Faculty Bibliography

Hypertension is a major modifiable risk factor for cardiovascular morbidity and mortality. Despite more than five decades of hypertension treatment, there still exist both a lack of evidence and a clear consensus to answer a fundamental question: What is the optimal blood pressure target in patients with hypertension? Early epidemiologic studies suggested the notion of the lower the blood pressure, the better the outcomes; however, others have demonstrated a J-curve phenomenon with worse outcomes at both low and very high blood pressures. Although the existence of such a J-curve remains a topic of debate, there is now increasing recognition of target organ heterogeneity wherein the optimal blood pressure depends on the target organ in question. For cardiac protection, the current body of evidence does not support a systolic blood pressure goal of lower than 130-140 mmHg. For cerebrovascular protection, however, lower blood pressure seems to be better with a sustained reduction in events down to a systolic blood pressure of 110-120 mmHg. The J-curve phenomenon is therefore both fact and fiction based on the target organ in question.

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 (CAD) and left ventricular hypertrophy (LVH) are prevalent in the chronic kidney disease (CKD) and renal transplant population. We hypothesised that the myocardial oxygenation response to stress would be impaired in CKD Methods: Fifty-three subjects: twenty-three subjects with CKD, ten renal transplant (RT) recipients, ten hypertensive (HT) controls, and ten normal controls without known heart disease underwent CMR scanning at 3T. The RT and HT groups also had late gadolinium CMR to assess infarction/ replacement fibrosis. The CKD group underwent 2D echocardiography strain to assess fibrosis. Results: 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 modelling. Diabetes mellitus (p= 0.47) and hypertension (p= 0.57) were similar between CKD, RT, and HT groups. The mean BOLD SI 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, p< 0.0001). BOLD SI Change was associated with eGFR (beta= 0.16, 95% CI= 0.10 to 0.22, p<0.0001). Left ventricular mass index and left ventricular septal wall diameter was similar between the CKD pre-dialysis, RT, and HT groups. None of the CKD patients had impaired global longitudinal strain (GLS) and none of the RT group had late gadolinium hyperenhancement. Conclusion: Myocardial oxygenation response to stress is impaired in CKD and RT patients, and unlikely to be solely accounted for by the presence of diabetes mellitus

Objectives: We sought to update our meta-analysis on clinical outcomes with aspiration thrombectomy prior to primary percutaneous coronary intervention (PPCI) compared with conventional PPCI alone due to the availability of additional trial data. Background: The clinical efficacy of adjunctive aspiration thrombectomy in ST-elevation myocardial infarction (STEMI) patients undergoing PPCI remains controversial. A recent large-scale randomized trial showed no benefit in terms of mortality at 30 days. Methods: Clinical trials that randomized STEMI patients to aspiration thrombectomy prior to PPCI compared with conventional PPCI alone were included. Results: A total of 11,321 patients from 20 randomized controlled trials were included. The composite major adverse cardiac event (MACE) endpoint was lower in the aspiration thrombectomy arm compared with conventional PPCI alone (Risk Ratio [RR]=0.81, 95% CI 0.70-0.94; p=0.006). Although all-cause mortality was similar between the adjunctive aspiration thrombectomy arm and PPCI arms (RR=0.83, 95% CI 0.67-1.01; p=0.06), late mortality (6-12 months) was significantly reduced (RR=0.64; 95% CI 0.44-0.92; p=0.016). Reinfarction (RR=0.64, 95% CI 0.44-0.92; p=0.017) and stent thrombosis (RR=0.54; 95% CI 0.32-0.91; p=0.021) were similarly lower. Differences in target vessel revascularization were of borderline significance (RR=0.83, 95% CI 0.68-1.01; p=0.06) Conclusions: Our meta-analysis including all randomized controlled trials on aspiration thrombectomy to date demonstrates a significant reduction in adverse clinical outcomes including stent thrombosis compared with conventional PCI alone. (c) 2014 Wiley Periodicals, Inc.

OBJECTIVES: To investigate the relative benefits of unfractionated heparin, low molecular weight heparin(LMWH), fondaparinux, and bivalirudin as treatment options for patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). DESIGN: Mixed treatment comparison and direct comparison meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors. DATA SOURCES AND STUDY SELECTION: A search of Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) for randomized trials comparing unfractionated heparin plus glycoprotein IIb/IIIa inhibitor(GpIIb/IIIa inhibitor), unfractionated heparin, bivalirudin, fondaparinux, or LMWH plus GpIIb/IIIa inhibitor for patients undergoing primary PCI. OUTCOMES: The primary efficacy outcome was short term (in hospital or within 30 days) major adverse cardiovascular event; the primary safety outcome was short term major bleeding. RESULTS: We identified 22 randomized trials that enrolled 22 434 patients. In the mixed treatment comparison models, when compared with unfractionated heparin plus GpIIb/IIIa inhibitor, unfractionated heparin was associated with a higher risk of major adverse cardiovascular events (relative risk 1.49 (95% confidence interval 1.21 to 1.84), as were bivalirudin (relative risk 1.34 (1.01 to 1.78)) and fondaparinux (1.78 (1.01 to 3.14)). LMWH plus GpIIb/IIIa inhibitor showed highest treatment efficacy, followed (in order) by unfractionated heparin plus GpIIb/IIIa inhibitor, bivalirudin, unfractionated heparin, and fondaparinux. Bivalirudin was associated with lower major bleeding risk compared with unfractionated heparin plus GpIIb/IIIa inhibitor (relative risk 0.47 (0.30 to 0.74)) or unfractionated heparin (0.58 (0.37 to 0.90)). Bivalirudin, followed by unfractionated heparin, LMWH plus GpIIb/IIIa inhibitor, unfractionated heparin plus GpIIb/IIIa inhibitor, and fondaparinux were the hierarchy for treatment safety. Results were similar in direct comparison meta-analyses: bivalirudin was associated with a 39%, 44%, and 65% higher risk of myocardial infarction, urgent revascularization, and stent thrombosis respectively when compared with unfractionated heparin with or without GpIIb/IIIa inhibitor. However, bivalirudin was associated with a 48% lower risk of major bleeding compared with unfractionated heparin plus GpIIb/IIIa inhibitor and 32% lower compared with unfractionated heparin alone. CONCLUSIONS: In patients undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor and LMWH plus GpIIb/IIIa inhibitor were most efficacious, with the lowest rate of major adverse cardiovascular events, whereas bivalirudin was safest, with the lowest bleeding. These relationships should be considered in selecting anticoagulant therapies in patients undergoing primary PCI.

Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled hypertension despite the use of >/=3 antihypertensive medication classes or controlled hypertension while treated with >/=4 antihypertensive medication classes. Although a high prevalence of aTRH has been reported, few data are available on its association with cardiovascular and renal outcomes. We analyzed data on 14 684 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants to determine the association between aTRH (n=1870) with coronary heart disease, stroke, all-cause mortality, heart failure, peripheral artery disease, and end-stage renal disease. We defined aTRH as blood pressure not at goal (systolic/diastolic blood pressure >/=140/90 mm Hg) while taking >/=3 classes of antihypertensive medication or taking >/=4 classes of antihypertensive medication with blood pressure at goal during the year 2 ALLHAT study visit (1996-2000). Use of a diuretic was not required to meet the definition of aTRH. Follow-up occurred through 2002. The multivariable adjusted hazard ratios (95% confidence intervals) comparing participants with versus without aTRH were as follows: coronary heart disease (1.44 [1.18-1.76]), stroke (1.57 [1.18-2.08]), all-cause mortality (1.30 [1.11-1.52]), heart failure (1.88 [1.52-2.34]), peripheral artery disease (1.23 [0.85-1.79]), and end-stage renal disease (1.95 [1.11-3.41]). aTRH was also associated with the pooled outcomes of combined coronary heart disease (hazard ratio, 1.47; 95% confidence interval, 1.26-1.71) and combined cardiovascular disease (hazard ratio, 1.46; 95% confidence interval, 1.29-1.64). These results demonstrate that aTRH increases the risk for cardiovascular disease and end-stage renal disease. Studies are needed to identify approaches to prevent aTRH and reduce risk for adverse outcomes among individuals with aTRH.

BACKGROUND: The long-term efficacy of beta-blockers in patients with and without myocardial infarction (MI) is controversial. METHODS AND RESULTS: This is post hoc analysis from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial of 4772 patients with prior MI, 7804 patients with known atherothrombosis, and 2101 patients with risk factors alone but without heart failure. Primary outcome was a composite of nonfatal MI, stroke, or cardiovascular mortality. The cohorts were divided into 2 groups based on baseline beta-blocker use. In the propensity score-matched prior MI cohort, after 28 months of follow-up, beta-blocker use was associated with a 31% lower risk of the primary outcome (70 [7.1%] versus 100 [10.2%]; hazards ratio, 0.69; 95% confidence interval, 0.50-0.94; P=0.021), driven by a lower risk of recurrent MI (33 [3.4%] versus 48 [4.9%]; hazards ratio, 0.62; 95% confidence interval, 0.39-1.00; P=0.049) with no difference in mortality (52 [5.3%] versus 66 [6.7%]; P=0.20). In the known atherothrombotic disease and the risk factors alone cohorts, beta-blocker use was not associated with lower ischemic outcomes, whereas a trend toward a higher risk of stroke (3.5% versus 1.5%; hazards ratio, 2.13; 95% confidence interval, 0.92-4.92; P=0.079) was observed in the risk factors alone cohort. This higher stroke risk was significant in the regression model adjusted to the propensity score (hazards ratio, 2.69; 95% confidence interval, 1.33-5.44; P=0.006) and in the multivariable models. CONCLUSIONSBeta: -blocker use in patients with prior MI but no heart failure was associated with a lower composite cardiovascular outcome driven by lower risk of recurrent MI with no difference in mortality. However, beta-blocker use was not associated with lower cardiovascular events in those without MI, with a suggestion of inferior outcome with regard to stroke risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00050817.