Citations

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCAs) and angina with nonobstructive coronary arteries (ANOCAs) present diagnostic and therapeutic challenges. We assessed the frequency of coronary microvascular disease (CMD) and its subtypes in MINOCA compared with ANOCA and evaluated long-term cardiovascular outcomes. METHODS: Patients with nonobstructive coronary arteries undergoing invasive coronary function testing from 2012 to 2022 were prospectively enrolled and retrospectively classified as MINOCA or ANOCA (reference group). Myocardial infarction due to atherothrombosis, myocarditis, and Takotsubo syndrome were excluded. Invasive provocation testing was performed. CMD was classified as endothelium-independent (coronary flow reserve <2.5 with adenosine) and endothelium-dependent (<50% increase in coronary blood flow with acetylcholine). Major adverse cardiovascular events (cardiac death, nonfatal myocardial infarction, heart failure hospitalization, urgent revascularization, stroke) were recorded over 8 years. RESULTS: Of 622 patients, 73 (12%) had MINOCA (69% female, median age 56 years) and 549 (88%) ANOCA (72% female, median age 53 years). CMD was common in both groups (71% versus 64%; P =0.271), while endothelium-independent CMD was more frequent in MINOCA (41% versus 21%; P <0.001). Over a median follow-up of 4.5 years, major adverse cardiovascular events occurred more often in MINOCA (40% versus 11%; adjusted hazard ratio, 2.4; P =0.001). CMD predicted higher major adverse cardiovascular events in both MINOCA (hazard ratio, 3.6 [95% CI, 1.1–12.0]; P =0.038) and ANOCA (hazard ratio, 7.9 [95% CI, 2.9–21.8]; P <0.001). CONCLUSIONS: CMD is common in both MINOCA and ANOCA. The higher prevalence of endothelium-independent CMD in MINOCA suggests a potential mechanistic role in infarction. Patients with MINOCA have a worse prognosis than ANOCA, particularly when CMD is present.

Abstract Aims Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce major adverse cardiovascular events in diabetics. This study aimed to investigate the cardiac, cancer, and overall mortality effects of GLP-1 RAs in diabetics treated with anthracyclines. Methods and results We retrospectively identified 1384 diabetics treated with anthracyclines from 2013 to 2023; 56 received GLP-1 RAs between their first and last dose of anthracycline. These patients were propensity score matched 4:1 to 224 controls without concurrent GLP-1 RA use. Because stage was not available for 10 of the 56 patients, a repeat analysis was conducted with additional matching for cancer stage in 46 cases and 92 controls. Major endpoints were rate of all-cause and cancer-related and cardiovascular disease (CVD)–related mortality, no evidence of disease (NED), and hospitalization for CVD including heart failure (HF), over 5 years. Survival analyses were conducted using cause-specific hazards Cox regression. Patients on GLP-1 RAs had a significantly lower 5 year overall mortality (HR 0.46, CI 0.24–0.87, P = 0.007) and cancer-related mortality (HR 0.42, CI 0.19–0.91, P = 0.03). This mortality risk reduction remained significant even when accounting for covariates (HR 0.39, CI 0.20–0.75, P = 0.002). The percentage of patients with NED was higher in the GLP-1 RA than control group (60.9% vs. 38.0%, P = 0.007). A decline in left ventricular ejection fraction was seen in controls but not in patients on GLP-1 RAs. There was no significant difference in CVD hospitalization; the rate of HF-related hospitalization was very low overall. Conclusion GLP-1 RAs may offer survival benefits and better cancer- and cardiac function-related outcomes in diabetics undergoing anthracycline chemotherapy.

Abstract Aims Acute myocardial infarction (AMI) patients face a substantial risk of cardiovascular events and rehospitalization. The impact of the SmartHeart 12-lead electrocardiogram (ECG) telemedicine device on healthcare utilization has not been tested in a US randomized trial. Methods and results Patients with AMI were randomized at discharge to standard of care without (control group) or with the SmartHeart 12-lead ECG device (intervention group). The primary endpoint was the rate of emergency department (ED) visits, hospital readmissions, and any cardiovascular testing from discharge to 90 days of follow-up. The primary endpoint was reached in 57 (59%) patients in the control group and 53 (63%) patients in the intervention group (P = 0.61). However, in the intervention group, only 30% of patients complied with two follow-up training SmartHeart 12-lead ECG transmissions after discharge, and only 24% used the device thereafter. Among device users, ED presentations were lower in the intervention group than in the control group (8.0% vs. 29%, P = 0.04). In all patients advised to present to the ED upon device use (38%), a clinically relevant cardiovascular diagnosis was made. One patient survived a ventricular fibrillation cardiac arrest as advised to present to ED urgently after device use. Conclusion In this US-based RCT, there were no significant differences in the primary outcome in the intention-to-treat analysis. However, according to per-protocol analysis, proper use of the SmartHeart ECG device with 24/7 telemedicine support reduced inappropriate and increased appropriate ED presentations after hospitalization for AMI.

Background We tested whether biologic age, as estimated by deficits, functional impairments, or Age‐Gap or their combination, provide improved estimation of cause‐specific death as compared with chronological age. Methods Cardiovascular and noncardiovascular deficits, functional impairments, and Age‐Gap were prospectively collected in 535 patients aged ≥55 years undergoing percutaneous coronary interventions between August 1, 2014, and March 31, 2018. Age‐Gap was calculated as the difference between chronological age and age estimated by artificial intelligence ECG using a convolutional neural network. The full biological age model included deficits, functional impairments, and Age‐Gap >2 SD. A multivariable reduced model with the least number of variables was also created to provide a comparable C index to the full model. Results The average chronological age was 72.1±9.5 years, and there were 68% of men. During a median follow‐up of 2.61 years, 124 (23%) patients died. There was a modest correlation between Age‐Gap and biological age ( r =0.28 [95% CI, 0.20–0.35]; P <0.001). When modeled with chronologic age as a covariate, Age‐Gap predicted all‐cause (hazard ratio [HR], 1.07 [95% CI, 1.04–1.10]; P <0.001) and cardiovascular (HR, 1.07 [95% CI, 1.04–1.11]; P <0.001) mortality. As compared with chronological age, the full biological age model noted significant improvement in the prediction of long‐term overall (95% CI, 0.65–0.78), cardiovascular (95% CI, 0.69–0.77), and noncardiovascular (95% CI, 0.55–0.86) mortality. In the reduced models, most prognostic information for noncardiovascular mortality (C index: 0.79) was obtained by subjective difficulty in performing tasks, whereas the deficit‐based estimation predicted cardiovascular mortality (C index: 0.72). Conclusions Estimated biological age from deficits and functional impairments was superior to chronological age in predicting long‐term cause‐specific mortality following percutaneous coronary interventions.

Background Coronary microvascular dysfunction (CMD) represents an early functional characteristic of coronary vascular aging. Klotho (α‐klotho) is a circulating protein inversely linked to physiological aging. We examined low klotho as a potential marker for vascular aging in patients with CMD and no coronary artery disease. Methods and Results Patients undergoing nonurgent angiogram for chest pain who had no coronary artery disease underwent invasive coronary microvascular and endothelial function testing. CMD was defined by ≤50% increase in coronary blood flow (percentage change in coronary blood flow) in response to intracoronary acetylcholine or coronary flow reserve ≤2. Fresh arterial whole blood was used to analyze circulating endothelial progenitor cells with flow cytometry. Stored arterial plasma was used for klotho analysis by ELISA. Participants with CMD (n=62) were compared with those without CMD (n=36). Those with CMD were age 55±10 years (versus 51±11 years; P =0.07) and 73% women (versus 81%; P =0.38). Traditional risk factors for coronary artery disease were similar between groups. Patients with CMD had less klotho (0.88±1.50 versus 1.75±2.38 ng/mL; P =0.03), and the odds of low klotho in CMD were significant in a logistic regression model after adjusting for traditional cardiovascular risk factors (odds ratio [OR], 0.80 [95% CI, 0.636–0.996]; P =0.05). Higher klotho was associated with higher numbers of endothelial progenitor cells with vascular regenerative potential (CD34 + and CD34 + CD133 + KDR + ). Among a subgroup of patients with atherosclerotic cardiovascular disease risk <5% (n=58), CMD remained associated with lower klotho (OR, 0.80 [95% CI, 0.636–0.996]; P =0.047). Conclusions Klotho may be a biomarker for CMD and may be a therapeutic target for groups of patients without significant traditional cardiovascular risk.

Background 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. Methods and Results 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). Conclusions 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.

Introduction: Rate of aortic stenosis (AS) progression in patients with concurrent atrial fibrillation (AF) has not been previously described. Objectives: To describe changes over time in aortic valve area (AVA) and associated hemodynamics during AS progression in patients in AF versus sinus rhythm (SR). Methods: Patients with AVA ≤ 1 cm 2 and preserved left ventricular ejection fraction ≥50% were identified from the Mayo Clinic Echocardiographic Laboratory Database. Serial echocardiograms prior to the development of AVA ≤ 1 cm 2 (Time 0) were examined. Inverse probability weighting was used for statistical analysis. Results: A total of 166 patients were included (SR=79 and AF=87), mean age 78.1 ± 7.8 years, females 31%. The rates of AVA reduction (-0.14±0.01 vs -0.12±0.01 cm2/year, p=0.31) and increase in trans-aortic peak velocity (+0.23 ± 0.02 vs +0.22 ± 0.02 m/sec, p=0.55) and mean gradient (MG) (3.9 ± 0.3 vs 3.8 ± 0.4 mmHg, p=0.83) did not differ between AF and SR (Figure 1). However, AF was associated with systematically lower forward stroke volume index (SVi), peak velocity and MG for the same AVA compared to SR (p<0.04 for all) throughout AS progression. When AVA reached 1 cm 2 , SVi (38.8±6.6 vs 45.7 ±8.9, p=0.02), peak velocity (3.9 ± 0.6 vs 4.1 ± 0.6 m/sec, p=0.04) and MG (36.6±10.9 vs 41±12.8 mmHg, p=0.03) were lower in AF compared to SR. Conclusions: The rate of AS progression was not different in AF versus SR. However, forward flow was systematically lower in AF resulting in discordant AS during AS progression and when AVA reached 1 cm 2 . Doppler velocity and MG criteria for severe AS appear to be lower in AF versus SR which has implications for timely diagnosis of severe AS and patient management.

Abstract Aims The objective of this study was to assess the effect of HER2-directed therapy (HER2-Tx) on peripheral vasoreactivity and its correlation with cardiac function changes and the additive effects of anthracycline/cyclophosphamide (AC) therapy and baseline cardiovascular risk. Methods and results Single-centre, prospective cohort study of women with newly diagnosed stage 1–3 HER2-positive breast cancer undergoing HER2-Tx +/− AC. All participants underwent baseline and 3-monthly evaluations with Endo-Peripheral Arterial Tonometry (Endo-PAT), vascular biomarkers [C-type natriuretic peptide (CNP) and neuregulin-1 beta (NRG-1β)], and echocardiography. Cardiotoxicity was defined as a decrease in the left ventricular ejection fraction (LVEF) of &gt;10% to a value &lt;53%. Of the 47 patients enrolled, 20 (43%) received AC in addition to HER2-Tx. Deterioration of reactive hyperaemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs. 22%; P = 0.003). A decrease in CNP and log NRG-1β levels by 1 standard deviation did not differ significantly between the AC and non-AC groups (CNP: 20.0% vs. 7.4%; P = 0.20 and NRG-1β: 15% vs. 11%; P = 0.69) nor did GLS (35% vs. 37%; P = 0.89). Patients treated with AC had a significantly lower 3D LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3% (SD 3) vs. 63.8% (SD 4); P = 0.02). Reactive hyperaemia index and GLS were the only parameters correlating with LVEF change. Conclusion Combination therapy with AC, but not HER2-Tx alone, leads to a decline in peripheral vascular and cardiac function. Larger studies will need to define more precisely the causal correlation between vascular and cardiac function changes in cancer patients.

Background: Previous percutaneous coronary intervention risk models were focused on single outcome, such as mortality or bleeding, etc, limiting their applicability. Our objective was to develop contemporary percutaneous coronary intervention risk models that not only determine in-hospital mortality but also predict postprocedure bleeding, acute kidney injury, and stroke from a common set of variables. Methods: We built risk models using logistic regression from first percutaneous coronary intervention for any indication per patient (n=19 322, 70.6% with acute coronary syndrome) using the Mayo Clinic registry from January 1, 2000 to December 31, 2016. Approval for the current study was obtained from the Mayo Foundation Institutional Review Board. Patients with missing outcomes (n=4183) and those under 18 (n=10) were removed resulting in a sample of 15 129. We built both models that included procedural and angiographic variables (Models A) and precatheterization model (Models B). Results: Death, bleeding, acute kidney injury, and stroke occurred in 247 (1.6%), 650 (4.3%), 1184 (7.8%), and 67 (0.4%), respectively. The C statistics from the test dataset for models A were 0.92, 0.70, 0.77, and 0.71 and for models B were 0.90, 0.67, 0.76, and 0.71 for in-hospital death, bleeding, acute kidney injury, and stroke, respectively. Bootstrap analysis indicated that the models were not overfit to the available dataset. The probabilities estimated from the models matched the observed data well, as indicated by the calibration curves. The models were robust across many subgroups, including women, elderly, acute coronary syndrome, cardiogenic shock, and diabetes. Conclusions: The new risk scoring models based on precatheterization variables and models including procedural and angiographic variables accurately predict in-hospital mortality, bleeding, acute kidney injury, and stroke. The ease of its application will provide useful prognostic and therapeutic information to both patients and physicians.