Faculty Bibliography

BACKGROUND Dual calcium-channel blocker (CCB) with a dihydropyridine (DHP) and a nondihydropyridine (NDHP) has been proposed for hypertension treatment. However, the safety and efficacy of this approach is not well known. METHODS A MEDLINE/EMBASE/CENTRAL search for randomized clinical trials published on this topic from 1966 to February 2012 was performed. Efficacy outcomes of decrease in systolic (SBP) and diastolic (DBP) blood pressures from baseline, changes in heart rate (HR), and adverse effects were compared between dual CCB therapy vs. DHP or NDHP. SBP, DBP, and HR were expressed as weighted mean deviation (WMD). RESULTS A total of 6 studies with 153 patients were included. Dual CCB produced a significantly greater reduction in SBP (21.6+/-9.2 mmHg) from baseline than DHP (10.3+/-6.3 mmHg (WMD = 10.9 mmHg, P < 0.0001)) or NDHP (8.9+/-4.2 mmHg (WMD = 14.1 mmHg, P = 0.002)). Dual CCB therapy reduced DBP from baseline more than either monotherapy (dual CCB = 17.5+/-10.2 mmHg vs. DHP = 11.6+/-8.7 mmHg, WMD = 5.5 mmHg, P < 0.001; and NDHP = 10.5+/-5.6 mmHg, WMD = 5.3 mmHg, P = 0.03). Dual CCB therapy had significantly lower HR compared to DHP (P < 0.001) but was comparable to NDHP (P = 0.12) (Delta change dual CCB = -4.0+/-3.5 vs. DHP = -2.0+/-1.5 and NDHP = -6.0+/-5.0 beats/min). Dual CCB therapy did not increase adverse effects. CONCLUSIONS Dual CCB therapy lowers blood pressure significantly better than CCB monotherapy, without an increase in adverse events. However, given the lack of long-term outcome data on efficacy and safety, dual CCB therapy should be used with restraint, if at all. Large-scale long-term trials are needed to further evaluate such a strategy.

AIMS: The angiotensin-converting enzyme 2 (ACE2) and its end product angiotensin 1-7 (Ang1-7) are key counterregulatory proteins to offset the deleterious effects of angiotensin II. ACE2 is decreased in diabetic kidney disease but overexpressed in metabolically active atheroma. We tested the hypothesis that ACE2 is increased in diabetic peripheral atheroma, concomitantly with Ang1-7, angiotensin II receptor 1 (AT1R), proinflammatory cytokines, macrophage infiltration, and plaque neovascularization. METHODS AND RESULTS: Peripheral atherectomy plaques collected from 12 diabetic (DM) and 12 non-DM patients were immunostained for ACE2, Ang1-7, AT1R, and proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Macrophage infiltration and neovascularization were counted using double-label immunochemistry with CD68/CD3 and CD34, respectively. Quantification was performed blindly by randomly counting positively stained cells in 20 high-power fields using previously validated methods. Tissue content of ACE2, Ang1-7, and AT1R was increased in DM when compared to non-DM (P<.0001). IL-6 and TNF-alpha were also increased in DM when compared to non-DM (P<.0001), as well as macrophage infiltration score and neovessel counting (P<.0001). CONCLUSION: Expression of ACE2 and its end product Ang1-7 is increased in DM atheroma, along with overexpression of AT1R, IL6, TNF-alpha, macrophage infiltration, and neovascularization. These results suggest that the renin-angiotensin system counterregulatory pathway may be preserved in metabolically active atheroma, offering potential targets for future therapies in diabetic atherosclerosis.

We previously found paclitaxel-eluting polymer-coated stents causing more human platelet-monocyte complex formation than bare metal stents in vitro. Presently, we examined patterns of platelet activation and adhesion after exposure to 6 nanofilm HAp-coated (HAp-nano) stents, 6 HAp-microporous-coated (HAp-micro) stents, 5 HAp sirolimus-eluting microporous-coated (HAp-SES) stents and 5 cobalt-chromium stents (BMS) deployed in an in vitro flow system. Blood obtained from healthy volunteers was circulated and sampled at 0, 10, 30 and 60 min. By flow cytometry, there were no significant differences in P-Selectin expression between the 4 stent types (HAp-nano = 32.5%; HAp-micro = 42.5%, HAp-SES = 10.23%, BMS = 7% change from baseline at 60 min, p = NS); PAC-1 antibody binding (HAp-nano = 11.8%; HAp-micro = 2.9%, HAp-SES = 18%, BMS = 6.4% change from baseline at 60 min, p = NS) or PMC formation (HAp-nano = 21.6%; HAp-micro = 4%, HAp-SES = 6.6%, BMS = 17.4% change from baseline at 60 min, p = NS). The 4 stent types did not differ in the average number of platelet clusters >10 μm in diameter by SEM (HAp-nano = 2.39 ± 5.75; HAp-micro = 2.26 ± 3.43; HAp-SES = 1.93 ± 3.24; BMS = 1.94 ± 2.41, p = NS). The majority of the struts in each stent group were only mildly covered by platelets, (HAp-nano = 80%, HAp-micro = 61%, HAp-SES = 78% and BMS = 52.1%, p = NS). The HAp-microporous-coated stents (ECD) attracted slightly more proteinaceous material than bare metal stents (HAp-micro = 35% struts with complete protein coverage, P < 0.0001 vs. other 3 stent types). In conclusion, biomimetic stent coating with nanofilm or microporous hydroxyapatite, even when eluting low-dose sirolimus, does not increase the platelet activation in circulating human blood, or platelet adhesion to stent surface when compared to bare metal stents in vitro.

The presence of false negative nuclear stress test in the settings of positive electrocardiographic changes is a very unusual phenomenon and is usually secondary to balanced ischemia of the myocardial segments evaluated by SPECT-TL. We present a case of an 81-year old post-menopausal female who presented to her primary care physician for evaluation of a 6-week dyspnea on exertion and was referred to our institution for exercise stress test with Thallium SPECT with the objective of ruling out coronary artery disease and identifying possible areas of myocardial ischemia. The resting electrocardiogram was unremarkable and stress test evaluation was made. The patient was admitted to the cardiac care unit and coronary artery bypass grafting was successfully performed. The presence of false negative nuclear stress test in the settings of positive electrocardiographic changes is a very unusual phenomenon and is usually secondary to balanced ischemia of the myocardial segments evaluated by SPECT-TL. Patients undergoing stress tests with these characteristics should undergo careful evaluation and a high level of suspicion should be adopted for further diagnostic assessment of coronary artery disease.

OBJECTIVES/OBJECTIVE:We aimed to evaluate the correlation of angiographic late loss (LL) with the degree of in-stent neointimal proliferation assessed by optical coherence tomography (OCT) and histology. BACKGROUND:Angiographic LL is the most common endpoint used in clinical trials for the evaluation of the efficacy of drug-eluting stents (DES). However, there are few data in regards to the accuracy of angiographic LL in the evaluation of DES displaying lower degrees of neointimal proliferation. METHODS:A total of 49 stents (36 DES and 13 bare-metal stents) were deployed in coronary arteries of 23 domestic swine and followed up for 28 or 90 days, thus obtaining different degrees of neointimal proliferation. Each stent was divided into 8 to 9 segments along the longitudinal axis to match corresponding histological cross sections. Angiographic LL was calculated at each segment throughout the entire length of the stent and compared with in-stent neointimal thickness (NT) obtained by OCT and histology. RESULTS:A total of 382 angiographic segments were suitable for matched comparison with both OCT and histological findings. The mean LL at follow-up was 0.60 ± 0.57 mm (range: -0.46 to 2.3 mm) for all segments. Approximately 13.9% of stent segments had a LL between -0.5 and 0 mm, and 22.5% had a LL greater than 1.0 mm. The correlation between OCT and histology for the evaluation of NT was adequate regardless the level of angiographic LL. In addition, overall correlations between angiographic LL and NT by OCT or histology were adequate (R = 0.77 and 0.63, respectively). However, angiographic LL showed a poor correlation with NT by OCT or histology at a value <0.55 mm (R = 0.38 and 0.15, respectively). CONCLUSIONS:Angiographic LL below a threshold value of 0.55 mm correlates poorly with NT obtained by OCT and histology. These results suggest a cautious interpretation is needed to evaluate angiographic endpoints in DES trials in which LL values below this threshold are reported.

INTRODUCTION/BACKGROUND:Furosemide is a potent loop diuretic that is widely used in the management of heart failure. Several reports have suggested that continuous intravenous administration of loop diuretics may be superior to intermittent administration. In addition the effect of low-dose dopamine to improve renal perfusion might be of benefit to this patient cohort. METHODS:We retrospectively evaluated 116 consecutive cardiac care unit patients, who were admitted with acute decompensated heart failure and were divided into two equal groups according to diuretic protocol. Group A patients received furosemide by continuous infusion combined with low-dose dopamine infusion. Group B patients received bolus therapy of intravenous furosemide. The effect on renal function and readmission rate was recorded. RESULTS:Among 116 patients (60% males, average age 71, range 46-96 years) 41% had ischemic cardiomyopathy, NYHA functional Class was 3.5 ± 0.5 and average EF was 21% ± 7%. On admission, patients in Group A had creatinine (Cr) 2.3 ± 0.2 mg/dL, blood urea nitrogen (BUN) 49.2 ± 25 mg/100 ml and median b-type natriuretic peptid (BNP) 1340 pg/mL, compared to group B patients with Cr 1.7 ± 1.2 mg/dL, BUN 32 ± 22 mg/100 ml and median BNP 1106 pg/mL. The average furosemide dose in group A was 7.9 ± 3.5 mg/hr compared to 7.6 ± 2.7 mg/hr for group B (p=NS). At the end of the study, patients in group A had lower Cr 1.8 ± 0.9 (p=0.0001), lower BUN 43.6 ± 22.9 (p=NS), an increase in estimated glomerular filtration rate 57.4 ± 27.4, a shorter hospital stay (p=0.015) and lower readmission rates at 30 days (p=0.0003). CONCLUSIONS:Continuous infusion of furosemide in addition to low-dose dopamine is safe, effective and less nephrotoxic than intermittent boluses in patients admitted with acute decompensated heart failure and portends a shorter hospital stay and lower readmission rates at 30 days.

Visceral angioedema is an uncommon but serious complication of therapy with angiotensin-converting enzyme (ACE) inhibitors. We report a case, review the literature, and discuss the incidence, features, and clinical recognition of this condition.

Bochdalek hernia occurs from a congenital defect of the diaphragm, allowing the passage of abdominal structures into the thoracic cavity, limiting lung expansion and ventilatory function. Bochdalek hernia is common in neonates but rarely occur in adults; there are only 4 documented cases in the elderly population. We present a case of an 88-year-old woman with severe hypoxia and respiratory failure that required ventilatory support, in whom bilateral Bochdalek hernias progressed over the years and severely invaded the thoracic cavity, causing acute decompensation. This is a rare condition in adults but can cause substantial morbidity when the involvement of the thoracic cavity is severe.

Among the multiple factors involved in the pathophysiology of heart disease, infections have been proposed to play a role in atherosclerosis with most of the available evidence implicating Chlamydia pneumonia, influenza virus and Mycoplasma pneumoniae. Based on a model case presentation, we speculate that in the absence of traditional risk factors and in the context of an ongoing respiratory infection caused by a pro-inflammatory pathogen (M. pneumoniae) along with a past positive serologic history for potentially proven atherogenic microorganism (C. pneumoniae) and infection may elicit potentially pathogenic events on vascular wall cells and leukocytes of atheromatous lesions, supporting the hypothesis that such infections may potentiate atherosclerotic cardiovascular disease (CVD).