Hussein Abu Daya

Celiac Disease in the Developing World

The prevalence of celiac disease (CD) in many developing countries is similar to that of developed areas, in both low- and high-risk groups. The disorder is underestimated because of lack of disease awareness. CD is strongly associated with HLA-DQ2 in developing countries. Clinical presentation may be characterized by chronic diarrhea, anemia, stunting and increased mortality. Few studies have addressed atypical or silent CD. Diagnosis is initially made by serologic tests and is confirmed by small intestinal biopsies. In developing countries the adherence to the treatment is still difficult because of poor availability of dedicated gluten-free food.

Temporal relation between myocardial fibrosis and heart failure with preserved ejection fraction: Association with baseline disease severity and subsequent outcome

Importance Among myriad changes occurring during the evolution of heart failure with preserved ejection fraction (HFpEF), cardiomyocyte–extracellular matrix interactions from excess collagen may affect microvascular, mechanical, and electrical function. Objective To investigate whether myocardial fibrosis (MF) is similarly prevalent both in those with HFpEF and those at risk for HFpEF, similarly associating with disease severity and outcomes. Design, Setting, and Participants Observational cohort study from June 1, 2010, to September 17, 2015, with follow-up until December 14, 2015, at a cardiovascular magnetic resonance (CMR) center serving an integrated health system. Consecutive patients with preserved systolic function referred for CMR were eligible. Cardiovascular magnetic resonance was used to exclude patients with cardiac amyloidosis (n = 19). Exposures Myocardial fibrosis quantified by extracellular volume (ECV) CMR measures. Main Outcome and Measures Baseline BNP; subsequent hospitalization for heart failure or death. Results Of 1174 patients identified (537 [46%] female; median [interquartile range {IQR}] age, 56 [44-66] years), 250 were “at risk” for HFpEF given elevated brain-type natriuretic peptide (BNP) level; 160 had HFpEF by documented clinical diagnosis, and 745 did not have HFpEF. Patients either at risk for HFpEF or with HFpEF demonstrated similarly higher prevalence/extent of MF and worse prognosis compared with patients with no HFpEF. Among those at risk for HFpEF or with HFpEF, the actual diagnosis of HFpEF was not associated with significant differences in MF (median ECV, 28.2%; IQR, 26.2%-30.7% vs 28.3%; IQR, 25.5%-31.4%; P = .60) or prognosis (log-rank 0.8; P = .38). Over a median of 1.9 years, 61 patients at risk for HFpEF or with HFpEF experienced adverse events (19 hospitalization for heart failure, 48 deaths, 6 with both). In those with HFpEF, ECV was associated with baseline log BNP (disease severity surrogate) in multivariable linear regression models, and was associated with outcomes in multivariable Cox regression models (eg, hazard ratio 1.75 per 5% increase in ECV, 95% CI, 1.25-2.45; P = .001 in stepwise model) whether grouped with patients at risk for HFpEF or not. Conclusions and Relevance Among myriad changes occurring during the apparent evolution of HFpEF where elevated BNP is prevalent, MF was similarly prevalent in those with or at risk for HFpEF. Conceivably, MF might precede clinical HFpEF diagnosis. Regardless, MF was associated with disease severity (ie, BNP) and outcomes. Whether cells and secretomes mediating MF represent therapeutic targets in HFpEF warrants further evaluation.

Echocardiography-guided left ventricular lead placement for cardiac resynchronization therapy in ischemic vs nonischemic cardiomyopathy patients

BACKGROUND Echocardiography-guided (EG) left ventricular (LV) lead placement at the site of latest mechanical activation improves outcome in heart failure (HF) patients receiving a cardiac resynchronization therapy (CRT)-defibrillator (CRT-D). OBJECTIVE The purpose of this study was to examine the effect of a strategy of EG LV lead placement in each of ischemic (ICM) vs nonischemic (NICM) cardiomyopathy patients. METHODS Patients enrolled in the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) prospective, randomized trial who were treated with a CRT-D device (108 EG strategy and 75 routine strategy) were followed to the end-points of death, appropriate CRT-D therapy, or HF hospitalization. RESULTS Of the patients enrolled in STARTER, 115 had ICM and 68 had NICM. Over mean follow-up of 3.7 ± 2.1 years, 62 patients died, 40 received appropriate CRT-D therapy, and 67 had HF hospitalizations. Compared to NICM patients, patients with ICM had worse survival (P = .0003), worse survival free from implantable cardioverter-defibrillator therapy (P = .004), and survival free from HF hospitalization (P = .0001). A strategy of EG LV lead placement improved the outcome of CRT-D therapy-free survival primarily in ICM patients and the outcome of HF hospitalization-free survival in both ICM and NICM patients. Achieving LV resynchronization was most critical in ICM patients in whom arrhythmic and HF outcomes improve with resynchronization to levels comparable to those of NICM patients. CONCLUSION A strategy of EG LV lead placement improves HF-free survival equally in ICM and NICM patients and CRT-D therapy-free survival more favorably in ICM patients to levels comparable to those of NICM patients.

Opposing effects of aspirin and anticoagulants on morbidity and mortality in patients with upper gastrointestinal bleeding

We aimed to determine the effect of antithrombotics on in‐hospital mortality and morbidity in patients with peptic ulcer disease‐related upper gastrointestinal bleeding (PUD‐related UGIB).

Effects of rosiglitazone (PPAR γ agonist) on the myocardium in non‐hypertensive diabetic rats 罗格列酮（PPAR γ 激动剂）对非高血压糖尿病大鼠的心肌的影响

There is ongoing controversy regarding the safety of rosiglitazone and its effects on the myocardium, in some cases causing severe cardiac pathology and even in some instances mortality. In this study we aimed at examining the effects of pharmacologic doses of rosiglitazone on cardiomyocytes in diabetic non‐cardiac rats receiving sub‐optimal doses of insulin.

Homozygosity for Non-H1069Q Missense Mutations in ATP7B Gene and Early Severe Liver Disease: Report of Two Families and a Meta-analysis

Most patients with Wilsons disease (WD) are compound heterozygote, which complicates establishing genotype-phenotype correlations. We identified five patients who presented with early and/or severe hepatic disease who are homozygous for W939C missense mutation on exon 12 of ATP7B. We therefore conducted a meta-analysis to determine the phenotype of patients homozygous for missense or nonsense mutations in all ATP7B exons.The meta-analysis showed that 69% and 31% of patients are homozygous for H1069Q and non-H1069Q mutations, respectively. Compared to patients with H1069Q, those with non-H1069Q mutations were significantly more likely to have a hepatic phenotype, severe liver disease, a mixed phenotype, and less likely to have a neurologic phenotype. Compared to patients with nonsense mutations, those with non-H1069Q ones were equally likely to present with a hepatic phenotype and to have severe liver disease. Mean age at symptom onset in the non-H1069Q versus the H1069Q group was 15.5 versus 20.5years (p<0.001).Our data suggest that mutation W939C and other non-H1069Q missense mutations are associated with early disease onset, a hepatic phenotype, and a high risk of hepatic failure in homozygous patients. Early identification of such patients by genetic screening is important for timely initiation of treatment and prevention of complications.

Diffuse Myocardial Fibrosis Reduces Electrocardiographic Voltage Measures of Left Ventricular Hypertrophy Independent of Left Ventricular Mass

Background Myocardial fibrosis quantified by myocardial extracellular volume fraction (ECV) and left ventricular mass (LVM) index (LVMI) measured by cardiovascular magnetic resonance might represent independent and opposing contributors to ECG voltage measures of left ventricular hypertrophy (LVH). Diffuse myocardial fibrosis can occur in LVH and interfere with ECG voltage measures. This phenomenon could explain the decreased sensitivity of LVH detectable by ECG, a fundamental diagnostic tool in cardiology. Methods and Results We identified 77 patients (median age, 53 [interquartile range, 26–60] years; 49% female) referred for contrast‐enhanced cardiovascular magnetic resonance with ECV measures and 12‐lead ECG. Exclusion criteria included clinical confounders that might influence ECG measures of LVH. We evaluated ECG voltage‐based LVH measures, including Sokolow‐Lyon index, Cornell voltage, 12‐lead voltage, and the vectorcardiogram spatial QRS voltage, with respect to LVMI and ECV. ECV and LVMI were not correlated (R 2=0.02; P=0.25). For all voltage‐related parameters, higher LVMI resulted in greater voltage (r=0.33–0.49; P<0.05 for all), whereas increased ECV resulted in lower voltage (r=−0.32 to −0.57; P<0.05 for all). When accounting for body fat, LV end‐diastolic volume, and mass‐to‐volume ratio, both LVMI (β=0.58, P=0.03) and ECV (β=−0.46, P<0.001) were independent predictors of QRS voltage (multivariate adjusted R 2=0.39; P<0.001). Conclusions Myocardial mass and diffuse myocardial fibrosis have independent and opposing effects upon ECG voltage measures of LVH. Diffuse myocardial fibrosis quantified by ECV can obscure the ECG manifestations of increased LVM. This provides mechanistic insight, which can explain the limited sensitivity of the ECG for detecting increased LVM.

Radionuclide Assessment of Left Ventricular Dyssynchrony.

Phase analysis of gated myocardial perfusion single-photon emission computed tomography is a widely available and reproducible measure of left ventricular (LV) dyssynchrony, which also provides comprehensive assessment of LV function, global and regional scar burden, and patterns of LV mechanical activation. Preliminary studies indicate potential use in predicting cardiac resynchronization therapy response and elucidation of mechanisms. Because advances in technology may expand capabilities for precise LV lead placement in the future, identification of specific patterns of dyssynchrony may have a critical role in guiding cardiac resynchronization therapy.

Effect of aminophylline administration on the diagnostic yield of vasodilator myocardial perfusion imaging

The last few decades have witnessed a steady increase in the proportion of myocardial perfusion imaging (MPI) tests that utilize pharmacologic stress instead of exercise. Currently regadenoson, a pyrazole derivative of adenosine selective for the A2A receptor, is the most commonly used vasodilator agent accounting for more than 80% of all pharmacological stress tests performed in the USA. The widespread utilization of regadenoson is supported by multiple factors including its similar diagnostic and prognostic performance to adenosine when used for MPI, the simpler and more rapid infusion protocol, and the better safety profile in specific patient groups. Although better tolerated by patients, regadenoson shares with adenosine similar adverse effects such as flushing, headaches, and gastrointestinal symptoms. Aminophylline, a nonselective adenosine receptor antagonist, has been available on the market for decades and used to reverse the adverse effects of dipyridamole and adenosine and more recently been shown to be safe and effective for use with regadenoson. In this issue of the Journal, Fughhi et al. address the concern that use of aminophylline to ameliorate the adverse effects of regadenoson may reverse its effects on coronary vasodilation and subsequent myocardial hyperemia reducing the sensitivity of MPI for detecting perfusion abnormalities. The data for the current study were pooled from two double-blinded, placebo-controlled randomized clinical trials, the ASSUAGE and ASSUAGE-CKD trials, which demonstrated the effectiveness of aminophylline in attenuating the adverse effects associated with regadenoson in patients undergoing MPI. In both trials, patients were randomized to receive 75 mg of intravenous aminophylline or placebo administered at 90 seconds after radioisotope injection (*2 minutes following regadenoson). The primary end point of the current report was the degree of reversibility of the perfusion defect on imaging as measured by the semi-quantitative summed difference score (SDS). The secondary end point was the presence of myocardial ischemia as defined by SDS C2. The authors also examined the effect of aminophylline use on the prognostic value of myocardial ischemia detection by MPI for cardiac events including cardiac death, myocardial infarction (MI), and coronary revascularization over a follow-up period of 29 ± 14 months. The myocardial ischemic burden (primary outcome) and the presence of myocardial ischemia (secondary outcome) on MPI were similar between the two groups. However, there was a trend towards a higher proportion of abnormal perfusion (summed stress score, SSS C4, 34% vs 27%, P = .08) in the placebo group that the authors attributed to the significantly higher rate of prior MI (20% vs 13%, P = .03) in this group. To account for this imbalance, the authors performed a sensitivity analysis in patients without clinical or MPI evidence (summed rest score, SRS C4) of prior MI, and demonstrated similar prevalence of myocardial ischemia and abnormal perfusion between the two groups. There was no difference in the event-free survival between the study groups after adjusting for SDS, SRS, prior MI, and left ventricular ejection fraction, and no interaction Reprint requests: Fadi Hage, MD, FACC, FASH, FASNC, University of Alabama at Birmingham, Lyons Harrison Research Building 306, 1900 University BLVD, Birmingham, AL 35294; fadihage@uab.edu J Nucl Cardiol 2017;24:1579–82. 1071-3581/

Aspirin use for primary prophylaxis: Adverse outcomes in non-variceal upper gastrointestinal bleeding

34.00 Copyright 2016 American Society of Nuclear Cardiology.