Nader Makki

The Epidermal Growth Factor Receptor and Its Ligands in Cardiovascular Disease

The epidermal growth factor receptor (EGFR) family and its ligands serve as a switchboard for the regulation of multiple cellular processes. While it is clear that EGFR activity is essential for normal cardiac development, its function in the vasculature and its role in cardiovascular disease are only beginning to be elucidated. In the blood vessel, endothelial cells and smooth muscle cells are both a source and a target of EGF-like ligands. Activation of EGFR has been implicated in blood pressure regulation, endothelial dysfunction, neointimal hyperplasia, atherogenesis, and cardiac remodeling. Furthermore, increased circulating EGF-like ligands may mediate accelerated vascular disease associated with chronic inflammation. Although EGFR inhibitors are currently being used clinically for the treatment of cancer, additional studies are necessary to determine whether abrogation of EGFR signaling is a potential strategy for the treatment of cardiovascular disease.

Do implantable cardioverter defibrillators improve survival in patients with chronic kidney disease at high risk of sudden cardiac death? A meta-analysis of observational studies

AIMS Prospective randomized clinical trials show that implantable cardioverter defibrillators (ICDs) can reduce the risk of total mortality in select populations. However, data regarding patients with chronic kidney disease (CKD) are inconclusive. The aim of this study was to evaluate if ICDs affect total mortality in CKD patients at high risk of sudden cardiac death. METHODS AND RESULTS Two separate meta-analyses were performed to (i) assess the effect of ICD on all-cause mortality in CKD patients at high risk of sudden cardiac death and (ii) assess the effect of CKD on all-cause mortality in patients who already had an ICD for primary or secondary prevention purposes. Medline and EMBASE were searched from 1966 to 2013. A manual search by cross-referencing was performed. Five observational studies with 17 460 CKD patients considered at high risk of sudden cardiac death were included to evaluate the effect of ICDs on patients with severe CKD. Patients with ICD implants had a reduction in all-cause mortality (adjusted hazard ratio (HR) = 0.65, 95% confidence interval (CI) = 0.47-0.91, P < 0.05) compared with a matched control group. Based on 15 observational studies with 5233 patients as part of our second comparison that evaluated the effect of CKD on patients who received an ICD, CKD was associated with higher mortality risk (HR = 2.86, 95% CI = 1.91-4.27, P < 0.05) despite an ICD. CONCLUSION The meta-analysis indicates that for patients undergoing ICD implant, CKD is associated with greater risk of dying. However, ICD placement reduces mortality in CKD patients at high risk of sudden cardiac death.

Evaluation of a home-based colorectal cancer screening intervention in a rural state

PURPOSE Distance from health care facilities can be a barrier to colorectal cancer (CRC) screening, especially for colonoscopy. Alternatively, an improved at-home stool-based screening tool, the fecal immunochemical test (FIT), requires only a single sample and has a better sensitivity-specificity balance compared to traditional guaiac fecal occult blood tests. Our objective was to determine if FITs mailed to asymptomatic, average-risk patients overdue for screening resulted in higher screening rates versus mailing educational materials alone or no intervention (ie, usual care). METHODS Veterans ages 51-64, asymptomatic, at average risk for CRC, overdue for screening and in a veterans administration (VA) catchment area covering a large rural population were randomly assigned to 3 groups: (1) education only (Ed) group: mailed CRC educational materials and a survey of screening history and preferences (N = 499); (2) FIT group: mailed the FIT, plus educational materials and survey (N = 500); and (3) usual care (UC) group: received no mailings (N = 500). FINDINGS At 6 months postintervention, 21% of the FIT group had received CRC screening by any method compared to 6% of the Ed group (and 6% of the UC group) (P < .0001). Of the 105 respondents from the FIT group, 71 (68%) were eligible to take the FIT. Of those, 64 (90%) completed the FIT and 8 (12%) tested positive. CONCLUSIONS This low-intensity intervention of mailing FITs to average risk patients overdue for screening resulted in a significantly higher screening rate than educational materials alone or usual care, and may be of particular interest in rural areas.

Does cardiac resynchronization therapy benefit patients with ischemic and non-ischemic cardiomyopathy similarly?

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Veterans' Continued Participation in an Annual Fecal Immunochemical Test Mailing Program for Colorectal Cancer Screening

Objective: The objective of this study was to determine what proportion of veterans previously screened for colorectal cancer (CRC) using fecal immunochemical testing (FIT) would be willing to undergo a second round of FIT screening. Methods: Patients in the Iowa City Veterans Affairs Health Care System (<65 years old, asymptomatic, average risk, overdue for CRC screening) who completed a mailed FIT (April 2011 to May 2012) were contacted 1 year later by telephone to collect demographic and recent CRC screening information, and were offered a second mailed FIT if eligible. Results: Of 204 veterans who completed initial FIT testing, 159 were eligible to participate in a second round of FIT screening; 132 (83%) participated in the telephone survey, and 126 (79%) completed a second annual FIT, with 10 (8%) individuals testing positive. The majority of participants (67%) reported being more likely to take a yearly FIT than a colonoscopy every 10 years. Participants overwhelmingly reported that the FIT was easy to use and convenient (89%), and they were likely to complete a mailed FIT each year (97%). Conclusions: Those willing to take a mailed FIT seem satisfied with this method and willing to do it annually. Population-based or provider-based FIT mailing programs have the potential to increase CRC screening in overdue populations.

A Meta-analysis of Ostial and Trunk versus Distal Lesions in Unprotected Left Main Coronary Artery Stenting.

Aims: To assess outcomes for percutaneous coronary intervention (PCI) in ostial and trunk versus distal unprotected left main coronary artery (LMCA) lesions in the drugeluted stent (DES) era. Study Design: A meta-analysis and systematic review. Methods: With the help of a librarian, we searched Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and the Clinical Trials Registry from 2001 to July 2012.We included studies that enrolled ≥ 50 patients and had ≥6 months of follow-up. Our co-primary endpoints were the incidence of major adverse cardiac events (MACE) and target lesion/vessel revascularization

Heart Failure with Preserved Ejection Fraction and Therapeutic Approaches: A Systematic Review and Meta-analysis

Aims: Evidence is still lacking regarding optimal treatment for patients with heart failure with preserved ejection fraction (HfPEF). Our objective is to present an individual evaluation foreach of the current available heart failure medications using a meta analytical model. Methods and Results: Using meta-analytical techniques we assessed the impact of standard systolic heart failure medications on the combined endpoint of all -cause mortality and/or hospitalization for heart failure as a primary endpoint and on mortality and heart failure hospitalization as separate secondary endpoints for patients with HfPEF. Studies were heterogeneous (Q test, p