Faculty Bibliography

Giant cell myocarditis is a rare and often fatal disease. The most obvious presentation often described in the literature is one of rapid hemodynamic deterioration due to cardiogenic shock necessitating urgent consideration of mechanical circulatory support and heart transplantation. We present the case of a 60-year-old man whose initial presentation was consistent with myopericarditis but who went on to develop a rapid decline in left ventricular systolic function without overt hemodynamic compromise or dramatic symptomatology. Giant cell myocarditis was confirmed via endomyocardial biopsy. Combined immunosuppression with corticosteroids and calcineurin inhibitor resulted in resolution of symptoms and sustained recovery of left ventricular function one year later. Our case highlights that giant cell myocarditis does not always present with cardiogenic shock and should be considered in the evaluation of new onset cardiomyopathy of uncertain etiology as a timely diagnosis has distinct clinical implications on management and prognosis.

BACKGROUND: Coronary artery disease and left ventricular hypertrophy are prevalent in the chronic kidney disease (CKD) and renal transplant (RT) population. Advances in cardiovascular magnetic resonance (CMR) with blood oxygen level-dependent (BOLD) technique provides capability to assess myocardial oxygenation as a measure of ischemia. We hypothesized that the myocardial oxygenation response to stress would be impaired in CKD and RT patients. METHODS AND RESULTS: Fifty-three subjects (23 subjects with CKD, 10 RT recipients, 10 hypertensive (HT) controls, and 10 normal controls without known coronary artery disease) underwent CMR scanning. All groups had cine and BOLD CMR at 3 T. The RT and HT groups also had late gadolinium CMR to assess infarction/replacement fibrosis. The CKD group underwent 2-dimensional echocardiography strain to assess fibrosis. Myocardial oxygenation was measured at rest and under stress with adenosine (140 mug/kg per minute) using BOLD signal intensity. A total of 2898 myocardial segments (1200 segments in CKD patients, 552 segments in RT, 480 segments in HT, and 666 segments in normal controls) were compared using linear mixed modeling. Diabetes mellitus (P=0.47) and hypertension (P=0.57) were similar between CKD, RT, and HT groups. The mean BOLD signal intensity change was significantly lower in the CKD and RT groups compared to HT controls and normal controls (-0.89+/-10.63% in CKD versus 5.66+/-7.87% in RT versus 15.54+/-9.58% in HT controls versus 16.19+/-11.11% in normal controls, P<0.0001). BOLD signal intensity change was associated with estimated glomerular filtration rate (beta=0.16, 95% CI=0.10 to 0.22, P<0.0001). Left ventricular mass index and left ventricular septal wall diameter were similar between the CKD predialysis, RT, and HT groups. None of the CKD patients had impaired global longitudinal strain and none of the RT group had late gadolinium hyperenhancement. CONCLUSIONS: Myocardial oxygenation response to stress is impaired in CKD patients and RT recipients without known coronary artery disease, and unlikely to be solely accounted for by the presence of diabetes mellitus, left ventricular hypertrophy, or myocardial scarring. The impaired myocardial oxygenation in CKD patients may be associated with declining renal function. Noncontrast BOLD CMR is a promising tool for detecting myocardial ischemia in the CKD population.

INTRODUCTION: Perflutren microbubble/microsphere ultrasound contrast agents have a black-box warning based on case reports of serious cardiopulmonary events. There have been several subsequent observational safety studies. Large spontaneous reporting databases may help detect/refine signals of rare adverse events that elude other data sources/study designs. OBJECTIVE: The objective of this study was to supplement existing knowledge of the reported safety of perflutren using statistical analysis of spontaneous reports. METHODS: We analyzed information from the US Food and Drug Administration Adverse Event Reporting System using a disproportionality analysis. Analysis of overall reporting for perflutren was supplemented by subset (age, indication) analysis. A signal of disproportionate reporting (SDR) was defined as EB05 >2. RESULTS: Overall, 18/380 Preferred Terms and 1/83 Standardized Medical Queries had SDRs. Most were small (EB05 = 2-4). Back pain and flank pain were the largest SDRs followed by events compatible with signs/symptoms of hypersensitivity. The general pattern of SDRs in the subset analysis was consistent with the overall analysis. Almost all events with SDRs were literally or conceptually labeled. Except for chest pain (higher in the age <65 years subgroup) and back pain (higher in the age >/=65 years subgroup), there were no statistically significant differences between age subsets. Except for the Preferred Terms Pruritus and Urticaria and the narrow Standardized Medical Queries Ventricular tachyarrhythmia, Angioedema, Oropharyngeal allergic conditions, and Hypersensitivity (higher in the stress test subgroup), there were no statistically significant reporting differences between indication subsets. There were no SDRs associated with the major cardiovascular events of death, myocardial infarction/ischemia, angina, arrhythmias, or convulsions in any analysis. CONCLUSIONS: Our combined signal detection/evaluation analysis did not identify SDRs of novel adverse events or major cardiovascular events associated with perflutren ultrasound contrast agents. The negative results for major cardiovascular events extend previous signal evaluation exercises supporting the relative cardiovascular safety of these agents.

Various scientific societies have recently published practice guidelines for the diagnosis and management of arterial hypertension with no clear consensus on a blood pressure target. This article reviews those recommendations and critically examines if they are based on sound evidence.

INTRODUCTION: Women with acute myocardial infarction are treated less aggressively than men and have a higher mortality. It is possible that these sex-related differences in outcome are a result of differences in baseline risk and management. METHODS AND RESULTS: We undertook a meta-analysis to study the differences in mortality among women and men with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (P-PCI). Studies reporting sex-specific crude mortality rates and/or adjusted effect estimates in STEMI patients undergoing P-PCI were identified. Among 48 studies, involving 103,895 patients, (26,556 women and 77,337 men), the crude in-hospital [pooled relative risk (RR): 1.94, 95% confidence interval (CI): 1.74-2.16, p<0.001; 23 studies (n=43,872)], 30-day [RR: 1.76, 95% CI: 1.50-2.07, p<0.001; 20 studies (n=43,279)], and long-term [RR: 1.60, 95% CI: 1.46-1.76, p<0.001; 26 studies (n=51,656)] mortality was significantly higher in women compared to men. When meta-analysis using adjusted effect estimates from individual studies was performed, in-hospital [RR: 1.31, 95% CI: 1.08-1.65, p=0.007; 14 studies (n=33,380)] and 30-day mortality [RR: 1.19, 95% CI: 1.01-1.39, p=0.03; 14 studies (n=28,564)] remained significant while long-term mortality [RR: 1.01, 95% CI: 0.93-1.11, p=0.75; 20 studies (n=52,492)] was no longer different between women and men. CONCLUSIONS: Sex-based differences exist in short and long-term mortality among patients with STEMI undergoing P-PCI. However, these differences were markedly attenuated following adjustment for clinical differences and/or hospital course. Despite adjustment, short-term mortality remains higher in women than men, while long-term mortality was no longer significantly different.

BACKGROUND: In patients with diabetes mellitus and multivessel disease, coronary artery bypass graft surgery and percutaneous coronary intervention are treatment options. However, there is paucity of data comparing coronary artery bypass graft surgery against newer generation stents. METHODS AND RESULTS: Patients included in the New York State registries who had diabetes mellitus and underwent isolated coronary artery bypass graft surgery or percutaneous coronary intervention with everolimus eluting stent (EES) for multivessel disease were included. Propensity score matching was used to assemble a cohort with similar baseline characteristics. The primary outcome was all-cause mortality. Secondary outcomes were myocardial infarction (MI), stroke, and repeat revascularization. Short-term (within 30 days) and long-term outcomes were evaluated. Among 16 089 patients with diabetes mellitus and multivessel disease, 8096 patients with similar propensity scores were included. At short-term, EES was associated with a lower risk of death (hazard ratio [HR] =0.58; 95% confidence interval [CI], 0.34-0.98; P=0.04) and stroke (HR=0.14; 95% CI, 0.06-0.30; P<0.0001) but higher risk of MI (HR=2.44; 95% CI, 1.13-5.31; P=0.02). At long-term, EES was associated with a similar risk of death (425 [10.50%] versus 414 [10.23%] events; HR=1.12; 95% CI, 0.96-1.30; P=0.16), a lower risk of stroke (118 [2.92%] versus 157 [3.88%] events; HR=0.76; 95% CI, 0.58-0.99; P=0.04) but a higher risk of MI (260 [6.42%] versus 166 [4.10%] events; HR=1.64; 95% CI, 1.32-2.04; P<0.0001) and repeat revascularization (889 [21.96%] versus 421 [10.40%] events; HR=2.42; 95% CI, 2.12-2.76; P<0.0001). The higher risk of MI was not seen in the subgroup of EES patients who underwent complete revascularization (HR=1.37; 95% CI, 0.76-2.47; P=0.30). CONCLUSIONS: In patients with diabetes mellitus and multivessel disease, EES was associated with lower upfront risk of death and stroke when compared with coronary artery bypass graft surgery. However, at long-term, EES was associated with similar risk of death, a higher risk of MI (in those with incomplete revascularization), and repeat revascularization but a lower risk of stroke.

Newer oral P2Y12 inhibitors are more potent and have faster onset of action than clopidogrel. However, the efficacy and safety in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are not well studied. A systemic search of MEDLINE and EMBASE databases was performed to identify randomized clinical trials comparing newer oral P2Y12 inhibitors (prasugrel or ticagrelor) to clopidogrel in patients with NSTE-ACS. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and stroke (major cardiovascular events [MACE]). Secondary outcomes were individual components of the primary outcome, all-cause mortality, and Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding. A total of 31,470 patients with NSTE-ACS from 4 randomized clinical trials were included (newer oral P2Y12 inhibitors: 15,951; clopidogrel: 15,519). Newer oral P2Y12 inhibitors significantly decreased MACE (relative risk [RR] 0.87, 95% confidence interval [CI] 0.80 to 0.95) and MI (RR 0.85, 95% CI 0.75 to 0.96) and showed a trend toward reduction of cardiovascular death (RR 0.89, 95% CI 0.71 to 1.01). There was a significant increase in TIMI major bleeding (RR 1.27, 95% CI 1.07 to 1.50) and TIMI major or minor bleeding (RR 1.20, 95% CI 1.02 to 1.42). Results were largely similar when stratified by ticagrelor versus prasugrel (pinteraction >0.05) except for increased TIMI major/minor bleeding with prasugrel than ticagrelor (pinteraction = 0.01). In conclusion, in patients with NSTE-ACS, newer oral P2Y12 inhibitors decrease MACE and MI at the expense of a significant increase in the risk of bleeding. Treatment of 1,000 patients with newer oral P2Y12 inhibitors will prevent 16 MACE and 13 MIs at the expense of increase in 6 major bleeding events.

BACKGROUND: Angiotensin converting enzyme inhibitors (ACEi) are widely used in the treatment of patients with hypertension. However, their efficacy in hypertensive blacks when compared with other antihypertensive agents is not well established. METHODS: Cohort study of patients using data from a clinical data warehouse of 434,646 patients from New York City's Health and Hospitals Corporation (HHC) from January 2004 - December 2009. Patients were divided into the following comparison groups: ACEi vs. Calcium Channel Blocker (CCB); ACEi vs. thiazide diuretics and ACEi vs. beta-blockers. Primary outcome was a composite of death, myocardial infarction or stroke. Secondary outcomes include the individual components and heart failure. RESULTS: In the propensity score matched ACEi vs. CCB comparison cohort (4,506 blacks in each group), ACEi was associated with higher risk of primary outcome (HR=1.45; 95% CI 1.19, 1.77; P=0.0003), myocardial infarction (HR=3.40; 95% CI 1.25, 9.22; P=0.02), stroke (HR=1.82; 95% CI 1.29, 2.57; P=0.001) and heart failure (HR=1.77; 95% CI 1.30, 2.42; P=0.0003) when compared with CCB. For the ACEi vs. thiazide diuretics comparison (5,337 blacks in each group), ACEi was associated with higher risk of primary outcome (HR=1.65; 95% CI 1.33, 2.05; P<0.0001), death (HR=1.35; 95% CI 1.03, 1.76; P=0.03), myocardial infarction (HR=4.00; 95% CI 1.34, 11.96; P=0.01), stroke (HR=1.97; 95% CI 1.34, 2.92; P=0.001) and heart failure (HR=3.00; 95% CI 1.99, 4.54; P<0.0001). For the ACEi vs. beta-blocker comparison, the outcomes between the groups were not significantly different. CONCLUSIONS: In a real-world cohort of hypertensive blacks, ACEi was associated with higher risk of cardiovascular events when compared with CCB or thiazide diuretics.

Despite increasing use of the transradial approach (TRA) for coronary angiography, TRA failure and subsequent access site crossover remain a barrier to TRA adoption. The aim of this study was to elucidate patient and procedural characteristics associated with TRA to transfemoral approach (TFA) crossover and examine TRA to TFA crossover by operator experience over time. This retrospective analysis identified 1,600 patients who underwent coronary angiography with possible percutaneous coronary intervention through TRA by operators with varied TRA experience in an urban tertiary care center from October 2010 to August 2013. Univariate and multivariable logistic regression were used to identify independent predictors of access site crossover, from TRA to TFA, and strength of association is presented as odds ratio (OR, 95% confidence interval [CI]). Access site crossover was noted in 166 patients (10.4%). Multivariable predictors of access site crossover included age >75 years (OR 1.90, 95% CI 1.23 to 2.91, p = 0.004) and operator experience (OR 2.98, 95% CI 1.96 to 4.52, p <0.0001). Less experienced operators (5 years TRA experience) had no significant change in proportion of access site crossover over time (quartile 1: 2.8%, quartile 2: 6.4%, quartile 3: 5.6%, quartile 4: 5.8%, p = 0.54). In conclusion, rate of access site crossover in the contemporary era is relatively low and can be mitigated with operator experience.