Faculty Bibliography

CONTEXT/BACKGROUND:Over the past three decades, industry sponsored research expanded in the United States. Financial incentives can lead to potential conflicts of interest (COI) resulting in underreporting of negative study results. OBJECTIVE:We hypothesized that over the three decades, there would be an increase in: a) reporting of conflict of interest and source of funding; b) percentage of randomized control trials c) number of patients per study and d) industry funding. DATA SOURCES AND STUDY SELECTION/METHODS:Original articles published in three calendar years (1988, 1998, and 2008) in The Lancet, New England Journal of Medicine and Journal of American Medical Association were collected. DATA EXTRACTION/METHODS:Studies were reviewed and investigational design categorized as prospective and retrospective clinical trials. Prospective trials were categorized into randomized or non-randomized and single-center or multi-center trials. Retrospective trials were categorized as registries, meta-analyses and other studies, mostly comprising of case reports or series. Study outcomes were categorized as positive or negative depending on whether the pre-specified hypothesis was met. Financial disclosures were researched for financial relationships and profit status, and accordingly categorized as government, non-profit or industry sponsored. Studies were assessed for reporting COI. RESULTS:1,671 original articles were included in this analysis. Total number of published studies decreased by 17% from 1988 to 2008. Over 20 year period, the proportion of prospective randomized trials increased from 22 to 46% (p < 0.0001); whereas the proportion of prospective non-randomized trials decreased from 59% to 27% (p < 0.001). There was an increase in the percentage of prospective randomized multi-center trials from 11% to 41% (p < 0.001). Conversely, there was a reduction in non-randomized single-center trials from 47% to 10% (p < 0.001). Proportion of government funded studies remained constant, whereas industry funded studies more than doubled (17% to 40%; p < 0.0001). The number of studies with negative results more than doubled (10% to 22%; p<0.0001). While lack of funding disclosure decreased from 35% to 7%, COI reporting increased from 2% to 84% (p < 0.0001). CONCLUSION/CONCLUSIONS:Improved reporting of COI, clarity in financial sponsorship, increased publication of negative results in the setting of larger and better designed clinical trials represents a positive step forward in the scientific publications, despite the higher percentage of industry funded studies.

BACKGROUND:Right Atrial Volume Index (RAVI) measured by echocardiography is an independent predictor of morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). The aim of this study is to evaluate the predictive value of RAVI assessed by cardiac magnetic resonance (CMR) for all-cause mortality in patients with HFrEF and to assess its additive contribution to the validated Meta-Analysis Global Group in Chronic heart failure (MAGGIC) score. METHODS AND RESULTS/RESULTS:We identified 243 patients (mean age 60 ± 15; 33% women) with left ventricular ejection fraction (LVEF) ≤ 35% measured by CMR. Right atrial volume was calculated based on area in two- and four -chamber views using validated equation, followed by indexing to body surface area. MAGGIC score was calculated using online calculator. During mean period of 2.4 years 33 patients (14%) died. The mean RAVI was 53 ± 26 ml/m2; significantly larger in patients with than without an event (78.7±29 ml/m2 vs. 48±22 ml/m2, p<0.001). RAVI (per ml/m2) was an independent predictor of mortality [HR = 1.03 (1.01-1.04), p = 0.001]. RAVI has a greater discriminatory ability than LVEF, left atrial volume index and right ventricular ejection fraction (RVEF) (C-statistic 0.8±0.08 vs 0.55±0.1, 0.62±0.11, 0.68±0.11, respectively, all p<0.02). The addition of RAVI to the MAGGIC score significantly improves risk stratification (integrated discrimination improvement 13%, and category-free net reclassification improvement 73%, both p<0.001). CONCLUSION/CONCLUSIONS:RAVI by CMR is an independent predictor of mortality in patients with HFrEF. The addition of RAVI to MAGGIC score improves mortality risk stratification.

BACKGROUND:Identification of the infarct-related artery (IRA) in patients with STEMI using coronary angiography (CA) is often based on the ECG and can be challenging in patients with severe multi-vessel disease. The current study aimed to determine how often percutaneous intervention (PCI) is performed in a coronary artery different from the artery supplying the territory of acute infarction on cardiac magnetic resonance imaging (CMR). METHODS:We evaluated 113 patients from the Reduction of infarct Expansion and Ventricular remodeling with Erythropoetin After Large myocardial infarction (REVEAL) trial, who underwent CMR within 4±2 days of revascularization. Blinded reviewers interpreted CA to determine the IRA and CMR to determine the location of infarction on a 17-segment model. In patients with multiple infarcts on CMR, acuity was determined with T2-weighted imaging and/or evidence of microvascular obstruction. RESULTS:A total of 5 (4%) patients were found to have a mismatch between the IRA identified on CMR and CA. In 4/5 cases, there were multiple infarcts noted on CMR. Thirteen patients (11.5%) had multiple infarcts in separate territories on CMR with 4 patients (3.5%) having multiple acute infarcts and 9 patients (8%) having both acute and chronic infarcts. CONCLUSIONS:In this select population of patients, the identification of the IRA by CA was incorrect in 4% of patients presenting with STEMI. Four patients with a mismatch had an acute infarction in more than one coronary artery territory on CMR. The role of CMR in patients presenting with STEMI with multi-vessel disease on CA deserves further investigation.

BACKGROUND:Recent studies suggest that papillary muscle infarction (PMI) following recent myocardial infarction (MI) correlates with adverse cardiovascular outcomes. The purpose of this study is to determine the prevalence and prognostic significance of PMI by cardiac magnetic resonance (CMR) in a large cohort of patients. METHODS:Retrospective study of patients who underwent CMR between January 2007 and December 2009 were evaluated for the presence of PMI in one or both of the left ventricle papillary muscles. The primary outcome was a time to a combined endpoint of all-cause mortality and worsening heart failure. Secondary outcomes were time to individual components of the combined outcome. RESULTS:419 patients were included in our analysis, 232 patients (55%) had ischemic cardiomyopathy. Patients were followed at six-month intervals for a median follow-up time of 3.7 (interquartile range (IQR): 1.6; 6.3) years after initial imaging. During this period 196 patients (46.8%) had a primary outcome and 92 patients (22%) died. PM infarct was identified in 204 (48.7%) patients with twice as many posteromedial (PRM) (27%) than anterolateral (ARL) lesions (11%) and a similar number with infarct in both (11%). There was no association between studied outcomes and the presence of PMI in either PRM or ARL PM. The presence of infarct in both PM was a predictor of both the primary outcome (HR 1.69, CI[1.01-2.86], p<0.049.) and mortality (HR 1.69, CI[1.01-4.2], p<0.046). CONCLUSION/CONCLUSIONS:The presence of infarct in either papillary muscle was not associated with outcomes. However, infarct involving both papillary muscles was associated with worse outcomes.

BACKGROUND:Right ventricular (RV) failure has proven to be independently associated with adverse outcomes. Electrocardiographic parameters assessing RV function are largely unknown, making echocardiography the first line for RV function assessment. It is however, limited by geometrical assumptions and is inferior to cardiac magnetic resonance imaging (CMRI) which is widely regarded as the most accurate tool for assessing RV function. METHODS:We seek to determine the correlation of ECG parameters of right bundle branch block (RBBB) with RV ejection fraction (EF) and RV dimensions using the CMRI. QRS duration, R amplitude and R' duration were obtained from precordial lead V1; S duration and amplitude were obtained from lead I and AVL. RV systolic dysfunction was defined as RV EF <40%. RV systolic dysfunction group (mean EF of 24±10%) were compared with normal RV systolic function group which acted as control (mean EF of 48±8%). CMRI and ECG parameters were compared between the two groups. Rank correlations and scatter diagrams between individual CMRI parameters and ECG parameters were done using medcalc for windows, version 12.5. Sensitivity, specificity and area under the curve (AUC) were calculated. RESULTS:84±18 msec, P=0.005) as compared to the control group. The specificity of R' duration >100 msec to detect RV systolic dysfunction was found to be 93%. R' duration was found to have an inverse correlation with RV EF (r=-0.49, P=0.007). CONCLUSIONS:Larger RV end systolic volumes seen with RV dysfunction can affect the latter part of right bundle branch leading to prolonged R' duration. We here found prolonged R' duration in lead V1 to have a highly specific inverse correlation to RV systolic function. ECG can be used as an inexpensive tool for RV function assessment and should be used alongside echocardiography to evaluate RV dysfunction when CMRI is not available.

OBJECTIVES/OBJECTIVE:To assess the diagnostic performance of stress cardiac magnetic resonance (stress CMR) vs stress single-photon emission computed tomography (SPECT) in patients presenting to the emergency department (ED) with chest pain. BACKGROUND:SPECT imaging is the most utilized outpatient procedure in the United States. The diagnostic accuracy of SPECT can be limited by soft tissue attenuation and low spatial resolution. Stress CMR has much higher spatial resolution and without the susceptibility to soft tissue attenuation. METHODS:Eighty-seven patients without a history of CAD presenting to the ED with chest pain were prospectively enrolled. Patients underwent both stress CMR and stress SPECT imaging within 12 hours of presentation. Both the stress imaging tests were interpreted immediately for clinical purposes and coronary angiography was performed if either was abnormal. Patients were considered to have significant CAD if identified by angiography (≥50%) or if a cardiac event (cardiac death, myocardial infarction or revascularization) occurred during follow-up (mean 2.6 ± 1.1 years). RESULTS:Thirty-seven patients were referred for coronary angiography; 29 due to a positive stress test and eight patients for persistent chest pain despite two negative stress tests. There were 22 patients who had significant CAD (≥50%). The remaining patients were followed for 2.6 ± 1.1 years. At the conclusion of the follow-up period, there were four clinical events. The sensitivity, specificity, and diagnostic accuracy of CMR are 85%, 93%, and 89%, respectively. The sensitivity, specificity, and diagnostic accuracy of stress SPECT are 84%, 91%, and 88%, respectively. CONCLUSION/CONCLUSIONS:Stress CMR has similar diagnostic accuracy as stress SPECT in diagnosis of CAD.

OBJECTIVE:To assess the added value of pulmonary function tests (PFTs) and different classifications of chronic obstructive pulmonary disease (COPD) to the Society of Thoracic Surgeons (STS) risk model using a clinical definition of lung disease for predicting outcomes after cardiothoracic (CT) surgery. METHODS:We evaluated consecutive patients who underwent nonemergency cardiac surgery and underwent PFTs before CT surgery. We used the STS risk model 2.73 to estimate the postoperative risk for respiratory failure (RF; defined as the need for mechanical ventilation for ≥72 hours, or reintubation), prolonged postoperative stay (PPLS; defined as >14 days), and 30-day all-cause mortality. We plotted the receiver operating characteristics curve for STS score for each adverse event, and compared the resulting area under the curve (AUC) with the AUC after adding PFT parameters and COPD classifications. RESULTS:Of the 1412 patients with a calculated STS score, 751 underwent PFTs. The AUC of the STS score was 0.65 (95% confidence interval [CI], 0.55-0.74) for RF, 0.67 (95% CI, 0.6-0.74) for prolonged postoperative length of stay (PPLS), and 0.74 (95% CI, 0.6-0.87) for death. None of the PFT parameters or COPD classifications added to the predictive ability of STS for RF, PPLS, or 30-day mortality. CONCLUSIONS:Adding individual PFT parameters or different COPD classifications to STS score calculated using clinically based classification of lung disease did not improve model discrimination. Thus, routine preoperative PFTS may have limited clinical utility in patients undergoing CT surgery when the STS score is readily available.

BACKGROUND:Heart failure (HF) with preserved ejection fraction patients have equally impaired health-related quality of life (HRQL) compared with those with HF with reduced ejection fraction, but limited studies have evaluated the impact of therapies on changes in HRQL. METHODS AND RESULTS/RESULTS:Patients ≥50 years of age, with symptomatic HF and left ventricular ejection fraction ≥45%, were enrolled in Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) and randomized to spironolactone or placebo. Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), which was the primary HRQL instrument, and EQ5D visual analog scale at baseline, 4 months, 12 months, and annually thereafter. McMaster Overall Treatment Evaluation was assessed at 4 and 12 months to assess global change scores. Change scores (+SD) were calculated to determine between-group differences, and multivariable repeated-measures models were created to identify other factors associated with change scores. Paired KCCQ data were available for 91.7% of 3445 TOPCAT patients. By 4 months, the mean change in KCCQ was 7.7±16 and mean change in EQ5D visual analog scale was 4.7±16. Adjusted mean changes in KCCQ for the spironolactone group were significantly better than those for the placebo group at 4-month (1.54 better; P=0.002), 12-month (1.35 better; P=0.02), and 36-month (1.86 better; P=0.02) visits. No between-group differences in EQ5D visual analog scale change scores or McMaster Overall Treatment Evaluation were noted. Older age, obesity, current smoking, New York Heart Association class III/IV, and comorbid illnesses were associated with declines in KCCQ scores. Use of spironolactone was an independent predictor of improved KCCQ scores. CONCLUSIONS:In symptomatic HF with preserved ejection fraction patients, use of spironolactone was associated with an improvement in HF-specific HRQL. Several modifiable risk factors were associated with HRQL deterioration. CLINICAL TRIAL REGISTRATION/BACKGROUND:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.

BACKGROUND:Takotsubo cardiomyopathy (TTC) is a condition of reversible left ventricular (LV) systolic dysfunction. However, the diastolic function (DF) manifestations of TTC have not been widely investigated. We performed a bicentric study with retrospective analysis of DF in patients with TTC, during onset and at follow-up. METHODS:Twenty-eight patients with TTC (64 ± 10 years, F 24) were included. All underwent echocardiograms acutely and at the recovery phase (average three months later). Diastolic and systolic function parameters were recorded, including E-wave velocity (E), A-wave velocity, E/A ratio, relaxation (e') and contractility (S') based on tissue Doppler velocities of the mitral annuli, ejection fraction (EF), left atrial (LA) size and DF stages. RESULTS:Recovery, including the mean difference with 95% confidence interval, was associated with tending improvement (i.e. uncorrected significance) in E [13 cm s(-1) (-24, -2·3), P = 0·02] and in E/A ratio [0·2 (-0·41, -0·02), P = 0·04], as well as significant improvement (after multiple comparison correction) in mean e' [2·0 cm s(-1) (-3·3, -1·2), P<0·001] and in A-wave duration [29 ms (-46·7, -12·7), P = 0·002]. LA area tended to decrease during recovery [-2 cm² (0·33, 2·4), P = 0·01]. Improvement in DF stages was significant between the phases (21% versus 58% defined as normal DF, P = 0·016). Improvement in LVEF correlated with improvement in mean e' (r = 0·52, P = 0·02). CONCLUSIONS:TTC is associated with an acute impairment of conventional DF variables, which improves during recovery. DF recovery seems to occur in parallel with systolic recovery in patients with TTC.