Faculty Bibliography

We present a 47-year-old man with acute lymphocytic leukemia with a pericardial friction rub heralding pericardial aspergillosis. The clinical course was complicated by pneumopericardium, likely secondary to a direct connection between the lung parenchyma and the pericardial space. Bronchoalveolar lavage cultures returned positive for methicillin-resistant Staphylococcus aureus and Aspergillus niger. Combination voriconazole and vancomycin resulted in symptomatic improvement within 2 weeks of hospitalization.

Heroin administration by "chasing the dragon," whereby the user places freebase heroin on aluminum foil, heats it below with a flame, and inhales the pyrolysate through a straw, can be associated with the rare development of a delayed-onset spongiform leukoencephalopathy. We report the case of a 46-year-old woman with a psychiatric diagnosis of depression and heroin dependence by "chasing the dragon" admitted with features of altered mental status and later development of catatonia, abulia, and akinetic mutism. A brain magnetic resonance image evidenced bilateral symmetric high-signal lesions in the white matter of the cerebrum and cerebellum on T2-weighted images compatible with toxic leukoencephalopathy. The patient's condition resolved after a hospital stay of 2 months with supportive treatment. Acute onset of neurobehavioral changes, including confusion, apathy, and cerebellar signs in a person with exposure to heroin, should prompt one to consider toxic leukoencephalopathy as a cause of presentation.

BACKGROUND:There is controversy about preferred methods to relieve obstruction in hypertrophic cardiomyopathy patients still symptomatic after β-blockade or verapamil. METHODS AND RESULTS/RESULTS:Of 737 patients prospectively registered at our institution, 299 (41%) required further therapy for obstruction for limiting symptoms, rest gradient 61 ± 45, provoked gradient 115 ± 49 mm Hg, and followed up for 4.8 years. Disopyramide was added in 221 (74%) patients and pharmacological control of symptoms was achieved in 141 (64%) patients. Overall, 138 (46%) patients had surgical relief of obstruction (91% myectomy) and 6 (2%) alcohol septal ablation. At follow-up, resting gradients in the 299 patients had decreased from 61 ± 44 to 10 ± 25 mm Hg (P<0.0001); New York Heart Association class decreased from 2.7 ± 0.7 to 1.8 ± 0.5 (P<0.0001). Kaplan-Meier survival at 10 years in the 299 advanced-care patients was 88% and did not differ from nonobstructed patients (P=0.28). Only 1 patient had sudden death, a low annual rate of 0.06%/y. Kaplan-Meier survival at 10 years in the advanced-care patients did not differ from that expected in a matched cohort of the US population (P=0.90). CONCLUSIONS:Patients with obstruction and symptoms resistant to initial pharmacological therapy with β-blockade or verapamil may realize meaningful symptom relief and low mortality through stepped management, adding disopyramide in appropriately selected patients, and when needed, by surgical myectomy.

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.