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Madias C.,Rush University Medical Center | Fitzgibbons T.P.,University of Massachusetts Medical School | Alsheikh-Ali A.A.,Institute of Cardiac science | Alsheikh-Ali A.A.,Institute for Clinical Research and Health Policy Studies | And 7 more authors.
Heart Rhythm | Year: 2011

Background: Stress cardiomyopathy (SCM) is a syndrome of transient ventricular dysfunction triggered by severe emotional or physical stress, likely resulting from catecholamine-mediated myocardial toxicity. Repolarization abnormalities associated with other hyperadrenergic states can cause QT prolongation and lethal arrhythmia including torsades de pointes (TdP). Despite the development of repolarization abnormalities and QT prolongation in SCM, little is known about the risk of ventricular fibrillation (VF) and TdP. Objective: The aim of this study was to assess the prevalence and clinical predictors of ventricular arrhythmias in a cohort of patients with SCM. Methods: Data from a registry of consecutive patients with SCM from 2 institutions were reviewed. Patients who developed VF or TdP were identified. Clinical characteristics and outcomes were analyzed and compared with a control group of patients with SCM without VF/TdP. Results: Of 93 patients with SCM, 8 (8.6%) experienced VF/TdP. Of these 8 patients, 2 presented with VF and were subsequently diagnosed with SCM. Six other patients experienced pause-dependent TdP or VF after SCM diagnosis in the setting of substantial QT prolongation. Prolongation of the corrected QT interval (QTc) was significantly associated with the occurrence of ventricular arrhythmia (odds ratio 1.28 for each 10 ms increase in QTc, 95% confidence interval 1.10 to 1.50). Conclusion: SCM can be associated with life-threatening ventricular arrhythmia in over 8% of cases. SCM should be recognized among the causes of acquired long QT syndrome and can be associated with a risk of TdP. © 2011 Heart Rhythm Society.


Alsheikh-Ali A.A.,Institute of Cardiac science | Kitsios G.D.,Institute for Clinical Research and Health Policy Studies | Balk E.M.,Institute for Clinical Research and Health Policy Studies | Lau J.,Institute for Clinical Research and Health Policy Studies | Ip S.,Institute for Clinical Research and Health Policy Studies
Annals of Internal Medicine | Year: 2010

The scope of recent literature on the concept of "vulnerable plaque" was reviewed by examining 463 abstracts of primary and review articles identified through MEDLINE (2003 to April 2010). Proposed definition criteria of vulnerable plaque included active inflammation, a thin cap with a large lipid core, endothelial denudation, fissured cap, severe stenosis, or combinations of these findings. In 242 primary studies, histopathology, biomarkers, and imaging of carotid and coronary artery plaques were evaluated for features suggestive of vulnerability. Notably, 89% of these studies were cross-sectional in design and were exclusively conducted in patients with known cardiovascular disease. None of the imaging studies documented whether the identified lesions were responsible for cardiovascular events. Cross-sectional design precludes evaluation of the predictive utility of biomarkers. Because vulnerable plaque is not an established medical diagnosis, no studies have been done that explicitly evaluate the treatment of vulnerable plaques. Few studies examined potential systemic treatments (for example, statins) to modify vulnerability features. Large prospective studies in patients with and without previous cardiovascular events during long follow-up are required to validate this concept. © 2010 American College of Physicians.


Alsheikh-Ali A.A.,Institute of Cardiac science | Alsheikh-Ali A.A.,Clinical Translational Science Institute | Qureshi W.,Ford Motor Company | Al-Mallah M.H.,Cardiac Guard | And 6 more authors.
PLoS ONE | Year: 2011

Background: There is increasing interest to make primary data from published research publicly available. We aimed to assess the current status of making research data available in highly-cited journals across the scientific literature. Methods and Results: We reviewed the first 10 original research papers of 2009 published in the 50 original research journals with the highest impact factor. For each journal we documented the policies related to public availability and sharing of data. Of the 50 journals, 44 (88%) had a statement in their instructions to authors related to public availability and sharing of data. However, there was wide variation in journal requirements, ranging from requiring the sharing of all primary data related to the research to just including a statement in the published manuscript that data can be available on request. Of the 500 assessed papers, 149 (30%) were not subject to any data availability policy. Of the remaining 351 papers that were covered by some data availability policy, 208 papers (59%) did not fully adhere to the data availability instructions of the journals they were published in, most commonly (73%) by not publicly depositing microarray data. The other 143 papers that adhered to the data availability instructions did so by publicly depositing only the specific data type as required, making a statement of willingness to share, or actually sharing all the primary data. Overall, only 47 papers (9%) deposited full primary raw data online. None of the 149 papers not subject to data availability policies made their full primary data publicly available. Conclusion: A substantial proportion of original research papers published in high-impact journals are either not subject to any data availability policies, or do not adhere to the data availability instructions in their respective journals. This empiric evaluation highlights opportunities for improvement. © 2011 Alsheikh-Ali et al.


Alsheikh-Ali A.A.,Institute of Cardiac science | Madias C.,Cardiac Arrhythmia Center | Supran S.,Clinical Care Research Division | Link M.S.,Cardiac Arrhythmia Center
Circulation | Year: 2010

Background- Precordial blows in sports and daily activities can trigger ventricular fibrillation (VF) (commotio cordis). Whereas chest wall blows are common, commotio cordis is rare. Although factors such as timing, location, orientation, and energy of impact are critically important, we also hypothesize that there is individual susceptibility to commotio cordis. Using our model of commotio cordis, we evaluated individual animal susceptibility to VF induction and assessed animal characteristics that might be involved. Methods and Results- This retrospective analysis included 139 juvenile swine (weight, 8 to 54 kg) that were anesthetized and placed prone in a sling to receive chest wall strikes with a ball propelled at 30 to 40 mph. Each animal received a minimum of 4 impacts directly over the cardiac silhouette, all timed to a narrow vulnerable window during cardiac repolarization. Of 1274 total impacts, 360 impacts (28%) resulted in VF. There was wide variability in individual animal susceptibility to VF. In 38 animals, none of the impacts resulted in VF (range, 4 to 18 impacts per animal). The majority of animals (91; 65%) were induced into VF with <30% of the strikes. In fact, only 19 animals (14%) had >50% occurrence of VF with chest wall impacts, and only 7 (5%) had >80% occurrence of chest impacts that induced VF. In the animal-based analysis, individual correlates of VF included animal weight, mean impact velocity, mean left ventricular pressure generated by the blow, mean QRS duration, mean QTc, and QTc variability. In multivariable analysis, mean left ventricular pressure generated by the blow, mean QRS duration, and QTc variability remained significant correlates of risk, and number of impacts gained statistical significance such that animals with more impacts were less susceptible to VF. Conclusions- Swine display a wide range of individual vulnerability to VF triggered by chest wall impact, with a distinct minority being uniquely susceptible. Mild abnormalities in cardiac depolarization and repolarization might underlie this susceptibility. Such individual susceptibility may also be present in humans and contribute to the rarity of commotio cordis. © 2010 American Heart Association, Inc.


Haffajee J.A.,Tufts Medical Center | Lee Y.,Tufts University | Alsheikh-Ali A.A.,Tufts University | Alsheikh-Ali A.A.,Institute of Cardiac science | And 3 more authors.
JACC: Cardiovascular Imaging | Year: 2011

Objectives: The purpose of this study was to examine whether left atrial (LA) mechanical function, as measured by LA total emptying fraction (TEF), is a predictor for the development of post-operative atrial fibrillation (POAF) following cardiac surgery. Background: POAF is an important and frequent complication of cardiac surgery. LA enlargement has been reported to be a risk factor for POAF, but the relationship between LA mechanical function and POAF is not well understood. We examined the relationship between pre-operative LA function and POAF in patients without a history of atrial fibrillation. Methods: A total of 101 subjects (mean age 64 ± 13 years) underwent pre-operative transthoracic echocardiograms and were followed for occurrence of POAF during the hospitalization for cardiac surgery. The left atrial maximum volume (LAVmax) and left atrial minimum volume (LAVmin) were measured and indexed to body surface area (LAVmaxI and LAVminI, respectively). LA TEF was calculated as: {[(LAVmax LAVmin)/LAVmax] × 100%}. Univariate and multivariate analyses examined clinical and echocardiographic predictors of POAF. Results: POAF occurred in 41% of subjects. Mean LA TEF was 49 ± 15%, mean LAVmaxI was 38 ± 15 ml/m 2, and mean LAVminI was 20 ± 13 ml/m 2. Age, LA TEF, and LAVminI were independent predictors of POAF. LA TEF was lower in patients with POAF compared with those without POAF (43 ± 15% vs. 55 ± 13%, p < 0.001), and patients with a LA TEF <50% had a high risk of POAF (odds ratio: 7.94, 95% confidence interval: 3.23 to 19.54, p < 0.001). Compared with LAVmaxI >32 ml/m 2, LA TEF <50% had higher discriminatory power for POAF, which remained significantly higher when adjusted for age (p = 0.04). Conclusions: LA TEF is an independent predictor of POAF and is a stronger predictor of POAF than LAVmaxI is. Impaired LA mechanical function may help to identify patients who are most likely to benefit from prophylaxis for POAF. © 2011 American College of Cardiology Foundation.


Patel R.B.,Northwestern University | Ng J.,Northwestern University | Reddy V.,Northwestern University | Chokshi M.,Northwestern University | And 9 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2010

Background-Early repolarization, indicated on the standard 12-lead ECG, has recently been associated with idiopathic ventricular fibrillation in patients without structural heart disease. It is unknown whether there is an association between early repolarization and ventricular arrhythmias in the coronary artery disease (CAD) population. Methods and Results-Patients with CAD with implantable cardioverter-defibrillators in the healed phase of myocardial infarction were analyzed. In a case-control design, 60 patients who had ventricular arrhythmic events were matched for age and sex with 60 control subjects. ECGs were analyzed for early repolarization, defined as notching or slurring morphology of the terminal QRS complex or J-point elevation ≥0.1 mV above baseline in at least 2 lateral or inferior leads. Results were adjusted for left ventricular ejection fraction. Overall, early repolarization in 2 or more leads was more common in cases than control subjects (32% versus 8%, P=0.005). Early repolarization was noted more commonly in inferior leads (23% versus 8%, P=0.03), and a trend was noted in leads V4 through V6 (12% versus 3%, P=0.11). Early repolarization was uncommon in leads I and aVL in cases and control subjects (3% versus 0%). Notching was more common in cases than control subjects (28% versus 7%, P=0.008). Slurring and J-point elevation were not associated with ventricular arrhythmias. Conclusions-Early repolarization and, in particular, notching in the inferior leads is associated with increased risk of life-threatening ventricular arrhythmias in patients with CAD, even after adjustment for left ventricular ejection fraction. Our findings suggest early repolarization, and a notching morphology should be considered in a risk prediction model for arrhythmias in patients with CAD. © 2010 American Heart Association, Inc.


Kalin J.,Cardiac Arrhythmia Center | Madias C.,Rush University Medical Center | Alsheikh-Ali A.A.,Institute of Cardiac science | Alsheikh-Ali A.A.,Tufts University | Link M.S.,Cardiac Arrhythmia Center
Heart Rhythm | Year: 2011

Background: Sudden death due to low-energy blunt trauma to the precordium (commotio cordis) has been described with a variety of sporting objects. However, the risk of ventricular fibrillation (VF) relative to the shape of the impact object is not known. Objective: The objective of the current experiment is to test whether the impact object shape is a clinical variable that affects the risk for commotio cordis. Methods: In a juvenile swine model, impacts were given in random order with two different spherical shapes (72 mm diameter, equivalent to a baseball; 42 mm diameter, equivalent to a golf ball) and a flat round object 72 mm in diameter. Objects were equal in weight (150 g), thrown at 30 mph, and gated to the vulnerable portion of the cardiac cycle. Results: Sixteen swine received 144 impacts. The flat object did not cause VF (P =.01 compared with the two spherical objects), nonsustained VF, ST elevation, or bundle branch block. The smaller diameter sphere caused VF in nine of 48 impacts (19%), and the larger diameter sphere caused VF in five of 48 impacts (10%; P =.25). The smaller diameter sphere was associated with a greater increase in left ventricular pressure (P <.0001 and P =.001 compared with larger sphere only) and a higher likelihood of ST segment elevations (P <.001 and P =.08 compared with larger sphere only) and bundle branch block (Fisher's exact P =.008, and Fisher's exact P =.18 compared with larger sphere only). Conclusion: The shape of the projectile markedly influences the risk of VF from chest wall impact. This effect is likely mediated via a greater increase in left ventricular pressure with smaller diameter objects. Spreading the impact force over a larger area may decrease the risk of sudden death and has implications for the design of protective athletic equipment. © 2011 Heart Rhythm Society.


Jafri H.,Molecular Cardiology Research Institute | Alsheikh-Ali A.A.,Tufts University | Alsheikh-Ali A.A.,Institute of Cardiac science | Karas R.H.,Molecular Cardiology Research Institute
Journal of the American College of Cardiology | Year: 2010

Objectives: We sought to examine the relationship between high-density lipoprotein cholesterol (HDL-C) levels and the risk of the development of cancer in large randomized controlled trials (RCTs) of lipid-altering interventions. Background: Epidemiologic data demonstrate an inverse relationship between serum total cholesterol levels and incident cancer. We recently reported that lower levels of low-density lipoprotein cholesterol are associated with a significantly higher risk of incident cancer in a meta-analysis of large RCTs of statin therapy. However, little is known about the relationship between HDL-C levels and cancer risk. Methods: A systematic MEDLINE search identified lipid intervention RCTs with ≥1,000 person-years of follow-up, providing baseline HDL-C levels and rates of incident cancer. Using random-effects meta-regressions, we evaluated the relationship between baseline HDL-C and incident cancer in each RCT arm. Results: A total of 24 eligible RCTs were identified (28 pharmacologic intervention arms and 23 control arms), with 625,477 person-years of follow-up and 8,185 incident cancers. There was a significant inverse association between baseline HDL-C levels and the rate of incident cancer (p = 0.018). The inverse association persisted after adjusting for baseline low-density lipoprotein cholesterol, age, body mass index (BMI), diabetes, sex, and smoking status, such that for every 10-mg/dl increment in HDL-C, there was a 36% (95% confidence interval: 24% to 47%) relatively lower rate of the development of cancer (p < 0.001). Conclusions: There is a significant inverse association between HDL-C and the risk of incident cancer that is independent of LDL-C, age, BMI, diabetes, sex, and smoking. © 2010 American College of Cardiology Foundation.


Jafri H.,Molecular Cardiology Research Institute | Alsheikh-Ali A.A.,Institute of Cardiac science | Karas R.H.,Molecular Cardiology Research Institute
Annals of Internal Medicine | Year: 2010

Background: Low levels of high-density lipoprotein cholesterol (HDL-C) are associated with an increased risk for myocardial infarction (MI). Although statins reduce the risk for MI, most cardiovascular events still occur despite statin treatment. Purpose: Using meta-analysis of large randomized, controlled trials (RCTs) of statins to determine whether statins alter the relationship between HDL-C level and MI. Data Sources: MEDLINE search to February 2010, ClinicalTrials.gov, and reference lists from eligible studies. Study Selection: English-language RCTs of statin-treated patients versus control participants with 1000 or more person-years of follow-up and reported HDL-C levels and MI. Data Extraction: Two independent investigators extracted data from eligible RCTs. Data Synthesis: Twenty eligible RCTs were identified (543 210 person-years of follow-up and 7838 MIs). After adjustment for on-treatment LDL-C levels, age, hypertension, diabetes, and tobacco use, there was a significant inverse association between HDL-C levels and risk for MI in statin-treated patients and control participants. In Poisson meta-regressions, every 0.26-mmol/L (10-mg/dL) decrease in HDL-C was associated with 7.1 (95% CI, 6.8 to 7.3) and 8.3 (CI, 8.1 to 8.5) more MIs per 1000 person-years in statin-treated patients and control participants, respectively. The inverse association between HDL-C levels and MI did not differ between statin-treated patients and control participants (P = 0.57). Limitation: The observed associations may be explained by unmeasured confounding and do not imply causality in the relationship between HDL-C level and cardiovascular risk. Conclusion: Statins do not alter the relationship between HDL-C level and cardiovascular risk, such that low levels of HDL-C remain significantly and independently associated with increased risk despite statin treatment. The remaining risk seen in statin-treated patients may be partly explained by low HDL-C levels or other factors associated with low levels of HDL-C. Primary Funding Source: None © 2010 American College of Physicians.


Hadi H.A.R.,Institute of Cardiac science | Alsheikh-Ali A.A.,Institute of Cardiac science | Mahmeed W.A.L.,Institute of Cardiac science | Suwaidi J.M.A.,Institute of Cardiac science
Journal of Inflammation Research | Year: 2010

Atrial fibrillation (AF) is the most common sustained arrhythmia and a challenging clinical problem encountered in daily clinical practice. There is an increasing body of evidence linking inflammation to a broad spectrum of cardiovascular conditions including AF. Historical evidence supports an association between AF and inflammation and is consistent with the association of AF with inflammatory conditions of the heart, such as myocarditis and pericarditis. AF has been associated with myocardial oxidative stress, and antioxidant agents have demonstrated antiarrhythmic benefit in humans. Increased plasma interleukin (IL)-6, C-reactive protein (CRP), and plasma viscosity support the existence of an inflammatory state among "typical" populations with chronic AF. These indexes of inflammation are related to the prothrombotic state and may be linked to the clinical characteristics of the patients (underlying vascular disease and comorbidities), rather than simply to the presence of AF itself. It has been suggested that inflammation may have a role in the development of atrial arrhythmias after cardiac surgery, and that a genetic predisposition to develop postoperative complications exists. Cytokines can have a prognostic significance; IL-6 levels, CRP, and other cytokines may have prognostic value in AF. Cytokine lowering therapies, statins, angiotensin converting enzyme inhibitors and other anti-inflammatory agents may have a role in the treatment of AF. The present article provides an overview of the evidence linking inflammatory cytokines to AF and their therapeutic and prognostic implications.

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