Future Major Adverse Cardiac Events Research Articles

Abstract 4144520: Glucagon-like Peptide-1 Receptor Agonists for the Primary Prevention of Major Adverse Cardiac Events in Drug-naïve Type 2 Diabetes: A Propensity-score Analysis

Background: The effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RA) as a first-line agent for the primary prevention of major adverse cardiac events (MACE) in obese patients with diabetes mellitus (DM) is unknown. Research Question: Does initial treatment with GLP-1 RA in obese drug-naïve patients with type 2 DM prevent future MACE? Aims: To examine the association between GLP-1 RA treatment and the primary prevention of MACE in drug-naïve type 2 DM patients with obesity. Methods: A retrospective propensity score-matched (PSM) analysis was conducted using the TriNetX Global database. We implemented a new-user design, including adult overweight/obese patients with drug-naive type 2 DM between January 1 st , 2019 and May 1 st , 2023. Patients with prior heart failure (HF), myocardial infarction (MI), coronary revascularization, stroke, or cardiac arrest were excluded. We compared those starting GLP-1 RA versus starting non GLP-1 RA. Medication starting window spans from the first diagnosis to 3 months afterwards. Patients with insulin were excluded if they had any emergency or inpatient encounters during this window. The primary outcome was incident MACE, defined as any death, decompensated HF, MI, cardiac arrest, or ventricular tachycardia/fibrillation, within 5 years of initial drug dispense. Secondary outcomes were individual MACE. Gastrointestinal bleeding was set as a falsification endpoint. Results: Of 1,245,340 patients with A1c <10% and 293,072 patients with A1c ≥10%, 7,483 and 1,563 patients started on GLP-1 RA as a single agent and part of a combined approach, respectively. After PSM, baseline covariates were balanced between the two treatment groups and no significant differences were observed in the falsification endpoint by treatment arm (Figure) . Compared with non-GLP-1 RA, with the exception of sodium-glucose cotransporter-2 (SGLT2i), starting a GLP-1 RA first was associated with a significant reduction in MACCE, primarily driven by reductions in decompensated HF (Figure) . Conclusions: Initiation of a GLP-1 RA as the first agent for obese patients with drug-naïve type 2 DM was associated with a significant reduction in MACE compared to all other diabetes medications, with the exception of SGLT2i.

Endothelial dysfunction in acute coronary syndrome: a complex association with cardiovascular risk factors, sleep quality and cardiorespiratory capacity

Abstract Introduction It is widely acknowledged that normal endothelial function plays a pivotal role in conferring cardioprotective effects against ischemia-reperfusion injury following acute myocardial infarction (AMI) treated by a primary percutaneous coronary intervention (PCI), thereby limiting infarct size (1). However, endothelial dysfunction (ED) has been extensively documented in patients with cardiovascular (CV) risk factors (2). This study proposes a novel perspective, positing that ED could be intricately linked not only with traditional CV risk factors, but also it can be associated with poor sleep quality. Consequently, this interplay might significantly contribute to the attenuation of exercise capacity. Objective The aim of this study was to assess endothelial function following AMI treated with a PCI and investigate the link between endothelial function, CV risk factors, sleep quality and exercise capacity. Furthermore, the study aimed to determine if endothelial function could serve as a predictive factor for future major adverse acute cardiac events (MAACE) following AMI. Materials and methods Sixty-three patients with AMI (56.21 ± 7.6 years) volunteered to participate in this study, . Endothelial function was assessed using the Endothelium Quality Index (EQI) . Sleep quality was evaluated using both actigraphy and the PSQI (Pittsburgh Sleep Quality Index) questionnaire. Exercise capacity was quantified through the 6-minute walking test (6mwt). Results ED was evident, as indicated by an EQI of 1.4 ± 0.7. Furthermore, ED was notably influenced by CV risk factors such as low physical activity level, age, and smoking. A significant correlation was found between EQI and both sleep efficiency (r = 0.340; p = 0.006) and PSQI score (r = -0.533; p < 0.001). Additionally, a strong association was observed between endothelial function and the results of the 6mwt (r = 0.291; p = 0.021). Furthermore, during a follow up period ( near 4 months) following PCI, MAACE were observed in patients with severe ED only. Conclusion In summary, findings of this study may emphasize the importance of enhancing sleep quality and advocating for an active lifestyle as modifiable elements to enhance endothelial function, which can be regarded as a prognostic tool subsequent to AMI, ultimately contributing to improved clinical outcomes. Moreover, this study concluded that AMI patients with severe endothelial dysfunction were more likely to develop MAACE.Endothelial Dysfunction after AMIED following AMI : Causes and effect

Complete revascularisation versus culprit lesion only PCI in patients with non-ST-elevation myocardial infarction and multivessel disease.

Abstract Background The incidence of non-ST-elevation myocardial infarction (NSTEMI) is escalating, with patients diagnosed with multivessel disease (MVD) facing more adverse clinical outcomes. Yet, optimal treatment strategies for NSTEMI patients with MVD remain uncertain. Objectives This study aimed to assess the clinical outcome of NSTEMI patients with MVD who underwent complete revascularization compared to those treated with the culprit lesion only. Methods Between 2014 and 2017, patients presenting with NSTEMI and MVD undergoing successful percutaneous coronary intervention (PCI) were retrospectively included. MVD was defined as patients having more than one lesion considered angiographically significant, exhibiting at least 50% stenosis of the vessel diameter on visual estimation, or having a Coronary Angiography-Derived Fractional Flow Reserve (caFFR) measurement of 0.80 or less. The main exclusion criteria were single vessel disease, and previous coronary-artery bypass grafting surgery. The primary endpoint of this study was major adverse cardiac events (MACE) at 3 years, defined as a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. Results A total of 358 patients were included (mean age: 67.34±12.77; male: 70.1%), 155 and 203 patients were stratified into complete revascularisation group and culprit-lesion-only PCI group respectively. During 3-year follow-up, the culprit-lesion-only PCI group exhibited a significantly elevated risk of MACE compared to the complete revascularization group (17.7% vs 7.74%; hazard ratio [HR] 2.412, 95% confidence interval [CI] 1.255 - 4.636, P = 0.008). The increase 3-year MACE rate was mainly driven by the higher rate of ischaemia-driven revascularization in the culprit-lesion-only PCI group (11.3% vs 3.23%, HR 3.637, 95% CI 1.383 - 9.566, P = 0.009). Conclusion In NSTEMI patients with MVD, complete revascularization was superior to culprit-lesion-only PCI in mitigating the risk of future MACE at 3 years, which is predominantly attributed by a reduced incidence of repeat revascularisations.

Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation

Bruton’s tyrosine kinase inhibitors (BTKi) have dramatic efficacy against B-cell malignancies, but link with cardiotoxicity, including atrial fibrillation (AF). Burden, severity, and implications of BTKi-related AF are unknown. Leveraging a large-cohort of consecutive B-cell malignancy patients initiated on BTKi from 2009–2020, we identified patients with extended ambulatory rhythm monitoring. The primary outcome was AF burden after BTKi-initiation. Secondary outcomes included ventricular arrhythmia burden and other arrhythmias. Observed incident-AF rates and burden with next-generation BTKi’s were compared to ibrutinib. Multivariable regression defined association between rhythm measures and major adverse cardiac events (MACE), and mortality. There were 98 BTKi-treated patients [38.8% next-generation BTKi’s, 14.3% prior-AF], with 28,224 h of monitoring. Median duration BTKi-use was 34 months. Over mean duration 12 days monitoring, 72.4% developed arrhythmias (16.3% incident-AF, 31.6% other SVTs, 14.3% ventricular tachycardia). 14.3% had high AF-burden. AF-burden was similar between ibrutinib and next-generation BTKi’s. No single antiarrhythmic-therapy prevented BTKi-related AF. However, antiarrhythmic initiation associated with reduction in arrhythmic burden (P = 0.009). In a multivariable model accounting for traditional cardiovascular risk factors, prior-AF associated with increased post-BTKi AF-burden. In follow-up, high AF burden associated with MACE (HR 3.12, P = 0.005) and mortality (HR 2.97, P = 0.007). Among BTKi-treated patients, high AF burden prognosticates future MACE and mortality risk.

Role of Lipid-Lowering and Anti-Inflammatory Therapies on Plaque Stabilization.

Atherosclerosis is the predominant underlying etiopathology of coronary artery disease. Changes in plaque phenotype from stable to high risk may spur future major adverse cardiac events (MACE). Different pharmacological therapies have been implemented to mitigate this risk. Over the last two decades, intravascular imaging modalities have emerged in clinical studies to clarify how these therapies may affect the composition and burden of coronary plaques. Lipid-lowering agents, such as statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors, were shown not only to reduce low-density lipoprotein levels and MACE but also to directly affect features of coronary plaque vulnerability. Studies have demonstrated that lipid-lowering therapy reduces the percentage of atheroma volume and number of macrophages and increases fibrous cap thickness. Future studies should answer the question of whether pharmacological plaque stabilization may be sufficient to mitigate the risk of MACE for selected groups of patients with atherosclerotic coronary disease.

Predictive Value of Artificial Intelligence-Enabled Electrocardiography in Patients With Takotsubo Cardiomyopathy.

Recent studies have indicated high rates of future major adverse cardiovascular events in patients with Takotsubo cardiomyopathy (TC), but there is no well-established tool for risk stratification. This study sought to evaluate the prognostic value of several artificial intelligence-augmented ECG (AI-ECG) algorithms in patients with TC. This study examined consecutive patients in the prospective and observational Mayo Clinic Takotsubo syndrome registry. Several previously validated AI-ECG algorithms were used for the estimation of ECG- age, probability of low ejection fraction, and probability of atrial fibrillation. Multivariable models were constructed to evaluate the association of AI-ECG and other clinical characteristics with major adverse cardiac events, defined as cardiovascular death, recurrence of TC, nonfatal myocardial infarction, hospitalization for congestive heart failure, and stroke. In the final analysis, 305 patients with TC were studied over a median follow-up of 4.8 years. Patients with future major adverse cardiac events were more likely to be older, have a history of hypertension, congestive heart failure, worse renal function, as well as high-risk AI-ECG findings compared with those without. Multivariable Cox proportional hazards analysis indicated that the presence of 2 or 3 high-risk findings detected by AI-ECG remained a significant predictor of major adverse cardiac events in patients with TC after adjustment by conventional risk factors (hazard ratio, 4.419 [95% CI, 1.833-10.66], P=0.001). The combined use of AI-ECG algorithms derived from a single 12-lead ECG might detect subtle underlying patterns associated with worse outcomes in patients with TC. This approach might be beneficial for stratifying high-risk patients with TC.

Long-term prognosis and prognostic factors after primary prophylactic implantable cardioverter-defibrillator therapy

BackgroundLittle is known regarding which patients with ischemic cardiomyopathy (ICM) should be considered for prophylactic therapies, such as an implantable cardioverter-defibrillator (ICD), in the primary percutaneous intervention era. The aim of this study was to investigate the influence of non-sustained ventricular tachycardia (NSVT) on major adverse cardiac events (MACE) in heart failure with reduced ejection fraction (HFrEF) patients. MethodsWe retrospectively analyzed patients of ICM and non-ICM who underwent ICD implantation at our institute from October 2006 to August 2020. MACE were defined as composite outcome of cardiovascular death, heart failure hospitalization, and appropriate ICD therapies. ResultsA total of 167 patients were enrolled [male, 138 (83 %); age, 62.1 ± 11.7 years; left ventricular ejection fraction, 23.5 ± 6.1 %; left ventricular diastolic diameter, 67.4 ± 9.0 mm; atrial fibrillation, 47 (28 %); NSVT, 124 (74 %); use of class III antiarrhythmic drugs, 55 (33 %); ischemic cardiomyopathy, 56 (34 %); cardiac resynchronization therapy, 73 (44 %)]. The median follow-up duration was 61 months. MACE occurred with 71 patients (43 %). When comparing baseline characteristics of the patients, left ventricular ejection fraction (p = 0.02) and atrial fibrillation (p = 0.04) were significantly associated with MACE. The multivariable Cox analysis for the target variable MACE identified atrial fibrillation (hazard ratio 2.00; 95 % confidence index 1.18–3.37; p = 0.01) as an independent predictor for MACE. ConclusionsPrior NSVT before ICD implantation was not an independent predictor of future MACE in patients with HFrEF with primary prophylactic ICD. In contrast, atrial fibrillation was associated with worse prognosis. To predict the prognosis of patients with primary prophylactic ICD, these factors should be assessed as comprehensive risk stratification factors for MACE.

Abstract 13214: Arrhythmic Burden After Bruton's Tyrosine Kinase Inhibitor Initiation and Major Cardiovascular Events

Background: Bruton’s tyrosine kinase inhibitors (BTKi) have dramatic efficacy against B cell malignancies. BTKi’s also cause cardiotoxic arrhythmias, including atrial fibrillation (AF) and ventricular arrhythmias (VA). Yet, the true burden and long term effects of arrhythmias after BTKi therapy are unknown. Research Question: In patients with suspected BTKi related arrhythmias, what is the relative AF burden? Does it prognosticate future events? Methods: Leveraging a cohort of consecutive B cell malignancy patients initiated on BTKi from 2009-2020, we identified patients with available ambulatory rhythm monitors. The primary outcome was AF burden after BTKi initiation. Secondary outcomes included VA burden, conduction blocks, and other arrhythmias of probable or definite BTKi association. Observed incident AF rates and burden with next generation BTKi’s were compared to ibrutinib. Multivariable regression and survival analysis were used to define factors associated with AF related hospitalizations and major adverse cardiac events (MACE), as well as the relationship between AF burden and mortality. Outcomes were stratified by high (≥5%) vs low (<5%) AF burden. Results: Of 890 BTKi treated patients, 98 wore ambulatory rhythm monitors, including 38 on next generation BTKi’s [age 67.7 years, 24.2% prior AF]. Median duration BTKi use was 34 months. Among next generation BTKi treated patients, 8.7% developed incident AF compared to 25.5% with ibrutinib ( P =0.048). Ten patients (26.3%) developed symptomatic or >1% PVCs, at a mean burden of 7.1% compared to eight patients (13.3%) with mean burden 9.4% on ibrutinib. In a multivariable model accounting for traditional CV risk factors, prior AF associated with increased post BTKi AF burden. In follow up, high AF burden associated with increased MACE (HR 3.49, P =0.001) and mortality (HR 3.2, P =0.002); Figure . Conclusions: In BTKi treated patients, cardiotoxic AF burden prognosticates future MACE and mortality.

Diagnosis and Prognostic Value of the Underlying Cause of Acute Coronary Syndrome in Optical Coherence Tomography-Guided Emergency Percutaneous Coronary Intervention.

Background The prognostic impact of optical coherence tomography-diagnosed culprit lesion morphology in acute coronary syndrome (ACS) has not been systematically examined in real-world settings. Methods and Results This investigator-initiated, prospective, multicenter, observational study was conducted at 22 Japanese hospitals to identify the prevalence of underlying ACS causes (plaque rupture [PR], plaque erosion [PE], and calcified nodules [CN]) and their impact on clinical outcomes. Patients with ACS diagnosed within 24 hours of symptom onset undergoing emergency percutaneous coronary intervention were enrolled. Optical coherence tomography-guided percutaneous coronary intervention recipients were assessed for underlying ACS causes and followed up for major adverse cardiac events (cardiovascular death, myocardial infarction, heart failure, or ischemia-driven revascularization) at 1 year. Of 1702 patients with ACS, 702 (40.7%) underwent optical coherence tomography-guided percutaneous coronary intervention for analysis. PR, PE, and CN prevalence was 59.1%, 25.6%, and 4.0%, respectively. One-year major adverse cardiac events occurred most frequently in patients with CN (32.1%), followed by PR (12.4%) and PE (6.2%) (log-rank P<0.0001), primarily driven by increased cardiovascular death (CN, 25.0%; PR, 0.7%; PE, 1.1%; log-rank P<0.0001) and heart failure trend (CN, 7.1%; PR, 6.8%; PE, 2.2%; log-rank P<0.075). On multivariate Cox regression analysis, the underlying ACS cause was associated with 1-year major adverse cardiac events (CN [hazard ratio (HR), 4.49 [95% CI, 1.35-14.89], P=0.014]; PR (HR, 2.18 [95% CI, 1.05-4.53], P=0.036]; PE as reference). Conclusions Despite being the least common, CN was a clinically significant underlying ACS cause, associated with the highest future major adverse cardiac events risk, followed by PR and PE. Future studies should evaluate the possibility of ACS underlying cause-based optical coherence tomography-guided optimization.

Comparison of Plan Quality Metrics after Left Anterior Descending Coronary Artery Sparing in VMAT Esophageal Radiotherapy

Cardiotoxicity is a significant late effect of esophageal radiotherapy (RT). Mean heart dose has been implicated with major adverse cardiac events (MACE) and emerging evidence increases MACE association with left anterior descending (LAD) coronary artery specific dose. This retrospective planning study investigates the dosimetric impact of including the LAD as an OAR-sparing objective for VMAT-based plan optimization in patients previously treated for esophageal cancers. A retrospective cohort was identified of patients who underwent neoadjuvant RT for esophageal cancers between 2017-2020 without intentional LAD sparing. Treatment planning was performed using Eclipse™ treatment planning system. Doses were calculated using Acuros® XB algorithm or anisotropic analytical algorithm with a 2-2.5mm calculation grid. For each patient, the LAD was delineated and the treated VMAT plan was re-optimized to reduce the dose to the LAD receiving 15 Gy to less than 10%, when possible. Re-plans were performed such that 95% of the PTV received the prescription dose. Institutional constraints were used to minimize the dose to the heart, lung, and spinal cord (Table 1). A paired t-test was used to compare the dose between the original VMAT plan used for treatment (Esophagus Original) against those re-optimized (Esophagus + LAD), with significance of p<0.05. A total of 19 patients were identified. Of those treated, 12 of 19 original plans (63%) exceeded the LAD constraint (V15<10%) with a mean V15 Gy of 47.1%. Plan re-optimization accounting for the LAD allowed for 66.7% (9/12) of cases to meet LAD V15 constraints. Aside from increased sparing of the mean heart dose, there were no statistically significant impacts on target coverage and OAR doses otherwise, including to that of the lung and spinal cord (Table 1). Accounting for LAD dose in treatment planning may help reduce future MACE risks. LAD dose can be significantly reduced without compromising PTV coverage or having significant effects on other OAR dose sparing.

Association of strain echocardiography with cardiovascular outcomes in patients with heart failure with preserved ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Background Speckle Tracking Echocardiography (STE) with measurement of Left Ventricular Global Longitudinal Strain (LVGLS) is an important predictor of morbidity and mortality in Heart Failure with Reduced Ejection Fraction (HFrEF), but its prognostic importance in Heart Failure with Preserved Ejection Fraction (HFpEF) is less clear. The purpose of this meta-analysis is to analyze the association between LVGLS and Major Adverse Cardiac Events (MACE) in HFpEF. Methods A literature search was conducted for studies reporting on STE in patients with HFpEF and the association between LVGLS and MACE. The databases queried were Pubmed, Embase, and Web of Science. The search was not restricted to time or publication status. Results A total of 9 studies with 2,082 total patients met inclusion criteria. Among these, 5 studies with 944 HFpEF patients (300 with future MACE, 644 without future MACE) compared baseline mean LVGLS. Mean follow up duration was 28 months (ranging 12–48 months), mean age was 67 years old, 39.4% were male. LVGLS was significantly reduced in patients who eventually had MACE compared to those without MACE on follow-up (MD −2.09, 95% CI −2.17, −2.01, p &amp;lt; 0.01). 4 studies with 1,138 HFpEF patients (676 with impaired LVGLS below cutoff, 462 with unimpaired LVGLS above cutoff) compared all-cause mortality or heart failure hospitalization. Mean follow up was 35 months, mean age was 71 years old, 38.3% were male, and the average LVGLS cutoff was 14. Impaired LVGLS below cutoff was associated with significantly higher risk of MACE (OR 2.13, 95% CI 1.67, 2.72, p &amp;lt; 0.01). Subgroup analysis demonstrated that impaired LVGLS below cutoff was associated with significantly higher risk of both all-cause mortality (OR 2.11, 95% CI 1.40, 2.97, p &amp;lt; 0.01) and heart failure hospitalization (OR 2.16, 95% CI 1.53, 3.06, p &amp;lt; 0.01). Conclusions STE and measurement of LVGLS may represent a useful clinical tool in risk stratification of HFpEF patients at risk for future mortality and adverse cardiac events.

A Coronary CT Angiography Radiomics Model to Identify Vulnerable Plaque and Predict Cardiovascular Events.

Background A noninvasive coronary CT angiography (CCTA)-based radiomics technique may facilitate the identification of vulnerable plaques and patients at risk for future adverse events. Purpose To assess whether a CCTA-based radiomic signature (RS) of vulnerable plaques defined with intravascular US was associated with increased risk for future major adverse cardiac events (MACE). Materials and Methods In a retrospective study, an RS of vulnerable plaques was developed and validated using intravascular US as the reference standard. The RS development data set included patients first undergoing CCTA and then intravascular US within 3 months between June 2013 and December 2020 at one tertiary hospital. The development set was randomly assigned to training and validation sets at a 7:3 ratio. Diagnostic performance was assessed internally and externally from three tertiary hospitals using the area under the curve (AUC). The prognostic value of the RS for predicting MACE was evaluated in a prospective cohort with suspected coronary artery disease between April 2018 and March 2019. Multivariable Cox regression analysis was used to evaluate the RS and conventional anatomic plaque features (eg, segment involvement score) for predicting MACE. Results The RS development data set included 419 lesions from 225 patients (mean age, 64 years ± 10 [SD]; 68 men), while the prognostic cohort included 1020 lesions from 708 patients (mean age, 62 years ± 11; 498 men). Sixteen radiomic features, including two shape features and 14 textural features, were selected to build the RS. The RS yielded a moderate to good AUC in the training, validation, internal, and external test sets (AUC = 0.81, 0.75, 0.80, and 0.77, respectively). A high RS (≥1.07) was independently associated with MACE over a median 3-year follow-up (hazard ratio, 2.01; P = .005). Conclusion A coronary CT angiography-derived radiomic signature of coronary plaque enabled the detection of vulnerable plaques that were associated with increased risk for future adverse cardiac outcomes. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by De Cecco and van Assen in this issue.

Abstract 13156: The Location of Combined High-Risk Low Endothelial Shear Stress and High Plaque Structural Stress is Distant From the Minimal Lumen Area in the Majority of Coronary Plaques Responsible for Major Adverse Cardiac Events

Introduction: The presence of multiple high-risk prognostic features enhances risk-stratification of plaques prone to destabilization and major adverse cardiac events (MACE). Spatial superimposition of high-risk features (concordance) likely amplifies local risk. Local endothelial shear stress (ESS) and plaque structural stress (PSS) metrics predict MACE, but their spatial concordance and their location relative to the minimal lumen area (MLA) is unknown. If the highest-risk plaque area is distant from the MLA, then PCI of the MLA alone will leave high-risk plaque areas untreated. Purpose: To identify the site of high-risk features of low ESS and high PSS heterogeneity (HI) along the course of a plaque in patients who develop MACE, and the site of their spatial concordance relative to the MLA. Methods: We examined ESS, PSS, and PSS HI in 22 non-culprit lesions (NCL) leading to MACE, and 64 randomly selected control NCLs without MACE from the PROSPECT study. ESS was calculated by computational fluid dynamics and PSS by finite element analysis on co-registered lesions. We examined high-risk plaques with empirically-derived (ROC curve) ESS &lt; 1.3 Pa and PSS HI &gt; 0.29 in 16 lesions leading to future MACE, and 11 control lesions without MACE. Results: MACE outcomes were significantly more frequent in plaques with combined low ESS+high PSS HI vs plaques with low ESS alone (72.7% vs 27.3%, p&lt;0.001) at 3 years follow-up. Of the 16 MACE plaques with both low ESS+high PSS HI, 14 exhibited high-risk values that were spatially concordant vs 2 that were discordant (87.5% v 12.5%, p=0.01). In the 14 plaques with concordant values, there were 26 focal plaque areas with high-risk concordance. The mean distance from the concordant high-risk areas to the MLA was 13.2 ± 11.6 mm (Figure). Conclusion: High-risk ESS and PSS measures frequently co-localize in plaques responsible for future MACE, and are substantially distant from the MLA. PCI of the MLA area alone may leave many high-risk areas untreated.

Morphological characteristics of lesions with thin cap fibroatheroma-a substudy from the COMBINE (OCT-FFR) trial.

To study if any qualitative or quantitative optical coherence tomography (OCT) variables in combination with thin cap fibroatheroma (TCFA) patients could improve the identification of lesions at risk for future major adverse cardiac events (MACEs). From the combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) trial database (NCT02989740), we performed a detailed assessment OCT qualitative and quantitative variables in TCFA carrying diabetes mellitus (DM) patients with vs. without MACE during follow-up. MACEs were defined as a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and hospitalization for unstable angina. From the 390 fractional flow reserve (FFR)-negative DM patients, 98 (25.2%) had ≥1 OCT-detected TCFA, of which 13 (13.3%) had MACE and 85 (86.7%) were event-free (non-MACE). The baseline characteristics were similar between both groups; however, a smaller minimal lumen area (MLA) and lower mean FFR value were observed in MACE group (1.80 vs. 2.50 mm2, P = 0.01, and 0.85 vs. 0.89, P = 0.02, respectively). Prevalence of healed plaque (HP) was higher in the MACE group (53.85 vs. 21.18%, P = 0.01). TCFA were predominantly located proximal to the MLA. TCFA area was smaller in the MACE group, while no difference was observed regarding the lesion area. Within TCFA carrying patients, a smaller MLA, lower FFR values, and TCFA location adjacent to a HP were associated with future MACE. Carpet-like measured lesion area surface was similar, while the TCFA area was smaller in the MACE arm, and predominantly located proximal to the MLA.

Long-term clinical course and prognostic factors of heart failure with reduced ejection fraction (HFrEF) patients underwent primary prophylactic implantable cardioverter defibrillator (ICD)

Abstract Background For decades, ICD is a well-established therapy for improving prognosis of structural heart disease with severe cardiac dysfunction, and ICD for primary prophylaxis against sudden cardiac death were routinely provided. However, long-term prognosis and clinical course are different in each individual patient with an ICD, and it is moreover unclear what kind of factors might have influences on their clinical outcomes. Purpose The aim of this study is to clarify long-term prognosis and predictors of future major adverse cardiac events (MACEs) in HFrEF patients with an ICD as primary prophylaxis in Japanese population. Methods We retrospectively analyzed our ICD database. Patients underwent primary prophylactic ICD implantation from 2006 to 2020 at our institute and met the criteria of ICD recommendation of the latest Japanese guideline. Its requirements are receiving optimal medication therapy, symptomatic heart failure (New York Heart Association classification II or greater), and severe cardiac dysfunction (left ventricular ejection fraction (LVEF) is 35% or less). Additionally, prior NSVT is considered Class I ICD recommendation. In the case of ischemic cardiomyopathy (ICM), ICD implantation was done at least 40 days after myocardial infarction and at least 90 days after revascularization. MACEs were defined as composite outcome of cardiovascular death, heart failure hospitalization, and appropriate ICD therapies. Results A total of 148 consecutive patients were enrolled (male, 120 (81%); age, 62.1±11.8 years; LVEF, 23.0±5.86%; left ventricular end-diastolic diameter (LVDd), 67.6±9.26mm; paroxysmal or persistent atrial fibrillation (AF), 38 (26%); NSVT, 113 (76%); use of class III antiarrhythmic drugs, 48 (32%); ICM, 49 (33%); cardiac resynchronization therapy (CRT), 63 (43%)). One hundred twenty patients (81%) were programmed with a shock-only zone over 200 beats per minute. The median follow-up duration was 58.5 months. Among those 148 patients, MACEs were occurred to 60 patients (41%). As a result of dividing all patients into two groups by the occurrence of MACE, LVEF and LVDd were worse in MACE(+) group, whereas, MACE(−) had greater number of co morbidities. The results of cox-regression analysis showed LVDd (HR: 1.07, 95% CI: 1.03–1.12, p&amp;lt;0.001), AF (HR: 2.88, 95% CI: 1.56–5.31, p&amp;lt;0.001) and ICM (HR: 1.78, 95% CI: 1.00–3.16, p=0.049) were the independent predictors of MACEs (Table). However, initial ICD programming was not related to the occurrence of MACE. Conclusions The incidence of MACEs in patients with an ICD and severe HFrEF was substantially high in this Japanese population. Etiology of ICM, left ventricle size, and AF were the potential risk factors for future MACEs. Funding Acknowledgement Type of funding sources: None.

MicroRNA-134-5p and the Extent of Arterial Occlusive Disease Are Associated with Risk of Future Adverse Cardiac and Cerebral Events in Diabetic Patients Undergoing Carotid Artery Stenting for Symptomatic Carotid Artery Disease.

There is little known about the prognostic value of serum microRNAs (miRs) in diabetic patients with symptomatic internal carotid artery disease (ICAS) who underwent stent supported angioplasty (PTA) for ICAS. The present study aimed to investigate expression levels of selected miRs for future major adverse cardiac and cerebral events (MACCE) as a marker in diabetic patients following ICAS-PTA. The expression levels of 11 chosen circulating serum miRs were compared in 37 diabetic patients with symptomatic ICAS and 64 control group patients with symptomatic ICAS, but free of diabetes. The prospective median follow-up of 84 months was performed for cardiovascular outcomes. Diabetic patients, as compared to control subjects, did not differ with respect to age (p = 0.159), distribution of gender (p = 0.375), hypertension (p = 0.872), hyperlipidemia (p = 0.203), smoking (p = 0.115), coronary heart disease (p = 0.182), lower extremities arterial disease (LEAD, p = 0.731), and miRs expressions except from lower miR-16-5p (p < 0.001). During the follow-up period, MACCE occurred in 16 (43.2%) diabetic and 26 (40.6%) non-diabetic patients (p = 0.624). On multivariate Cox analysis, hazard ratio (HR) and 95% Confidence Intervals (95%CI) for diabetic patients associated with MACCE were miR-134-5p (1.12; 1.05–1.21, p < 0.001), miR-499-5p (0.16; 0.02–1.32, p = 0.089), hs-CRP (1.14; 1.02–1.28; p = 0.022), prior myocardial infarction (8.56, 1.91–38.3, p = 0.004), LEAD (11.9; 2.99–47.9, p = 0.005), and RAS (20.2; 2.4–167.5, p = 0.005), while in non-diabetic subjects, only miR-16-5p (1.0006; 1.0001–1.0012, p = 0.016), miR-208b-3p (2.82; 0.91–8.71, p = 0.071), and hypertension (0.27, 0.08–0.95, p = 0.042) were associated with MACCE. Our study demonstrated that different circulating miRs may be prognostic for MACCE in diabetic versus non-diabetic patients with symptomatic ICAS. Higher expression levels of miR-134 were prognostic for MACCE in diabetic patients, while higher expression levels of miR-16 were prognostic in non-diabetic patients.

Prognostic Significance of Myocardial Blood Flow Quantification for Major Adverse Cardiac Events: A Systematic Review and Meta-analysis.

Chronic coronary syndromes involve reduced myocardial blood flow (MBF). MBF is a reliable predictor of outcomes, independent of the presence of significant stenosis. Whether MBF can predict major adverse cardiac events (MACE) during long-term follow-up is unknown. PubMed, Embase, Cochrane, CNKI, and WANFANG were searched for papers published up to January 2021. The exposure was the incremental unit of stress MBF (mL/g/min) or low MBF versus high MBF. The imaging examinations included positron emission tomography/computed tomography and coronary magnetic resonance. The study outcome was the occurrence of MACE during follow-up, summarized as time-to-event hazard ratios (HRs) and 95% confidence intervals (CIs). Six studies (300 MACEs in 2326 patients) were included. Four studies presented stress MBF data by unit increments. The pooled HR showed that an increase in stress MBF by 1 mL/g/min is a protective factor for MACE (HR = 0.32; 95% CI, 0.18-0.57; I2 = 62.9%, Pheterogeneity = 0.044). Two studies reported stress MBF as low/high. The results showed that a high-stress MBF was protective against MACEs (HR = 0.43; 95% CI, 0.24-0.78; I2 = 39.5%, Pheterogeneity = 0.199). Quantification of stress MBF using positron emission tomography/computed tomography and coronary magnetic resonance might have incremental predictive value for future MACEs in a population at intermediate to high cardiovascular risk. The results will require validation in large prospective randomized controlled trials.

Ticagrelor is more effective than clopidogrel in carrier of nonfunctional CYP2C19 allele who has diabetes and acute coronary syndrome - case report and literature review.

Clopidogrel is a purinergic receptor P2Y12 (P2RY12)-blocking pro-drug used to inhibit platelet aggregation in patients at risk for major adverse cardiac events (MACE), such as coronary artery disease and stroke. Despite clopidogrel therapy, some patients may still present with recurrent cardiovascular events. One possible cause of recurrence are variants in the cytochrome P450 2C19 (CYP2C19) gene. CYP2C19 is responsible for the metabolism of many drugs including clopidogrel. Recent studies have associated pharmacogenetics testing of CYP2C19 variants to guide clopidogrel therapy with a decreased risk of certain recurrent MACEs. Through a different mechanism, diabetes mellitus (DM) and obesity are also associated with clopidogrel treatment failure. We describe the case of a 64-year-old Caucasian woman with a history of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI), and DM/obesity, who presented to University of Texas Medical Branch (UTMB) in 2019 with a transient ischemic attack (TIA) while on clopidogrel/aspirin dual anti-platelet therapy. After CYP2C19 genetic testing revealed that she was an intermediate metabolizer with a heterozygous *2 genotype, ticagrelor replaced the clopidogrel treatment regimen. No future MACEs were documented in the two-year patient follow-up. Thus, ACS patients with DM/obesity who have undergone PCI and are intermediate CYP2C19 metabolizers may yield better treatment outcomes if prescribed ticagrelor instead of clopidogrel. Whether this improvement was due to genotype-guided therapy or the differing interactions of clopidogrel/ticagrelor in DM/obese patients is unknown based on available data. Regardless, CYP2C19 genotype-guided treatment of ACS/PCI patients, with consideration of DM/obesity status, may provide effective individualized therapy compared to standard treatment. The inclusion of DM/obesity in this study is clinically relevant because DM/obesity has become a major health issue in the United States and worldwide.

Quantitative plaque assessment by coronary computed tomography angiography: An up-to-date review

Abstract Coronary computed tomography angiography has an emerging role in the diagnostic workup of coronary artery disease. Due to its high sensitivity and negative predictive value, coronary computed tomography angiography can rule out obstructive coronary artery diseases and substitute invasive coronary angiography in many cases. In addition, coronary computed tomography angiography provides a unique information beyond stenosis grading as it can visualize atherosclerosis and quantify its extent. Qualitative and quantitative plaque assessment provides an incremental value in the prediction of future major adverse cardiac events. Moreover, determining adverse plaque features has a potential to identify advanced atherosclerosis and patients at increased risk of acute coronary syndrome. Nevertheless, challenges may emerge with the process of quantifying coronary plaques due to limited reproducibility, lack of automated, standardized and validated techniques. Therefore, reliable quantified data are scarce due to the various computed tomography scanners and software platforms and investigations with small sample sizes. Radiomics and machine learning-based image processing methods are relatively new in the field of cardiovascular plaque imaging. These techniques hold the promise to improve diagnostic performance, reproducibility and prognostic value of computed tomography based plaque assessment.

Coronary Artery Calcium Versus Pooled Cohort Equations Score for Primary Prevention Guidance: Randomized Feasibility Trial

ObjectivesThis study sought to determine the feasibility of performing an extensive randomized outcomes trial comparing a coronary artery calcium (CAC)- versus a pooled cohort equations (PCE) risk score–based strategy for initiating statin therapy for primary atherosclerotic cardiovascular disease (ASCVD) prevention. BackgroundStatin therapy is standard for the primary prevention of ASCVD in subjects at increased risk. National guidelines recommend using the American College of Cardiology/American Heart Association PCE risk score to guide a statin recommendation. Whether guidance by a CAC score is equivalent or superior is unknown. MethodsCorCal (Effectiveness of a Proactive Cardiovascular Primary Prevention Strategy, With or Without the Use of Coronary Calcium Screening, in Preventing Future Major Adverse Cardiac Events) was a randomized trial consenting 601 patients without known ASCVD, diabetes, or prior statin therapy recruited from primary care clinics and randomized to CAC- (n = 302) or PCE guidance (n = 299) of statin initiation for primary prevention. Enrolled subjects and their physicians made final treatment decisions. Primary outcomes compared the proportion of statin recommendations received and subject adherence over 1 year between CAC- and PCE-arm subjects. Modeled medical costs, adverse effects, and low-density lipoprotein–cholesterol (LDL-C) were additional measures of interest. ResultsSubjects were well matched, and 540 (89.9%) completed entry testing and received a protocol-based recommendation. A statin was recommended in 101 (35.9%) CAC-arm and 124 (47.9%) PCE-arm subjects (P = 0.005). Compared to PCE-based recommendations, CAC-arm subjects were reclassified from statin to no statin in 36.0% and from no statin to statin in 5.6% of cases, resulting in a total reclassification of 20.6%. Physicians accepted the study-dictated recommendation to start a statin in 88.1% of CAC-arm vs 75.0% of PCE-arm subjects (P = 0.01). Patient-reported adherence to this recommendation at 3 months was 62.2% vs 42.2%, respectively (P = 0.009). At 1 year, statin adherence remained superior, LDL-C levels were lower, estimated costs were similar or reduced in CAC subjects, and few events occurred. ConclusionsCAC guidance may be a more efficient, personalized, cost-effective, and motivating approach to statin initiation and maintenance in primary prevention. This feasibility phase of CorCal should be regarded as hypothesis-generating with respect to cardiovascular outcomes, which is being addressed in a large, longer-term outcomes trial. (Effectiveness of a Proactive Cardiovascular Primary Prevention Strategy, With or Without the Use of Coronary Calcium Screening, in Preventing Future Major Adverse Cardiac Events [CorCal]; NCT03439267)