Mustafa Toma

Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction: insights from the APEX-AMI trial

AIMS To examine the incidence of and propensity for non-culprit interventions performed at the time of the primary percutaneous coronary intervention (PCI) and its association with 90-day outcomes. METHODS AND RESULTS We examined the incidence, propensity for, and associated 90-day outcomes following non-culprit interventions performed at the time of primary PCI among ST-elevation myocardial infarction patients with multi-vessel coronary artery disease (MVD). Of the 5373 patients who underwent primary PCI in the APEX-AMI trial, 2201 had MVD. Of those, 217 (9.9%) underwent non-infarct-related arteries (IRA) PCI, whereas 1984 (90.1%) underwent PCI of the IRA alone. Ninety-day death and death/CHF/shock were higher in the non-IRA group compared with the IRA-only PCI group (12.5 vs. 5.6%, P (log-rank) < 0.001 and 17.4 vs. 12.0%, P (log-rank) = 0.020, respectively). After adjusting for patient and procedural characteristics as well as propensity for performing non-IRA PCI, this procedure remained independently associated with an increased hazard of 90-day mortality [adjusted hazard ratio 2.44, 95% CI (1.55-3.83), P < 0.001]. CONCLUSION Non-culprit coronary interventions were performed at the time of primary PCI in 10% of MVD patients and were significantly associated with increased mortality. Our data support current guideline recommendations discouraging the performance of such procedures in stable primary PCI patients. Prospective randomized study of this issue may be warranted.

Testosterone Supplementation in Heart Failure: A Meta-Analysis

Background— Low testosterone is an independent predictor of reduced exercise capacity and poor clinical outcomes in patients with heart failure (HF). We sought to determine whether testosterone therapy improves exercise capacity in patients with stable chronic HF. Methods and Results— We searched Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (1980–2010). Eligible studies included randomized controlled trials (RCTs) reporting the effects of testosterone on exercise capacity in patients with HF. Reviewers determined the methodological quality of studies and collected descriptive, quality, and outcome data. Four trials (n=198; men, 84%; mean age, 67 years) were identified that reported the 6-minute walk test (2 RCTs), incremental shuttle walk test (2 RCTs), or peak oxygen consumption (2 RCTs) to assess exercise capacity after up to 52 weeks of treatment. Testosterone therapy was associated with a significant improvement in exercise capacity compared with placebo. The mean increase in the 6-minute walk test, incremental shuttle walk test, and peak oxygen consumption between the testosterone and placebo groups was 54.0 m (95% CI, 43.0–65.0 m), 46.7 m (95% CI, 12.6–80.9 m), and 2.70 mL/kg per min (95% CI, 2.68–2.72 mL/kg per min), respectively. Testosterone therapy was associated with a significant increase in exercise capacity as measured by units of pooled SDs (net effect, 0.52 SD; 95% CI, 0.10–0.94 SD). No significant adverse cardiovascular events were noted. Conclusions— Given the unmet clinical needs, testosterone appears to be a promising therapy to improve functional capacity in patients with HF. Adequately powered RCTs are required to assess the benefits of testosterone in this high-risk population with regard to quality of life, clinical events, and safety.

Modification of the relationship between simple anthropometric indices and risk factors by ethnic background.

Current targets for body mass index (BMI) and waist circumference (WC) may not be appropriate for those of South Asian origin. The objectives of this study were to determine whether the relationship between BMI and WC with risk factors for cardiovascular disease (CVD) is the same for men and women of South Asian and European descent. Apparently healthy men and women of European (n = 88) and South Asian (n = 93) descent were recruited from 3 hospital communities and assessed for BMI, WC, waist-to-hip ratio (WHR), blood pressure (BP), lipids, insulin, glucose, and CRP. The study cohort was stratified by sex, and regression analyses were performed with individual risk factors as outcomes and ethnicity with either BMI or WC as predictors adjusting for age and height (WC only). BMI and WC were similar between the European and South Asian men and women. South Asian men had significantly higher values for total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), total cholesterol:high-density lipoprotein-cholesterol (HDL-C) and CRP, and significantly lower values of HDL-C. South Asian women had significantly higher values for TG, TC:HDL-C and CRP and significantly lower values of HDL-C, glucose, systolic BP and diastolic BP. In men, ethnicity was an independent predictor for all risk factors except for glucose and insulin, after adjusting for either BMI or WC independent of age and height. For women, ethnicity was an independent predictor for all risk factors except for total cholesterol (WC model only) and insulin (BMI model only), after adjusting for either BMI or WC independent of age and height. The relationship between BMI or WC and risk factors is such that men and women of South Asian descent present with a more adverse risk profile than those of European descent at the same BMI and/or WC.

Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review

BackgroundScreening for organ rejection is a critical component of care for patients who have undergone heart transplantation. Endomyocardial biopsy is the gold standard screening tool, but non-invasive alternatives are needed. Cardiovascular magnetic resonance (CMR) is well suited to provide an alternative to biopsy because of its ability to quantify ventricular function, morphology, and characterize myocardial tissue. CMR is not widely used to screen for heart transplant rejection, despite many trials supporting its use for this indication. This review summarizes the different CMR sequences that can detect heart transplant rejection as well as the strengths and weaknesses of their application.ResultsT2 quantification by spin echo techniques has been criticized for poor reproducibility, but multiple studies show its utility in screening for rejection. Human and animal data estimate that T2 quantification can diagnose rejection with sensitivities and specificities near 90%. There is also a suggestion that T2 quantification can predict rejection episodes in patients with normal endomyocardial biopsies.T1 quantification has also shown association with biopsy proven rejection in a small number of trials. T1 weighted gadolinium early enhancement appeared promising in animal data, but has had conflicting results in human trials. Late gadolinium enhancement in the diagnosis of rejection has not been evaluated.CMR derived measures of ventricular morphology and systolic function have insufficient sensitivity to diagnose mild to moderate rejection. CMR derived diastolic function can demonstrate abnormalities in allografts compared to native human hearts, but its ability to diagnose rejection has not yet been tested.There is promising animal data on the ability of iron oxide contrast agents to illustrate the changes in vascular permeability and macrophage accumulation seen in rejection. Despite good safety data, these contrast agents have not been tested in the human heart transplant population.ConclusionT2 quantification has demonstrated the best correlation to biopsy proven heart transplant rejection. Further studies evaluating diastolic function, late gadolinium enhancement, and iron oxide contrast agents to diagnose rejection are needed. Future studies should focus on combining multiple CMR measures into a transplant rejection scoring system which would improve sensitivity and possibly reduce, if not eliminate, the need for endomyocardial biopsy.

Correlation of cardiovascular magnetic resonance imaging findings and endomyocardial biopsy results in patients undergoing screening for heart transplant rejection.

BACKGROUND Endomyocardial biopsy (EMB) is the current gold standard to screen for heart transplant rejection but has important risks and limitations. Cardiovascular magnetic resonance imaging (CMRI) is increasingly used to characterize cardiac function and myocardial tissue. We evaluated the diagnostic accuracy of CMRI compared with EMB and clinically diagnosed heart transplant rejection. METHODS Comprehensive CMRI scans were performed on adult heart transplant recipients within 24 hours of EMB (routine or clinically indicated), before initiation of any anti-rejection therapy, and blinded to EMB results. Multivariable analysis was used to create CMRI diagnostic criteria for comparison with a positive EMB (Grade ≥ 2R or antibody-mediated rejection) and clinical rejection (change in medical therapy to treat rejection). RESULTS Sixty participants (75% male; mean age, 51 ± 14 years) were recruited, providing 73 comparisons between CMRI and EMB for the diagnosis of rejection. Multivariable logistic regression identified myocardial edema (T2 relaxation time) and right ventricular end-diastolic volume index as independent predictors of a positive EMB. Combining threshold right ventricular end-diastolic volume index and edema values predicted a positive EMB with very good accuracy: sensitivity, 93%; specificity, 78%; positive predictive value, 52%; and negative predictive valve, 98%. CMRI was more sensitive than EMB at predicting clinical rejection (sensitivity of 67% vs 58%). CONCLUSIONS CMRI has high sensitivity and high negative predictive value in predicting biopsy-positive heart transplant rejection and may be useful as a screening test before routine EMB. CMRI also has better sensitivity for clinically diagnosed heart transplant rejection and could be helpful in cases of negative rejection on the biopsy specimen.

The relationship between left ventricular ejection fraction and mortality in patients with acute heart failure: insights from the ASCEND-HF Trial

Acute decompensated heart failure (ADHF) is associated with significant morbidity and mortality but the relationship between LVEF and outcomes is unclear. We explored the association between LVEF and 30 and 180 day mortality in 7007 ADHF patients enrolled in the Acute Studies of Nesiritide in Decompensated Heart Failure (ASCEND‐HF) trial.

Cardiovascular responses to incremental and sustained submaximal exercise in heart transplant recipients.

The cardiovascular response to exercise in heart transplant recipients (HTR) has been compared with that of healthy individuals matched to the recipient age (RM controls). However, no study has compared HTR with donor age-matched (DM) controls. Moreover, the cardiovascular response to sustained submaximal exercise in HTR requires further evaluation. We therefore examined cardiovascular responses during incremental exercise and sustained (1 h) submaximal aerobic exercise in 9 clinically stable HTR [63 +/- 10 yr of age, 24.2 +/- 10.9 ml x kg(-1) x min(-1) peak O(2) uptake (Vo(2peak))] and 11 healthy age-matched controls (60 +/- 11 yr of age and 36.3 +/- 10.7 ml.kg(-1) x min(-1) Vo(2peak) for 6 RM controls and 35 +/- 8 yr of age and 51.1 +/- 10.4 ml x kg(-1) x min(-1) Vo(2peak) for 5 DM controls). Heart rate (HR) and left ventricular systolic and diastolic volumes (2-dimensional echocardiography) indexed to body surface area [end-systolic and end-diastolic volume indexes (EDVI and ESVI)], cardiac output (CI), ejection fraction (EF), systemic vascular resistance (SVRI), end-systolic elastance index, and arterial elastance index were determined. Although systolic function was maintained during incremental exercise, peak CI was significantly reduced (6.7 +/- 2.4 vs. 11.6 +/- 1.4 l x min(-1) x m(-2)), secondary to blunted HR, EDVI, and increased peak SVRI, in HTR compared with DM controls. The lower peak CI in HTR than in RM controls was due to blunted peak EDVI (54.1 +/- 13.2 vs. 68.6 +/- 5.7 ml/m(2)). During sustained submaximal exercise, HTR exhausted their preload reserve, a response for which changes in ESVI, HR, or EF did not fully compensate. Thus it appears that HTR are limited by impaired preload reserve, HR reserve, and vascular reserve during exercise conditions.

Late Gadolinium Enhancement in Cardiac Transplant Patients Is Associated With Adverse Ventricular Functional Parameters and Clinical Outcomes

BACKGROUND Heart transplant recipients (HTRs) experience multiple cardiac complications, many of which might produce myocardial fibrosis. Cardiovascular magnetic resonance imaging (CMR) can image myocardial fibrosis using late gadolinium enhancement (LGE) imaging. We hypothesized that the presence and volume of LGE in heart transplant recipients correlates with left ventricular (LV) functional parameters and clinical outcomes. METHODS Thirty-eight stable HTRs underwent a CMR study and clinical follow-up. RESULTS In 38 stable HTRs, LGE was seen in 19 patients (50%), of which 15 (79%) had a nonischemic pattern and 4 (21%) had an ischemic pattern. LGE volume was associated with reduced LV ejection fraction (EF) (R(2) = 0.57; P = 0.001) and increased LV end-diastolic volume (R(2) = 0.59; P = 0.001). The presence of LGE was associated with cardiovascular death or hospitalization within the next year (P = 0.04), and patients who died or were hospitalized had more LGE than those that were not hospitalized (15 g vs 7 g; P = 0.03). CONCLUSIONS LGE is common in HTR and is associated with adverse ventricular remodelling and adverse clinical outcomes. LGE might be a useful noninvasive approach to monitor graft disease in asymptomatic patients after heart transplant.

Does silent myocardial infarction add prognostic value in ST-elevation myocardial infarction patients without a history of prior myocardial infarction? Insights from the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) Trial

BACKGROUND ST-elevation myocardial infarction (STEMI) patients with a prior MI history have worse outcomes. The prognostic significance of silent MI (pathologic Q waves outside the ST-elevation territory) in STEMI is unclear. METHODS A total of 5,733 STEMI patients from 296 clinical centers in 17 countries were classified as (1) silent MI-baseline Q waves outside the infarct-related artery territory and no history of prior MI, (2) history of prior MI (HxMI), or (3) no prior MI. RESULTS Of 5,733 STEMI patients, 419 (7.3%) had silent MI, 693 (12.1%) had HxMI, and 4,621 (80.6%) had no prior MI. Ninety-day death and death/congestive heart failure/shock were higher in patients with HxMI (8.4% and 15.3%, respectively) and silent MI (6.7% and 13.9%, respectively) compared with patients with no prior MI (4.0% and 9.1%, respectively) (P ≤ .001 for all). After baseline adjustment, patients with HxMI were at increased risk for 90-day death (adjusted hazard ratio [HR] 1.62, 95% CI 1.18-2.21), whereas both those with HxMI and those with silent MI had increased risk of 90-day death/congestive heart failure/shock compared with those with no prior MI (adjusted HR 1.54, 95% CI 1.23-1.93 and adjusted HR 1.46, 95% CI 1.10-1.93, respectively). CONCLUSIONS Seven percent of STEMI patients had a silent MI. They represent a novel subgroup at increased risk comparable to those with known prior MI. Hence, in future studies, acquiring baseline Q wave data outside the distribution of acute injury should broaden the prognostic insights from STEMI patients with a prior MI.

Multicentre Canadian experience with the HeartWare ventricular assist device: concerns about adverse neurological outcomes.

BACKGROUND The HeartWare left ventricular assist device (HVAD; HeartWare Inc, Framingham, MA) was first implanted in Canada in 2010. We performed a multicentre analysis of the real world outcomes associated with its use. METHODS Between May 2010 and January 2013, 4 Canadian centres inserted a total of 72 HVADs in 71 patients. Data were collected prospectively and analyzed retrospectively for the 1-year estimate of the principal outcome of transplant, explant for recovery, or death in patients who had a bridge to transplantation indication. Adverse event rates were estimated as events per patient-year (PPY). RESULTS In the 67 patients who received the HVAD with the indication of bridge to transplant, 26 (38.8%) received a successful transplant, 2 (3%) received an explant for recovery, and 10 (14.9%) patients died during support. Median follow-up time with the HVAD was 6.9 months (range, 2 days to 30.4 months). Despite having 74% of the patients with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scores of level 1 and 2 at the time of implantation, the rate estimate for survival at 1 year was 86.3% (95% confidence interval, 76.7-93.3). With 48.2 total patient years of support, the rates of ischemic and hemorrhagic strokes were 0.21 and 0.19 events PPY, respectively. Women made up 40% of the cohort and an adverse neurologic event occurred with an event rate of 0.38 PPY in women. CONCLUSIONS The HVAD adequately supports acutely ill heart failure patients until the time of transplant or recovery. A high incidence of adverse neurologic outcomes might be related to the large percentage of female patients, the high INTERMACS levels, or unknown factors; further surveillance is required.