Laxmi S. Mehta

Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association

Cardiovascular disease is the leading cause of mortality in American women. Since 1984, the annual cardiovascular disease mortality rate has remained greater for women than men; however, over the last decade, there have been marked reductions in cardiovascular disease mortality in women. The dramatic decline in mortality rates for women is attributed partly to an increase in awareness, a greater focus on women and cardiovascular disease risk, and the increased application of evidence-based treatments for established coronary heart disease. This is the first scientific statement from the American Heart Association on acute myocardial infarction in women. Sex-specific differences exist in the presentation, pathophysiological mechanisms, and outcomes in patients with acute myocardial infarction. This statement provides a comprehensive review of the current evidence of the clinical presentation, pathophysiology, treatment, and outcomes of women with acute myocardial infarction.

Safety and efficacy of drug-eluting stents in women: a patient-level pooled analysis of randomised trials

BACKGROUND The safety and efficacy of drug-eluting stents (DES) in the treatment of coronary artery disease have been assessed in several randomised trials. However, none of these trials were powered to assess the safety and efficacy of DES in women because only a small proportion of recruited participants were women. We therefore investigated the safety and efficacy of DES in female patients during long-term follow-up. METHODS We pooled patient-level data for female participants from 26 randomised trials of DES and analysed outcomes according to stent type (bare-metal stents, early-generation DES, and newer-generation DES). The primary safety endpoint was a composite of death or myocardial infarction. The secondary safety endpoint was definite or probable stent thrombosis. The primary efficacy endpoint was target-lesion revascularisation. Analysis was by intention to treat. FINDINGS Of 43,904 patients recruited in 26 trials of DES, 11,557 (26·3%) were women (mean age 67·1 years [SD 10·6]). 1108 (9·6%) women received bare-metal stents, 4171 (36·1%) early-generation DES, and 6278 (54·3%) newer-generation DES. At 3 years, estimated cumulative incidence of the composite of death or myocardial infarction occurred in 132 (12·8%) women in the bare-metal stent group, 421 (10·9%) in the early-generation DES group, and 496 (9·2%) in the newer-generation DES group (p=0·001). Definite or probable stent thrombosis occurred in 13 (1·3%), 79 (2·1%), and 66 (1·1%) women in the bare-metal stent, early-generation DES, and newer-generation DES groups, respectively (p=0·01). The use of DES was associated with a significant reduction in the 3 year rates of target-lesion revascularisation (197 [18·6%] women in the bare-metal stent group, 294 [7·8%] in the early-generation DES group, and 330 [6·3%] in the newer-generation DES group, p<0·0001). Results did not change after adjustment for baseline characteristics in the multivariable analysis. INTERPRETATION The use of DES in women is more effective and safe than is use of bare-metal stents during long-term follow-up. Newer-generation DES are associated with an improved safety profile compared with early-generation DES, and should therefore be thought of as the standard of care for percutaneous coronary revascularisation in women. FUNDING Women in Innovation Initiative of the Society of Cardiovascular Angiography and Interventions.

Preventing and Experiencing Ischemic Heart Disease as a Woman: State of the Science: A Scientific Statement From the American Heart Association.

The Institute of Medicine has defined sex as “the classification of living things, generally as male or female according to their reproductive organs and functions assigned by the chromosomal complement.”1 The term sex means biological differences between women and men, including chromosomes, sex organs, and hormonal contributions.2 Sex differences result from true biological differences in the structure and function of the cardiovascular systems of men and women. In contrast, gender differences ensue from a person’s self-representation, resulting in psychosocial roles and behaviors imposed by society; gender implies social roles, behaviors, and cultural norms. Gender differences play a role in the treatment of cardiovascular disease (CVD) and affect outcomes, but they are very different from sex differences that arise from the genetic differences between men and women. Sex differences are a result of a single chromosomal difference between men (XY) and women (XX). Gender, however, is a social construct that differentiates men from women in a society as they assume their social roles. Gender develops on the basis of cultural norms and is articulated through values, perceptions, psychosocial characteristics, and behaviors.1,3,4 Sex- and gender-specific science addresses how experiences of the same disease, for example, ischemic heart disease (IHD), are similar and different with respect to biological sex and gender. For instance, women tend to have smaller coronary arteries than men, and women have less obstructive IHD than men.5–7 However, gender differences, which are influenced by ethnicity, culture, and socioeconomic environment, are intimately involved in risk factors and risk behaviors (eg, psychosocial risk factors, physical inactivity [PI], cardiac rehabilitation participation, obesity, and tobacco use) that play a far greater role in outcomes among women with IHD than biological sex differences, given that 80% of heart disease is preventable. These differences affect the mechanism and expression of …

Cardiovascular Effects of Exposure to Cigarette Smoke and Electronic Cigarettes : Clinical Perspectives From the Prevention of Cardiovascular Disease Section Leadership Council and Early Career Councils of the American College of Cardiology

Cardiovascular morbidity and mortality as a result of inhaled tobacco products continues to be a global healthcare crisis, particularly in low- and middle-income nations lacking the infrastructure to develop and implement effective public health policies limiting tobacco use. Following initiation of public awareness campaigns 50 years ago in the United States, considerable success has been achieved in reducing the prevalence of cigarette smoking and exposure to secondhand smoke. However, there has been a slowing of cessation rates in the United States during recent years, possibly caused by high residual addiction or fatigue from cessation messaging. Furthermore, tobacco products have continued to evolve faster than the scientific understanding of their biological effects. This review considers selected updates on the genetics and epigenetics of smoking behavior and associated cardiovascular risk, mechanisms of atherogenesis and thrombosis, clinical effects of smoking and benefits of cessation, and potential impact of electronic cigarettes on cardiovascular health.

Resolution of refractory no‐reflow with intracoronary epinephrine

Refractory no‐reflow is associated with adverse outcomes in patients undergoing percutaneous coronary intervention. Charts were reviewed to identify 29 consecutive patients in whom intracoronary epinephrine was administered for refractory no‐reflow. The effects of intracoronary epinephrine on coronary flow (TIMI grade), cardiac rhythm, and systolic blood pressure in the cardiac catheterization laboratory were assessed. Administration of intracoronary epinephrine (mean dose, 139 ± 189 μg) resulted in significant improvement in coronary flow. After administration, TIMI 3 flow was established in 69% of patients. Overall, TIMI flow significantly increased (mean TIMI flow form 1.0 ± 1.0 to 2.66 ± 0.55; P = 0.0001). Intracoronary epinephrine resulted in significant but tolerable increase in heart rate (72 ± 19 to 86 ± 26 beats/min; P = 0.009), but no cases of acute dysrhythmia. These findings indicate that intracoronary epinephrine may exert salutary effects in patients suffering refractory no‐reflow following elective or acute coronary interventions. Cathet Cardiovasc Intervent 2002;57:305–309.

Mortality Risk Associated With Bundle Branch Blocks and Related Repolarization Abnormalities (from the Women's Health Initiative [WHI])

Electrocardiographic bundle branch block (BBB) has higher cardiac and all-cause death. However, reports on the association between BBBs and mortality in the general populations are conflicting. The aim of this study was to evaluate the risk for coronary heart disease (CHD) and all-cause death associated with left BBB (LBBB) and right BBB (RBBB) during 14 years of follow-up in 66,450 participants from the Womens Health Initiative (WHI) study. Cox proportional-hazards regression was performed for mortality risk in Women with LBBB (n = 714) and those with RBBB (n = 832). In risk models adjusted for demographic and clinical risk factors in women with cardiovascular disease (CVD), hazard ratios for CHD death were 2.92 (95% confidence interval 2.08 to 4.08, p <0.001) for LBBB and 1.62 (95% confidence interval 1.08 to 2.43, p <0.05) for RBBB, and only LBBB was a significant predictor of all-cause death (hazard ratio 1.43, 95% confidence interval 1.11 to 1.83, p <0.01). In CVD-free women, only LBBB was a significant predictor of CHD death (fully adjusted hazard ratio 2.17, 95% confidence interval 1.37 to 3.43, p <0.01), and neither blocks was predictive of all-cause death. From several repolarization variables that were significant mortality predictors in univariate risk models, after adjustment for other electrocardiographic covariates and risk factors, ST J-point depression in lead aVL ≤-30 μV in women with LBBB was an independent predictor of CHD death, with a more than fivefold increase in risk. None of the repolarization variables were independent predictors in women with RBBB. In conclusion, prevalent LBBB in CVD-free women and LBBB and RBBB in women with CVD were significant predictors of CHD death. In women with LBBB, ST J-point depression in lead aVL was a strong independent predictor of CHD death.

Rationale and study design of the CardioGene Study: genomics of in-stent restenosis

BACKGROUND AND AIMS in-stent restenosis is a major limitation of stent therapy for atherosclerosis coronary artery disease. The CardioGene Study is an ongoing study of restenosis in bare mental stents (BMS) for the treatment of coronary artery disease. The overall goal is to understand the genetic determinants of the responses to vascular injury that result in the development of restenosis in some patients but not in others. Gene expression profiling at transcriptional and translational levels provides global assessment of gene activity after vascular injury and mechanistic insight. Furthermore, the delineation of genetic biomarkers would be of value in the clinical setting of risk-stratify patients prior to stent therapy. Prospective risk stratification would allow for the rational selection of specialized treatments against the development of in-stent restenosis (ISR), such as drug-eluting stents. SETTING Patients are enrolled at two sites in the US with high-volume cardiac catheterization facilities: the William Beaumont Hospital in Royal Oak, MI, USA, and the Mayo Clinic in Rochester, MN, USA. STUDY DESIGN Two complementary study designs are used to understand the molecular mechanisms of restenosis and the genetic biomarkers predictive of restenosis. First, 350 patients are enrolled prospectively at the time of stent implantation. Blood is sampled prior to stent placement and afterwards at 2 weeks and 6 months. The clinical outcome of restenosis is determined 6 and 12 months after stent placement. The primary outcome is clinical restenosis at 6 months. The major secondary outcome is clinical restenosis at 12 months. Second, a corollary case-control analysis will be carried out with the enrollment of an additional 250 cases with a history of recurrent restenosis after treatment with BMS. Controls for this analysis are derived from the prospective cohort. PATIENTS AND METHODS Consecutive patients presenting to the cardiac catheterization laboratory are screened, informed about the study and enrolled after signing the consent form. Enrollment has been completed for the prospective cohort, and enrollment of the additional group is ongoing. A standardized questionnaire is used to collect clinical data primarily through direct patient interview to assess medical history, medication use, functional status, family history, environmental factors, and social history. Further data are abstracted from the medical charts and catheterization reports. A total of 276 clinical variables are collected per individual at baseline, and 49 variables are collected at each of the 6- and 12-month follow-up visits. A Clinical Events Committee adjudicates clinical outcomes. Blood samples are processed at each clinical enrollment site using standardized operating procedures. From each blood sample, several aliquots are prepared and stored of peripheral blood mononuclear cells, granulocytes, platelets, serum, and plasma. Additionally, a portion of each patients leukocytes is cryopreserved for future cell-line creation. Samples are frozen and shipped to the National Heart, Lung and Blood Institute (NHLBI). Additional materials generated in the analysis of the samples at the NHLBI are frozen and stored, including isolated genomic DNA, total RNA, reverse transcribed cDNA libraries and labeled RNA hybridization mixtures used in microarray analysis. Per individual in the prospective cohort, high-quality transcript profiles of peripheral blood mononuclear cells at each time of blood sampling are obtained using Affymetrix U133A microarrays (Affymetrix, Santa Clara, CA, USA). Per chip, this yields 495,930 features per individual per time of sampling. This represents expression levels for 22,283 genes per patients oer time of blood sampling, including 14,500 well-characterized human genes. Proteomics of plasma is performed with multidimensional liquid chromatography and tandem mass spectrometry. Protein expression is examined similarly to mRNA expression as a measure of gene expression. Genotyping is performed in two manners. First, those genes showing differential expression at the levels of mRNA and protein are investigated using a candidate gene approach. Specific variants in known gene regulatory regions, such as promoters, are sought initially, as those variants may explain differences in expression level. Second, a genome-wide scan is used to identify genetic loci that are associated with ISR. Those regions identified are further examined for genes that show differential expression in the mRNA microarray profiling or proteomics investigations. These genes are finely investigated for candidate SNPs and other gene variants. Complementary genomic and proteomic approaches are expected to be robust. Integration of data sets is accomplished using a variety of informatics tools, organization of gene expression into functional pathways, and investigation of physical maps of up- and downregulated sets of genes. CONCLUSIONS The CardioGene Study is designed to understand ISR. Global gene and protein expression profiling define molecular phenotypes of patients. Well-defined clinical phenotypes will be paired with genomic data to define analyses aimed to achieve several goals. These include determining blood gene and protein expression in patients with ISR, investigating the genetic basis of ISR, developing predictive gene and protein biomarkers, and the identification of new targets for treatment.

Safety and Efficacy of New-Generation Drug-Eluting Stents in Women Undergoing Complex Percutaneous Coronary Artery Revascularization from the WIN-DES Collaborative Patient-Level Pooled Analysis

OBJECTIVES The purpose of this study was to investigate the safety and efficacy of new-generation drug-eluting stents (DES) versus early-generation DES in women undergoing complex percutaneous coronary intervention (CPCI). BACKGROUND Whether the benefits of new-generation DES are preserved in women undergoing complex percutaneous revascularization is unknown. METHODS We pooled patient-level data from women enrolled in 26 randomized trials of DES. Study population was categorized according to the presence or absence of CPCI, which was defined as the composite of total stent length >30 mm, ≥2 stents implanted, ≥2 lesions treated, or bifurcation lesion as target vessel. The primary endpoint was major adverse cardiovascular events (MACE) defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up. RESULTS Of 10,241 women included in the pooled database, 4,629 (45%) underwent CPCI. Compared with non-CPCI, women who underwent CPCI had a higher 3-year risk of MACE (adjusted hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.45 to 1.83; p < 0.0001). In women who underwent CPCI, use of new-generation DES was associated with significantly lower 3-year risk of MACE (adjusted HR: 0.81; 95% CI: 0.68 to 0.96), target lesion revascularization (adjusted HR: 0.74; 95% CI: 0.57 to 0.95), and definite or probable stent thrombosis (ST) (adjusted HR: 0.50; 95% CI: 0.30 to 0.83). The benefit of new-generation DES on efficacy and safety outcomes was uniform between CPCI and non-CPCI groups, without evidence of interaction. By landmark analysis, new-generation DES were associated with low rates (≤0.4%) of very-late ST irrespective of procedural complexity. CONCLUSIONS Women undergoing CPCI remain at higher risk of adverse events. The long-term ischemic benefits of new-generation DES platforms are uniform among complex and non-complex percutaneous revascularization procedures in women.

2015 ACC/AHA/HRS Advanced Training Statement on Clinical Cardiac Electrophysiology (A Revision of the ACC/AHA 2006 Update of the Clinical Competence Statement on Invasive Electrophysiology Studies, Catheter Ablation, and Cardioversion)

Eric S. Williams, MD, MACC, Chair Jonathan L. Halperin, MD, FACC, Co-Chair James A. Arrighi, MD, FACC Eric H. Awtry, MD, FACC Eric R. Bates, MD, FACC John E. Brush, Jr, MD, FACC Salvatore Costa, MD, FACC Lori Daniels, MD, MAS, FACC Akshay Desai, MD, FACC[‡][1] Douglas E. Drachman, MD,

Changes in the Professional Lives of Cardiologists Over 2 Decades

The American College of Cardiology third decennial Professional Life Survey was completed by 2,313 cardiologists: 964 women (42%) and 1,349 men (58%). Compared with 10 and 20 years ago, current results reflect a substantially lower response rate (21% vs. 31% and 49%, respectively) and an aging workforce that is less likely to be in private practice. Women continue to be more likely to practice in academic centers, be pediatric cardiologists, and have a noninvasive subspecialty. Men were more likely to indicate that family responsibilities negatively influenced their careers than previously, whereas women remained less likely to marry or have children. Men and women reported similar, high levels of career satisfaction, with women reporting higher satisfaction currently. However, two-thirds of women continue to experience discrimination, nearly 3 times the rate in men. Personal life choices continue to differ substantially for men and women in cardiology, although differences have diminished.