Histological features of restenosis associated with paclitaxel drug-coated balloon: implications for therapy.

PURPOSE: To investigate the cellular and extracellular changes induced by drug-coated balloons (DCB) in the treatment of superficial femoral artery (SFA) restenosis, and to compare histopathological features with those observed after plain old balloon angioplasty (POBA) from the same patients. METHODS AND RESULTS: Plaque samples for five patients with SFA restenosis (first-time) after POBA were collected using atherectomy and DCB. These samples constitute the POBA restenosis group. The same five patients developed recurrent restenosis (RR) after DCB, at the same intervention site. These SFA-RR lesions were again treated using atherectomy and POBA. These samples constitute the DCB restenosis group. DCB restenosis group plaques showed significant reduction in neointima, smooth muscle cells, fibroblast densities, and Ki67 index; and increase in caspase 3, features of apoptosis and type III collagen deposition in comparison to the POBA restenosis group. CONCLUSION: Plaque tissue from the DCB restenosis group show reductions in neointimal thickness, cellularity, and cellular proliferation, along with increased apoptosis, and Type III collagen content. These results suggest a different mechanistic pathway for DCB restenosis, in which neointimal proliferation is reduced but reparative fibrosis is increased. The treatment for SFA-RR after DCB may therefore benefit from different forms of therapy including scaffolding, rather than recurrent anti-proliferative therapy.

Incremental effects of diabetes mellitus and chronic kidney disease in medial arterial calcification: Synergistic pathways for peripheral artery disease progression.

Diabetes mellitus (DM) and chronic kidney disease (CKD) separately are known to facilitate the progression of medial arterial calcification (MAC) in patients with symptomatic peripheral artery disease (PAD), but their combined effect on MAC and associated mediators of calcification is not well studied. The association of MAC and calcification inducer bone morphogenetic protein (BMP-2) and inhibitor fetuin-A, with PAD, is well known. Our aim was to investigate the association of MAC with alterations in BMP-2 and fetuin-A protein expression in patients with PAD with DM and/or CKD. Peripheral artery plaques (50) collected during directional atherectomy from symptomatic patients with PAD were evaluated, grouped into no-DM/no-CKD (n = 14), DM alone (n = 10), CKD alone (n = 12), and DM+CKD (n = 14). MAC density was evaluated using hematoxylin and eosin, and alizarin red stain. Analysis of inflammation, neovascularization, BMP-2 and fetuin-A protein density was performed by immunohistochemistry. MAC density, inflammation grade and neovessel content were significantly higher in DM+CKD versus no-DM/no-CKD and CKD (p < 0.01). BMP-2 protein density was significantly higher in DM+CKD versus all other groups (p < 0.01), whereas fetuin-A protein density was significantly lower in DM+CKD versus all other groups (p < 0.001). The combined presence of DM+CKD may be associated with MAC severity in PAD plaques more so than DM or CKD alone, as illustrated in this study, where levels of calcification mediators BMP-2 and fetuin-A protein were related most robustly to DM+CKD. Further understanding of mechanisms involved in mediating calcification and their association with DM and CKD may be useful in improving management and developing therapeutic interventions.

Outcomes of a Combined Approach of Percutaneous Coronary Revascularization and Cardiac Valve Surgery.

A subset of patients requiring coronary revascularization and valve surgery may benefit from a combined approach of percutaneous coronary intervention (PCI) and valve surgery, as opposed to the standard median sternotomy approach of combined coronary artery bypass and valve surgery. To evaluate its potential benefits and limitations, a literature search was performed using PubMed, EMBASE, Ovid, and the Cochrane library, through March 2016 to identify all studies involving a combined approach of PCI and valve surgery in patients with coronary artery and valvular disease. There were five studies included in the study with a total of 324 patients, of which 75 (23.1%) had a history of previous cardiac surgery. The interval between PCI and surgery ranged from simultaneous intervention to a median of 38 days (interquartile range, 18-65 days). The surgical approach performed consisted of a minimally invasive one or median sternotomy. There were 275 single valve surgery (84.9%) and 49 double-valve surgery (15.1%) with a 30-day mortality ranging from 0% to 5.5%. The 1-year survival ranged from 78% to 96%, and the follow-up period ranged from 1.3 to 5 years. Herein, we present a review of the literature using this technique.

Percutaneous Closure of Intracardiac Defects in Adults: State of the Art.

The number of adults with congenital heart disease is expected to increase over the next decade. Although acquired defects are being increasingly recognized in adults, congenital heart disease remains the most common etiology. With advances in cardiac imaging, device technology, and transcatheter techniques, percutaneous closure is now feasible and safe for most intracardiac defects. Device closure is considered the first-line therapy for a variety of congenital intracardiac defects, including ostium secundum atrial septal defects and muscular ventricular septal defects. Percutaneous closure may prevent recurrent cerebrovascular events after a cryptogenic stroke in high-risk patients with patent foramen ovale. It is also an alternative therapeutic option for patients with acquired defects such as posttraumatic or postinfarction ventricular septal defects and paravalvular regurgitation associated with prosthetic valves. Complications after device closure are uncommon, and may be avoided with appropriate patient and device selection. This is a comprehensive review of the current transcatheter management of the most common intracardiac defects encountered in the adult population.

Rare cause of hemolytic anemia.

Hemolysis is commonly seen in patients with mechanical heart valves and is secondary to destruction of red blood cells by mechanical action of artificial valve. It is very unusual after repair of native heart valve. Here we present a case of hemolytic anemia in association with mitral valve repair.

Regulation of autophagy and apoptosis in response to ox-LDL in vascular smooth muscle cells, and the modulatory effects of the microRNA hsa-let-7 g.

OBJECTIVES: Regulation of autophagy and apoptosis during treatment of vascular smooth muscle cells (VSMCs) with pro-atherogenic stimuli, such as oxidized low density lipoprotein (ox-LDL), remains unclear. METHODS AND RESULTS: We examined the expression of autophagy and apoptosis upon treatment of VSMCs with ox-LDL. Exposure to ox-LDL in modest amounts (10-40 µg/ml) enhanced autophagy (expression of beclin-1, LC3-II/LC3-1 ratio and Atg5) and apoptosis (expression of caspase-3, Bax, Bcl-2 and Bcl-xL); however, exposure to higher concentrations (≥ 60 µg/ml) induced high levels of apoptosis but autophagy declined. Pretreatment of VSMCs with the miRNA hsa-let-7 g inhibited autophagy, as LOX-1 expression and apoptosis declined. Hsa-let-7 g treatment also resulted in a decrease in intracellular ROS generation. Treatment with LOX-1 antibody had similar effects as hsa-let-7 g. Next, we studied autophagy and apoptosis in aortic segments from wild-type and LOX-1 knockout mice fed a high cholesterol diet, and observed increased autophagy as well as apoptosis in lipid-rich sections of aortas from wild-type mice and LOX-1 knockout mice (vs. corresponding controls); however, both autophagy and apoptosis in lipid-rich areas in aortic sections of LOX-1 knockout mice were less than in WT mice. These in vivo data are in keeping with in vitro data showing enhanced autophagy and apoptosis of VSMCs exposed to modest amount of ox-LDL. CONCLUSION: This study provides first set of data on the regulation of autophagy and apoptosis in ox-LDL-treated VSMCs. Our observations also suggest that hsa-let-7 g acts as a critical regulator of autophagy and apoptosis by modulating LOX-1.

Amiodarone-related hyponatremia: rare but potentially lethal.

Amiodarone is a one of the most commonly used antiarrhythmic drug with efficacy in both supraventricular and ventricular tachycardia. Hepatic, pulmonary, and thyroid adverse effect profiles of this drug are well described and mandate a close follow-up. We report a case of amiodarone-related hyponatremia, which is one of the rarest side effects associated with this medication and our case was unlike other previous case reports because severity of symptoms required hemodialysis for correction of hyponatremia despite trying dose reduction strategy.

The risk of adverse cardiac and bleeding events following noncardiac surgery relative to antiplatelet therapy in patients with prior percutaneous coronary intervention.

Noncardiac surgery (NCS) may be required within the first year after percutaneous coronary intervention (PCI) in approximately 4% of patients and is the second most common reason for premature discontinuation of antiplatelet therapy (APT),which may, in turn, increase the risk of perioperative ischemic events, particularly stent thrombosis. Its continuation may increase the risk of perioperative bleeding. We review current information on the incidence of these events, particularly related to APT, describe potentially useful strategies to minimize the risks of adverse outcomes, and provide recommendations on APT use.

Bilateral microvascular second toe transfer for bilateral post-traumatic thumb amputation.

In bilateral thumb amputations, the functional impairment is serious and every attempt should be made to reconstruct the thumb. We report a case of bilateral post traumatic thumb amputation, reconstructed with bilateral second toe transfer. Only two such cases have been reported in literature so far. Though there are various modalities for the reconstruction of thumb, microvascular toe transfer has its own merits. The convalescent period is minimal with excellent function. It is bilaterally symmetric and aesthetically superior to the osteoplastic reconstruction. The technical details are discussed, and the long term functional and aesthetic results are presented.

Bilateral Pleural Effusions due to Pulmonary Amyloidosis as the Presenting Manifestation of Multiple Myeloma.

Multiple Myeloma is a hematologic malignancy of plasma cell origin. Pleural effusion may develop in the setting of myeloma due to various reasons but is extremely uncommon as a presenting symptom. A 69-year-old Caucasian man presented with pleural effusions of undetermined etiology after extensive work up, and multiple failed pleurodesis. Lung biopsy revealed pulmonary amyloidosis and led to the diagnosis of multiple myeloma. Patient was started on chemotherapy but died within 6 weeks of his diagnosis due to multiorgan failure. Pulmonary amyloidosis should be suspected as a cause of intractable pleural effusions, even in patient who do not have evidence of lung involvement on imaging studies or typical features of multiple myeloma. Pleural effusions due to amyloidosis are often refractory to treatment, and a high index of suspicion is required for early diagnosis and treatment.

Current Concepts of the Role of Oxidized LDL Receptors in Atherosclerosis.

Atherosclerosis is characterized by accumulation of lipids and inflammatory cells in the arterial wall. Oxidized low-density lipoprotein (ox-LDL) plays important role in the genesis and progression of atheromatous plaque. Various scavenger receptors have been recognized in the past two decades that mediate uptake of ox-LDL leading to formation of foam cells. Inhibition of scavenger receptor A and CD36 has been shown to affect progression of atherosclerosis by decreasing foam cell formation. Lectin-type oxidized LDL receptor 1 (LOX-1) participates at various steps involved in the pathogenesis of atherosclerosis, and in experimental studies its blockade has been shown to affect the progression of atherosclerosis at multiple levels. In this review, we summarize the role of ox-LDL and scavenger receptors in the formation of atheroma with emphasis on effects of LOX-1 blockade.

Cannabinoids and atherosclerotic coronary heart disease.

Marijuana is the most abused recreational drug in the United States. Cannabinoids, the active ingredients of marijuana, affect multiple organ systems in the human body. The pharmacologic effects of marijuana, based on stimulation of cannabinoid receptors CB1 and CB2, which are widely distributed in the cardiovascular system, have been well described. Activation of these receptors modulates the function of various cellular elements of the vessel wall, and may contribute to the pathogenesis of atherosclerosis. Clinically, there are reports linking marijuana smoking to the precipitation of angina and acute coronary syndromes. Recently, large published clinical trials with CB1 antagonist rimonabant did not show any significant benefit of this agent in preventing progression of atherosclerosis. In light of these findings and emerging data on multiple pathways linking cannabinoids to atherosclerosis, we discuss the literature on the role of cannabinoids in the pathophysiology of atherosclerosis. We also propose a marijuana paradox, which implies that inhalation of marijuana may be linked to precipitation of acute coronary syndromes, but modulation of the endocannabinoid system by a noninhalation route may have a salutary effect on the development of atherosclerosis.