PCI in LMCA disease in diabetic patients at a 14-year follow-up. Methods We prospectively included 228 consecutive patients (71 ± 11 years, 70.2% male) with LMCA disease treated with PCI between June 2006 and June 2020. We evaluated the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death, nonfatal myocardial infarction, target lesion revascularization (TLR) and stent thrombosis after a 14-year clinical follow-up (median 66 months). Results 53.1% of patients had stable coronary disease and 46.9% acute coronary syndrome (42.1% Non-STEMI and 4.8% STEMI). 40.3% of patients presented moderate-severe left ventricular systolic dysfunction. 63.6% had LMCA and ≥ 2 vessels disease and 43% had a SYNTAX score ≥ 33. Mean Logistic Euroscore was 7.2%. The most frequent bifurcation technique employed in LMCA was "provisional stenting" in 65.4% and zotarolimus-eluting stent was used in 75.8% of cases. Angiographic success rate was 99.6% and complication rate intra-procedure was 3.1% without intraoperative death. During follow-up, MACE rate at 14 years was 19.8% (14.4% of cardiac death, 6.6% of nonfatal myocardial infarction, 5.7% of TLR and thrombosis rate 0.4%). Higher MACE rate was significantly associated to left ventricular systolic dysfunction (p=0.04) and chronic kidney insufficiency (p=0.02). 22.2% of patients had angiographic follow-up. Conclusions PCI on LMCA in diabetic patients is safe and effective, with low complication rate and a low rate of long-term follow-up events. Left ventricular systolic dysfunction and chronic kidney insufficiency showed a significantly worse outcome.

The prognostic implications of ST-segment and T-wave abnormalities in patients undergoing regadenoson stress SPECT myocardial perfusion imaging

BackgroundThe prognostic implications of ST-segment and T-wave (ST/T) abnormalities in patients undergoing stress SPECT-myocardial perfusion imaging (MPI) are not well defined. Methods and ResultsThis was a single-center, retrospective cohort study of consecutive patients who underwent regadenoson stress SPECT-MPI. Patients with baseline electrocardiogram (ECG) abnormalities that impede ST/T analysis or those with known coronary artery disease were excluded. Patients were categorized as having primary ST abnormalities, secondary ST/T abnormalities due to ventricular hypertrophy or right bundle branch block, T-wave abnormalities, or normal ECG. The primary outcome was major adverse cardiovascular events (MACE) defined as the composite of cardiac death or myocardial infarction. Among 6,059 subjects, 1912 (32%) had baseline ST/T abnormalities. During a mean follow-up of 2.3 ± 1.9 years, the incidence of MACE was significantly higher among patients with secondary ST/T abnormalities compared to those with normal ECG (HR 2.05; 95% confidence interval [CI], 1.04-4.05; P = 0.039). No significant difference in MACE was observed among patients with primary ST abnormalities (HR 1.64; CI 0.87-3.06; P = 0.124) or T-wave abnormalities (HR 1.15; CI 0.62-2.16; P = 0.658) compared with patients who had normal ECG. Among patients with secondary ST/T changes, abnormal MPI was not associated with a significant increase in MACE rates compared to normal MPI (HR 1.18; CI 0.31-4.58; P = 0.808). However, abnormal MPI was associated with higher MACE rates among patients with primary ST abnormalities (HR 4.50; CI 1.44-14.10; P = 0.005) and T-wave abnormalities (HR 3.74; CI 1.20-11.68; P = 0.015). Similarly, myocardial ischemia on regadenoson stress SPECT-MPI was not associated with a significant increase in MACE rates in patients with secondary ST/T abnormalities (HR 1.45; CI 0.38-5.61; P = 0.588), while it was associated with a higher incidence of MACE in patients with primary ST abnormalities (HR 3.012; CI 0.95-9.53; P = 0.049) and T-wave abnormalities (HR 5.06; CI 1.60-15.96; P = 0.002). ConclusionWhile patients with secondary ST/T abnormalities had significantly higher MACE risk, abnormal MPI or presence of myocardial ischemia on regadenoson SPECT-MPI in this group does not add prognostic information. Patients with primary ST abnormalities and T-wave abnormalities do not seem to have a significantly higher MACE risk compared to those with normal ECG; however, abnormal MPI or presence of myocardial ischemia, in these groups, correlates with higher MACE rates.

Use and outcomes of dual antiplatelet therapy for acute coronary syndrome in patients with chronic kidney disease: insights from the Canadian Observational Antiplatelet Study (COAPT).

Chronic kidney disease (CKD) increases the risk of adverse outcomes in acute coronary syndrome (ACS). The optimal regimen of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) in CKD poses a challenge due to the increased bleeding and clotting tendencies, particularly since patients with CKD were underrepresented in randomized controlled trials. We examined the practice patterns of DAPT prescription stratified by the presence of CKD. The multicentre prospective Canadian Observational Antiplatelet Study (COAPT) enrolled patients with ACS between December 2011 and May 2013. The present study is a subgroup analysis comparing type and duration of DAPT and associated outcomes among patients with and without CKD (eGFR < 60ml/min/1.73m2, calculated by CKD-EPI). Patients with CKD (275/1921, 14.3%) were prescribed prasugrel/ticagrelor less (18.5% vs 25.8%, p = 0.01) and had a shorter duration of DAPT therapy versus patients without CKD (median 382 vs 402days, p = 0.003). CKD was associated with major adverse cardiovascular events (MACE) at 12months (p < 0.001) but not bleeding when compared to patients without CKD. CKD was associated with MACE in both patients on prasugrel/ticagrelor (p = 0.017) and those on clopidogrel (p < 0.001) (p for heterogeneity = 0.70). CKD was associated with increased bleeding only among patients receiving prasugrel/ticagrelor (p = 0.007), but not among those receiving clopidogrel (p = 0.64) (p for heterogeneity = 0.036). Patients with CKD had a shorter DAPT duration and were less frequently prescribed potent P2Y12 inhibitors than patients without CKD. Overall, compared with patients without CKD, patients with CKD had higher rates of MACE and similar bleeding rates. However, among those prescribed more potent P2Y12 inhibitors, CKD was associated with more bleeding than those without CKD. Further studies are needed to better define the benefit/risk evaluation, and establish a more tailored and evidence-based DAPT regimen for this high-risk patient group.

Prediction of Reperfusion Outcome using Platelet Indices in Primary Percutaneous Coronary Intervention- A Prospective Cohort Study

Introduction: Platelets play a vital role in systemic inflammation and thrombus formation in ST Elevation Myocardial Infarction (STEMI). Understanding its role has diagnostic and prognostic implications in developing therapeutic strategies. Aim: To estimate the prognostic accuracy of platelet indicesMean Platelet Volume (MPV), Platelet Distribution Width (PDW) and MPV/Platelet Count (PC) Ratio (MPV/PC ratio) on reperfusion outcome in STEMI patients. Materials and Methods: This prospective cohort study enrolled 262 subjects, who presented with acute chest pain within a window period of 12 hours, and an Electrocardiogram (ECG) suggestive of STEMI. Blood samples collected on admission were measured for MPV and PDW. The major endpoints studied were angiographic thrombus burden and in-hospital Major Adverse Cardiovascular Events (MACE). Data was summarised by Mean and SD for continuous variables, frequency and percentage for categorical variables. Results: This study demonstrated that Acute Coronary Syndrome- STEMI (ACS-STEMI) patients with larger PDW had Larger Thrombus Burden (LTB). PDW of more than 13 fL was the best cut off for predicting LTB with a sensitivity of 67.01% and a specificity of 53.23%. There was no significant difference between the means of MPV in LTB and small thrombus burden. The total in-hospital MACE at the end of one week was 20.99% (n=55/262 patients). The maximum MACE was contributed by acute heart failure (12.6%), followed by cardiac death (6.1%) and stent thrombosis (1.5%). There was a significant association between increased PDW and in-hospital MACE, mortality and acute heart failure (p-value=0.024, p-value=0.03, p-value=0.02, respectively). The best cut-off PDW value for prediction of the composite MACE endpoint was 14.7 fL with sensitivity of 75.6% and specificity of 51.4% and the area under the Receiver Operating Characteristic (ROC) curve was 0.63 (95% CI, 0.57 to 0.69). Conclusion: The study emphasises the use of platelet indices, especially PDW, as a predictor of poorer reperfusion outcomes in primary Percutaneous Coronary Intervention (PCI) as evidenced by higher MACE rates in patients with higher PDW. Hence, PDW can help in predicting the thrombus burden even before doing the angiogram and such high-risk patients could benefit from early initiation of stronger antiplatelets, Gp IIb/IIIa (Glycoprotein) antagonist drugs and thrombus aspiration techniques.

New-onset atrial fibrillation in chronic coronary syndrome outpatients: Insights from the international CLARIFY registry

Although the association of atrial fibrillation (AF) and coronary artery disease is a growing public health concern, data in patients with chronic coronary syndrome (CCS) is scarce. We aimed to describe the incidence rate and predictors of new-onset AF in CCS outpatients as well as its association with major adverse cardiovascular events (MACE) using a large-scale registry. The international ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease (CLARIFY), provides real-world data from 32,703 outpatients with CCS from 45 countries. Our analysis included 29,001 patients without prior AF at baseline. Over the median 5-year follow-up, 1453 (5%) had a new-onset AF diagnosed with an annual incidence rate of around 1%. Independent predictors of AF were increased age, treated hypertension, history of peripheral artery disease and an alcohol intake ≥ 1 drink per week. Left ventricular ejection fraction value and a high triglyceride level were independent predictors of lower new-onset AF rate. As rhythmic status was a variable that changed during follow-up, incident AF was included as a time-varying covariate in the Cox regression model. Compared to CCS patients without AF, those with new-onset AF had a higher rate of MACE, including the composite endpoint of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, hazard ratio (HR) 2.52 (95% CI 2.11-3.01); cardiovascular death, HR 3.22 (2.63-3.94); stroke, HR 2.80 (2.01-3.91); all cause death, HR 2.64 (2.23-3.11); hospitalization for heart failure, HR 9.38 (8.02-10.97); major bleeding, HR 4.33 (2.94-6.39), P < 0.001 for each and myocardial infarction, HR 1.55 (1.08-2.22), P < 0.016 ( Table 1 , Fig. 1 ). New-onset AF is strongly associated with the risk of MACE and should be considered as a prognostic turning point in CCS patients. Many predictors have been identified which presence should lead to broader screening for arrhythmias in CCS patients.

Proteomics profiling reveals distinct molecular subtypes of hypertrophic cardiomyopathy with differential risks of major adverse cardiovascular events

Abstract Background Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease, and a subset (10–15%) of patients per year experience major adverse cardiovascular events (MACE). Current risk prediction models based solely on clinical data have yielded limited power in predicting MACE. Although the diagnosis of HCM is made based on clinical features, the heterogeneity of HCM suggests that “HCM” may actually encompass several subtypes of disease with distinct biological mechanisms that can only be elucidated via molecular-level investigation. Proteomics profiling measures concentrations of thousands of proteins simultaneously and has the potential to reveal underlying molecular mechanisms of disease and distinct subtypes of HCM. Purpose Our aim was to derive distinct subtypes of HCM in our multi-center biorepository of patients with HCM using proteomics profiling, and to examine their associations with MACE. Methods We applied unsupervised machine learning methods to derive HCM molecular subtypes using plasma proteomics profiling data from 258 patients in our multi-center HCM prospective cohort study. The primary outcome was MACE, defined as a composite of arrhythmias, progressive heart failure, stroke, and sudden cardiac death. We performed time-to-event analysis with a Cox proportional hazards model, using the subtype with the lowest risk as the reference group. We also performed pathway analysis of proteins differentially regulated in patients in the highest-risk subtype. Results We identified 4 distinct HCM subtypes. Patients in subtype D (n=74) were older on average compared to the other groups and more likely to be female. 50% of patients in subtype D had NYHA class II or greater heart failure symptoms compared to 37% in the rest of the groups combined. There were no significant differences in echocardiographic parameters or rates of genotype positivity between the four subtypes. Compared to the reference group (i.e., subtype A), patients in subtype D had a higher rate of MACE with a hazard ratio of 2.59 (95% CI 1.21–5.57, p=0.01 compared to subtype A; Figure). Pathway analysis identified significantly upregulated signaling pathways in the high-risk subtype D compared to the other subtypes (Table), with a number of upstream and downstream pathways associated with the Ras-MAPK pathway (FDR 0.0005). Conclusions Our study exhibits not only the presence of HCM molecular subtypes but also their distinct pathobiological mechanisms associated with different MACE risks. The four subtypes identified bore similar clinical characteristics and would not have been distinguishable based on the conventional analysis of clinical and echocardiographic parameters alone, but rather required deeper investigation at the molecular level. Furthermore, pathway analysis revealed an upregulation of Ras-MAPK pathways in the subtype with the highest risk of MACE, implicating this pathway as a potential underlying mechanism of more severe disease. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NIH

Sex-specific differences in total ischemic time coincide with similar cardiovascular outcome in patients with acute coronary syndrome: a Swiss multicentre cohort study

Abstract Background Previous studies showed prolonged patient and system delay in female patients with acute coronary syndromes (ACS) which is thought to be a major driver of discrepancies in their cardiovascular (CV) outcomes. Indeed, timely management is particularly important in patients with ST-segment elevation myocardial infarction (STEMI), as increased total ischemic time augments infarct size and relates to poor CV survival. However, contemporary evidence on sex-specific differences in ACS management and discrepancies in outcomes is limited and controversial. Purpose We sought to systematically investigate whether a sex-gap in symptom-to-door (STD), door-to-balloon (DTB)/door-to-PCI (DTP) time exists in a prospective ACS cohort and if such differences translate into different rates of major adverse cardiovascular events (MACE) at one year. Methods From 2009 to 2019, 4'930 ACS patients with a main diagnosis of NSTEMI (43.3%), STEMI (53.3%) or unstable angina (3.4%) were enrolled in the multicentre, prospective SPUM-ACS study of which 4'671 completed follow-up at one year. STD, DTB and DTP time was analyzed. The primary endpoint, a composite measure of all-cause death, nonfatal myocardial infarction, nonfatal stroke and ischemia-driven revascularization, was adjudicated by an independent clinical endpoint committee. Kaplan-Meier and multivariate-adjusted Cox proportional hazard regression models were used for time-to-event analyses. Results A total of 1'019 (20.7%) women and 3'911 (79.3%) men with a main diagnosis of ACS were included in the study. At presentation, women were older (69.6±12.0 vs. 62.2±12.1 years, P&amp;lt;0.001), more likely to have impaired renal function (median, 81.2 vs. 89.2 ml/min/1.73m2, P&amp;lt;0.001) and a history of hypertension (63.9% vs. 54.3%, P&amp;lt;0.001). STD time was significantly higher in female STEMI (median, 3.2 vs. 2.5 hours, P&amp;lt;0.001) and NSTEMI patients (median, 7.0 vs. 5.0 hours, P=0.015). Importantly, DTB time did not differ between sexes in STEMI patients (1.0 vs. 1.0 hour, P=0.430). Similarly, DTP time of female NSTEMI patients was comparable to males (4.3 vs. 4.4 hours, P=0.855). In the entire cohort, female ACS patients did not show a higher occurrence of the primary endpoint at one year (crude HR 0.86, 95% CI 0.72–1.04; adjusted HR 0.83, 95% CI, 0.66–1.05). In a multivariate-adjusted subgroup analysis, neither female STEMI (adjusted HR 0.82, 95% CI 0.59–1.15) nor NSTEMI patients (adjusted HR 0.87, 95% CI 0.61–1.24) showed higher hazards for the primary endpoint compared to male patients. Conclusions Women with a main diagnosis of STEMI show considerably higher prehospital delay, thus prolonged total ischemic time which is mainly driven by increased STD time. Intriguingly, this does not translate into higher rates of MACE compared to men at one year. Women with ACS may particularly benefit from measures aimed at reducing prehospital delay, as this may further improve long-term prognosis after the acute event. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Swiss National Science Foundation - SNFFoundation for Cardiovascular Research - Zurich Heart House

USE AND OUTCOME OF DUAL ANTIPLATELET THERAPY FOR ACUTE CORONARY SYNDROME IN PATIENTS WITH CHRONIC KIDNEY DISEASE: INSIGHTS FROM THE CANADIAN OBSERVATIONAL ANTIPLATELET STUDY (COAPT), A MULTICENTRE PROSPECTIVE COHORT STUDY

<h3>BACKGROUND</h3> Chronic kidney disease (CKD) increases the risk of adverse outcomes in acute coronary syndrome (ACS). The optimal regimen of dual antiplatelet therapy (DAPT) post percutaneous coronary intervention (PCI) is challenging due to both increased bleeding and thrombotic risks in patients with CKD, particularly since these patients were under-represented in randomized controlled trials. We examined the patterns of DAPT use in ACS patients post PCI stratified by presence of CKD. <h3>METHODS AND RESULTS</h3> The multi-centre prospective Canadian Observational Antiplatelet Study (COAPT) enrolled patients with an ACS diagnosis from 43 hospitals between December 2011-May 2013. The present study is a subgroup analysis comparing type and duration of DAPT, and associated outcomes among patients with and without CKD defined as eGFR < 60 ml/min/1.73m2 (calculated by CKD-EPI). COAPT enrolled 1921 patients (mean age: 61; 21.4% female) with a median eGFR of 85 ml/min/1.73 m2 (25th and 75th percentiles [69, 97]). Of those, 275 (14.3%) had CKD. CKD patients were older, more likely to be female and have comorbidities including previous ACS, heart failure, hypertension, cerebrovascular disease, atrial fibrillation and gastrointestinal bleeding. Patients with CKD were less frequently prescribed the more potent P2Y12 inhibitors prasugrel/ticagrelor (18.5% vs 25.8%, p=0.01) and had a shorter duration of DAPT therapy than patients without CKD (median 382 vs 402 days, p=0.003). CKD was associated with major adverse cardiovascular events (MACE) at 12 months (p < 0.001) but not bleeding when compared to patients without CKD (figure 1). CKD was associated with MACE in both patients on prasugrel/ticagrelor (p=0.017) and those on clopidogrel (p < 0.001) (p for heterogeneity=0.70). CKD was associated with increased bleeding only among patients receiving prasugrel/ticagrelor (p=0.007), but not among those receiving clopidogrel (p=0.64) (p for heterogeneity=0.036). Patients with CKD were more frequently considered to have an ongoing indication for DAPT therapy during follow-up. Discontinuation of DAPT was more likely in patients with CKD due to the need for an oral anticoagulant. <h3>CONCLUSION</h3> Patients with CKD had a shorter DAPT duration and were less frequently prescribed potent P2Y12 inhibitors than patients without CKD. Overall, compared with patients without CKD, patients with CKD had higher rates of MACE and similar bleeding rates. However, among those prescribed more potent P2Y12 inhibitors, CKD was associated with more bleeding than those without CKD. Further studies are needed to better define the benefit/risk ratio, and establish a more tailored and evidence-based DAPT regimen for this high-risk patient group.

Effect of diabetic kidney disease on therapeutic strategies for coronary artery disease: ten year follow-up.

Background: The best treatment for coronary artery disease (CAD) in patients with type 2 diabetes (DM2) and chronic kidney disease is unknown.Methods: This retrospective study included MASS registry patients with DM2 and multivessel CAD, stratified by kidney function. Primary endpoint was combined of mortality, myocardial infarction, or additional revascularization.Results: Median follow-up was 9.5 years. Primary endpoint occurrences among strata 1 and 2 were 53.4% and 40.7%, respectively (P=.020). Mortality rates were 37.4% and 24.6% in strata 1 and 2, respectively (P<.001). We observed a lower rate of major adverse cardiovascular events (MACE) (P=.027 for stratum 1 and P<.001 for stratum 2) and additional revascularization (P=.001 for stratum 1 and P<.001 for stratum 2) for those in the surgical group. In a multivariate analysis, eGFR was an independent predictor of MACE (P=.034) and mortality (P=.020).Conclusions: Among subjects with DM2 and CAD the presence of lower eGFR rate was associated with higher rates of MACE and mortality, irrespective of treatment choice. CABG was associated with lower rates of MACE in both renal function strata. eGFR was an independent predictor of MACE and mortality in a 10-year follow-up.