Characteristics and Outcomes of MI with Non-obstructive Coronary Arteries in a South-east Asian Cohort

Background: MI with non-obstructive coronary arteries (MINOCA) is caused by a heterogenous group of conditions with clinically significant sequelae. Aim: This study aimed to compare the clinical characteristics and prognosis of MINOCA with MI with obstructive coronary artery disease (MICAD). Methods: Data on patients with a first presentation of MI between 2011 and 2014 were extracted from the Singapore Cardiac Longitudinal Outcomes Database and patients were classified as having either MINOCA or MICAD. The primary outcomes were all-cause mortality (ACM) and major adverse cardiac events (MACE), defined as a composite of ACM, recurrent MI, heart failure hospitalisation and stroke. Results: Of the 4,124 patients who were included in this study, 159 (3.9%) were diagnosed with MINOCA. They were more likely to be women, present with a non-ST-elevation MI, have a higher left ventricular ejection fraction and less likely to have diabetes, previous stroke or smoking history. Over a mean follow-up duration of 4.5 years, MINOCA patients had a lower incidence of ACM (10.1% versus 16.5%) and MACE (20.8% versus 35.5%) compared with MICAD. On multivariable analysis, patients with MINOCA had a lower risk of ACM (HR 0.42; 95% CI [0.21–0.82]) and MACE (HR 0.42; 95% CI [0.26–0.69]). Within the MINOCA group, older age, higher creatinine, a ST-elevation MI presentation, and the absence of antiplatelet use predicted ACM and MACE. Conclusion: While patients with MINOCA had better clinical outcomes compared with MICAD patients, MINOCA is not a benign entity, with one in five patients experiencing an adverse cardiovascular event in the long term.

The utility of SYNTAX score predictability by electrocardiogram parameters in patients with unstable angina

Background SYNTAX score is one of the risk assessment systems to predict cardiac events in acute coronary syndrome patients. Despite the large number of SYNTAX score benefits, invasive methods such as coronary angiography are necessary to perform the scoring. We hypothesized that ECG parameters could predict the SYNTAX score in unstable angina patients. Methods During the retrospective cohort study, a total number of 876 patients were diagnosed with unstable angina. After applying the exclusion criteria, 600 patients were divided into tertiles based on the SYNTAX scores as low (0–22), intermediate (23–32), and high (≥ 33). The association between ECG parameters and SYNTAX score was investigated. Results The study included 65% men and 35% women with a mean age of 62.4 ± 9.97 years. The delayed transition zone of QRS complex, ST-depression in inferior-lateral territories or/and in all three territories, and T-wave inversion in lateral territory were significant (p < 0.05) independent predictors of intermediate SYNTAX score. High SYNTAX score was predicted by the presence of prolonged P wave duration, ST-depression in lateral territory or/and anterior-lateral territories, ST-elevation in aVR–III leads or/and aVR–III–V1 leads. Among those, all three territories ST-depression (AUC: 0.611, sensitivity: 75%, specificity: 51%) and aVR + III ST-elevation (AUC: 0.672, sensitivity: 50.12%, specificity: 80.50%) were the most accurate parameters to predict intermediate and high SYNTAX scores, respectively. Conclusion The present study demonstrates that accompanying the STE in the right side leads (aVR, III, V1) with ST-depression in other leads indicates the patients with high SYNTAX score; meanwhile, diffuse ST-depression without ST-elevation is a marker for intermediate SYNTAX score in unstable angina patients and can be applied for early risk stratification and intervention.

Impact analysis of expanding anti-TNF therapy for Crohn’s disease

Aim: To estimate the impact of universal anti-TNF therapy in patients with moderate-to-severe Crohn’s disease. Materials & methods: Developed a population-level Markov model to estimate the impact on health outcomes and medical expenditures of expanding anti-TNF therapy use versus current treatment practices. Results: Reductions in deaths (2600), hip fractures (980), major adverse cardiac events (2700) and patient out-of-pocket medical spending (2%) over 5 years. Total societal costs would be US$22,100 higher per patient per year, primarily due to the high cost of anti-TNF therapy. Conclusion: Expanding anti-TNF therapy use among US adult patients with moderate-to-severe Crohn’s disease would reduce morbidity and mortality, decrease disease-related medical costs and increase treatment costs compared with current practice. Despite the higher costs, this approach could substantially benefit patients.

Comparison of Intracoronary Epinephrine and Adenosine for No-Reflow in Normotensive Patients With Acute Coronary Syndrome (COAR Trial)

Background: Intracoronary epinephrine has been effectively used in treating refractory no-reflow, but there is a dearth of data on its use as a first-line drug in normotensive patients in comparison to the widely used adenosine. Methods: In this open-labeled randomized clinical trial, 201 patients with no-reflow were randomized 1:1 into intracoronary epinephrine as the treatment group and intracoronary adenosine as the control group and followed for 1 month. The primary end points were improvement in coronary flow, as assessed by TIMI (Thrombolysis in Myocardial Infarction) flow, frame counts, and myocardial blush. Secondary end points were in-hospital and short-term mortality and major adverse cardiac events. Results: In all, 101 patients received intracoronary epinephrine and 100 patients received adenosine. Epinephrine was generally well tolerated with no immediate table death or ventricular fibrillation. No-reflow was more effectively improved with epinephrine with final TIMI III flow (90.1% versus 78%, P =0.019) and final corrected TIMI frame count (24±8.43 versus 26.63±9.22, P =0.036). However, no significant difference was observed in final grade III myocardial blush (55.4% versus 45%, P =0.139), mean reduction of corrected TIMI frame count (−25.71±11.79 versus −26.08±11.71, P =0.825), in-hospital and short-term mortality, and major adverse cardiac events. Conclusions: Epinephrine is relatively safe to use in no-reflow in normotensive patients. A significantly higher frequency of post-treatment TIMI III flow grade and lower final corrected TIMI frame count with relatively better achievement of myocardial blush grade III translate into it displaying relatively better efficacy than adenosine. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04699110.

Biomarkers-in-Cardiology 8 RE-VISITED—Consistent Safety of Early Discharge with a Dual Marker Strategy Combining a Normal hs-cTnT with a Normal Copeptin in Low-to-Intermediate Risk Patients with Suspected Acute Coronary Syndrome—A Secondary Analysis of the Randomized Biomarkers-in-Cardiology 8 Trial

Regarding the management of suspected Non-ST-segment-elevation acute coronary syndrome (ACS), the main Biomarker-in-Cardiology (BIC)-8 randomized controlled trial study had reported non-inferiority for the incidence of major adverse cardiac events at 30 days in the Copeptin group (dual marker strategy of copeptin and hs-cTnT at presentation) compared to the standard process (serial hs-cTnT testing). However, in 349 (38.7%) of the 902 patients, high-sensitivity cardiac troponin was not available for the treating physicians. High sensitivity cardiac troponin T was re-measured from thawed blood samples collected at baseline. This cohort qualified for a re-analysis of the 30-day incidence rate of MACE (death, survived cardiac death, acute myocardial infarction, re-hospitalization for acute coronary syndrome, acute unplanned percutaneous coronary intervention, coronary bypass grafting, or documented life-threatening arrhythmias), or components of the primary endpoint including death or death/MI. After re-measurement of troponin and exclusion of 9 patients with insufficient blood sample volume, 893 patients qualified for re-analysis. A total of 57 cases were detected with high sensitivity cardiac troponin T ≥ 14 ng/L who had been classified as “troponin negative” based on a conventional cardiac troponin T or I < 99th percentile upper limit of normal. Major adverse cardiac events rates after exclusion were non-inferior in the Copeptin group compared to the standard group (4.34% (95% confidence intervals 2.60–6.78%) vs. 4.27% (2.55–6.66%)). Rates were 53% lower in the per-protocol analysis (HR 0.47, 95% CI: 0.18–1.15, p = 0.09). No deaths occurred within 30 days in the discharged low risk patients of the Copeptin group. Copeptin combined with high sensitivity cardiac troponin is useful for risk stratification and allows early discharge of low-to-intermediate risk patients with suspected acute coronary syndrome is as safe as a re-testing strategy at 3 h or later.

Human iPSC-Cardiomyocytes as an Experimental Model to Study Epigenetic Modifiers of Electrophysiology

The epigenetic landscape and the responses to pharmacological epigenetic regulators in each human are unique. Classes of epigenetic writers and erasers, such as histone acetyltransferases, HATs, and histone deacetylases, HDACs, control DNA acetylation/deacetylation and chromatin accessibility, thus exerting transcriptional control in a tissue- and person-specific manner. Rapid development of novel pharmacological agents in clinical testing—HDAC inhibitors (HDACi)—targets these master regulators as common means of therapeutic intervention in cancer and immune diseases. The action of these epigenetic modulators is much less explored for cardiac tissue, yet all new drugs need to be tested for cardiotoxicity. To advance our understanding of chromatin regulation in the heart, and specifically how modulation of DNA acetylation state may affect functional electrophysiological responses, human-induced pluripotent stem-cell-derived cardiomyocyte (hiPSC-CM) technology can be leveraged as a scalable, high-throughput platform with ability to provide patient-specific insights. This review covers relevant background on the known roles of HATs and HDACs in the heart, the current state of HDACi development, applications, and any adverse cardiac events; it also summarizes relevant differential gene expression data for the adult human heart vs. hiPSC-CMs along with initial transcriptional and functional results from using this new experimental platform to yield insights on epigenetic control of the heart. We focus on the multitude of methodologies and workflows needed to quantify responses to HDACis in hiPSC-CMs. This overview can help highlight the power and the limitations of hiPSC-CMs as a scalable experimental model in capturing epigenetic responses relevant to the human heart.

Ticagrelor Versus Clopidogrel in The Treatment of Elderly Chinese Chronic Total Occlusion Patients Undergoing PCI

Background: Taking thrombosis and bleeding risks into consideration, little real world study data is available to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in elderly Chinese chronic total occlusion (CTO) patients. Methods: We assigned 504 CTO patients aged ≥75 years who successfully underwent PCI from December 2009 to May 2020. The patients were randomized to Clopidogrel and Ticagrelor group and received DAPT for up to 12 months. Efficacy endpoints were evaluated by major adverse cardiac events (MACE) consisting of all-cause death, nonfatal myocardial infarction (MI) and clinically driven revascularization. The safety endpoints were recorded as the incidence of Bleeding Academic Research Consortium (BARC) bleeding. Results: Patients in Clopidogrel group were older, they had a higher percentage of BMI, diastolic blood pressure and HDL-C than those in Ticagrelor group. Clopidogrel group had a lower percentage of hyperlipidemia, prior PCI, glucose, TG and LDL-C. No significant difference was found as to the Angiographic and procedural characteristics (P＞0.05 for all). After 12 months' follow-up, the incidence of MACE (12.19% vs. 11.04%, P=0.763) and bleeding (9.38% vs. 13.64%, P=0.205) had no significant difference. After clinical characteristics balanced matching by IPTWs model, we found that Ticagrelor had an unfavorable effect on reducing the incidence of bleeding with the IPTWs model (IPTW-OR, 1.81, 95% CI: 1.18-2.76, P=0.006). Conclusions: This clinical study demonstrated that Clopidogrel should be recommended to elderly CTO patients after PCI, especially those with a high bleeding risk. Trial registration: The study protocol was approved by the Ethics Committee of Air Force Medical University (KY20172019-1).

What are the prognostic implications and factors relating to exercise induced electrocardiographic ST segment changes in the setting of a non-ischaemic stress echocardiogram?

Background. Electrocardiographic (ECG) changes during stress testing are a common and perplexing finding during non-ischaemic stress echocardiography (SE). Research has provided conflicting results regarding the implications. Methods. SE was performed after maximal Bruce protocol treadmill exercise. Results. 3020 consecutive patients, mean age 58±12 years, 36% female, were followed-up for up to 9 years (mean 36±21 months) post SE. Time to first cardiac event (composite of heart failure admission, worsening New York Heart Association class, worsening ejection fraction, acute coronary syndrome, revascularization, angina or cardiovascular death) was analyzed and adjusted using Cox proportional hazards regression. Prognostic significance was found with 1.5mm of downsloping or horizontal ST depression. Adjusting for baseline differences, increased risk of composite major adverse cardiac events was shown with at least 1.5mm of exercise induced ST depression (Hazard ratio [HR] of 2.47, 95% Confidence ratio [CI] 1.67-3.72, p<0.0001). Patients achieving high level exercise capacity (≥13 metabolic equivalents or METs) with ST depression lower risk of cardiac events during follow-up Conclusion. Patients with ST segment depression but non-ischaemic stress imaging have poorer prognosis compared to patients with non-ischaemic stress echocardiograms with normal stress ECGs. ST depression of 1.5mm or more was established as a prognostically significance value. High exercise capacity improves prognosis, and ECG changes in that setting can be regarded as false positives. Overall, however, ST depression during non-ischaemic stress imaging is not a benign finding.