Risk Of Cardiac Events Research Articles

Multicenter analysis to assess risk of major adverse cardiac events in patients undergoing high-sensitivity troponin testing in the emergency department.

Our objective was to evaluate 30-day major adverse cardiac events (MACE) in emergency department (ED) patients with normal high-sensitivity troponins (hs-trop). We hypothesized that MACE rates would be<1% in patients with (1) two normal troponins regardless of change in troponin (delta) and (2) index hs-trop below the limit of quantitation (LOQ) regardless of the institution modified HEART score. This was a multicenter, retrospective, cohort study of adult patients who presented to 1 of 18 EDs between July 2020 and April 2021 with acute coronary syndrome as defined by an institutional-modified HEART score completed by their treating physician or midlevel, no evidence of ST-elevation myocardial infarction, and an index or serial gender-adjusted hs-trop within normal limits. The primary outcome was MACE within 30 days of index ED encounter. A detailed case review was then performed for those patients experiencing a MACE. Of the 9084 patients who had single or serial normal troponins, 31 (0.34%; confidence interval [CI] 0.23%-0.48%) experienced MACE. Of the 6140 patients with 2 normal hs-trop and a delta (change in troponin)<4, 27 patients (0.44%; CI 0.29%-0.64%) experienced MACE. Only 1 of the 69 patients with 2 normal hs-trop results but delta (change in troponin) ≥ 4 (1.45%; CI 0.04%-7.81%) suffered MACE. This patient was classified as non-low risk by our institutional HEART score. Of 7498 patients with an index hs-trop<LOQ, 14 (0.19%; CI 0.10%-0.31%) experienced MACE, with 57% (N=8) deemed non-low risk by HEART score. Patients with 2 normal hs-trop values in the ED are unlikely to suffer 30-day MACE. Although it remains unclear whether patients with delta (change in troponin) ≥4 despite normal troponins will have a 30-day MACE, this situation is rare. Additionally, a single index hs-trop<6ng/L demonstrated a low risk for 30-day MACE independent of the institutional HEART score.

Perioperative myocardial infarction: An anesthesiologist’s nightmare!

Abstract An acute ST elevation myocardial infarction (STEMI) in the perioperative period can be challenging. Effective cardiopulmonary resuscitation with multidisciplinary support systems including percutaneous coronary intervention within the recommended times enhances recovery and outcomes. We present a case of a young patient who developed STEMI despite being a low risk for intraoperative major adverse cardiac events.

Does Dual Anti-HER2 Therapy Increase Early Cardiac Toxicity in Comparison with Trastuzumab Alone in Breast Cancer Patients Receiving Adjuvant Radiotherapy? A Multicenter Retrospective Study

Adjuvant trastuzumab in combination with RT has proved its safety in terms of cardiac events. Dual anti-HER2 therapy with pertuzumab is currently standard adjuvant therapy in N+ and high-risk N0 early breast cancer (BC) patients. Our study aims to find if it increases early cardiac toxicity compared with trastuzumab alone in BC patients receiving adjuvant radiotherapy. Operable BC patients who received adjuvant radiotherapy (RT) and trastuzumab with or without pertuzumab between January 2017 and September 2020 in 7 Chinese centers were retrospectively reviewed. The cardiac examination included ultrasonography, electrocardiogram (ECG), NT-proBNP, and cTnI before RT and during follow-up. The cardiac event was any new-onset symptomatic heart disease or abnormality in the cardiac examination after RT. In total, 711 patients with a median age of 52 years were included, of whom 567 (79.7%) patients were treated with trastuzumab-only and 144 (20.3%) patients received dual anti-HER2 therapy. Adjuvant RT was given concurrently in 140/144 (97.2%) of dual anti-HER2 therapy and 562/567 (99.1%) of trastuzumab alone, respectively. With a median follow-up of 11 months, no patients developed symptomatic heart diseases. Among patients with normal baseline, 17 (2.4%), 86 (12.1%), 18 (2.5%) and 14 (7.3%) developed new-onset diastolic dysfunction, left ventricular ejection fraction (LVEF) decline, abnormal ECG, and abnormal NT-proBNP, respectively. No significant difference was found between the trastuzumab-only and dual anti-HER2 cohort in the incidence of all kinds of new-onset cardiac events (all p > 0.1). Multivariate analysis showed that left-sided (vs right-sided) RT significantly increased the risk of ECG abnormality (HR = 2.32, 95% CI 1.62-3.32, p<0.001). Increased age was an independent risk factor for diastolic dysfunction (HR = 1.1, 95% CI 1.02-1.18, p = 0.0098). Dosimetric analysis showed that patients who developed any cardiac events had increased mean heart dose (397.67±251.08 vs 344.87±236.75 cGy, p = 0.032). A significant increase in risk of cardiac events was found in patients with mean heart dose > 450 cGy (HR = 1.55, 95% CI 1.17-2.05, p = 0.0024), V5 > 26% (HR = 1.51, 95% CI 1.09-2.09, p = 0.013), and V30 > 5.5% (HR = 1.49, 95% CI 1.09-2.04, p = 0.0117), respectively. Further analysis was done in the subgroup of patients treated with left-sided RT, internal mammary nodes RT, or anthracyclines, no difference in risk of cardiac events was found between trastuzumab alone and dual anti-HER2 therapy in concurrent with RT (all p > 0.05). Compared with trastuzumab-only, dual anti-HER2 therapy does not increase early cardiac toxicity in combination with adjuvant RT in BC patients. Cardiac radiation exposure remains the primary risk factor associated with early cardiac toxicity.

Simulation CT Features and Radiation Cardiotoxicity in Non-Small Cell Lung Cancer

Radiation cardiotoxicity is a significant clinical dilemma in non-small cell lung cancer (NSCLC) radiation therapy (RT). Baseline cardiovascular (CV) status may influence the risk of cardiotoxicity, and may be ascertainable from the appearance of the heart on simulation computed tomography (CT). We examined the association of CT features with incidental heart dose and risk of cardiac events in NSCLC. Patients treated with curative-intent RT between 2015 and 2020 at a regional center were identified. Clinical notes were interrogated for baseline patient and CV health details, and follow-up CV events. Cardiac events were verified by a cardiologist. A deep learning-based auto-segmentation tool was applied, allowing extraction of a pre-specified list of volume parameters in a programming environment. CAC was graded as none, mild, moderate and severe in patients with a non-contrast scan. The craniocaudal relationship of the PTV and heart (Feng atlas) were annotated. A total of 478 patients were included, with a median age of 70 and Charlson Index of 5. The median mean heart dose was 6.3 Gy (IQR 2.7-11.4). The median lung V20 was 20.0% (IQR 14.8-27.1). Cardiovascular risk factors were common, with most patients having 2 (39%) or 3 (31%). A history of previous cardiac events was common, including myocardial infarction (14%), arrhythmia (11%) or heart failure (9%). A total of 6.9% and 7.1% patients developed a new atrial arrhythmia (AA) or heart failure (HF) after completing RT. The volume metrics with the highest AUC for AA and HF events were the left atrium (LA) (AUC 0.67, p = 0.0002) and left ventricle:right ventricle (LV:RV) ratio (AUC 0.66, p = 0.0021). Kaplan-Meier analysis for cardiac events dichotomizing at the optimal cut-point for maximum sensitivity and specificity demonstrated significantly different rates for both AA (LA 109cc, HR 3.35, 95% CI 1.64-6.83, p = 0.0009) and HF (LV:RV ratio 1.61, HR 2.37, 95% CI 1.19-4.74, p = 0.0143). Only 2 patients with non-contrast scans developed a myocardial infarction, both had mild CAC. The incidence of pooled cardiac events was not significantly different between patients with no (n = 2/21, 9.5%), mild (n = 10/38, 26.3%), moderate (n = 8/53, 15.1%) and severe (n = 7/24, 29.2%) CAC (p = 0.3916). Where the inferior border of the PTV was above the superior border of the heart, mean heart dose was significantly lower than compared with overlap of levels (1.9 Gy v 9.7 Gy, p<0.0001), and this was true for 3DCRT (n = 139, p<0.001), IMRT (n = 94, p<0.001) and VMAT (n = 145, p<0.001) patients. LA volume and LV:RV volume ratio are predictive for the development of AA and HF respectively. CAC grade did not differentiate patients by risk of cardiac events. Where the craniocaudal level of the PTV doesn't overlap with the level of the heart, the cardiac dose is likely to be very low. Several simulation CT features are associated with cardiac events following treatment for NSCLC and prospective evidence of cardiac risk could enable medical optimization prior to RT.

Early Cardiotoxicity in Patients Receiving Hypofractionated Radiotherapy after Breast Conserving Surgery: Analysis of a Prospective Study

To evaluate the early cardiotoxicity of hypofractionated radiotherapy (HFRT) in patients with left-sided breast cancer after breast-conserving surgery, and to investigate the correlation between cardiotoxicity and cardiac dose. A total of 103 women from 2017 to 2018 who received left-sided whole-breast with or without regional nodal irradiation either using deep inspiration breath-hold (DIBH) or free-breathing (FB) technique were prospectively enrolled. N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiogram, and radionuclide myocardial perfusion imaging were conducted before and after HFRT. Logistic regression analyses were performed to determine the association of cancer treatment, cardiac dose, and cardiovascular risk factors with cardiotoxic effects. The mean dose (Dmean) of the heart, left anterior descending coronary artery (LAD), left ventricular (LV), and right ventricular (RV) in all patients was 403 cGy, 1685 cGy, 627 cGy, and 444 cGy, respectively. In comparison to FB, DIBH significantly reduced cardiac dose (heart Dmean 250 cGy vs. 570 cGy, LAD Dmean 1250 cGy vs. 2170 cGy, LV Dmean 420 cGy vs. 850 cGy, RV Dmean 260 cGy vs. 650 cGy; all p<0.001). With a median follow-up of 49 months (range, 2-65 months), no patients had clinical cardiac abnormalities or cardiac-related symptoms, but 42 (41%) patients had subclinical cardiac events. Among them, 41 were electrocardiogram changes, and one had LV ejection fraction decreased by 10% compared with the baseline level. Twenty-five (60%) recovered during follow-up, of which 17 (40%) experienced subclinical changes only once. The mean value of NT-proBNP did not change significantly before and after HFRT. In univariate analyses, DIBH technique significantly decreased the risk of subclinical cardiac events compared with FB (OR 0.31, 95% CI 0.14-0.71; p = 0.006); however, higher mean doses of heart and LV, anthracycline-based chemotherapy, obesity, and hypertension were associated with increased risk of subclinical cardiac events (all p<0.05). Early subclinical cardiac damage after HFRT in left-sided breast cancer is dose-related, and mostly manageable and reversible without medical intervention.

Convolution Neural Network-Based Automatic Scoring of Coronary Artery Calcification and Its Value to Identify the Risk of Radiation-Induced Cardiac Toxicity on Radiotherapy Planning CT Scans in Breast Cancer Patients

To develop an automatic scoring of coronary artery calcification (CAC) on breast cancer radiotherapy (RT) planning computed tomography (CT) scans, and to explore its predictive value of CAC for radiation-induced cardiac toxicity. Planning CT scans of 668 breast cancer patients from two prospective clinical trials (NCT02942615, NCT03829553) were retrospectively reviewed. In total, 34 CTs containing CAC were identified. The training and test samples were 29 and 5, respectively. We proposed a two-stage model for CAC segmentation task with nnU-Net as backbone. The segmentation results were processed by threshold extraction and region growth algorithm. We also employed transfer learning to automatically identify calcification of left anterior descending artery (LAD), right coronary artery (RCA), left circumflex artery (LCX), and left main coronary artery (LM) based on a public dataset of 430 cases from Stanford University. The data of cardiac examination of these 34 patients before and during the follow-up after RT were collected. The cardiac event was any symptomatic heart disease or new-onset abnormality in the cardiac examination after RT. The mean dice coefficients (DSC) and 95% Harsdorf distance (95HD) of test samples were 0.992 and 0.599 mm, respectively. The mean absolute error (MAE) of CAC Angaston score between ground truth (GT) and predictions was 0.532. The detailed consistency parameters of 5 test samples were shown in Table 1. After 1:2 propensity score matching (PSM), 21 patients had CAC and 42 patients had no CAC were selected. The number of patients with CAC scores of 1 to 10, 11 to 100, and greater than 100 was 10, 9 and 2, respectively. During median follow-up of 9.2 months (range, 1-42.7), 90.5% and 38.1% of patients in CAC cohort and no CAC cohort developed cardiac event (p<0.001). Patients with CAC had significantly increased cardiac events (HR = 2.4; 95% CI, 1.22-4.75; p = 0.0117). The risk of cardiac events increased with CAC scores ([HR]1-10 = 2.1, 95% CI 0.9-4.9; [HR]11-100 = 2.5, 95% CI 1.0-5.9; [HR]>100 = 4.0, 95% CI 0.9-17.4). Our primary results showed that this two-stage segmentation model is capable of achieving automatic CAC scoring which might assist to predict the risk of post-RT cardiac events in breast cancer patients.

The Impact of Tumor Location on Cardiac Toxicity in Patients Receiving Partial Breast Irradiation

Accelerated partial breast irradiation (APBI) is an appropriate modality for select women with low-risk breast cancer. While APBI delivers radiation dose to a smaller volume of breast tissue compared to whole breast irradiation, dose to the heart and coronary vessels may be relatively high, depending on the proximity of the tumor bed to these structures. The purpose of this study is to determine if there is a correlation between tumor location and risk of adverse cardiac events in women receiving APBI. This retrospective study included 341 women who received ABPI from 1993 to February 2017 at a single institution. APBI was delivered by catheter-based high-dose-rate (HDR) brachytherapy via single lumen or multi-channel devices (n = 340), or external beam brachytherapy (n = 1). Neither the heart nor cardiac substructures were contoured for patients receiving APBI with HDR brachytherapy. Univariate analysis (UVA) and multivariable analysis (MVA) were conducted to correlate patient age, smoking status, Charlson Comorbidity Index score (CCI), receipt of systemic therapy, and tumor location (right outer, right inner/central, left outer, left inner/central) with subsequent cardiac events. Univariate analyses for patient age, smoking status, CCI, receipt of systemic therapy, and tumor location in correlation to subsequent cardiac events were performed. On UVA, age at diagnosis and CCI score ≥2 were both significant with HR of 1.07 [1.05-1.10] (p<0.001) and HR of 7.02 [3.22-15.3] (p<0.001), respectively. On MVA, age at diagnosis and CCI score ≥2 remained significant with HR of 1.06 [1.03-1.09] (p = <0.001) and HR of 4.56 [2.02-10.40] (p = <0.001), respectively. There was a trend of statistically significant correlation between cardiac events and left inner/central tumor location when compared to right outer tumor location with a HR of 2.06 [1.00,4.24] (p = 0.05). Treatment of tumor beds located in the inner/central portion of the left breast may increase the risk of developing cardiac toxicity in patients receiving APBI. These data support careful contouring and avoidance of cardiac structures during APBI treatment planning, including HDR brachytherapy.

Nonadherence to ticagrelor versus clopidogrel and clinical outcomes in patients with ACS. Results from the CREA-ARIAM registry

Introduction and objectivesPrior studies have not determined whether the effect of dual antiplatelet therapy (DAPT) cessation on the subsequent risk of major adverse cardiac events (MACE) varies by the choice of P2Y12-inhibitor after acute coronary syndrome (ACS). MethodsWe performed a prespecified subanalysis of a multicenter, prospective registry of ACS patients discharged on ticagrelor or clopidogrel between 2015 and2019. Nonadherence to DAPT was categorized as physician-guided discontinuation and disruption due to adverse effects, nonadherence, or bleeding. The association between DAPT cessation and 1-year MACE was analyzed using multivariate time-updated Cox models with inverse probability of censoring weighted estimators. ResultsOut of 2180 patients, 174 (8.3%) prematurely discontinued DAPT (physician-guided, n=126; disruption, n=48). Nonadherent patients were older and had more comorbidities than those on DAPT. Compared with physician-guided discontinuation, disruption occurred earlier after discharge and was more frequent with ticagrelor than with clopidogrel. In time-varying analysis, DAPT cessation was associated with an increased risk of MACE (adjusted HR, 1.32, 95%CI, 1.10-1.76), largely driven by disruption (adjusted HR, 1.47, 95%CI, 1.22-1.73). There was an exponential increase in MACE risk after DAPT cessation within 90 days after ACS, especially after disruption of ticagrelor compared with clopidogrel (Pinteraction<.001). After adjustment for DAPT duration, this interaction was not statistically significant on the additive scale (relative excess risk due to interaction 0.12, 95%CI,−0.99-1.24). ConclusionsIn this all-comers registry, 1 in 12 patients prematurely discontinued DAPT within 1 year after ACS. Compared with physician-recommended discontinuation, disruption resulted in a significantly higher risk of MACE. After adjustment for DAPT duration, this association was not moderated by the choice of P2Y12-inhibitor.Clinical trial registered at ClinicalTrials.gov (Identifier: NCT02500290)

Association of Left Anterior Descending Coronary Artery Calcium Progression and Radiation Dose with Major Adverse Cardiac Events in Breast Cancer

Coronary artery calcium (CAC) is associated with increased risk of major adverse cardiac events (MACE). Accelerated CAC progression has been observed in patients with breast cancer after radiotherapy (RT) and there is a relationship between left anterior descending (LAD) coronary artery RT dose and the risk of coronary events. However, there is lack of consensus on LAD dose constraints for breast RT and limited data on the extent and impact of CAC progression. Our objective was to evaluate the association of LAD dose exposure and CAC progression with the risk of MACE in patients with breast cancer following RT. Retrospective analysis of 181 patients with breast cancer treated with RT between 2008 and 2019. CAC was manually measured on RT planning and follow-up CTs (with at least one-year interval) using the Agatston method. Coronary arteries were segmented using a deep learning-based automated algorithm and dosimetric parameters collected. MACE cumulative incidence was estimated, and Fine and Gray regressions performed, accounting for non-cardiac death as a competing risk. The median follow-up following RT was 70 months (interquartile range [IQR], 53-86). The median age was 63 years (IQR, 53-72), 43% had hypertension, 40% hyperlipidemia, 8% coronary heart disease (CHD). Most had pathologic stage I-II disease (76%). RT was targeted to breast/chest wall only in 60% and included regional nodes in 40% (internal mammary chain in 4%). The most common dose/fractionation was 48-50.4 Gy/25-28 fractions (67%) and 42.6-42.7 Gy/16 fractions (30%). At the time of RT, 68 (38%) had at least moderate CAC burden (CAC >100; statin-therapy indicated), but only 29 (43%) were on statin therapy. At a median interval of 44 months (IQR, 26-63), 55% (n = 84) had CAC progression, with a median increase of 52%/year (IQR, 18-193). The median time to MACE was 68 months (IQR, 53-85), with a 5-year cumulative incidence of 7.3% (15 MACE overall). Accounting for age and CHD, there was an increased risk of MACE with LAD CAC progression (subdistribution hazard ratio [SHR] 1.02/10 CAC points; 95% confidence interval [CI] 1.01 = 1.03; p = .007) and the volume of LAD receiving 15 Gy (LAD V15 Gy; SHR 1.03/%; 95% CI, 1.01-1.06; p = .004). There was no association between mean heart dose, chemotherapy, or Her2 therapy exposure and MACE (p>.05). LAD CAC progression and LAD V15 Gy dose exposure were associated with an increased risk of MACE following RT. Accelerated CAC progression was commonly observed, however most patients were under-optimized for cardiovascular (CV) risk, with less than half of statin-eligible patients with at least moderate CAC burden on statin therapy. Together, these data support more aggressive cardiac risk mitigation approaches, including guidelines-based CV risk factor modification and optimized sparing of LAD radiation dose.

The Impact of Cardiac Sparing Techniques on Major Cardiac Events for Patients Undergoing Breast Radiotherapy

In radiotherapy, studies with historical estimates have shown a linear relationship between cardiac dose and risk of major cardiac events with no safe dose threshold. This study investigates the relationship between cardiac dose and event rates for patients undergoing breast radiotherapy with modern heart-sparing techniques, where substantially lower cardiac doses are achieved. From 2008 to 2018, all patients undergoing curative whole breast or chest wall radiotherapy at a tertiary care center were included. In this study, the deep-inspiration breath hold (DIBH) technique was implemented in 2013 as the standard of care for left-sided patients. Cardiacdosimetricdata from the clinical treatment plan was extracted and matched to patients from the ongoing, prospectively collected Alberta Provincial Project for Outcome Assessment in Coronary Heart disease (APPROACH) database that experienced a major adverse cardiac event (MACE). MACE was defined as myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure,or clinically indicated coronary revascularization.For all the left- and right-sided patients, the population event rates, the median time to event, and the average (± standard deviation) of the mean heart physical dose is reported. The proportion of left- and right-sided patients experiencing a major cardiac event were tested for independence using a two-sample z-test for proportions. A student's t-test was used to measure significance for mean heart dose. An alpha of 0.05 was used to indicate significance for both tests. A total of 4893 patients received breast radiotherapy with 2429 left-sided, 2429 right-sided, and 35 synchronous bilateral. For all patients, Table 1 describes laterality, treatment characteristics, and prescription. The median (range) age at the time of first radiotherapy treatment was 59 (23-94). Of these patients with contours available, 96 left-sided (3.9%) and 69 right-sided (2.8%) patients experienced a MACE (p = 0.03) with a mean heart dose of 1.4 (±0.7)Gyand 0.5 (±0.2)Gy, in the event cohorts respectively (p < 0.001). The mean time to event was 4.7 (±3.2) years and 4.8 (±3.0) years for left- and right-sided patients, respectively (p = 0.83). For the left-sided cohort treated with DIBH, the mean heart dose is 1.0 (±0.8)Gy. In the era of modern radiotherapy and cardiac-sparing techniques, mean heart dose and corresponding event rates are stillsignificantlyhigher for left-sided patients than right-sided patients. Future work will aim to test whether there is a safe threshold for cardiac dose in the context of these results.

Decreased cholinesterase level combined with renal dysfunction and sympathetic denervation associated with increased cardiac mortality in systolic heart failure.

Cardiac mortality in patients with heart failure (HF) is likely to be aggravated by malnutrition, assessed by serum cholinesterase (ChE) level, as well as by kidney dysfunction or impairment of cardiac sympathetic denervation. Their prognostic interactions, however, have not been determined. A total of 991 systolic HF patients were enrolled in our HF database following clinical evaluation including evaluation of the nutrition state and assessment of standardized heart-to-mediastinum ratio (sHMR) of iodine-123-labeled meta-iodobenzylguanidine activity. Patients were followed up for an average of 43 months with the primary endpoint of fatal cardiac events (CEs). The CE patient group had a lower level of ChE, lower estimated glomerular filtration rate (eGFR) and lower late sHMR than those in the non-CE patient group. A five-parameter model with the addition of serum ChE selected in the multivariate logistic analysis (model 2) significantly increased the AUC predicting risk of cardiac events compared with a four-parameter model without serum ChE (model 1), and net reclassification analysis also suggested that the model with the addition of serum cholinesterase significantly improved cardiac event prediction. Moreover, in overall multivariate Cox hazard analysis, serum ChE, eGFR and late sHMR were identified to be significant prognostic determinants. HF patients with two or all of the prognostic variables of serum ChE < 230 U/L, eGFR < 48.8 ml/min/1.73 m2 and late sHMR < 1.90 had significantly and incrementally increased CE rates compared to those in HF patients with none or only one of the prognostic variables. Decreases in cholinesterase level and kidney function further increase cardiac mortality risk in HF patients with impairment of cardiac sympathetic innervation.

Quantitative Risk Stratification Models for Coronary Heart Disease in Primary and Secondary Prevention

Review Quantitative Risk Stratification Models for Coronary Heart Disease in Primary and Secondary Prevention Wei Jia#, Yang Qiang #, lin Lin , Canzhan Zhu , and Wei Jin * Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China. * Correspondence: weijin@mail.xjtu.edu.cn；Tel: +86 13572140118 # Jia Wei and Qiang Yang are equally contributed to the manuscript. Received: 30 April 2023 Accepted: 13 June 2023 Abstract: Coronary heart disease (CHD) is the most prevalent non-communicable disease globally and has high morbidity, mortality and healthcare cost. Thus early and precise risk stratification is an important issue in the detection, diagnosis and therapy for CHD. There are a number of primary screening tools and risk scores involving CHD risk factors for cardiovascular disease worldwide, such as Framingham Risk Score, World Health Organization/International Society of Hypertension and Cardiovascular disease (CVD) risk prediction charts (RiskWHO), American College of Cardiology/American Heart Association (ACC/AHA) pooled cohort equations (RiskACC/AHA), ADAPT Protocol for Cardiac Event Risk. Those models calculate CHD risk based on CHD risk factors, including age, gender, hypertension, and diabetes mellitus. This review will summarize the risk stratification models of CHD and related clinical evidence. It will also include a thorough analysis of the current risk stratification models and offer some advice for future risk stratification model development.

Baseline High-Sensitivity C-Reactive Protein as a Predictor of Adverse Clinical Events in Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Meta-Analysis.

Inflammation in patients with coronary artery disease (CAD) has been linked to adverse clinical outcomes. A useful biomarker for measuring inflammation levels, high-sensitivity C-reactive protein (hs-CRP) in the blood can be used to detect the presence of low-grade inflammation. This study sought to assess the predictive value of baseline hs-CRP levels for adverse clinical events in CAD patients undergoing percutaneous coronary intervention (PCI). To investigate this topic, a meta-analysis was performed. We conducted a systematic search of PubMed, Embase, and the Cochrane Library for original articles reporting the correlation between hs-CRP levels and adverse clinical events in CAD patients undergoing PCI. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and conducted a meta-analysis by extracting relevant data. Our pooled calculations yielded hazard ratios or odds ratios with 95% confidence intervals. A total of 28 studies comprising 60544 patients were included in this analysis. High baseline hs-CRP levels predicted increased risk for major adverse cardiac events (P = 0.037), major adverse cardiac and cerebrovascular events (P = 0.020), all-cause mortality (P = 0.001), cardiovascular mortality (P < 0.001), death and/or myocardial infarction (P = 0.017) in patients, as well as restenosis (P < 0.001). However, there was no association between elevated baseline hs-CRP levels and thrombosis. In conclusion, in CAD patients undergoing PCI, baseline hs-CRP levels are reliable predictors of major adverse cardiac events, major adverse cardiac and cerebrovascular events, all-cause mortality, cardiovascular mortality, death and/or myocardial infarction, and restenosis. Therefore, hs-CRP can effectively assist in prognosis determination for CAD patients undergoing PCI.

Validation of Risk Stratification for Cardiac Events in Pregnant Women With Valvular Heart Disease

BackgroundMost risk stratification tools for pregnant patients with heart disease were developed in high-income countries and in populations with predominantly congenital heart disease, and therefore, may not be generalizable to those with valvular heart disease (VHD). ObjectivesThe purpose of this study was to validate and establish the clinical utility of 2 risk stratification tools—DEVI (VHD-specific tool) and CARPREG-II—for predicting adverse cardiac events in pregnant patients with VHD. MethodsWe conducted a cohort study involving consecutive pregnancies complicated with VHD admitted to a tertiary center in a middle-income setting from January 2019 to April 2022. Individual risk for adverse composite cardiac events was calculated using DEVI and CARPREG-II models. Performance was assessed through discrimination and calibration characteristics. Clinical utility was evaluated with Decision Curve Analysis. ResultsOf 577 eligible pregnancies, 69 (12.1%) experienced a component of the composite outcome. A majority (94.7%) had rheumatic etiology, with mitral regurgitation as the predominant lesion (48.2%). The area under the receiver-operating characteristic curve was 0.884 (95% CI: 0.844-0.923) for the DEVI and 0.808 (95% CI: 0.753-0.863) for the CARPREG-II models. Calibration plots suggested that DEVI score overestimates risk at higher probabilities, whereas CARPREG-II score overestimates risk at both extremes and underestimates risk at middle probabilities. Decision curve analysis demonstrated that both models were useful across predicted probability thresholds between 10% and 50%. ConclusionsIn pregnant patients with VHD, DEVI and CARPREG-II scores showed good discriminative ability and clinical utility across a range of probabilities. The DEVI score showed better agreement between predicted probabilities and observed events.

Gender-Based Differences in Outcomes After Percutaneous Coronary Intervention of Chronic Total Occlusions (Insights from a Large Single-Center Registry)

Patients who undergo percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) are at a high risk for both periprocedural and post-procedural adverse events. Whether gender-differences in outcomes exist after PCI of CTO remain unclear. Therefore, we sought to investigate gender-based differences in outcomes after CTO-PCI. All patients who underwent elective CTO intervention from January 2012 to December 2017 at The Mount Sinai Hospital (New York, New York) were included. The primary end point of interest was major adverse cardiac events defined as the composite of death, myocardial infarction, and target vessel revascularization at 1year of follow-up. A total 1,897 patients were included, of which 368 were women (19.4%). Mean follow-up time was 174days. Women were older (66.8 ± 11.3years vs 62.6 ± 10.9years) and had a higher prevalence of co-morbidities including diabetes and chronic kidney disease. There were no significant differences in the rate of successful CTO-PCI between groups (73.5% vs 73.2%, p=0.91). Women had higher rates of procedure-related complications including increased risk of post-procedural bleeding (4.1% vs 1.8%, p=0.009) and acute vessel closure (1.36% vs 0.2%, p=0.009). In multivariable-adjusted analysis, female gender was associated with higher risk of major adverse cardiac event and target vessel revascularization at 1year. In conclusion, in this large single-center study, women who underwent percutaneous CTO revascularization experienced higher rates of periprocedural complications and worse clinical outcomes at 1year compared with men. Further research is needed to address disparities in gender-specific outcomes of CTO-PCI.

The prognostic value of coronary flow reserve in patients with non-obstructive coronary artery disease and microvascular dysfunction: a systematic review and meta-analysis with focus on imaging modality and sex difference.

To clarify prognosis of patients with non-obstructive coronary artery disease (NOCAD) and coronary microvascular disease (CMD) assessed as low coronary flow reserve (CFR) according to imaging modalities and sex difference. Comprehensive systematic literature review and meta-analyses were conducted. Risk of death and major adverse cardiac events (MACE) were pooled and compared in patients with abnormally low versus normal CFR using cut-off limits 2.0-2.5. Random effects model used for estimation of odds ratios (OR) and hazard ratios (HR) with 95% confidence interval (CI). Nineteen eligible observational studies provided data for death and MACE, publication bias was insignificant, p = 0.62. Risk of death and MACE were significantly higher in patients with low (n = 4.612, 29%) than normal CFR (n = 11.367, 71%): using transthoracal echocardiography (TTE) (OR 4.25 (95% CI 2.94, 6.15) p < 0.001) and (OR 6.98 (95% CI 2.56, 19.01) p < 0.001), positron emission tomography (PET) (OR 2.51 (CI 95%: 1.40, 4..49) p = 0.002) and (OR 2.87 (95% CI 2.16, 3.81) p < 0.001), and invasive intracoronary assessment (OR 2.23 (95% CI 1.15, 4.34) p < 0.018), and (OR 4.61 (95% CI 2.51, 8.48) p < 0.001), respectively. Pooled adjusted HR for death and MACE were (HR 2.45(95% CI 1.37, 3.53) p < 0.001) and (HR 2.08 (95% CI 1.54, 2.63) p < 0.001) respectively. Studies comparing men and women with abnormally low CFR demonstrated similar worse prognosis in both sexes. Low CFR is associated with poorer prognosis in patients with NOCAD regardless of sex. TTE may overestimate risk of death and MACE, while PET seems to be more appropriate. Future studies are needed to consolidate the current evidence.

Neonatal Cardiac Arrest Following Lacosamide Treatment: A Case Report

BackgroundLacosamide is an antiepileptic drug with US Food and Drug Administration approval for the treatment of partial-onset seizures in patients older than one month. Lacosamide works by selective enhancement of proteins that induce preferential slow promotion of sodium channels to the hyperpolarized inactive state. Lacosamide is generally well-tolerated; however, clinical and nonclinical studies have linked its use with cardiac side effects including PR prolongation and atrioventricular (AV) block. ResultsWe present the case of a three-week-old female neonatal patient born at 25 weeks’ gestation who developed second-degree AV heart block and cardiac arrest after initiating lacosamide therapy. The patient was being treated for neonatal seizure complicated by intraventricular hemorrhage (grade II) and electrolyte disturbances with phenobarbital, levetiracetam, and phenytoin. Before addition of lacosamide therapy, the patient had an unremarkable electrocardiogram and no known cardiac risk factors for lacosamide. After medication discontinuation, the patient experienced no reoccurring episodes or other cardiac events. ConclusionUse of lacosamide for neonatal populations is currently under evaluation. This is the first report of adverse cardiac event (AV block) in the setting of neonatal lacosamide use. Risk of future adverse cardiac events should be evaluated when determining the safety and efficacy of lacosamide in the neonatal population.

Age-Specific Cardiovascular Risk Factors for Major Adverse Cardiac Events in Patients Undergoing Myocardial Perfusion Imaging.

The prevalence of traditional cardiovascular risk factors shows different age-specific patterns. It is not known whether the prognostic impact of risk factors is similarly age-specific. We evaluated the profiles of cardiovascular risk factors and their prognostic impact on coronary artery disease (CAD) in relation to age. We included 3667 patients with suspected or known CAD undergoing stress myocardial perfusion imaging (MPI). We evaluated the risk for major adverse cardiac events (MACE) within three years from the index MPI in patients belonging to three groups according to age tertile distribution: <59, 59-68, and >68 years. Gender, body mass index, diabetes, hypertension, dyslipidemia, family history of CAD, smoking, angina, dyspnea, previous CAD, and MPI outcome were assessed as risk factors by a multivariable Cox's regression. The three-year risk of MACE increased progressively with age and was 9%, 13%, and 18% for each group, respectively (p < 0.0001). Dyspnea and abnormal MPI outcome were significant risk factors for all age groups. Diabetes and smoking were significant from the age of 59 onwards, while hypertension resulted significant for patients older than 68 years. The number of risk factors was significantly associated with the occurrence of MACE increase with age. It is noteworthy that a personal history of CAD was not useful for risk stratification, while MPI results were.

Osteoarthritis knee and modifiable cardiovascular risk factors: play in tandem.

To know the frequency of modifiable cardiovascular risk factors in knee osteoarthritis patients. Cross sectional study was done at Department of Rheumatology Indus Medical College, Tando Mohammad Khan from March 25, 2022 to November 24, 2022. Total 246 Osteoarthritis of knee cases with (Kellgren-Lawrence grad-II and above) on x-ray, were selected after demographic details, blood pressure, body mass index and physical examination was done, 5ml of venous blood was drawn by phlebotomist, sent for fasting blood sugar, serum lipids analysis and Framingham 10years risk score was calculated afterward for each participant. In this study males (126) and females (120). Overall (78%) had risk factors, Patients having one CVD risk factor were (22.8%), two risk factors in (21.1%), three in (21.5%), four (9.8%) and five factors in (1.6%) while frequency of modifiable cardiovascular risk shows obesity (45.5%) hypertension (40.2%) intermediate to high risk of framingham score (40%) diabetes mellitus (25%), smoking (17%), high low density lipoproteins (8.1%). In males obesity(54.2%), hypertension (47.5% ) and (45.8%) were on medication, diabetes mellitus(31.7%), smoker(31%), high risk FRS(39.2%), K-L grade-IV(58.4%) and in females: obesity (42%), hypertension (43.7%) and (40.5%) were on medication, diabetes mellitus in (19%), smoking (4%), high risk FRS (13.5%), K-L Grade-4 (42%), significant association of diabetes mellitus, smoking, FRS and K-L grades with gender (p<0.05). In OA knee there is high prevalence of modifiable cardiovascular risk factors and together these imposes a major health risk for future cardiac events and disability.

SPECT for risk stratification in patients with advanced liver disease

BackgroundPatients with advanced liver disease (ALD) have unique hemodynamics including high resting cardiac output and low systemic vascular resistance which may reduce the sensitivity of pharmacological myocardial perfusion imaging (MPI). MPI is frequently ordered for patients with ALD if liver transplantation is being considered. Because of the limited data on effectiveness of MPI in the ALD population, we conducted this cohort study focused on cardiac outcomes after pharmacological MPI. MethodsWe conducted a cohort study comparing normal versus abnormal MPI among 454 patients with ALD between 1/1/2011 and 06/01/2021 at a single tertiarycare academic medical center. Abnormal MPI was defined as summed stress score > 2 on LVEF < 40 %. The primary outcome was to compare the frequency of major adverse cardiovascular events (MACEs) among ALD patients with and without abnormal MPI. Secondary outcome included individual components of MACE analyzed by chi square. Kaplan-Meier survival curves and a logistic-regression model of associations with MACE were also performed. ResultsIn this cohort, 58 patients were observed to have an abnormal MPI. Baseline characteristics between the groups were similar, except prior coronary disease, which was more common among the abnormal MPI group (risk ratio 2.07, 95 % confidence interval 1.30–3.30, P = 0.003). MACE was more common in the group with abnormal MPI (n = 24, 41.4 % versus normal MPI n = 104, 26.3 %, P < .001). No difference in MACE was observed when stratified by liver disease type. In the logistic regression model, diabetes mellitus, stage 3 chronic kidney disease, and summed stress score >2 were retained as being associated with MACE. ConclusionsOur data suggest that MPI remains an effective test for identifying ALD patients at higher risk of mortality and cardiac events. Further study is needed to understand whether a strategy of routine MPI for liver transplant candidates effectively improves long term survival.