Zainab Samad

Predictive value of myocardial perfusion single-photon emission computed tomography and the impact of renal function on cardiac death.

Background— Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes than those without CKD. The prognostic utility of myocardial perfusion single-photon emission CT (MPS) in patients with varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction in patients undergoing MPS have not been investigated. Methods and Results— We followed up 1652 consecutive patients who underwent stress MPS (32% exercise, 95% gated) for cardiac death for a mean of 2.15±0.8 years. MPS defects were defined with a summed stress score (normal summed stress score <4, abnormal summed stress score≥4). Ischemia was defined as a summed stress score ≥4 plus a summed difference score ≥2, and scar was defined as a summed difference score <2 plus a summed stress score ≥4. Renal function was calculated with the Modified Diet in Renal Disease equation. CKD (estimated glomerular filtration rate <60 mL · min−1 · 1.73 m−2) was present in 36%. Cardiac death increased with worsening levels of perfusion defects across the entire spectrum of renal function. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher unadjusted cardiac death event rates than those with no CKD and normal MPS (2.7% versus 0.8%, P=0.001). Multivariate Cox proportional hazards models revealed that both perfusion defects (hazard ratio 1.90, 95% CI 1.47 to 2.46) and CKD (hazard ratio 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptom status. Both MPS and CKD had incremental power for cardiac death prediction over baseline risk factors and left ventricular dysfunction (global &khgr;2 207.5 versus 169.3, P<0.0001). Conclusions— MPS provides effective risk stratification across the entire spectrum of renal function. Renal dysfunction is also an important independent predictor of cardiac death in patients undergoing MPS. Renal function and MPS have additive value in risk stratisfying patients with suspected coronary artery disease. Patients with CKD appear to have a relatively less benign prognosis than those without CKD, even in the presence of a normal scan.

Effect of Escitalopram on Mental Stress–Induced Myocardial Ischemia: Results of the REMIT Trial

IMPORTANCE Mental stress can induce myocardial ischemia and also has been implicated in triggering cardiac events. However, pharmacological interventions aimed at reducing mental stress-induced myocardial ischemia (MSIMI) have not been well studied. OBJECTIVE To examine the effects of 6 weeks of escitalopram treatment vs placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters. DESIGN, SETTING, AND PARTICIPANTS The REMIT (Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment) study, a randomized, double-blind, placebo-controlled trial of patients with clinically stable coronary heart disease and laboratory-diagnosed MSIMI. Enrollment occurred from July 24, 2007, through August 24, 2011, at a tertiary medical center. INTERVENTIONS Eligible participants were randomized 1:1 to receive escitalopram (dose began at 5 mg/d, with titration to 20 mg/d in 3 weeks) or placebo over 6 weeks. MAIN OUTCOMES AND MEASURES Occurrence of MSIMI, defined as development or worsening of regional wall motion abnormality; left ventricular ejection fraction reduction of 8% or more; and/or horizontal or down-sloping ST-segment depression of 1 mm or more in 2 or more leads, lasting for 3 or more consecutive beats, during 1 or more of 3 mental stressor tasks. RESULTS Of 127 participants randomized to receive escitalopram (n = 64) or placebo (n = 63), 112 (88.2%) completed end point assessments (n = 56 in each group). At the end of 6 weeks, more patients taking escitalopram (34.2% [95% CI, 25.4%-43.0%]) had absence of MSIMI during the 3 mental stressor tasks compared with patients taking placebo (17.5% [95% CI, 10.4%-24.5%]), based on the unadjusted multiple imputation model for intention-to-treat analysis. A significant difference favoring escitalopram was observed (odds ratio, 2.62 [95% CI, 1.06-6.44]). Rates of exercise-induced ischemia were slightly lower at 6 weeks in the escitalopram group (45.8% [95% CI, 36.6%-55.0%]) than in patients receiving placebo (52.5% [95% CI, 43.3%-61.8%]), but this difference was not statistically significant (adjusted odds ratio; 1.24 [95% CI, 0.60-2.58]; P = .56). CONCLUSIONS AND RELEVANCE Among patients with stable coronary heart disease and baseline MSIMI, 6 weeks of escitalopram, compared with placebo, resulted in a lower rate of MSIMI. There was no statistically significant difference in exercise-induced ischemia. Replication of these results in multicenter settings and investigations of other medications for reducing MSIMI are needed. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00574847.

Prevalence and Clinical Characteristics of Mental Stress–Induced Myocardial Ischemia in Patients With Coronary Heart Disease

OBJECTIVES The goal of this study was to evaluate the prevalence and clinical characteristics of mental stress-induced myocardial ischemia. BACKGROUND Mental stress-induced myocardial ischemia is prevalent and a risk factor for poor prognosis in patients with coronary heart disease, but past studies mainly studied patients with exercise-induced myocardial ischemia. METHODS Eligible patients with clinically stable coronary heart disease, regardless of exercise stress testing status, underwent a battery of 3 mental stress tests followed by a treadmill test. Stress-induced ischemia, assessed by echocardiography and electrocardiography, was defined as: 1) development or worsening of regional wall motion abnormality; 2) left ventricular ejection fraction reduction ≥ 8%; and/or 3) horizontal or downsloping ST-segment depression ≥ 1 mm in 2 or more leads lasting for ≥ 3 consecutive beats during at least 1 mental test or during the exercise test. RESULTS Mental stress-induced ischemia occurred in 43.45%, whereas exercise-induced ischemia occurred in 33.79% (p = 0.002) of the study population (N = 310). Women (odds ratio [OR]: 1.88), patients who were not married (OR: 1.99), and patients who lived alone (OR: 2.24) were more likely to have mental stress-induced ischemia (all p < 0.05). Multivariate analysis showed that compared with married men or men living with someone, unmarried men (OR: 2.57) and married women (OR: 3.18), or living alone (male OR: 2.25 and female OR: 2.72, respectively) had higher risk for mental stress-induced ischemia (all p < 0.05). CONCLUSIONS Mental stress-induced ischemia is more common than exercise-induced ischemia in patients with clinically stable coronary heart disease. Women, unmarried men, and individuals living alone are at higher risk for mental stress-induced ischemia. (Responses of Myocardial Ischemia to Escitalopram Treatment [REMIT]; NCT00574847).

The MitraClip and survival in patients with mitral regurgitation at high risk for surgery: A propensity-matched comparison

BACKGROUND We compared 30-day and 1-year survival among high-risk mitral regurgitation (MR) patients treated with the MitraClip (Abbott Vascular, Abbott Park, IL) with matched non-surgically treated patients from the Duke Echocardiography Laboratory Database (DELD). METHODS AND RESULTS High-risk patients with 3+/4+ MR managed non-surgically between years 2000 and 2010 in the longitudinal DELD were matched to high-risk MitraClip patients. Patient matching was performed using the method of nearest available Mahalanobis distance metric within calipers defined by the propensity score. Kaplan-Meier estimates and stratified Cox proportional hazards models were used to compare survival at 30 days and 1 year. Among 953 high-risk DELD patients available for matching, 30-day and 1-year mortality were 6.5% and 26.2%. Close matches were obtained for 239 of the 351 MitraClip patients. The 30-day mortality in MitraClip patients was lower (4.2%) when compared with matched DELD patients (7.2%). The 1-year relative risk of mortality of the MitraClip compared with non-surgical treatment was 0.64 (95% CI 0.45-0.91; log-rank P = .013). These results in favor of the MitraClip remained significant upon further adjustment for baseline differences between groups (P = .043). CONCLUSIONS This matched comparison of severe MR patients at high surgical risk supports the safety of the MitraClip relative to medical therapy at 30 days and a survival benefit at 1 year.

Surgical revascularization is associated with maximal survival in patients with ischemic mitral regurgitation: a 20-year experience.

Background— The optimal treatment for ischemic mitral regurgitation remains actively debated. Our objective was to evaluate the relationship between ischemic mitral regurgitation treatment strategy and survival. Methods and Results— We retrospectively reviewed patients at our institution diagnosed with significant coronary artery disease and moderate or severe ischemic mitral regurgitation from 1990 to 2009, categorized by medical treatment alone, percutaneous coronary intervention, coronary artery bypass grafting (CABG), or CABG plus mitral valve repair or replacement. Kaplan-Meier methods and multivariable Cox proportional hazards analyses were performed to assess the relationship between treatment strategy and survival, with the use of propensity scores to account for nonrandom treatment assignment. A total of 4989 patients were included: medical treatment alone=36%, percutaneous coronary intervention=26%, CABG=33%, and CABG plus mitral valve repair or replacement=5%. Median follow-up was 5.37 years. Compared with medical treatment alone, significantly lower mortality was observed in patients treated with percutaneous coronary intervention (adjusted hazard ratio, 0.83; 95% confidence interval, 0.76–0.92; P=0.0002), CABG (adjusted hazard ratio, 0.56; 95% confidence interval, 0.51–0.62; P<0.0001), and CABG plus mitral valve repair or replacement (adjusted hazard ratio, 0.69; 95% confidence interval, 0.57–0.82; P<0.0001). There was no significant difference in these results based on mitral regurgitation severity. Conclusions— Patients with significant coronary artery disease and moderate or severe ischemic mitral regurgitation undergoing CABG alone demonstrated the lowest risk of death. CABG with or without mitral valve surgery was associated with lower mortality than either percutaneous coronary intervention or medical treatment alone.

Sex Differences in Platelet Reactivity and Cardiovascular and Psychological Response to Mental Stress in Patients With Stable Ischemic Heart Disease: Insights From the REMIT Study

BACKGROUND Although emotional stress is associated with ischemic heart disease (IHD) and related clinical events, sex-specific differences in the psychobiological response to mental stress have not been clearly identified. OBJECTIVES We aimed to study the differential psychological and cardiovascular responses to mental stress between male and female patients with stable IHD. METHODS Patients with stable IHD enrolled in the REMIT (Responses of Mental Stress-Induced Myocardial Ischemia to Escitalopram) study underwent psychometric assessments, transthoracic echocardiography, and platelet aggregation studies at baseline and after 3 mental stress tasks. Mental stress-induced myocardial ischemia (MSIMI) was defined as the development or worsening of regional wall motion abnormality, reduction of left ventricular ejection fraction (LVEF) ≥8% by transthoracic echocardiography, and/or ischemic ST-segment change on electrocardiogram during 1 or more of the 3 mental stress tasks. RESULTS In the 310 participants with known IHD (18% women, 82% men), most baseline characteristics were similar between women and men (including heart rate, blood pressure, and LVEF), although women were more likely to be nonwhite, living alone (p < 0.001), and unmarried (p < 0.001); they also had higher baseline depression and anxiety (p < 0.05). At rest, women had heightened platelet aggregation responses to serotonin (p = 0.007) and epinephrine (p = 0.004) compared with men. Following mental stress, women had more MSIMI (57% vs. 41%; p < 0.04), expressed more negative (p = 0.02) and less positive emotion (p < 0.001), and demonstrated higher collagen-stimulated platelet aggregation responses (p = 0.04) than men. Men were more likely than women to show changes in traditional physiological measures, such as blood pressure (p < 0.05) and double product. CONCLUSIONS In this exploratory analysis, we identified clear, measurable, and differential responses to mental stress in women and men. Further studies should test the association of sex differences in cardiovascular and platelet reactivity in response to mental stress and long-term outcomes. (Responses of Myocardial Ischemia to Escitalopram Treatment [REMIT]; NCT00574847).

Right Ventricular Mechanics using a Novel Comprehensive Three-View Echocardiographic Strain Analysis in a Normal Population

BACKGROUND Although quantitative right ventricular (RV) strain analysis may be useful in congenital and acquired heart disease populations with RV failure, a comprehensive, standardized approach is lacking. An 18-segment RV strain analysis obtained from three standardized RV apical echocardiographic images was used to determine the feasibility, normal values, and reproducibility of the method in normal adults. METHODS Forty healthy, prospectively enrolled volunteers with no cardiac histories and normal QRS durations underwent echocardiography optimized for strain analysis including three RV apical views. Two-dimensional speckle-tracking longitudinal strain analysis was performed using EchoPAC software. Eleven retrospectively identified subjects with RV disease were included as a pilot population. All had been imaged using the same protocol including the three RV apical views. RESULTS All control subjects had normal anatomic morphology and function by echocardiography. Feasibility of the RV strain analysis was good (adequate tracking in 696 of 720 segments [97%]). RV global peak systolic strain was -23 ± 2%. Peak strain was highest in the RV free wall and lowest in the septum. Dyssynchrony indices demonstrated no dyssynchrony using left ventricular criteria. Reproducibility of most strain measures was acceptable. This methodology identified important disease not seen in the four-chamber apical view alone in the pilot population of 11 patients with RV disease. Strain patterns and values were different from those in the control population, indicating that differences do exist from normal. CONCLUSIONS Eighteen-segment RV strain analysis is feasible, with strain measures falling into discrete ranges in this normal population. Those with RV disease illustrate the potential utility of this approach. These data indicate that this model can be used for more detailed studies evaluating abnormal RV populations, in which its full potential can be assessed.

Management and outcomes in patients with moderate or severe functional mitral regurgitation and severe left ventricular dysfunction

AIMS The management and outcomes of patients with functional moderate/severe mitral regurgitation and severe left ventricular (LV) systolic dysfunction are not well defined. We sought to determine the characteristics, management strategies, and outcomes of patients with moderate or severe mitral regurgitation (MR) and LV systolic dysfunction. METHODS AND RESULTS For the period 1995-2010, the Duke Echocardiography Laboratory and Duke Databank for Cardiovascular Diseases databases were merged to identify patients with moderate or severe functional MR and severe LV dysfunction (defined as LV ejection fraction ≤ 30% or LV end-systolic diameter > 55 mm). We examined treatment effects in two ways. (i) A multivariable Cox proportional hazards model was used to assess the independent relationship of different treatment strategies and long-term event (death, LV assist device, or transplant)-free survival among those with and without coronary artery disease (CAD). (ii) To examine the association of mitral valve (MV) surgery with outcomes, we divided the entire cohort into two groups, those who underwent MV surgery and those who did not; we used inverse probability weighted (IPW) propensity adjustment to account for non-random treatment assignment. Among 1441 patients with moderate (70%) or severe (30%) MR, a significant history of hypertension (59%), diabetes (28%), symptomatic heart failure (83%), and CAD (52%) was observed. Past revascularization in 26% was noted. At 1 year, 1094 (75%) patients were treated medically. Percutaneous coronary intervention was performed in 114 patients, coronary artery bypass graft (CABG) surgery in 82, CABG and MV surgery in 96, and MV surgery alone in 55 patients. Among patients with CAD, compared with medical therapy alone, the treatment strategies of CABG surgery [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.42-0.76] and CABG with MV surgery (HR 0.58, 95% CI 0.44-0.78) were associated with long-term, event-free survival benefit. Percutaneous intervention treatment produced a borderline result (HR 0.78, 95% CI 0.61-1.00). However, the relationship with isolated MV surgery did not achieve statistical significance (HR 0.64, 95% CI 0.33-1.27, P = 0.202). Among those with CAD, following IPW adjustment, MV surgery was associated with a significant event-free survival benefit compared with patients without MV surgery (HR 0.71, 95% CI 0.52-0.95). In the entire cohort, following IPW adjustment, the use of MV surgery was associated with higher event-free survival (HR 0.69, 95% CI 0.53-0.88). CONCLUSION In patients with moderate or severe MR and severe LV dysfunction, mortality was substantial, and among those selected for surgery, MV surgery, though performed in a small number of patients, was independently associated with higher event-free survival.

Responses of mental stress–induced myocardial ischemia to escitalopram treatment: Background, design, and method for the Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment trial

BACKGROUND Mental stress-induced myocardial ischemia (MSIMI) is common in patients with clinically stable coronary heart disease (CHD) and is associated with poor outcomes. Depression is a risk factor of MSIMI. The REMIT trial investigates whether selective serotonin reuptake inhibitor (SSRI) treatment can improve MSIMI. The rationale and outline of the study are described. METHOD In this single-center randomized clinical trial, adult patients with clinically stable CHD are recruited for baseline mental and exercise stress testing assessed by echocardiography. In addition, psychometric questionnaires are administered, and blood samples are collected for platelet activity analysis. Patients who demonstrate MSIMI, defined by new abnormal wall motion, ejection fraction reduction ≥8%, and/or development of ischemic ST change in electrocardiogram during mental stress testing, are randomized at a 1:1 ratio to escitalopram or placebo for 6 weeks. Approximately 120 patients with MSIMI are enrolled in the trial. The stress testing, platelet activity assessment, and psychometric questionnaires are repeated at the end of the 6-week intervention. The hypothesis of the study is that SSRI treatment improves MSIMI via mood regulation and modification of platelet activity. CONCLUSION The REMIT study examines the effect of SSRI on MSIMI in vulnerable patients with CHD and probes some potential underlying mechanisms.

Renal Function and Risk Stratification of Diabetic and Nondiabetic Patients Undergoing Evaluation for Coronary Artery Disease

OBJECTIVES The aim of this study was to evaluate the impact of renal function by estimated glomerular filtration rate (eGFR) on risk stratification of diabetic and nondiabetic patients undergoing myocardial perfusion imaging (MPI) by single-photon emission computed tomography for suspected ischemia. BACKGROUND Coronary artery disease is the leading cause of death among diabetic persons; however, diabetic persons are a very heterogeneous group in terms of cardiovascular risk, necessitating further risk stratification. METHODS Patients (n = 1,747, age 65 +/- 10 years, 37% diabetic) undergoing MPI were followed for cardiac death (CD) for a mean of 2.15 +/- 0.8 years. Chronic kidney disease (CKD) was defined by an eGFR <60 ml/min. RESULTS In the presence of a normal scan, annual CD rate was 0.9% for those with no diabetes mellitus (DM) and no CKD, 0.5% in the DM alone group, 2.35% in CKD alone, and 2.9% in those with both DM and CKD (p < 0.001). Patients with DM+CKD had a 2.7-fold risk of CD compared with no DM no CKD (p = 0.001) after controlling for age, ejection fraction, history of coronary artery disease, and other risk factors. The risk of CD increased as a function of the presence and severity of perfusion defects, regardless of CKD or DM status. Presence of CKD conferred a several-fold higher risk of CD for the various strata of perfusion defects. Log-rank test for difference in probability of CD was nonsignificant for comparison between patients with no DM no CKD and those with DM alone (p = 0.73) but was significant for comparison between patients with no DM no CKD and patients with CKD alone (p < 0.001) or DM+CKD (p < 0.001). CONCLUSIONS MPI and eGFR provide valuable risk stratification for diabetic and nondiabetic patients. Diabetic patients without CKD seem to have similar short-term cardiac outcomes compared with nondiabetic patients. Underlying CKD seems to identify a high-risk subgroup of diabetic patients.