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Comparison of quantity of left ventricular scarring and remodeling by magnetic resonance imaging in patients with versus without diabetes mellitus and with coronary artery disease

Donnino, Robert; Patel, Sajan; Nguyen, Andrew H; Sedlis, Steven P; Babb, James S; Schwartzbard, Arthur; Katz, Stuart D; Srichai, Monvadi B
Diabetic patients with coronary artery disease (CAD) are more likely to develop heart failure (HF) than nondiabetic patients, but the mechanism responsible is unclear. Evidence suggests that infarct size and accompanying remodeling may not explain this difference. We used cardiac magnetic resonance (CMR) imaging to compare degree of left ventricular (LV) myocardial scar and remodeling in diabetic and nondiabetic patients with CAD. We evaluated 85 patients (39 diabetic, 46 nondiabetic) who underwent coronary angiography showing obstructive CAD and CMR imaging within 6 months of each other. Myocardial scar was measured by late gadolinium enhancement on CMR imaging and was graded according to spatial and transmural extents on a semiquantitative scale. More diabetic than nondiabetic patients had HF (69% vs 43%, p <0.03); however, groups did not differ in total scar burden (0.94 +/- 0.60 vs 1.17 +/- 0.74, p = NS), spatial extent of scar, or extent of transmural scar. Diabetes remained an independent predictor of HF after adjustment for CAD and other variables. LV ejection fraction (36 +/- 12% vs 37 +/- 14%, p = NS) and end-diastolic volume (215 +/- 56 vs 217 +/- 76 ml, p = NS) were similar for diabetic and nondiabetic patients, respectively. In conclusion, although diabetic patients with CAD had a higher prevalence of HF than nondiabetic patients, there was no difference in myocardial scar, LV volume, or LV ejection fraction. These findings support the theory that mechanisms other than extent of myocardial injury and negative remodeling play a significant role in the development of HF in diabetic patients with CAD
PMID: 21439536
ISSN: 1879-1913
CID: 132572

Potential benefits of aliskiren beyond blood pressure reduction

Weintraub, Howard S; Tran, Henry; Schwartzbard, Arthur
There is now clear evidence that reducing blood pressure (BP) with a broad range of agents, including angiotensin converting enzyme inhibitors and angiotensin receptor blockers, improves cardiovascular and renal outcomes. There is also evidence suggesting that these drugs have beneficial effects that are independent of BP lowering. Aliskiren is a direct renin inhibitor that interrupts the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step. Unlike angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, aliskiren produces a sustained reduction in plasma renin activity and reduces plasma levels of angiotensin II and aldosterone. Preclinical data and clinical trials in high-risk patients using surrogate markers increasingly suggest that aliskiren can reduce the progression of end-organ damage beyond that afforded by BP control. With its unique mechanism of action, combining aliskiren with another RAAS-blocking agent that has a different mechanism of action may provide more comprehensive blockade of the RAAS, potentially conferring additional clinical benefits. Evaluation of these end-organ effects in humans is underway in clinical trials designed to assess the effects of aliskiren alone and in combination with other antihypertensive agents on cardiovascular and renal outcomes
PMID: 21285669
ISSN: 1538-4683
CID: 122546

Moderate doses of hGH (0.64 mg/d) improve lipids but not cardiovascular function in GH-deficient adults with normal baseline cardiac function

Newman, Connie B; Frisch, Katalin A; Rosenzweig, Barry; Roubenoff, Ronenn; Rey, Mariano; Kidder, Teresa; Kong, Yuan; Pursnani, Amit; Sedlis, Steven P; Schwartzbard, Arthur; Kleinberg, David L
CONTEXT: Data regarding effects of lower-dose GH on cardiopulmonary function in GH-deficient (GHD) adults are limited. OBJECTIVES: The objective was to assess effects of lower-dose GH on exercise capacity and echocardiographic parameters in GHD adults. DESIGN: The study was a 6-month double-blind, placebo-controlled randomized trial. SETTING: The study was conducted at the General Clinical Research Center. PARTICIPANTS: Thirty hypopituitary adults with GHD were studied. INTERVENTION: Subjects were randomized to recombinant human GH or placebo for 6 months, followed by open-label recombinant human GH for 12 months. MAIN OUTCOME MEASURES: Primary endpoints were exercise duration, maximal oxygen consumption, and left ventricular ejection fraction. Secondary endpoints were echocardiographic indices of systolic and diastolic function, left ventricular mass, lipids, and body composition. RESULTS: In the 6-month double-blind phase, mean GH dose was 0.64 mg/d. Mean IGF-I sd score increased from -4.5 to -1.0. Exercise duration, maximal oxygen consumption, left ventricular ejection fraction, and other echocardiographic parameters were normal at baseline and did not change. GH decreased total and low-density lipoprotein cholesterol by 7.5% (P = 0.016) and 14.7% (P = 0.002) (P = 0.04 vs. placebo). Mean lean body mass increased by 2.2 kg (P = 0.004), fat mass decreased by 1.7 kg (P = 0.21), and percent body fat decreased by 2.5% (P = 0.018), although between-group changes were not significant. CONCLUSIONS: Human GH did not improve exercise performance or echocardiographic parameters or decrease fat mass but significantly decreased total and low-density lipoprotein cholesterol, increased IGF-I, and increased lean body mass. These results indicate that responses to human GH are variable and should be assessed at baseline and during treatment
PMID: 20926529
ISSN: 1945-7197
CID: 138237

Fish oil for the treatment of cardiovascular disease

Weitz, Daniel; Weintraub, Howard; Fisher, Edward; Schwartzbard, Arthur Z
Omega-3 fatty acids, which are found abundantly in fish oil, are increasingly being used in the management of cardiovascular disease. It is clear that fish oil, in clinically used doses (typically 4 g/d of eicosapentaenoic acid and docosahexaenoic acid) reduce high triglycerides. However, the role of omega-3 fatty acids in reducing mortality, sudden death, arrhythmias, myocardial infarction, and heart failure has not yet been established. This review will focus on the current clinical uses of fish oil and provide an update on their effects on triglycerides, coronary artery disease, heart failure, and arrhythmia. We will explore the dietary sources of fish oil as compared with drug therapy, and discuss the use of fish oil products in combination with other commonly used lipid-lowering agents. We will examine the underlying mechanism of fish oil's action on triglyceride reduction, plaque stability, and effect in diabetes, and review the newly discovered anti-inflammatory effects of fish oil. Finally, we will examine the limitations of current data and suggest recommendations for fish oil use
PMCID:3217043
PMID: 20699674
ISSN: 1538-4683
CID: 111598

Ranolazine: a new approach to treating an old problem

Reddy, Bharath M; Weintraub, Howard S; Schwartzbard, Arthur Z
Chronic angina pectoris affects millions of patients every year. During the past 2 decades, advances in medical therapy have led to substantial reductions in the symptoms of angina. Nonetheless, many patients continue to experience persistent angina that causes debilitating symptoms and lifestyle changes. Moreover, many current therapeutic agents cause side effects that can induce substantial morbidity on their own. In major clinical trials, the drug ranolazine has been shown to bring symptomatic relief to large numbers of patients who have chronic angina. Herein, we review the physiology of the sodium channel; the pharmacology of ranolazine; clinical trials that support use of the drug; recent evidence about ranolazine's therapeutic effect on diastolic heart failure, glycemic control, and atrial fibrillation and other arrhythmias; officially approved clinical indications; and avenues of future study
PMCID:3014127
PMID: 21224931
ISSN: 1526-6702
CID: 119239

Cardiac complications of urologic surgery

Chapter by: Hong, SN; Schwartzbard, A
in: Complications of Urologic Surgery: Prevention and Management by
pp. 21-30
ISBN: 9781416045724
CID: 2292742

Reassessing the cardiovascular risks and benefits of thiazolidinediones

Zinn, Andrew; Felson, Sabrina; Fisher, Edward; Schwartzbard, Arthur
This article is designed for the general cardiologist, endocrinologist, and internist caring for patients with diabetes and coronary artery disease. Despite the burden of coronary disease in diabetics, little is known about the impact of commonly used oral hypoglycemic agents on cardiovascular outcomes. As the untoward effects of insulin resistance (IR) are increasingly recognized, there is interest in targeting this defect. Insulin resistance contributes to dyslipidemia, hypertension, inflammation, hypercoagulability, and endothelial dysfunction. The aggregate impact of this process is progression of systemic atherosclerosis and an increased risk of adverse cardiovascular outcomes. As such, much attention has been paid to the peroxisome-proliferator-activated receptor gamma (PPARg) agonists rosiglitazone and pioglitazone (thiazolidinediones [TZDs]). Many studies have demonstrated a beneficial effect on the atherosclerotic process; specifically, these agents have been shown to reduce markers of inflammation, retard progression of carotid intimal thickness, prevent restenosis after coronary stenting, and prevent cardiovascular death and myocardial infarction in 1 large trial. Such benefits come at the risk of fluid retention and heart failure (HF) exacerbation, and the net effect on plasma lipids is still poorly understood. Thus, the aggregate risk-benefit ratio is poorly defined. A recent meta-analysis has raised significant concerns regarding the overall cardiovascular safety of 1 particular PPARg agonist (rosiglitazone), prompting international debate and regulatory changes. This review scrutinizes the clinical evidence regarding the cardiovascular risks and benefits of PPARg agonists. Future studies of PPARg agonists, and other emerging drugs that treat IR and diabetes, must be designed to look at cardiovascular outcomes
PMID: 18781598
ISSN: 0160-9289
CID: 105305

Long-term outcomes in non-diabetic patients with metabolic syndrome undergoing revascularization for multi-vessel coronary artery disease

Yatskar, Leonid; Holper, Elizabeth; Bansilal, Sameer; Schwartzbard, Arthur; Lombardero, Manuel; Ramanathan, Krishnan; Feit, Frederick; Fisher, Edward; Faxon, David; Hochman, Judith S; Farkouh, Michael E
AIM: The influence of metabolic syndrome (MS) on long-term mortality and morbidity in multi-vessel coronary artery disease (MV-CAD) is unclear. We studied the impact of MS on long-term outcomes in non-diabetic patients (NDM) with MV-CAD undergoing coronary revascularization in the Bypass Angioplasty Revascularization Investigation (BARI) trial and registry. METHODS: BARI trial and registry patients were separated into those with diabetes (DM) and those without. NDM fulfilling the NCEP definition of MS were identified. Ten year follow-up data were obtained on mortality, MI and development of diabetes. The data were analyzed using Cox proportional hazard modeling. RESULTS: In the BARI trial and registry 2962 NDM were identified. Of those, 510 patients had 3 or more components of the BARI-modified NCEP definition for MS, while 445 patients had 2 components of the definition and were classified as the 'mixed group'. Compared to patients without MS, both MS group (RR=3.2, p<0.0001) and the mixed group (RR=1.9, p=0.02) had a higher incidence of DM over the 10-year follow-up. Type 2 DM was found to be highly associated with 10-year mortality (RR=1.65, p<0.0001). However, there was no statistically significant difference in the rate of death or MI at 5 and 10 years between NDM with or without MS. In multivariate analysis, the presence of MS was not associated with 10-year mortality in the BARI population (RR=0.93, p=0.62). CONCLUSION: In this BARI follow-up study, we have affirmed the role of MS in predicting the development of diabetes in NDM at baseline. The 10-year risk of mortality and MI was not greater in NDM with MS who had MV-CAD and underwent revascularization, compared to patients without MS. Further studies to evaluate MS patients with MV-CAD undergoing coronary revascularization are warranted
PMID: 18061192
ISSN: 1879-1484
CID: 79378

Fibrate therapy: an update

Remick, Joshua; Weintraub, Howard; Setton, Robert; Offenbacher, Joseph; Fisher, Edward; Schwartzbard, Arthur
Fibrates are a class of lipid-lowering medication primarily used as second-line agents behind statins. Acting via the peroxisome proliferators-activated receptor-alpha, their main lipoprotein effects are to lower serum triglyceride levels and to raise high-density lipoprotein-cholesterol, with modest effects on low-density lipoprotein-cholesterol. However, many clinical trials indicate that fibrates may have benefits beyond simply altering one's lipid profile. Several angiographic studies show retardation in the progression of atherosclerotic lesions in coronary vessels. Although clinical trials have failed to show a reduction in mortality with fibrates, several post hoc analyses indicate that there may be a mortality benefit in patients with features of the metabolic syndrome. Given that fibrates are often used as second-line agents, it is essential they are safe to be given in combination with other agents, particularly statins and ezetimibe. Although the side-effect profile of fibrates includes gastrointestinal symptoms, increased liver function tests, a reversible rise in creatinine and myositis, in general, fibrates seem to be safe to use in combination with other lipid lowering medications. Thus far, fibrates have not shown a mortality benefit in randomized clinical trials; as a result, they cannot be considered first-line medication for the primary or secondary prevention of coronary artery disease
PMID: 18414184
ISSN: 1538-4683
CID: 79383

Metabolic syndrome does not impact survival in patients treated for coronary artery disease

Shah, Binita; Kumar, Nidhi; Garg, Parveen; Kang, Eunice; Grossi, Eugene; Lorin, Jeffrey D; Schwartzbard, Arthur Z; Mass, Howard; Danoff, Ann; Sedlis, Steven P
OBJECTIVES: We evaluated the effect of metabolic syndrome (a risk factor for the development of coronary artery disease) on survival in patients with established coronary artery disease. METHODS: Survival was determined for 2886 patients with coronary artery disease diagnosed by cardiac catheterization performed between 1990 and 2005 at a Department of Veterans Affairs hospital. Variables obtained from the computerized medical record were evaluated in multivariate analysis by Cox regression. The analysis was performed for the entire population; separate analyses were performed for patient cohorts treated with percutaneous coronary intervention and medication (n=1274), coronary artery bypass grafting and medication (n=1096), or medication alone (n=516). RESULTS: Although age (odds ratio 0.948; P<0.000), left ventricular function (odds ratio 0.701; P<0.000), serum creatinine (odds ratio 0.841; P<0.000), and smoking (odds ratio 0.873; P=0.019) were all strong predictors of mortality. Metabolic syndrome had no independent effect irrespective of diabetic status. CONCLUSION: Metabolic syndrome does not impact survival patients with coronary artery disease treated by revascularization and/or medical therapy
PMID: 18300742
ISSN: 0954-6928
CID: 78361