Coronary Artery Disease: Park MH

Patel MR, Dehmer GJ, Hirshfeld JW, Smith PK, Spertus JA, Masoudi FA, Brindis RG, Beckman KJ, Chambers CE, Ferguson TB, Garcia MJ, Grover FL, Holmes DR, Klein LW, Limacher M, Mack MJ, Malenka DJ, Park MH, Ragosta M, Ritchie JL, Rose GA, Rosenberg AB, Shemin RJ, Weintraub WS, Wolk MJ, Allen JM, Douglas PS, Hendel RC, Peterson ED. · Division of Cardiology, Duke University Medical Center, Durham, NC, USA. · Catheter Cardiovasc Interv. · Pubmed #19127535 No free full text.

Abstract: The American College of Cardiology Foundation (ACCF), Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, and the American Association for Thoracic Surgery, along with key specialty and subspecialty societies, conducted an appropriateness review of common clinical scenarios in which coronary revascularization is frequently considered. The clinical scenarios were developed to mimic common situations encountered in everyday practice and included information on symptom status, extent of medical therapy, risk level as assessed by noninvasive testing, and coronary anatomy. Approximately 180 clinical scenarios were developed by a writing committee and scored by a separate technical panel on a scale of 1 to 9. Scores of 7 to 9 indicate that revascularization was considered appropriate and likely to improve health outcomes or survival. Scores of 1 to 3 indicate revascularization was considered inappropriate and unlikely to improve health outcomes or survival. The mid range (4 to 6) indicates a clinical scenario for which the likelihood that coronary revascularization would improve health outcomes or survival was considered uncertain. For the majority of the clinical scenarios, the panel only considered the appropriateness of revascularization irrespective of whether this was accomplished by percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). In a select subgroup of clinical scenarios in which revascularization is generally considered appropriate, the appropriateness of PCI and CABG individually as the primary mode of revascularization was considered. In general, the use of coronary revascularization for patients with acute coronary syndromes and combinations of significant symptoms and/or ischemia was viewed favorably. In contrast, revascularization of asymptomatic patients or patients with low-risk findings on noninvasive testing and minimal medical therapy were viewed less favorably. It is anticipated that these results will have an impact on physician decision making and patient education regarding expected benefits from revascularization and will help guide future research.

Park MH. · Ochsner Cardiomyopathy and Heart Transplantation Center, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121, USA. · Congest Heart Fail. · Pubmed #12937357 No free full text.

Abstract: Aspirin and angiotensin-converting enzyme (ACE) inhibitors are widely used in combination to treat a wide spectrum of cardiac disorders. Theoretically, a rationale for interaction between these two agents exists in the possible counterbalancing prostaglandin inhibiting actions of aspirin and the vasodilatory prostaglandin promoting effects of ACE inhibitors. Animal and human studies suggest such an interaction, but most are plagued by small numbers or retrospective designs. Large-scale trials are in progress to address this issue. Until then, the key factor in deciding whether a patient with ischemic heart disease on ACE inhibitor therapy should be placed on aspirin therapy may largely depend on the severity of heart failure. The more severe the heart failure, the more likely an appreciable interaction between aspirin and ACE inhibitors will occur. Treatment with either low-dose aspirin or with alternative agents, such as warfarin or clopidogrel, may be the best therapeutic approach for patients with severe systolic heart failure.

Mehra MR, Uber PA, Scott RL, Park MH. · The Ochsner Cardiomyopathy and Heart Transplantation Center, Ochsner Clinic Foundation, New Orleans, LA, USA. · Transplantation. · Pubmed #12490790 No free full text.

Abstract: BACKGROUND: Black American heart transplant recipients receiving cyclosporine-based primary immunoprophylaxis suffer higher rates of allograft rejection with hemodynamic compromise, infections, and posttransplant coronary artery disease. We examined the hypothesis that a combination of tacrolimus and mycophenolate mofetil "resurrects" clinical outcome of black Americans to those seen in white heart transplant recipients. METHODS: Sixty-three adult primary heart transplant recipients were included in this study. Twenty black American and 21 white patients who received tacrolimus-based primary immunoprophylaxis were enrolled in this prospective, observational parallel cohort investigation. A separate group of 22 black American patients were randomly allocated to receive cyclosporine-microemulsion-based primary prophylaxis and served as the control population for assessing outcomes in the black American group. Adjunctive immunosuppression included mycophenolate mofetil and corticosteroids. The primary end-point was the freedom from allograft rejection requiring treatment at 1 year. Secondary end-points included rejection with hemodynamic compromise, and patient or graft survival. Adverse events evaluated included development of infections requiring hospitalization and nonimmunological outcomes including hyperlipidemia, hypertension, and diabetes mellitus (new onset or worsened). RESULTS: Tacrolimus-treated black American patients had greater freedom from allograft rejection requiring treatment at 1 year than those treated with cyclosporine (64% vs. 37%, P=0.01). No differences were noted between tacrolimus-treated black Americans and whites in the primary end point (64% and 67% respectively, P=nonsignificant [NS]). Tacrolimus-based immunosuppression was associated with better 1-year survival in black Americans compared with cyclosporine (95% vs. 73%, P=0.04), and this end point was similar to that achieved in tacrolimus-treated white heart transplant recipients (95%). No differences in infection rates were noted among either group. Cyclosporine-treated black Americans suffered more hyperlipidemia and worse hypertension than tacrolimus-treated patients. CONCLUSIONS: Compared with cyclosporine, an immunosuppressive strategy using tacrolimus in black Americans achieves superior efficacy with regard to allograft rejection, higher allograft survival, and similar safety. Furthermore, tacrolimus-based immunosuppression is similar in immunological efficacy and safety in black Americans and in white heart transplant recipients.

Mehra MR, Uber PA, Potluri S, Ventura HO, Scott RL, Park MH. · Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, Louisiana 70121, USA. · Am J Cardiol. · Pubmed #15325928 No free full text.

Abstract: B-type natriuretic peptide (BNP) has emerged as an important marker of ventricular wall stress and is predictive of hemodynamic abnormalities in heart transplantation despite "preserved" systolic function. We evaluated the capacity of BNP to predict deaths due to allograft failure in 62 patients long after heart transplantation (mean 5 +/- 2.5 years). Based on the median tendency of measurement of BNP in the absence of rejection during stable surveillance, 2 distinct patient groups were identified as having low BNP (n = 39, < 250 pg/ml; median BNP 70 pg/ml) and high BNP (n = 23, > or =250 pg/ml; median BNP 592 pg/ml). No differences between the 2 BNP groups were noted with regard to age, gender, race, time after transplantation, diabetes mellitus, hypertension, and hyperlipidemia with measurement of BNP. Multivariable analysis showed that decreased left ventricular ejection fraction, angiographic coronary artery disease, and increased serum creatinine were independent predictors of elevated BNP. Cardiac deaths were significantly greater in those with high BNP levels (35%) than in those with low BNP (2.5%, p = 0.01). Absence of significant angiographic coronary artery disease coupled with a BNP of < 250 pg/ml was associated with the lowest event rate (0%), whereas patients with coronary artery disease and BNP > or =250 pg/ml exhibited a 50% cardiac death rate (p <0.01 for trend). Cox's model confirmed that increased BNP and decreased left ventricular ejection fraction are independent predictors of poor survival. Survival analysis associated lower BNP levels with an excellent long-term survival rate (95%) and higher BNP levels with a markedly decreased survival rate (60%, p = 0.002). Higher BNP levels in patients long after heart transplantation are associated with allograft dysfunction and cardiac allograft vasculopathy and are strongly and independently predictive of cardiovascular death.

Mehra MR, Uber PA, Park MH, Scott RL, Ventura HO, Harris BC, Frohlich ED. · Department of Cardiovascular Medicine, Ochsner Clinic Foundation, New Orleans, Louisiana 70121, USA. · J Am Coll Cardiol. · Pubmed #15120816 No free full text.

Abstract: OBJECTIVES: This investigation evaluated the relationship between obesity and B-type natriuretic peptide (BNP) in heart failure. BACKGROUND: Obesity is a major risk factor for the development of heart failure, but the precise mechanisms remain uncertain. Physiologically, natriuretic peptides and lipolysis are closely linked. METHODS: A total of 318 patients with heart failure were evaluated between June 2001 and June 2002. Levels of BNP were compared in obese (body mass index [BMI] > or =30 kg/m(2)) and nonobese (BMI <30 kg/m(2)) patients with respect to New York Heart Association functional class and lean body weight-adjusted peak aerobic oxygen consumption. In a subset of 36 patients, plasma levels of tumor necrosis factor-alpha, interleukin-6, and soluble intercellular adhesion molecule-1 were measured. RESULTS: The population's BMI was 29.4 +/- 6.6 kg/m(2); 24% were lean (BMI <25 kg/m(2)), 31% overweight (BMI > or =25 to 29.9 kg/m(2)), and 45% obese (BMI > or =30 kg/m(2)). Obese patients were younger, more often African American, and more likely to have a history of antecedent hypertension, but less likely to have coronary artery disease and with only a trend toward diabetes mellitus. Levels of BNP were significantly lower in obese than in nonobese subjects (205 +/- 22 and 335 +/- 39 pg/ml, respectively; p = 0.0007), despite a similar severity of heart failure and cytokine levels. Multivariate regression analysis identified BMI as an independent negative correlate of BNP level. There were no differences in emergency department visits, heart failure hospitalization, or death between the obese and nonobese patients at 12-month follow-up. CONCLUSIONS: Our investigation indicates that a state of reduced natriuretic peptide level exists in the obese individual with heart failure.

Mehra MR, Uber PA, Ventura HO, Scott RL, Park MH. · Ochsner Cardiomyopathy and Heart Transplantation Center, Ochsner Medical Institutions, New Orleans, Louisiana 70121, USA. · J Am Coll Cardiol. · Pubmed #14998621 No free full text.

Abstract: OBJECTIVES: We evaluated the association of mode of brain death with cardiac allograft vasculopathy. BACKGROUND: Explosive brain death (EBD) is accompanied by a sudden increase in intracranial pressure, with recruitment of pro-inflammatory cytokines, as well as adhesion cell and co-stimulatory molecules. Whether these early events influence the later development of cardiac allograft vasculopathy following heart transplantation remains unknown. METHODS: An inception cohort of 61 consecutive heart transplant recipients between 1993 and 1995 who underwent intravascular ultrasound examination of the coronary arteries were evaluated. Based on the mode of donor brain death, this cohort was divided into either an EBD group (n = 27) or non-EBD (n = 34), and the development of intimal thickness and cardiac events (sudden cardiac death, myocardial infarction, and need for coronary revascularization via percutaneous techniques or surgical bypass) was assessed. RESULTS: Despite similar posttransplant survival and distribution of nonimmunological and immunological variables, heart transplant recipients with EBD demonstrated greater intimal thickening (0.59 +/- 0.1 vs. 0.32 +/- 0.2 mm; p = 0.02) and higher cardiac events (37% vs. 12%; p = 0.01) when compared to those with non-EBD donors. Hearts from donors with EBD had lower survival (63 +/- 19 vs. 72 +/- 17 months) than with non-EBD donors (p = 0.04). CONCLUSIONS: Explosive brain death is a significant determinant for the late development of cardiac allograft vasculopathy and influences long-term allograft survival. Thus, strategies focusing on limitation of vascular allograft injury in the pre-engraftment phase of cardiac transplantation are warranted.