Risk Assessment in Patient Selection for Transcatheter Aortic Valve Replacement.

Risk assessment models for transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement in high-risk patients and TAVR versus palliation in inoperable patients are based on surgical data and have limited discrimination and calibration in the setting of TAVR. Several novel risk models specifically designed for TAVR have improved discrimination over existing models but require further validation. Several clinical and echocardiographic variables, such as chronic lung disease, mitral regurgitation, and stroke volume index, influence outcomes. This article reviews current and novel risk models and important predictors of TAVR outcomes and proposes a framework to integrate them into clinical decision-making for patients with severe, symptomatic aortic stenosis.

Clinical characteristics and outcomes associated with the natural history of early repolarization in a young, biracial cohort followed to middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND: Early repolarization (ER), a common electrocardiographic phenotype, has been associated with increased mortality risk in middle-aged adults. Data are sparse on long-term follow-up and outcomes associated with ER in younger adults. METHODS AND RESULTS: We prospectively examined 5039 participants (mean age, 25 years at baseline, 40% black) from the Coronary Artery Disease Risk in Adults (CARDIA) cohort for 23 years. Twelve-lead ECGs were recorded and analyzed at years 0, 7, and 20 and coded as definite or probable ER using a standardized algorithm. Cox regression was used, and models were adjusted for important baseline and clinical covariates. Kaplan-Meier curves were created for presence of ER and total mortality and cardiovascular mortality. Participants with ER were more likely to be black, male, smoke, have higher systolic blood pressure, lower heart rate and body mass index, higher exercise duration, and longer PR, QRS, and QT intervals. ER was associated with total mortality (hazard ratio, 1.77; confidence interval, 1.38-2.28; P<0.01) and cardiovascular mortality (hazard ratio, 1.59; confidence interval, 1.01-2.50; P=0.04) in unadjusted analyses, but adjustment for age, sex, and race attenuated associations almost completely. Sex-race stratified analyses showed no significant associations between ER and outcome for any of the subgroups except blacks. CONCLUSIONS: The presence of ER at any time point during 23 years of follow-up was not associated with adverse outcomes. Black race and male sex confound the unadjusted association of ER and outcomes, with no race-sex interactions noted. Additional studies are necessary to understand the factors associated with heightened risk of death in those who maintain ER into and beyond middle age.

Cangrelor for treatment of arterial thrombosis.

INTRODUCTION: Percutaneous coronary intervention (PCI) is a highly effective treatment for obstructive coronary artery disease. Oral platelet P2Y12 receptor antagonists reduce ischemic events in patients treated with PCI. However, there are several limitations to their use, including variable pharmacodynamics, a slow onset and offset, and in those patients who are pretreated but subsequently require cardiac surgery, increased bleeding. Cangrelor is an intravenous agent that provides rapid and intensive inhibition of the P2Y12 receptor that quickly dissipates after discontinuation. A recent, Phase III randomized clinical trial of PCI patients demonstrated that cangrelor bolus and infusion reduced ischemic events compared with conventional clopidogrel therapy without increasing major bleeding. AREAS COVERED: This review outlines the pharmacodynamics, pharmacokinetics, and the safety and efficacy of cangrelor for the acute treatment of patients undergoing planned PCI. EXPERT OPINION: Cangrelor is an important addition to the current armamentarium of platelet inhibitors as it significantly reduces periprocedural myocardial infarction and stent thrombosis in a broad spectrum of patients, without increasing major bleeding or the need for transfusion. Cangrelor will have particular benefit in clopidogrel-naïve patients with high anatomical complexity and/or increased clinical risk (where the absolute risk for thrombotic and ischemic complications of PCI is greatest).

Prognostic value of frontal QRS-T angle in patients without clinical evidence of cardiovascular disease (from the Multi-Ethnic Study of Atherosclerosis).

Abnormal frontal QRS-T angle on a 12-lead electrocardiogram is associated with incident coronary heart disease and total mortality in a biracial cohort, but there have been no studies to date examining QRS-T angle's prognostic value across multiple ethnicities. We studied 6,814 participants (52.7% women, mean age 62 years) from Multi-Ethnic Study of Atherosclerosis, a multiethnic cohort aged 45 to 84 years free of clinical cardiovascular disease (CVD) at enrollment. Baseline examination included measurement of traditional risk factors and 12-lead electrocardiograms. Frontal QRS-T axis was defined as normal (less than seventy-fifth percentile), borderline (seventy-fifth to ninety-fifth percentile), or abnormal (ninety-fifth percentile or more), and participants were followed for the composite end point of incident CVD events: cardiovascular death, myocardial infarction, angina pectoris, or heart failure. After 7.6 years of follow-up, there were 444 total events. Borderline (HR [hazard ratio] 1.37, 95% confidence interval [CI] 1.10 to 1.70) and abnormal QRS-T angles (HR 2.2, 95% CI 1.63 to 2.97) were associated with incident CVD events in multivariate-adjusted models. However, after adjusting for T-wave abnormalities, there was no statistically significant association of either borderline (HR 1.12, 95% CI 0.90 to 1.41) or abnormal (HR 1.31, 95% CI 0.93 to 1.84) QRS-T angle with incident CVD events. Abnormal frontal QRS-T angle predicts incident CVD events in a multiethnic population, and this increased risk is primarily mediated through T-wave abnormalities. QRS-T angle provides an easily interpretable continuous marker of abnormal ventricular repolarization that can aid the everyday clinician in risk prediction.

Minor isolated Q waves and cardiovascular events in the MESA study.

BACKGROUND: The significance of minor isolated Q waves in the resting electrocardiograms (ECGs) of apparently healthy individuals is unknown. OBJECTIVE: To examine the association between minor isolated Q waves and incident cardiovascular disease events in the Multi-Ethnic Study of Atherosclerosis (MESA). DESIGN: This analysis included 6551 MESA participants (38% white, 28% black, 22% Hispanic, 12% Chinese) who were free of cardiovascular disease at enrollment. Cox proportional hazards models were used to examine the association between minor isolated Q waves defined by the Minnesota ECG Classification with adjudicated incident cardiovascular events. RESULTS: During up to 7.8 years of follow-up, 423 events occurred, with a rate of 10.7 events per 1000 person-years. A significant interaction between minor isolated Q waves and race/ethnicity was observed (P=.030). In models stratified by race/ethnicity and adjusted for demographics, socioeconomic status, common cardiovascular risk factors, and other ECG abnormalities, presence of isolated minor Q waves was significantly associated with incident cardiovascular events in Hispanics (hazard ratio [HR] 2.62; 95% confidence interval [CI], 1.42-4.82), but not in whites (HR 0.65; 95% CI, 0.32-1.33) or blacks (HR 1.46; 95% CI, 0.74-2.89). Despite the statistically significant association in the Chinese population, the small number of events precluded solid conclusions in this race/ethnicity. CONCLUSION: The prognostic significance of minor isolated Q waves varies across races/ethnicities; they carry a high risk for future cardiovascular events in apparently healthy Hispanics, but not in whites or blacks.

Natural history of the early repolarization pattern in a biracial cohort: CARDIA (Coronary Artery Risk Development in Young Adults) Study.

OBJECTIVES: The objective of this analysis was to determine the natural history and prospective association of cardiovascular risk factors with early repolarization (ER). BACKGROUND: ER is common and has been suggested to increase risk for cardiovascular mortality in middle-aged adults. Data are sparse regarding the natural history of ER from young adulthood to middle age. METHODS: We examined 5,069 participants (mean age 25 years at baseline; 40% black) from the CARDIA (Coronary Artery Risk Development in Young Adults) cohort over 20 years. Electrocardiograms were recorded at years 0 (Y0), 7 (Y7), and 20 (Y20) and coded as either definite, probable, possible, or no ER. Logistic regression was used to determine the association of cardiovascular risk factors with the presence of ER cross-sectionally and prospectively. RESULTS: A total of 941 of the 5,069 participants (18.6%) had definite ER at baseline, and only 119 of 2,505 participants (4.8%) at the Y20 examination still demonstrated the presence of ER. Younger age, black race, male sex, longer exercise duration and QRS duration, and lower body mass index (BMI), heart rate, QT index, and Cornell voltage were associated cross-sectionally with the presence of ER. Predictors of maintenance of ER from Y0 to Y20 were black race (odds ratio [OR]: 2.62; 95% CI; 1.61 to 4.25), BMI (OR: 0.62 per 1 SD; 95% CI: 0.40 to 0.94), serum triglyceride levels (OR: 0.66 per 1 SD; 95% CI: 0.45 to 0.98), and QRS duration (OR: 1.68 per 1 SD; 95% CI: 1.37 to 2.06) at baseline. CONCLUSIONS: The prevalence of ER was significantly higher than previous estimates among asymptomatic young adults, and the majority of ER regressed by middle age. Black race, lower BMI, lower serum triglyceride levels, and longer QRS duration were independently associated with maintenance of ER over time.

Association of isolated minor non-specific ST-segment and T-wave abnormalities with subclinical atherosclerosis in a middle-aged, biracial population: Coronary Artery Risk Development in Young Adults (CARDIA) study.

AIMS: Isolated minor non-specific ST-segment and T-wave abnormalities (NSSTTAs) are common and known to be independent electrocardiographic risk markers for future cardiovascular disease (CVD) events. The association of NSSTTA with subclinical atherosclerosis is not well defined, but has been postulated as a potential mechanism of association with future clinical events. METHODS AND RESULTS: We studied participants from the Year 20 examination of the middle-aged, biracial CARDIA cohort. This examination included measurement of traditional risk factors, 12-lead electrocardiograms (ECGs), coronary artery calcium (CAC) measurement and common carotid intima-media thickness (CC-IMT). ECGs were coded using both Minnesota Code (MC) and Novacode (NC) criteria. Isolated minor STTA was defined by MC as presence of MC 4-3, 4-4, 5-3, or 5-4, and by NC as presence of NC 5.8. ECGs with secondary causes of STTA (i.e., LVH) were excluded. Multivariable logistic regression was used to determine the cross-sectional association of isolated minor NSSTTAs with CAC and CC-IMT. The study sample consisted of 2175 participants with an average age of 45 years (57% female and 43% Black). Isolated NSSTTAs were present in 5.1% of males and 6.3% of females. No association was observed between NSSTTA and CAC. After multivariable-adjustment for traditional CVD risk factors, the presence of isolated minor NSSTTAs remained significantly associated with the extent of CC-IMT (odds ratio 1.25 (1.06-1.48), p < 0.01). This association remained significant after further adjustment for CAC. CONCLUSIONS: Isolated minor NSSTTAs were associated with the extent of CC-IMT, but not with CAC, in this middle-aged biracial cohort. Further study is needed to elucidate potential mechanisms for these findings.

Prevalence of electrocardiographic abnormalities in a middle-aged, biracial population: Coronary Artery Risk Development in Young Adults study.

BACKGROUND: Few studies to date have described the prevalence of electrocardiographic (ECG) abnormalities in a biracial middle-aged cohort. METHODS AND RESULTS: Participants underwent measurement of traditional risk factors and 12-lead ECGs coded using both Minnesota Code and Novacode criteria. Among 2585 participants, of whom 57% were women and 44% were black (mean age 45 years), the prevalence of major and minor abnormalities was significantly higher (all P < .001) among black men and women compared to whites. These differences were primarily due to higher QRS voltage and ST/T-wave abnormalities among blacks. There was also a higher prevalence of Q waves (Minnesota Code 1-1, 1-2, 1-3) than described by previous studies. These racial differences remained after multivariate adjustment for traditional cardiovascular (CV) risk factors. CONCLUSIONS: Black men and women have a significantly higher prevalence of ECG abnormalities, independent of traditional cardiovascular risk factors, than whites in a contemporary cohort of middle-aged participants.

Association of electrocardiographic abnormalities with coronary artery calcium and carotid artery intima-media thickness in individuals without clinical coronary heart disease (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Isolated minor nonspecific ST-segment and T-wave abnormalities (NSSTAs), minor and major electrocardiographic (ECG) abnormalities are established, independent risk markers for incident cardiovascular events. Their association with subclinical atherosclerosis has been postulated but is not clearly defined. The aim of this study was to define the association between ECG abnormalities and measurements of subclinical atherosclerosis. We studied participants from MESA, a multiethnic sample of men and women 45 to 84 years of age and free of clinical cardiovascular disease at enrollment. Baseline examination included measurement of traditional risk factors, 12-lead electrocardiograms at rest, coronary artery calcium (CAC) measurement, and common carotid intima-media thickness (CC-IMT). Electrocardiograms were coded using Novacode criteria and were defined as having minor abnormalities (e.g., minor NSSTTAs, first-degree atrioventricular block, and QRS-axis deviations) or major abnormalities (e.g., pathologic Q waves, major STTAs, significant dysrhythmias, and conduction system delays). Multivariable logistic and linear regressions were used to determine cross-sectional associations of ECG abnormalities with CAC and CC-IMT. Of 6,710 participants, 52.7% were women, with a mean age of 62 years. After multivariable adjustment, isolated minor STTAs and minor and major ECG abnormalities were not associated with presence of CAC (>0) in men (odds ratio 1.04, 95% confidence interval 0.81 to 1.33; 1.10, 0.91 to 1.32; and 1.03, 0.81 to 1.31, respectively) or women (1.01, 0.82 to 1.24; 1.04, 0.87 to 1.23; and 0.94, 0.73 to 1.22, respectively). Lack of association remained consistent when using log CAC and CC-IMT as continuous variables. In conclusion, ECG abnormalities are not associated with markers of subclinical atherosclerosis in a large multiethnic cohort.