Stable coronary artery disease and left ventricular dysfunction: The role of revascularization.

The aim of this review is to present existing evidence of revascularization in patients with stable coronary artery disease (CAD) and left ventricular (LV) dysfunction. A literature review was performed for trials studying revascularization, via CABG or PCI, in patients with CAD and LV dysfunction. Pivotal, high-quality trials have investigated revascularization with CABG in stable CAD and LV dysfunction. CASS demonstrated improved 10-year survival in the surgical group compared to medically treated patients. While 56-month follow-up of the STICH trial found no statistically significant difference between CABG and medical therapy in patients with stable CAD and LV dysfunction, the long-term follow-up at 10 years (STICHES) demonstrated that CABG did significantly decrease death from any cause and all secondary outcomes. However, these pivotal trials have focused solely on surgical revascularization. Comparable studies regarding outcomes after contemporary PCI methods in this particular subset of patients are severely lacking. More recent studies have included very small numbers of patients with reduced EF. In conclusion, given advances in surgical and non-invasive fields, studies investigating long-term effects of PCI versus CABG, including combined hybrid revascularization techniques are warranted. This review sets the stage for a high-quality randomized, controlled trial comparing revascularization with PCI versus CABG in patients with stable CAD and LV dysfunction.

Hypoxia induces downregulation of PPAR-γ in isolated pulmonary arterial smooth muscle cells and in rat lung via transforming growth factor-ß signaling.

Chronic hypoxia activates transforming growth factor-ß (TGF-ß) signaling and leads to pulmonary vascular remodeling. Pharmacological activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) has been shown to prevent hypoxia-induced pulmonary hypertension and vascular remodeling in rodent models, suggesting a vasoprotective effect of PPAR-γ under chronic hypoxic stress. This study tested the hypothesis that there is a functional interaction between TGF-ß/Smad signaling pathway and PPAR-γ in isolated pulmonary artery small muscle cells (PASMCs) under hypoxic stress. We observed that chronic hypoxia led to a dramatic decrease of PPAR-γ protein expression in whole lung homogenates (rat and mouse) and hypertrophied pulmonary arteries and isolated PASMCs. Using a transgenic model of mouse with inducible overexpression of a dominant-negative mutant of TGF-ß receptor type II, we demonstrated that disruption of TGF-ß pathway significantly attenuated chronic hypoxia-induced downregulation of PPAR-γ in lung. Similarly, in isolated rat PASMCs, antagonism of TGF-ß signaling with either a neutralizing antibody to TGF-ß or the selective TGF-ß receptor type I inhibitor SB431542 effectively attenuated hypoxia-induced PPAR-γ downregulation. Furthermore, we have demonstrated that TGF-ß1 treatment suppressed PPAR-γ expression in PASMCs under normoxia condition. Chromatin immunoprecipitation analysis showed that TGF-ß1 treatment significantly increased binding of Smad2/3, Smad4, and the transcriptional corepressor histone deacetylase 1 to the PPAR-γ promoter in PASMCs. Conversely, treatment with the PPAR-γ agonist rosiglitazone attenuated TGF-ß1-induced extracellular matrix molecule expression and growth factor in PASMCs. These data provide strong evidence that activation of TGF-ß/Smad signaling, via transcriptional suppression of PPAR-γ expression, mediates chronic hypoxia-induced downregulation of PPAR-γ expression in lung.

Orbital Atherectomy for Treatment of Severely Calcified Coronary Artery Bifurcation Lesions: A Multicenter Analysis.

OBJECTIVE: This study evaluated the safety and efficacy of orbital atherectomy (OA) for the treatment of severely calcified coronary artery bifurcation lesions. BACKGROUND: Percutaneous coronary intervention (PCI) of severely calcified coronary artery lesions is associated with lower procedural success and higher rates of target lesion failure compared to non-calcified lesions. OA is an effective treatment for calcified coronary artery lesions prior to stent implantation. However, there is little data regarding the safety and efficacy of OA in patients with coronary artery bifurcation lesions. METHODS: Data were obtained from analysis of patients with severe coronary artery calcification who underwent OA and coronary stent implantation at ten high-volume institutions. Data were pooled and analyzed to assess peri-procedural outcomes and 30-day major adverse cardiac events (MACE). RESULTS: A total of 1156 patients were treated with OA and PCI. 363 lesions were at a coronary artery bifurcation. There were no statistically significant differences in baseline characteristics between the bifurcation and non-bifurcation groups. In the bifurcation group, treatment involved the left anterior descending artery and its branches more frequently and right coronary artery less frequently. After propensity score matching, the 30-day freedom from MACE was not statistically significant between the two groups. CONCLUSION: In this multicenter cohort analysis, patients with severely calcified coronary bifurcation lesions had low rates of MACE and target vessel revascularization at 30 days at rates comparable to non-bifurcation lesions. This analysis demonstrates that OA is safe and effective for complex coronary lesions at both bifurcation and non-bifurcation locations.

Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015.

BACKGROUND: The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world. OBJECTIVES: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden. METHODS: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. RESULTS: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75. CONCLUSIONS: CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD.

Identifying gaps for research prioritisation: Global burden of external causes of injury as reflected in the Cochrane Database of Systematic Reviews.

IMPORTANCE: Burden of disease should impact research prioritisation. OBJECTIVE: To analyse the Cochrane Database of Systematic Reviews (CDSR) and determine whether systematic reviews and protocols accurately represent disease burden, as measured by disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2010 Study. METHODS: Two investigators collected GBD disability metrics for 12 external causes of injury in the GBD 2010 Study. These external causes were then assessed for systematic review and protocol representation in CDSR. Data was collected during the month of April 2015. There were no study participants aside from the researchers. Percentage of total 2010 DALYs, 2010 DALY rank, and median DALY percent change from 1990 to 2010 of the 12 external causes of injury were compared with CDSR representation of systematic reviews and protocols. Data were analysed for correlation using Spearman rank correlation. RESULTS: Eleven of the 12 causes were represented by at least one systematic review or protocol in CDSR; the category collective violence and legal intervention had no representation in CDSR. Correlation testing revealed a strong positive correlation that was statistically significant. Representation of road injury; interpersonal violence; fire, heat, and hot substances; mechanical forces; poisonings, adverse effect of medical treatment, and animal contact was well aligned with respect to DALY. Representation of falls was greater compared to DALY, while self-harm, exposure to forces of nature, and other transport injury representation was lower compared to DALY. CONCLUSIONS AND RELEVANCE: CDSR representation of external causes of injury strongly correlates with disease burden. The number of systematic reviews and protocols was well aligned for seven out of 12 causes of injury. These results provide high-quality and transparent data that may guide future prioritisation decisions.

Ethics and equity in research priority-setting: stakeholder engagement and the needs of disadvantaged groups.

A transparent and evidence-based priority-setting process promotes the optimal use of resources to improve health outcomes. Decision-makers and funders have begun to increasingly engage representatives of patients and healthcare consumers to ensure that research becomes more relevant. However, disadvantaged groups and their needs may not be integrated into the priority-setting process since they do not have a "political voice" or are unable to organise into interest groups. Equitable priority-setting methods need to balance patient needs, values, experiences with population-level issues and issues related to the health system.

Incidence and predictors of myocardial recovery on long-term left ventricular assist device support: Results from the United Network for Organ Sharing database.

BACKGROUND: Mechanical circulatory support (MCS) leads to favorable changes in the failing heart at the molecular, cellular, and structural levels. However, myocardial recovery leading to device explantation is rare. We reasoned that the multicenter United Network for Organ Sharing (UNOS) registry might provide insights into clinical predictors and outcomes of the recovery process. METHODS: The MCS device data set of the UNOS registry was queried for patients with long-term continuous-flow left ventricular assist devices (CF-LVADs) that were explanted for heart transplantation or indication of recovery. Analysis was restricted to adult patients (≥18 years old) who were listed for an initial heart transplantation. Patients with CF-LVADs that were explanted because of recovery were compared with patients with CF-LVADs who underwent transplantation. RESULTS: We identified 594 patients with HeartMate II devices and 92 patients with HeartWare devices. Duration of support was on average 500.4 ± 325.3 days. In 34 (5.0%) patients, devices were explanted secondary to myocardial recovery. Univariate predictors of recovery in patients with long-term LVADs included younger age (40 years vs 53 years), female sex, lower body mass index (25.7 kg/m(2) vs 27.9 kg/m(2)), non-ischemic etiology (91% vs 59%), lack of implantable cardioverter defibrillator at the time of listing (44% vs 79%), and lower serum creatinine (0.97 mg/dl vs 1.28 mg/dl) (all p < 0.05). In the post-explantation period, freedom from death or transplantation was 66% at 1 year. CONCLUSIONS: The incidence of recovery on device support is low in the current MCS era and limited to a select cohort of predominantly young patients with non-ischemic myopathy. Given the high incidence of disease recurrence, patients should be closely followed after device explantation.

The accuracy of abnormal lumbar sonography findings in detecting occult spinal dysraphism: a comparison with magnetic resonance imaging.

OBJECT: The purpose of this study was to correlate lumbar ultrasound (LUS) and MRI findings in patients suspected of having occult spinal dysraphism (OSD). METHODS: Over a 5-year period, 1273 consecutive infants underwent an LUS study at a major pediatric tertiary referral center. Of these, 106 patients had abnormal LUS findings suggestive of an OSD, and 103 underwent subsequent MRI studies. The anatomical descriptions of the 2 studies were compared for agreement. RESULTS: The average age of the infants was 34 days at the time of the LUS study; OSD was suspected in these patients because of the presence of cutaneous stigmata and congenital defects. The most common anatomical descriptions from the LUS study included a thickened or fatty filum (32 cases), filum cyst (11 cases), and presence of a terminal ventricle or syrinx (9 cases). Using MRI findings as the standard reference, the sensitivity of LUS in detecting a thickened or fatty filum was 20%. The sensitivity of detecting an abnormal conus level at or below L-3 was 76.9%. CONCLUSIONS: In the patient population chosen to undergo LUS studies, abnormal findings had poor sensitivity at detecting anatomical findings consistent with OSD.