Risk Of Cardiac Events Research Articles

Pharmacogenomic evaluation of CYP2C19 alleles linking low clopidogrel response and the risk of acute coronary syndrome in Indians.

Clopidogrel is an antiplatelet drug widely prescribed to prevent atherothrombotic events in coronary artery disease patients. However, there is evidence to suggest that the effectiveness of clopidogrel varies owing to genetic diversity in CYP2C19. This heterogeneity in South Asians, who are also known to have high risk of cardiac events than other population groups, highlights the importance of investigating CYP2C19 variants to estimate the risk proportion in the groups. Given the high prevalence and genetic heterogeneity, the population-based case control was conducted in a cohort of 1191 subjects comprising 645 acute coronary syndrome (ACS) cases (unstable angina, ST-elevation myocardial infarction, and non-ST-elevation myocardial infarction) and 546 healthy controls of South Asian Indian origin. The metabolization status of CYP2C19 was assessed using *2, *3 and *17 variants in the stated cohorts to determine the prevalence of metabolization and its association with phenotypes. The results suggest a possible genetic association between studied CYP2C19 polymorphisms and ACS, since there was a higher proportion of intermediate and poor metabolizers present in the studied cohorts. The association analyses revealed that the *2 allele of CYP2C19 confers a significant risk for ACS, while the *17 allele provides protection. These findings contribute to the understanding of CYP2C19 genetic variants and their impact on clopidogrel response in South Asian Indians. Additionally, they underline the significance of assessing CYP2C19 variations in patients receiving clopidogrel therapy in order to improve therapeutic outcomes.

Cost-effectiveness of systematic screening and treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) in patients with heart failure with preserved ejection fraction (HFpEF) in United States

BackgroundTransthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure in clinical practice. 99mTc-pyrophosphate scintigraphy (PYP-scan) improves the accuracy of ATTR-CM detection, enabling timely initiation of tafamidis, a drug that slows the progression of ATTR-CM and lowers the risk of adverse cardiac events. PYP-scans, serum free light-chain (FLC) test and immunofixation electrophoresis (IFE) are critical components of a systematic screening. We assessed the cost-effectiveness of universal systematic screening (USS) compared to standard-of-care (SoC) selected clinical referrals for the systematic screening in patients aged 60 years or older with heart failure with preserved ejection fraction (HFpEF) and ventricular wall thickness of at least 12 mm. MethodsTwo screening strategies, USS versus SoC screening for ATTR-CM were compared in a model-based assessment. Treatment decisions were based upon the accuracy of each screening strategy, which was followed by Markov state transitions across New York Heart Association (NYHA) functional classes and death. Model inputs were identified from a literature review. We calculated lifetime cost in 2022 US dollars and quality adjusted life-years (QALYs) of each strategy. The primary outcome was the incremental cost-effectiveness ratio (ICER). ResultsThe USS was associated with a significant increase in lifetime costs ($124,380 vs. $70,412) and modest improvement in QALYs (4.42 QALYs vs 4.36 QALYs). The ICER for the USS was $919,509 per QALY gained. ICER was sensitive to the age at the time of ATTR-CM diagnosis, true prevalence rate of ATTR-CM, and daily cost of tafamidis. ConclusionsOwing to the high cost of treatment with tafamidis, USS along with PYP scan for ATTR-CM in older HFpEF patients with ventricular wall thickening is unlikely to become a cost-effective strategy at a liberal WTP threshold.

Efficacy of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Treatment for Repeated In-stent Restenosis in a Coronary Artery.

A 57-year-old woman experienced chest pain. A coronary angiogram revealed middle left anterior descending artery stenosis. Despite receiving adequate anti-hyperlipidemia treatment and undergoing percutaneous coronary intervention (PCI), she experienced angina and required PCI six more times for in-stent restenosis. As she had high lipoprotein (a) (LP-[a]) levels at the seventh PCI procedure, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) was administered, and a reduction in the LP-(a) and low-density lipoprotein cholesterol (LDL-C) values was observed. She experienced no recurrence of angina for five years with PCSK9i treatment. PCSK9i can reduce not only LDL-C but also LP-(a) levels, resulting in cardiac event risk reduction.

The Association of Incidental Radiation Dose to the Heart Base with Overall Survival and Cardiac Events after Curative-intent Radiotherapy for Non-small Cell Lung Cancer: Results from the NI-HEART Study

AimsCardiac disease is a dose-limiting toxicity in non-small cell lung cancer radiotherapy. The dose to the heart base has been associated with poor survival in multiple institutional and clinical trial datasets using unsupervised, voxel-based analysis. Validation has not been undertaken in a cohort with individual patient delineations of the cardiac base or for the endpoint of cardiac events. The purpose of this study was to assess the association of heart base radiation dose with overall survival and the risk of cardiac events with individual heart base contours. Materials and methodsPatients treated between 2015 and 2020 were reviewed for baseline patient, tumour and cardiac details and both cancer and cardiac outcomes as part of the NI-HEART study. Three cardiologists verified cardiac events including atrial fibrillation, heart failure and acute coronary syndrome. Cardiac substructure delineations were completed using a validated deep learning-based autosegmentation tool and a composite cardiac base structure was generated. Cox and Fine–Gray regressions were undertaken for the risk of death and cardiac events. ResultsOf 478 eligible patients, most received 55 Gy/20 fractions (96%) without chemotherapy (58%), planned with intensity-modulated radiotherapy (71%). Pre-existing cardiovascular morbidity was common (78% two or more risk factors, 46% one or more established disease). The median follow-up was 21.1 months. Dichotomised at the median, a higher heart base Dmax was associated with poorer survival on Kaplan–Meier analysis (20.2 months versus 28.3 months; hazard ratio 1.40, 95% confidence interval 1.14–1.75, P = 0.0017) and statistical significance was retained in multivariate analyses. Furthermore, heart base Dmax was associated with pooled cardiac events in a multivariate analysis (hazard ratio 1.75, 95% confidence interval 1.03–2.97, P = 0.04). ConclusionsHeart base Dmax was associated with the rate of death and cardiac events after adjusting for patient, tumour and cardiovascular factors in the NI-HEART study. This validates the findings from previous unsupervised analytical approaches. The heart base could be considered as a potential sub-organ at risk towards reducing radiation cardiotoxicity.

Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane + anthracycline versus taxane-based chemotherapy regimens: A SEER-medicare study

BackgroundTriple-negative breast cancer (TNBC) is more aggressive as compared to other subtypes of breast cancer with characteristic metastatic patterns and a poor prognosis. The standard of care for early-stage TNBC is historically anthracycline and taxane-based chemotherapy (ATAX). Despite the effectiveness of this regimen, anthracyclines carry a small but important risk of cardiotoxicity, which is specifically a concern in the older population. This study evaluates major adverse cardiovascular events (MACE) in older women with TNBC treated with ATAX compared to taxane-based chemotherapy (TAX). MethodsUsing the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified women aged 66 and older with TNBC diagnosed between 2010 and 2015 (N = 2215). We compared patient and clinical characteristics according to adjuvant chemotherapy regimen (chemotherapy versus no chemotherapy and ATAX versus TAX). Logistic regression was performed to estimate the odds ratios (OR) and 95% confidence intervals (CIs), Kaplan-Meier survival curves were generated to estimate three-year overall survival (OS) and cancer specific survival (CSS). Cox proportional hazards models were used to analyze OS and CSS while controlling for patient and tumor characteristics. MACE was defined as acute myocardial infarction, heart failure, potentially fatal arrhythmia, and cerebral vascular incidence. Few patients experienced a cardiac death and therefore this was excluded in the analysis. ResultsOf the 2215 patients in our cohort, most patients (n = 1334; 60.26%) received TAX compared to ATAX (n = 881; 39.78%). Patients who received ATAX were not statistically significantly more likely than those who received TAX to experience acute myocardial infarction, cerebral vascular accident (CVA), or potentially fatal arrhythmia when controlling for traditional risk factors. Among patients who experienced MACE, there was no difference in OS or CSS in patients who received TAX vs ATAX. Patients who received ATAX were less likely to develop heart failure than those who received TAX (OR 0.63, 95% CI [0.45–0.88], p < 0.01). Patients who developed MACE and who were > 76 years old had worse OS compared to those who experienced MACE and were age 66–75 years old (HR 1.67, 95% CI [1.07–2.62], p = 0.02). ConclusionAmong older women with TNBC, receipt of adjuvant chemotherapy with ATAX was not associated with increased risk of major adverse cardiac events. For those who experienced a cardiac event, there was no difference in survival amongst those who received TAX vs ATAX. Other factors including additional chemotherapy toxicities should be investigated as a potential etiology for the inferior OS previously observed with ATAX vs TAX in older women with node negative or 1–3 positive lymph nodes.

Cardiac events after using clarithromycin for anti-Helicobacter pylori therapy in patients with coronary artery disease.

Clarithromycin is an antibiotic commonly used to treat Helicobacter pylori infections. The US Food and Drug Administration (FDA) advises caution before prescribing clarithromycin to patients with cardiac diseases. This study aimed to evaluate cardiac events after anti-H pylori treatment in patients with coronary artery disease. A retrospective 5-year study was conducted on outpatients who received anti-H pylori therapy. Among the 7855 patients receiving therapy, 228 patients (2.9%) underwent angiography with coronary artery disease before therapy, and 193 patients received clarithromycin. Clarithromycin users seemed not to be at risk for cardiac events as compared with non-clarithromycin users at 3 months (4.7% vs 2.9%, P = .63) and 1 year (10.9% vs 5.7%, P = .35). Neither life-threatening dysrhythmia nor cardiac death was noted. The risk factors for cardiac events within 3 months after therapy were smoker (OR:5.38, 95% CI:1.39-20.78), and events within 1 year were smoker (OR:3.8, 95% CI:1.41-10.22), and diabetes mellitus (OR:5.68, 95% CI:1.9-16.98). Among patients with coronary artery disease who received anti-H pylori therapy, short-term cardiac events did not increase in clarithromycin users but should be considered in diabetic and smoking patients.

Asthma and the risk of cardiac events among patients with long QT Syndrome after age 40

Abstract Background The effect of asthma on the clinical course of long QT syndrome (LQTS) in the middle and old age population has not been studied. Purpose The present study was designed to investigate the association between asthma comorbidity, β2-agonist treatment and cardiac events among LQTS subjects after age 40 years. Methods The risk of cardiac events (comprising syncope, aborted cardiac arrest, implantable defibrillator shock, or sudden cardiac death) from age 40 through 75 years, by the presence of asthma and time-dependent β2-agonist use was assessed among 1020 LQTS patients from the LQTS Registry. Results Asthma was identified in 162 (16%) study patients and 63% of asthma patients received β2-agonist inhalers. Patients with asthma vs. no asthma had a higher cumulative rate of cardiac events during follow-up (44% vs. 26%, respectively; p&amp;lt;0.001 [Figure: left panel]). Consistently, multivariate analysis demonstrated that asthma was a powerful predictor of cardiac events with an associated 2-fold (HR=1.97, p=0.001) increased risk for cardiac events as compared to patients with no asthma. β2-agonist inhalers use was associated with a similar increased risk for cardiac events (HR =1.90, p=0.035) among all study patients (Figure: right panel]). Subgroup analysis did not show a statistically significant difference in the association of asthma with cardiac events by risk subsets of LQTS patients, including QTc duration, syncope prior to age 40 years, beta-blocker use, sex, and the LQTS genotype (all p-values for risk subset-by-asthma interaction &amp;gt;0.10). Conclusion The presence of asthma and β2-agonist treatment are associated with an increased risk of cardiac events among middle and old age patients with LQTS.

Progression of definite and non-definite Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) and risk of major adverse cardiac events

Abstract Background In patients with Arrhythmogenic right ventricular cardiomyopathy (ARVC, also called"Arrhythmogenic Cardiomyopathy"), it is a challenge to predict those at greatest risk of major adverse cardiac events (MACE). Our hypothesis is that risk of arrhythmia may be preceded by change in ventricular structure and function. Purpose To assess the association between change in ventricular structure and function over time and risk of (MACE) in ARVC. Methods 101 definite and non-definite ARVC patients (defined as per Revised Task Force criteria (TFC)) were included with at least two sequential echocardiography and ECGs between 2010 and 2022. Structural progression was defined as development of new 2010 TFC on echocardiography during follow-up. MACE were defined as ventricular fibrillation (VF), sustained ventricular tachycardia (Sus VT), appropriate implantable cardio-defibrillator (ICD) therapy (shock/anti-tachycardia pacing (ATP)), heart failure, cardiac transplantation and death. Results Of the 101 patients, 51 had a definite diagnosis of ARVC, and 50 had a non-definite ‘early’ diagnosis, of whom a total of 66 (68%) carried a pathogenic variant associated with ARVC. Most were male 58 (57%), and the median age at presentation was 39 years (IQR: 27 - 53). Palpitations 41 (41%) and syncope 25 (25%) were the most common symptoms at baseline. 21 (23%) of the entire population were engaged in competitive exercise. At baseline, 22/101 (22%) patients presented with MACE, in which 20 (91%) definite patients met either minor or major imaging criteria at inclusion. During 4 years follow up (IQR: 2 – 6), 22 patients experienced MACE, in which 11 with history of MACE and 11 without, of those (15 (68%)) had structural progression. Additionally, 9 patients had structural progression of which 5 patients had history of MACE and no second event during follow up and 4 patients had no MACE at baseline or during follow up. Results showed that the odds of structural progression were significantly higher in patients with MACE than without (Table 1). Conclusion Structural progression was strongly associated with MACE events. This finding raises the possibility that tracking change over time identifies those patients at greatest risk of arrhythmia, with significant changes in right ventricular measurements.

Predictability of noninvasive liver fibrosis score for cardiac events in patients with nonalcoholic fatty liver disease

Abstract Background Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. Although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events. Purpose To investigate the relationship between noninvasive liver fibrosis score and the future risk of cardiac events. Methods Among 13,368 patients with NAFLD diagnosed using ultrasonography, 4,071 patients were evaluated. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index (cut-off value of 1.30 and 2.67) and NAFLD fibrosis score (NFS) (cut-off values of -1.455 and 0.676), respectively. The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease. Results The median age of the evaluated patients was 61 [52–69] years, and 2,201 [54.1%] were male. After a median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan–Meier survival analysis demonstrated that MACE increased progressively with theFIB4 index (log-rank, p &amp;lt; 0.001) and NFS (log-rank, p &amp;lt; 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (compared to the group [reference] with low FIB4 index values, hazard ratio [HR] was 1.860 for the group with intermediate FIB4 index values [95% confidence interval (CI), 1.326–2.610; p&amp;lt;0.001] and 3.325 for the group with high FIB4 index values [95% CI, 2.017–5.479; p&amp;lt;0.001]), and the higher the NFS, the higher the risk for MACE (compared to the group [reference] with low NFSvalues, HR was 1.938 for the group with intermediate NFS values [95% CI, 1.391–2.699; p&amp;lt;0.001] and 3.492 for the group with high NFSvalues [95% CI, 1.997–6.105; p&amp;lt;0.001]). Conclusions The FIB4 index and NFS impacted the predictability of MACE in patients with NAFLD.Kaplan–Meier analysis for MACE

Peak VO2 and VE/VCO2 exhibit differential prognostic capacity for predicting cardiac events

Abstract Background Cardiopulmonary exercise testing (CPET) are commonly used to assess the functional capacity of patients with heart failure. While both peak oxygen uptake (VO2) and ventilatory efficiency (VE/CO2) are significant prognostic factors in heart failure, their values may not always be concordant. Methods This retrospective study included 688 patients who underwent both CPET and supine bicycle echocardiography (SBE) simultaneously. The primary endpoint of the study was defined as heart failure hospitalization or cardiac death. The patients were categorized into subgroups based on their VO2 and VE/VCO2 slope values. Results After median follow-up of 89 months, 111 (16.4%) patients developed cardiac events. The mean age and ejection fraction were 58 years and 59%. In multivariate analysis, both VO2 and VE/VCO2 remained powerful predictors of cardiac events after adjusting for age, ejection fraction, baseline or exercise E/e’, and peak TR velocity. Subgroup analysis revealed that Group III (VO2 &amp;gt;20 and VE/VCO2 &amp;gt;30) and IV (VO2 &amp;lt;20 and VE/VCO2 &amp;gt;30) had a significantly higher risk of cardiac events, with hazard ratios of 3.38 (CI 1.36-8.40) and 8.40 (CI 3.86-18.34), respectively, compared to Group I (VO2 &amp;gt;20 and VE/VCO2 &amp;lt;30). Group II (VO2 &amp;lt;20 and VE/VCO2 &amp;lt;30) had a non-significantly increased risk of cardiac events with a hazard ratio of 2.04 (CI 0.80-5.21) compared to Group I (Fig). Conclusion Both VO2 and VE/VCO2 slope were found to be excellent predictors of cardiac events in patients who underwent CPET and SBE. However, there is a slight difference between the two parameters, and poorer ventilatory inefficiency was found to be more associated with a worsened prognosis. The study suggests that the risk stratification using the VE/VCO2 slope and peak VO2 values can provide valuable information for clinicians in managing patients with heart failure.

Association between sarcopenia and risk of major adverse cardiac and cerebrovascular events-UK Biobank database.

Few studies on the risk of incident major adverse cardiac and cerebrovascular events (MACCEs) in sarcopenia have been reported. The objective was to assess the association between presarcopenia and sarcopenia and a higher risk of MACCEs. This study on the UK Biobank prospective cohort, used data collected between 2006 and 2021. Community-dwelling Caucasian participants aged 37 to 73 years were included if values for Handgrip Strength (HGS) and Skeletal Muscle Index (SMI) were available and if no history of MACCEs was reported. Exposure was assessed using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Muscle strength was measured using HGS, and muscle mass using the SMI. Presarcopenia was defined through the two definitions available in the literature, as low HGS with normal SMI and as normal HGS with low SMI, whereas sarcopenia was defined as low HGS with low SMI. The main outcome was to determine whether presarcopenia and/or sarcopenia were predictors of MACCEs (composite events). A total of 406,411 included participants (women: 55.7%) were included. At baseline, there were 18,257 (4.7%) presarcopenics-subgroup n°1 (low HGS only), 7940 (2.1%) presarcopenics-subgroup n°2 (low SMI only), and 1124 (0.3%) sarcopenics. Over a median follow-up of 12.1 years (IQR: [11.4; 12.8]), 28,300 participants (7.0%) were diagnosed with at least one event. Compared to NonSarc, presarcopenic (subgroups n°1 and n°2) and sarcopenic status were significantly associated with a higher risk of MACCEs (respectively fully adjusted HRs: HR = 1.25 [95% CI: 1.19; 1.31], HR = 1.33 [95% CI: 1.23; 1.45] and HR = 1.62 [95% CI: 1.34; 1.95]). In a community-dwelling population, the risk of MACCEs was higher in both presarcopenic and sarcopenic participants.

Association of physical activity with the risk of major adverse cardiac and cerebrovascular events and mortality in patients with concomitant atrial fibrillation and coronary artery disease

Abstract Background Although regular physical activity benefits cardiovascular health, there is a concern that intense exercise is linked to the promotion of atrial fibrillation (AF) and coronary plaque rupture. However, the impact of physical activity on the outcomes of patients with concomitant AF and coronary artery disease (CAD) remains unclear. Purpose This study aimed to evaluate the association with clinical outcomes according to the level of physical activity in patients with concomitant AF and CAD. Methods We assessed 551 patients with AF and CAD (mean age, 67.1±9.8 years) who completed a self-reported questionnaire for physical activity from 2015 to 2020 in a single tertiary-care hospital. Physical activity levels were converted into metabolic equivalent of task (MET) per week and categorized to correspond with multiple public health recommendations. We examined the association between physical activity, all-cause mortality, and major adverse cardiac and cerebrovascular events (MACCE). Results The risks of all-cause mortality (P for linear trend=0.017) and MACCE (P for linear trend=0.05) were appeared inverse trend with a greater level of physical activity. Compared with inactive patients, patients who met the recommended target range of physical activity (500–1,000 MET-min/week: unadjusted hazard ratio [HR]=0.58, 95% confidence interval [CI]=0.36–0.99) and highly active patients who exceeded the minimum recommended level (≥1,000 MET-min/week: unadjusted HR=0.47, 95% CI=0.25–0.88) had a lower risk of all-cause mortality in the unadjusted model; however, these associations did not remain significant after adjusting for the model. There was no evidence of increased risk of all-cause mortality and MACCE at levels of physical activity above the recommended target range, even with vigorous intensity physical activity exceeding the recommended target range. Conclusions There appears to be an inverse trend between physical activity levels and all-cause mortality and MACCE in patients with concomitant AF and CAD. No excess risk of mortality or MACCE was found at exercise levels above the recommended target range. Further large-scale studies are warranted to create an improved evidence base concerning the effects of physical activity in patients with AF and CAD.

Cardiorespiratory Fitness and Risk of Cardiovascular Events and Mortality in Middle Age Patients without Known Cardiovascular Disease.

Low cardiorespiratory fitness is an established risk predictor for chronic non-communicable diseases. We aimed to investigate the prognostic significance of fitness level on the risk of major adverse cardiac events (MACE, the composite of myocardial infarction, stroke, or all-cause death), in a contemporary cohort of middle-aged subjects without cardiovascular disease. Retrospective analysis of patients aged 40-60 years without a history of cardiovascular disease. Degree of fitness was determined according to a graded, maximal treadmill exercise stress testing (EST) time achieved, classified into age- and sex-specific quintiles (Q), and categorized as low (Q1), moderate (Q2-Q4) or high (Q5) fitness groups. A multivariable Cox proportional hazard regression model was used to assess the association of fitness level with the risk of MACE. A total of 6836 patients were included, of which 44.5% were women, and the mean age was 52 years. Overall, 289 MACE events occurred during a median follow-up of 7 years. Level of fitness was inversely associated with the presence of cardiovascular risk factors. The multivariable adjusted hazard ratio (95% confidence interval) for MACE was 1.65 (1.12-2.44) and 2.17 (1.40-3.38) in those at moderate and low fitness levels, compared to the high-fitness group (reference), respectively. For each decrease of one metabolic equivalent (MET) unit achieved at peak exercise, the relative risk for MACE increased by 18%. The association between low fitness and MACE was not modified by other risk factors (P-for-interaction non-significant). Low fitness level, as captured by a maximal treadmill EST, is an independent risk predictor for MACE among middle-age individuals without known cardiovascular disease. The association of low fitness with high burden of cardiometabolic risk factors highlight the importance of lifestyle intervention in this patient population.

Major adverse cardiovascular events in patients with ECG changes during dipyridamole infusion as a myocardial stress agent and normal MPI among filipino patients at a tertiary hospital

Abstract Introduction There is paucity and conflicting results of data regarding the prognostic significance of ST-segment depression during vasodilator stress testing in patients with normal myocardial perfusion imaging (MPI). It is even less well studied in minorities such as Filipino population. Purpose This study aims to determine the major adverse cardiovascular events (MACE) in patients with ECG changes during dipyridamole infusion as a myocardial stress agent and normal myocardial perfusion imaging. Methodology We performed a cross-sectional retrospective analysis of 266 adult patients aged 18 years and above who underwent dipyridamole MPI. Patients with abnormal baseline ECG, patients subjected to tests other than the Dipyridamole VST and those with missing clinical, electrocardiogram, or myocardial perfusion Imaging data were excluded. The primary endpoint was the composite MACE: of all-cause mortality, nonfatal MI, stroke, hospitalization because of heart failure, and revascularization. Results Among 226 included patients (mean age ‘61.11 + 10.72’ years; 58% women), those with ST segment depression &amp;gt;0.5mm were more likely to have MACE (OR 281.12; 95% CI 37.59 to 2101.82, p-value &amp;lt;0.001), female patients were more likely to have MACE compared to male patients (OR 2.1839; 95% CI 1.1373 to 4.1936; p-value 0.019), and patients with atypical type of chest pain were likely to have MACE (OR 2.1767; CI 1.1844 to 4.0003; p-value 0.012). During follow-up of 3 years, a total of 55 patients had MACE. All-cause mortality occurred in 3 patients, non-fatal MI in 40 patients, Hospitalization due to heart failure in 5 patients, stroke in 6 patients, and revascularization in 1 patient. Conclusion Dipyridamole-induced ischemic ST depression is more common in women, and is associated with increased risk for future cardiac events compared with similar patients without ECG evidence of ischemia. Ischemic ECG changes during dipyridamole MPI should warrant further evaluation and follow up, even when perfusion images are reassuring.

Coronary artery disease and the risk of life-threatening cardiac events after age 40 in long QT syndrome

Abstract Background Long QT syndrome (LQTS) and coronary artery disease (CAD) are both associated with increased risk of ventricular tachyarrhythmia. However, there are limited data on the incremental risk conferred by CAD in adult patients with congenital LQTS. Objective We aimed to investigate the risk associated with CAD and life threatening events (LTEs) in patients with LQTS after age 40 years. Methods The risk of LTEs (comprising aborted cardiac arrest, sudden cardiac death, or appropriate defibrillator shock) from age 40 through 75 years was examined in 1020 subjects from the Rochester LQTS registry, categorized to CAD (n=137) or no-CAD (n=883) subgroups. Results Survival analysis showed that patients with CAD had a significantly higher rate of LTEs from 40 through 75 years (35%) compared with those without CAD (7%; p&amp;lt;0.001 for the overall difference during follow-up [figure]). Consistently, multivariate analysis showed that the presence of CAD was associated with a 2.5-fold (HR=2.47; p=0.02) increased risk of LTEs after age 40 years. Subgroup analyses showed that the presence of CAD vs. no CAD was associated with a pronounced &amp;gt;4-fold (p=0.008) increased risk of LTEs among LQTS patients with a lower-range QTc (&amp;lt;500 msec). The increased risk of LTEs associated with CAD was not significantly different among the 3 main LQTS genotypes. Conclusions Our findings suggest that CAD is associated with incremental risk of life threatening cardiac events in patients with LQTS. The incremental risk associated with the presence of CAD is pronounced in lower risk LQTS patients with QTc&amp;lt;500 msec.

The electrophysiological substrate of biopsy-proven cardiac amyloidosis

Abstract Background Cardiac amyloidoses (CA) are an increasingly recognized group of infiltrative cardiomyopathies associated with high risk of major adverse cardiac events. Endomyocardial biopsy (EMB) may be required to differentiate the amyloid type (mainly, Immunoglobulin light chain [AL] versus transthyretin-related [ATTR]) in some cases. Purpose The aim of this study was to provide the first description of the right ventricular (RV) electroanatomical substrate of CA, and assess its association with EMB findings and clinical outcomes. Methods We enrolled ten consecutive patients undergoing EMB for suspected CA (median age, 68[63-77]; male, 50%) in a monocentric, observational, retrospective study. All patients had a clinical diagnosis of CA, but a diagnosis of CA type was hampered by the presence of inconclusive or discordant laboratory-imaging findings (abnormal serum free light chain assay and positive bone scintigraphy, n=5; ambiguous imaging results, n=4; abnormal serum free light chain assay and TTR gene mutation, n=1). Therefore, each patient underwent RV high-density electroanatomical voltage mapping (EVM) and EMB. The primary outcome was death or hospitalization at 1-year follow-up. We recorded electrogram features at EMB sampling sites and in the overall RV, and explored their correlations with histopathological findings and primary outcomes events. Results A final EMB-proven diagnosis of AL or ATTR CA was formulated in 6 and 4 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.58±0.65 mV, and 5.38±1.41 in the overall RV. We found a significant inverse correlation between unipolar electrogram amplitude and amyloid burden at EMB (p&amp;lt;0.001); the unipolar voltage cutoff that best identified regions with &amp;gt;15% amyloid tissue infiltration according to Youden index was 9.1 mV (sensitivity, 43%; specificity, 100%; accuracy, 77%). At 1-year follow-up, 6 patients (60%) experienced a primary outcome event. Compared to subjects with uneventful follow-up, patients with a primary outcome event had larger unipolar low-voltage zones (32.3 [6.1] cm2 vs. 20.7 [6.5] cm2, p=0.043) and bipolar dense scar areas (6.1 [2.3] cm2 vs. 1.8 [0.7] cm2, p=0.005), and after pooling mapping points from all patients, unipolar electrogram amplitude was moderately associated with primary outcome events (AUC: 0.65 [95% CI, 0.64-0.65]). Conclusions In CA, electrogram amplitudes are around the lower limit of normal, yet disproportionately low compared to the increased wall thickness. We found evidence that unipolar electrogram amplitude may be a quantitative marker of amyloid burden, possibly associated with adverse clinical outcomes.EVM and EMB in ATTR cardiac amyloidosisEVM and EMB in AL cardiac amyloidosis

Atherogenic lipid profile in patients with acute coronary syndrome

Abstract Background Adverse atherogenic lipid profile is associated with an increased risk of major adverse cardiac events in patients with acute coronary syndrome (ACS). Objective To evaluate the control status of atherogenic lipid profile among ACS patients within 12 months after discharge. Methods We retrospectively analyzed the data from the multi-center iHeart program. Twenty tertiary hospitals in China were included. Natural language processing technique was used to extract real-world data from electronic health records (EHRs). Patients with a diagnosis of ACS from January 2014 to December 2021 during index hospitalization and having at least one medical record after discharge within 12 months were enrolled. Measurements of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non–high-density lipoprotein cholesterol (non-HDL-C), triglycerides (TGs), apolipoprotein B (ApoB), lipoprotein (a) (Lp[a]) at baseline and follow-up were collected and analyzed. Remnant cholesterol (RC) was calculated as TC minus HDL-C minus LDL-C. The treatment goal of LDL-C was defined as &amp;lt;1.8 mmol/L according to the guideline. An even lower LDL-C goal of &amp;lt;1.4 mmol/L was recommended in specific patients at extremely high risk with concomitant diabetes or ischemic cerebral vascular diseases. Results Among the 3956 patients, the mean age was 72 (12) years, and 64.8% were men. Diabetes was common (22.7%). There were 1612 (40.7%) patients with unstable angina, 391(9.9%) patients with non-ST-elevation myocardial infarction, 1146 (29.0%) patients with ST-elevation myocardial infarction, and 807 (20.4%) patients with undetermined ACS category. At baseline, the mean values for TC, LDL-C, HDL-C, non-HDL-C, ApoB, and RC were 4.61 (1.26) mmol/L, 2.83 (0.98) mmol/L, 1.12 (0.30) mmol/L, 3.38 (0.75) mmol/L, 96 (34) mg/dL, and 0.65 (0.56) mmol/L, respectively. The median values for TGs and Lp(a) were 1.44 mmol/L [1.06, 2.00] and 27.22 mg/dL [12.34, 39.2], respectively. The rate of lipid-lowering treatment was 94.8% (statins 93.1%, PCSK9 inhibitors 0.4%). The levels of TC, TGs, LDL-C, HDL-C, non-HDL-C, and ApoB were significantly decreased (P &amp;lt; 0.001) within 12 months. Median Lp(a) was 19.52 mg/dL [8.73, 39.08] (P = 0.117). Mean RC was 0.69 (1.10) mmol/L (P &amp;lt; 0.001). Overall, the proportion of patients achieving the LDL-C level of &amp;lt;1.8 mmol/L at baseline increased from 13.42% to 36.6% during follow-up. In patients with concomitant diabetes or ischemic cerebral vascular diseases, the rate of LDL-C &amp;lt;1.4 mmol/L was 17.79% and 17.52%, respectively. Conclusion Only 1/3 of patients had LDL-C &amp;lt;1.8mmol/L within 12 months after ACS. Despite the high treatment rate of statins, Lp(a) level had no change beyond the reduction in LDL-C. Elevated remnant cholesterol may be a critical contributor to residual risk. Novel therapeutics targeting the whole atherogenic lipid profile will be warranted to improve cardiovascular outcomes.LDL-C control rate within 12 months

Machine learning-based prediction of 30-day major adverse cardiac and cerebrovascular events in non-cardiac surgery patients

Abstract Background The number of non-cardiac surgeries performed worldwide has been steadily increasing, presenting a challenge for clinicians to accurately identify patients at high risk of complications and to allocate the appropriate level of perioperative care. Accurate prediction of postoperative mortality is crucial not only for successful patient care, but also for information-based shared decision-making with patients and efficient allocation of medical resources. Purpose In this study, we aimed to develop a novel predictive model using machine learning methods applied to electronic health record data. Our objective is to identify the risk factors most likely to lead to 30-day major adverse cardiac and cerebrovascular events after non-cardiac surgery Methods We conducted a retrospective analysis of data from a single tertiary care institution that included patients aged 65 years or over who underwent non-cardiac surgery from May 2003 and December 2020. The Observational Medical Outcomes Partnership (OMOP) common data model (CDM) data was used to build predictive models, which allowed for the utilization of demographic data, as well as preoperative characteristics such as diagnosis, lab results, vital signs, medications, and information on operations and procedures from the electronic health records (EHRs) in a standardized way. We employed machine learning models, which were developed and validated using the OHDSI Patient-Level-Prediction framework. Results We included a total of 47,915 patients to train (75%) and test (25%) our predictive models. To compare prediction performances, we applied gradient boosting machine (GBM), logistic regression (LR), random forest (RF), AdaBoost (AB), and decision tree (DT). Our results for a test data (Fig 1.) showed that the GBM model had the best performance in terms of the area under the receiver operating characteristic curve (AUROC) (0.903) and the area under the precision-recall curve (AUPRC) (0.395). Conclusions Our study demonstrates that applying machine learning algorithms to electronic health record data can effectively identify patients at high risk of major adverse cardiac and cerebrovascular events following non-cardiac surgery. This algorithm has the potential to support clinicians in effectively identifying patients at high risk and provide appropriate perioperative care. Further work is needed to validate and refine the proposed model to ensure its external validity and broader applicability in clinical practice.We plan to validate the proposed model externally by testing it on a cohort of approximately 280,000 patients from other tertiary care institution, and present the results at the 2023 ESC Congress.

Exercise ECG and myocardial perfusion SPECT show high prognostic value up to four years after examination

Abstract Background Abnormal results of myocardial perfusion SPECT (MPS) or exercise ECG (Ex-ECG) is known to be associated with increased risk of ischemic cardiac events. The predictive value of stress testing however, is influenced by underlying risk factors as well as follow up duration and may vary considerably over time. With traditional Cox proportional hazards analysis the time-varying effects are not sufficiently accounted for. Purpose To evaluate the prognostic longevity of MPS and Ex-ECG using statistical methods that allow hazard ratio changes over time. Methods 908 patients (age 63 years, 49% male, 45% prior ischemic heart disease (IHD)) referred for MPS were prospectively included. Ex-ECG was performed in conjunction with MPS. Registry data were used for follow up. The outcome was a composite of acute myocardial infarction, unstable angina, unplanned revascularization, and cardiovascular death. Cox proportional hazard analysis and smoothed hazard functions with splines were used for risk assessment during follow up. Results Ex-ECG or MPS were abnormal in 198 (22%) or 148 (16%) of patients respectively. The mean follow up time was 8.2±2.6 years and the composite end point was reached in 189 patients (21%). The Kaplan-Meier curves suggest an interaction with time with the risk of event for subjects with abnormal test results being highest in the 2-3 of years after which the curves are approximately parallel (Figure 1). In multivariable models the best fit (lowest Akaike information criterion (AIC) value) was obtained with a logarithmic interaction term for time. With this approach and controlling for known risk factors the hazard ratio (HR) drops to 1 after approximately four years for both Ex-ECG and MPS (Figure 2). Age (HR=1.04, p&amp;lt;0.001), sex (HR=2.0, p&amp;lt;0.001), IHD (HR=1.7, p&amp;lt;0.001) and reduced exercise capacity (HR=0.99, p&amp;lt;0.001) were independent significant predictors of risk. Conclusions The high risk associated with abnormal MPS and Ex-ECG results decrease rapidly over time and after approximately 4 years the predictive value is lost. Thus, the long-term impact on prognosis of stress testing appear questionable. The time-varying effects on risk are substantial and warrant statistical considerations when designing clinical follow up studies of chronic coronary syndrome.

The prognostic impact of follow-up cardiac Metaiodobenzylguanidine imaging: relation to differential trajectories in left ventricular ejection fraction after acute decompensation

Abstract Background Cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with heart failure (HF). Recently, the trajectory of left ventricular ejection fraction (LVEF) has been focused in patients with reduced LVEF admitted for acute decompensated heart failure (ADHF). We sought to prospectively investigate the prognostic value of the follow-up cardiac MIBG imaging in ADHF patients with reduced LVEF, in relation to LVEF trajectory. Methods We prospectively studied 145 ADHF patients with reduced LVEF&amp;lt;40%. The cardiac MIBG heart-to-mediastinum ratio (late HMR) was measured on the delayed image at the discharge and 6 months’ follow-up (6FUP). HF recovered LVEF (HFrecEF) was defined as those with a second measurement of LVEF at 6FUP of ≥ 40% with a 10-point increase from baseline LVEF, according to the previous report. Furthermore, in the present study, HFrecEF was classified into the two groups; patients with partial recovery of LVEF (≥40%, &amp;lt;50%) (HFparEF) and complete recovery of LVEF (≥50%) (HFcorEF). The endpoint was a cardiac event (CE) defined as a composite of cardiac death and unplanned hospitalization for worsening HF. Results At 6 months after the discharge, HFrecEF was observed in 97 (67%) of 145 study patients and the remaining 48 (33%) patients did not have HFrecEF (HFnorEF). In the subgroup of HFrecEF, 43 (30%) patients had HFparEF and 54 (37%) patients had HFcorEF. Late HMR at 6FUP in HFcorEF patients was significantly greater than those in HFparEF and HFnorEF patients, which was also observed at the discharge with non-significant difference. The change of late HMR significantly correlated with the improvement in LVEF (r=0.33, p&amp;lt;0.001). During a follow-up period of 4.3 ± 2.6 years, 28 patients in HFnorEF, 11 patients in HFparEF and 4 patients in HFcorEF had CEs, respectively. Kaplan-Meier analysis revealed that HFnorEF patients had a significantly higher risk of cardiac events than those with HFparEF and HFcorEF. (58.3% vs 25.6% vs 7.4% P &amp;lt; 0.0001). Patients with lower late HMR at 6FUP had a greater risk of CEs than those with higher late HR at 6FUP in HFrecEF, especially in HFparEF, which was not observed in HFnorEF subgroup. Conclusion The follow-up MIBG imaging after the discharge could provide the additional prognostic information in ADHF patients with recovered LV function.