Effect of Mavacamten in Women Compared With Men With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM.

BACKGROUND: Compared with men, women with hypertrophic cardiomyopathy (HCM) have a higher incidence of heart failure and worse outcomes. We investigated baseline clinical and echocardiographic characteristics and response to mavacamten among women compared with men in the EXPLORER-HCM study (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy). METHODS: A prespecified post hoc analysis of sex from the blinded, randomized EXPLORER-HCM trial of mavacamten versus placebo in symptomatic patients with obstructive HCM was performed. Baseline characteristics were compared with t tests for continuous variables (expressed as mean values) and χ2 tests for categorical variables. Prespecified primary, secondary, and exploratory end points and echocardiographic measurements from baseline to end of treatment (week 30) were analyzed with ANCOVA for continuous end points and a generalized linear model with binomial distribution for binary end points, with adjustment for each outcome's baseline value, New York Heart Association class, ß-blocker use, and ergometer type. RESULTS: At baseline, women (n=102) were older (62 years versus 56 years; P<0.0001), had lower peak oxygen consumption (16.7 mL·kg-1·min-1 versus 21.3 mL·kg-1·min-1; P<0.0001), were more likely to be assigned New York Heart Association class III (42% versus 17%; P<0.0001), had worse health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 64 versus 75; P<0.0001), and had higher baseline plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels (1704 ng/L versus 990 ng/L; P=0.004) than men (n=149). After 30 weeks of mavacamten treatment, similar improvements were observed in women and men in the primary composite end point (percentage difference on mavacamten versus placebo, 22% versus 19%, respectively; P=0.759) and in the secondary end points of change in postexercise left ventricular outflow tract gradient (-42.4 mm Hg versus -33.6 mm Hg; P=0.348), change in peak oxygen consumption (1.2 mL·kg-1·min-1 versus 1.6 mL·kg-1·min-1; P=0.633), and percentage achieving ≥1 New York Heart Association class improvement (41% versus 28%; P=0.254). However, women had greater improvement in health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 14.8 versus 6.1; P=0.026) and in the exploratory end point of NT-proBNP levels (-1322 ng/L versus -649 ng/L; P=0.0008). CONCLUSIONS: Although at baseline women with symptomatic obstructive HCM enrolled in EXPLORER-HCM were older and had worse heart failure and health status than men, treatment with mavacamten resulted in similar improvements in the primary and most secondary EXPLORER-HCM end points and greater improvements in health status and NT-proBNP. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03470545.

In ischemic LV dysfunction, adding PCI to medical therapy did not reduce a composite of death or aborted sudden death.

SOURCE CITATION: Perera D, Morgan HP, Ryan M, et al; REVIVED-BCIS2 Investigators. Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: prespecified analyses from the REVIVED-BCIS2 trial. Circulation. 2023;148:862-871. 37555345.

In severe tricuspid regurgitation, tricuspid TEER improved QoL more than medical therapy at 1 y.

SOURCE CITATION: Sorajja P, Whisenant B, Hamid N, et al; TRILUMINATE Pivotal Investigators. Transcatheter repair for patients with tricuspid regurgitation. N Engl J Med. 4 Mar 2023. [Epub ahead of print]. 36876753.

DAPT de-escalation from ticagrelor to clopidogrel 1 mo after PCI for acute MI reduced net clinical events at 1 y.

SOURCE CITATION: Kim CJ, Park MW, Kim MC, et al. Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial. Lancet. 2021;398:1305-16. 34627490.

The Evolving Landscape of Impella Use in the United States Among Patients Undergoing Percutaneous Coronary Intervention With Mechanical Circulatory Support.

BACKGROUND: Impella was approved for mechanical circulatory support (MCS) in 2008, but large-scale, real-world data on its use are lacking. Our objective was to describe trends and variations in Impella use, clinical outcomes, and costs across US hospitals in patients undergoing percutaneous coronary intervention (PCI) treated with MCS (Impella or intra-aortic balloon pump). METHODS: From the Premier Healthcare Database, we analyzed 48 306 patients undergoing PCI with MCS at 432 hospitals between January 2004 and December 2016. Association analyses were performed at 3 levels: time period, hospital, and patient. Hierarchical models with propensity adjustment were used for association analyses. We examined trends and variations in the proportion of Impella use, and associated clinical outcomes (in-hospital mortality, bleeding requiring transfusion, acute kidney injury, stroke, length of stay, and hospital costs). RESULTS: Among patients undergoing PCI treated with MCS, 4782 (9.9%) received Impella; its use increased over time, reaching 31.9% of MCS in 2016. There was wide variation in Impella use across hospitals (>5-fold variation). Specifically, among patients receiving Impella, there was a wide variation in outcomes of bleeding (>2.5-fold variation), and death, acute kidney injury, and stroke (all ≈1.5-fold variation). Adverse outcomes and costs were higher in the Impella era (years 2008-2016) versus the pre-Impella era (years 2004-2007). Hospitals with higher Impella use had higher rates of adverse outcomes and costs. After adjustment for the propensity score, and accounting for clustering of patients by hospitals, Impella use was associated with death: odds ratio, 1.24 (95% CI, 1.13-1.36); bleeding: odds ratio, 1.10 (95% CI, 1.00-1.21); and stroke: odds ratio, 1.34 (95% CI, 1.18-1.53), although a similar, nonsignificant result was observed for acute kidney injury: odds ratio, 1.08 (95% CI, 1.00-1.17). CONCLUSIONS: Impella use is rapidly increasing among patients undergoing PCI treated with MCS, with marked variability in its use and associated outcomes. Although unmeasured confounding cannot be ruled out, when analyzed by time periods, or at the hospital level or the patient level, Impella use was associated with higher rates of adverse events and costs. More data are needed to define the appropriate role of MCS in patients undergoing PCI.

A novel genetic marker of decreased inflammation and improved survival after acute myocardial infarction.

The CHRNA5 gene encodes a neurotransmitter receptor subunit involved in multiple processes, including cholinergic autonomic nerve activity and inflammation. Common variants in CHRNA5 have been linked with atherosclerotic cardiovascular disease. Association of variation in CHRNA5 and specific haplotypes with cardiovascular outcomes has not been described. The aim of this study was to examine the association of CHRNA5 haplotypes with gene expression and mortality among patients with acute myocardial infarction (AMI) and explore potential mechanisms of this association. Patients (N = 2054) hospitalized with AMI were genotyped for two common variants in CHRNA5. Proportional hazard models were used to estimate independent association of CHRNA5 haplotype with 1-year mortality. Both individual variants were associated with mortality (p = 0.0096 and 0.0004, respectively) and were in tight LD (D' = 0.99). One haplotype, HAP3, was associated with decreased mortality one year after AMI (adjusted HR = 0.42, 95% CI 0.26, 0.68; p = 0.0004). This association was validated in an independent cohort (N = 637) of post-MI patients (adjusted HR = 0.23, 95% CI 0.07, 0.79; p = 0.019). Differences in CHRNA5 expression by haplotype were investigated in human heart samples (n = 28). Compared with non-carriers, HAP3 carriers had threefold lower cardiac CHRNA5 mRNA expression (p = 0.023). Circulating levels of the inflammatory marker hsCRP were significantly lower in HAP3 carriers versus non-carriers (3.43 ± 4.2 versus 3.91 ± 5.1; p = 0.0379). Activation of the inflammasome, an important inflammatory complex involved in cardiovascular disease that is necessary for release of the pro-inflammatory cytokine IL-1 ß, was assessed in bone marrow-derived macrophages (BMDM) from CHRNA5 knockout mice and wild-type controls. In BMDM from CHRNA5 knockout mice, IL-1ß secretion was reduced by 50% compared to wild-type controls (p = 0.004). Therefore, a common haplotype of CHRNA5 that results in reduced cardiac expression of CHRNA5 and attenuated macrophage inflammasome activation is associated with lower mortality after AMI. These results implicate CHRNA5 and the cholinergic anti-inflammatory pathway in survival following AMI.

Predicting long-term bleeding after percutaneous coronary intervention.

OBJECTIVES: To construct a model to predict long-term bleeding events following percutaneous coronary intervention (PCI). BACKGROUND: Treatment with dual antiplatelet therapy following PCI involves balancing the benefits of preventing ischemic events with the risks of bleeding. There are no models to predict long-term bleeding events after PCI. METHODS: We analyzed 1-year bleeding outcomes from 3,128 PCI procedures in the Patient Risk Information Services Manager (PRISM) observational study. Patient-reported bleeding events were categorized according to Bleeding Academic Research Consortium (BARC) definitions. Logistic regression analysis was used to develop a model predicting BARC ≥ 1 bleeding. RESULTS: BARC 0, 1, 2 or 3 bleeding was observed in 574 (18.4%); 2382 (76.2%); 114 (3.6%); and 58 (1.8%) patients, respectively. Compared to patients who had no bleeding, patients with BARC ≥ 1 bleeding were more often female (30 vs. 23%), Caucasian (94 vs. 83%), had a higher incidence of drug eluting stent (DES) implantation (83 vs. 76%) and warfarin therapy (7.4 vs. 3.9%), and a lower incidence of diabetes (31 vs. 45%; P-value <0.01 for all comparisons). A 27-variable model had moderate discrimination (c-statistic of 0.674), and good calibration, as did a parsimonious model with 10 variables (c-statistic = 0.667). This model performed well in predicting BARC ≥ 2 bleeding events as well (c-statistic = 0.653). CONCLUSIONS: Bleeding is common in the first year after PCI, and can be predicted by pre-procedural patient characteristics and use of DES. Objective estimates of bleeding risk may help support shared decision-making with respect to stent selection and duration of antiplatelet therapy following PCI. © 2016 Wiley Periodicals, Inc.

Association of Discharge Aspirin Dose With Outcomes After Acute Myocardial Infarction: Insights From the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) Study.

BACKGROUND: Aspirin is the most widely used antiplatelet drug postmyocardial infarction, yet its optimal maintenance dose after percutaneous coronary intervention with stenting remains uncertain. METHODS AND RESULTS: We compared outcomes of 10 213 patients with myocardial infarction who underwent percutaneous coronary intervention and were discharged on dual-antiplatelet therapy at 228 US hospitals in the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Major adverse cardiovascular events and bleeding within 6 months postdischarge were compared between high-dose (325 mg) and low-dose aspirin (81 mg) by using regression models with inverse probability-weighted propensity adjustment. Overall, 6387 patients (63%) received high-dose aspirin at discharge. Major adverse cardiovascular events risk was not significantly different between groups (high versus low: unadjusted 8.2% versus 9.2%; adjusted hazard ratio, 0.99; 95% confidence interval, 0.85-1.17). High-dose aspirin use was associated with greater risk of any Bleeding Academic Research Consortium-defined bleeding events (unadjusted 24.2% versus 22.7%; adjusted odds ratio, 1.19; 95% confidence interval, 1.06-1.33), driven mostly by minor Bleeding Academic Research Consortium type 1 or 2 bleeding events not requiring hospitalization (unadjusted 21.4% versus 19.5%; adjusted odds ratio, 1.19; 95% confidence interval, 1.05-1.34). Bleeding events requiring hospitalization were similar by aspirin dosing groups (unadjusted 2.8% versus 3.2%, adjusted odds ratio, 1.22; 95% confidence interval, 0.87-1.70). Similar associations were observed in landmark analyses accounting for aspirin dosing change over time, and across subgroup analyses by age, sex, baseline aspirin use, and type of ADP receptor inhibitor (clopidogrel versus prasugrel/ticagrelor). CONCLUSIONS: Among percutaneous coronary intervention-treated patients with myocardial infarction, high-maintenance-dose aspirin was associated with similar rates of major adverse cardiovascular events, but a greater risk of minor bleeding than those discharged on low-dose aspirin.

Impact of intravascular ultrasound on the long-term clinical outcomes in the treatment of coronary ostial lesions.

OBJECTIVES: To evaluate the long-term outcomes of patients with ostial lesions who underwent percutaneous coronary intervention (PCI) with and without the use of intravascular ultrasound (IVUS). BACKGROUND: A higher rate of adverse cardiac events is associated with PCI of ostial lesions as compared with nonostial disease. METHODS: From 7/2002 to 8/2010, 225 patients with 233 coronary ostial lesions underwent PCI with (n = 82) and without (n = 143) IVUS guidance. Ostial lesions included both native aorto-ostial or major coronary vessel (left anterior descending, left circumflex, and ramus intermedius) lesions. Clinical outcomes [cardiovascular death, myocardial infarction (MI), and target lesion revascularization (TLR)] at a mean follow-up of 4.2 ± 2.5 years were compared between patients undergoing PCI of an ostial lesion with and without use of IVUS using univariate and propensity score adjusted analyses. RESULTS: Aorto-ostial lesions (n = 109) comprised 47% of lesions, whereas the remaining lesions (53%) involved major coronary vessels. After propensity score adjustment, IVUS use was associated with lower rates of the composite of cardiovascular death, MI, or TLR (HR 0.54, 95% CI 0.29-0.99; P = 0.04), composite MI or TLR (HR 0.39, 95% CI 0.18-0.83; P = 0.01), and MI (HR 0.31, 95% CI 0.11-0.85; P = 0.02) as compared with no IVUS. The use of IVUS was also associated with a trend towards a lower rate of TLR (HR 0.42, 95% CI 0.17-1.02; P = 0.06). CONCLUSIONS: PCI of coronary ostial lesions with the use of IVUS was associated with significantly lower rates of adverse cardiac events.

Risk model for estimating the 1-year risk of deferred lesion intervention following deferred revascularization after fractional flow reserve assessment.

AIMS: Although lesions deferred revascularization following fractional flow reserve (FFR) assessment have a low risk of adverse cardiac events, variability in risk for deferred lesion intervention (DLI) has not been previously evaluated. The aim of this study was to develop a prediction model to estimate 1-year risk of DLI for coronary lesions where revascularization was not performed following FFR assessment. METHODS AND RESULTS: A prediction model for DLI was developed from a cohort of 721 patients with 882 coronary lesions where revascularization was deferred based on FFR between 10/2002 and 7/2010. Deferred lesion intervention was defined as any revascularization of a lesion previously deferred following FFR. The final DLI model was developed using stepwise Cox regression and validated using bootstrapping techniques. An algorithm was constructed to predict the 1-year risk of DLI. During a mean (±SD) follow-up period of 4.0 ± 2.3 years, 18% of lesions deferred after FFR underwent DLI; the 1-year incidence of DLI was 5.3%, while the predicted risk of DLI varied from 1 to 40%. The final Cox model included the FFR value, age, current or former smoking, history of coronary artery disease (CAD) or prior percutaneous coronary intervention, multi-vessel CAD, and serum creatinine. The c statistic for the DLI prediction model was 0.66 (95% confidence interval, CI: 0.61-0.70). CONCLUSION: Patients deferred revascularization based on FFR have variation in their risk for DLI. A clinical prediction model consisting of five clinical variables and the FFR value can help predict the risk of DLI in the first year following FFR assessment.

Intra-Aortic Balloon Counterpulsation in Patients With Chronic Heart Failure and Cardiogenic Shock: Clinical Response and Predictors of Stabilization.

OBJECTIVE: The aim of this work was to characterize the clinical response and identify predictors of clinical stabilization after intra-aortic balloon counterpulsation (IABP) support in patients with chronic systolic heart failure in cardiogenic shock before implantation of a left ventricular assist device (LVAD). BACKGROUND: Limited data exist regarding the clinical response to IABP in patients with chronic heart failure in cardiogenic shock. METHODS: We identified 54 patients supported with IABP before LVAD implantation. Criteria for clinical decompensation after IABP insertion and before LVAD included the need for more advanced temporary support, initiation of mechanical ventilation or dialysis, increase in vasopressors/inotropes, refractory ventricular arrhythmias, or worsening acidosis. The absence of these indicated stabilization. RESULTS: Clinical decompensation after IABP occurred in 23 patients (43%). Both patients who decompensated and those who stabilized had similar hemodynamic improvements after IABP support, but patients who decompensated required more vasopressors/inotropes. Clinical decompensation after IABP was associated with worse outcomes after LVAD implantation, including a 3-fold longer intensive care unit stay and 5-fold longer time on mechanical ventilation (P < .01 for both). Although baseline characteristics were similar between groups, right and left ventricular cardiac power indexes (cardiac power index = cardiac index × mean arterial pressure/451) identified patients who were likely to stabilize (area under the receiver operating characteristic curve = 0.82). CONCLUSIONS: Among patients with chronic systolic heart failure who develop cardiogenic shock, more than one-half of patients stabilized with IABP support as a bridge to LVAD. Baseline measures of right and left ventricular cardiac power, reflecting work performed for a given flow and pressure, may allow clinicians to identify patients with sufficient contractile reserve who will be likely to stabilize with an IABP versus those who may need more aggressive ventricular support.

The efficacy of ticagrelor is maintained in women with acute coronary syndromes participating in the prospective, randomized, PLATelet inhibition and patient Outcomes (PLATO) trial.

AIMS: The aim of this study was to assess the relationship between sex and clinical outcomes and treatment-related complications in patients with ST-elevation or non-ST-elevation acute coronary syndromes (ACS) randomized to treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial. METHODS: The associations between sex subgroup and the primary composite outcomes, secondary outcomes, and major bleeding endpoints as well as interaction of sex subgroup with treatment effects were analysed using Cox proportional-hazards models. RESULTS: Sex was not significantly associated with the probability of the primary composite endpoint [adjusted hazard ratio (HR): 1.02 (0.91-1.16)], or other adverse cardiovascular endpoints. Ticagrelor was similarly more effective than clopidogrel in reducing rates of the primary endpoint in women 11.2 vs. 13.2% [adjusted HR: 0.88 (0.74-1.06)] and men 9.4 vs. 11.1% [adjusted HR: 0.86 (0.76-0.97)] (interaction P-value 0.78), all-cause death in women 5.8 vs. 6.8% [adjusted HR: 0.90 (0.69-1.16)] and men 4.0 vs. 5.7% [adjusted HR: 0.80 (0.67-0.96)] (interaction P-value 0.49), and definite stent thrombosis in women 1.2 vs. 1.4% [adjusted HR: 0.71 (0.36-1.38)] and men 1.4 vs. 2.1% [adjusted HR: 0.63 (0.45-0.89)] (interaction P-value 0.78). The treatments did not differ for PLATO-defined overall major bleeding complications in women [adjusted HR: 1.01 (0.83-1.23)] or men [adjusted HR: 1.10 (0.98-1.24)]. Sex had no significant association with these outcomes (interactions P = 0.43-0.88). CONCLUSION: Female sex is not an independent risk factor for adverse clinical outcomes in moderate-to-high risk ACS patients. Ticagrelor has a similar efficacy and safety profile in men and women.

Rosiglitazone and outcomes for patients with diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

BACKGROUND: Rosiglitazone improves glycemic control for patients with type 2 diabetes mellitus, but there remains controversy regarding an observed association with cardiovascular hazard. The cardiovascular effects of rosiglitazone for patients with coronary artery disease remain unknown. METHODS AND RESULTS: To examine any association between rosiglitazone use and cardiovascular events among patients with diabetes mellitus and coronary artery disease, we analyzed events among 2368 patients with type 2 diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Total mortality, composite death, myocardial infarction, and stroke, and the individual incidence of death, myocardial infarction, stroke, congestive heart failure, and fractures, were compared during 4.5 years of follow-up among patients treated with rosiglitazone versus patients not receiving a thiazolidinedione by use of Cox proportional hazards and Kaplan-Meier analyses that included propensity matching. After multivariable adjustment, among patients treated with rosiglitazone, mortality was similar (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.58-1.18), whereas there was a lower incidence of composite death, myocardial infarction, and stroke (HR, 0.72; 95% CI, 0.55-0.93) and stroke (HR, 0.36; 95% CI, 0.16-0.86) and a higher incidence of fractures (HR, 1.62; 95% CI, 1.05-2.51); the incidence of myocardial infarction (HR, 0.77; 95% CI, 0.54-1.10) and congestive heart failure (HR, 1.22; 95% CI, 0.84-1.82) did not differ significantly. Among propensity-matched patients, rates of major ischemic cardiovascular events and congestive heart failure were not significantly different. CONCLUSIONS: Among patients with type 2 diabetes mellitus and coronary artery disease in the BARI 2D trial, neither on-treatment nor propensity-matched analysis supported an association of rosiglitazone treatment with an increase in major ischemic cardiovascular events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Conversations in cardiology: bridging antiplatelet therapy before surgery.

Bridging for antiplatelet therapy remains a subject of debate with data favoring GP blockers but at a risk of bleeding. This Conversation in Cardiology addresses a key and often asked question about use of alternatives to P2Y12 agents in patients requiring surgery within 6 months after drug eluting stent implantation.

CHRNA5 variant predicts smoking cessation in patients with acute myocardial infarction.

INTRODUCTION: While smoking is a major modifiable risk factor for secondary prevention of myocardial infarction (MI), active smoking is common among patients hospitalized with acute MI. Recent studies suggest that nicotinic receptor variants, and specifically the high-risk CHRNA5 rs16969968 A allele, are associated with cessation failure among noncardiac patients. This study investigates the association between CHRNA5 rs16969968 and smoking cessation in patients hospitalized with acute MI. METHODS: Using data from the TRIUMPH study, we ascertained smoking status at the time of index hospitalization for acute MI and 1 year after hospitalization. After adjusting for age and sex, we used logistic regression to model the association between smoking cessation and CHRNA5 rs16969968. RESULTS: At index admission, 752 Caucasian subjects were active smokers and 699 were former smokers. Among these ever-smokers, the A allele was associated with significantly decreased abstinence (45.0% abstinence for A allele carriers vs. 51.7% for GG homozygotes; odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.56-0.88, p = .0027). The A allele was also significantly associated with decreased abstinence at 1 year (69.1% abstinence for A allele carriers vs. 76.0% for GG homozygotes; OR = 0.70, 95% CI = 0.53-0.94, p = .0185). CONCLUSIONS: Among patients who have smoked and who are hospitalized with acute MI, the high-risk CHRNA5 allele was associated with lower likelihood of quitting before hospitalization and significantly less abstinence 1 year after hospitalization with MI. The CHRNA5 rs16969968 genotype may therefore identify patients who would benefit from aggressive, personalized smoking cessation intervention.

Exercise Testing to Unmask Latent LVOT Obstruction in a Highly Symptomatic Patient With Hypertrophic Cardiomyopathy.

Rest imaging in hypertrophic cardiomyopathy may underestimate or miss left ventricular outflow tract obstruction, leading to suboptimal management decisions that negatively affect symptomatic patients. The 2024 hypertrophic cardiomyopathy guidelines describe exercise stress testing as an important tool to determine overall exercise tolerance and latent, exercise-provoked left ventricular outflow tract obstruction.