Homaa Ahmad

Converting the Informed Consent From a Perfunctory Process to an Evidence-Based Foundation for Patient Decision Making

Background—Standard consent forms result in highly variable communication between patients and physicians. To enhance the consent process and facilitate shared decision making, we developed a World Wide Web–based program, PREDICT (Patient Refined Expectations for Deciding Invasive Cardiac Treatments), to systematically embed patient-specific estimates of death, bleeding, and restenosis into individualized percutaneous coronary intervention informed consent documents. We then compared patients’ experiences with informed consent before and after implementation of PREDICT. Methods and Results—Between August 2006 and May 2007, patients undergoing nonemergent cardiac catheterization who received the original consent form (n=142) were interviewed and compared with those who received the PREDICT consent form (n=193). Hierarchical modified Poisson regression models were used to adjust for clustering of patients within physicians. Compared with the original consent group, those in the PREDICT group reported higher rates of reading the consent form (72% versus 44%, relative risk [RR] 1.64, 95% confidence interval [CI] 1.24 to 2.16), increased perception of shared decision making (67% versus 45%, RR 1.48, 95% CI 0.99 to 2.22), and decreased anxiety (35% versus 55%, RR 0.70, 95% CI 0.53 to 0.91). Although there were no differences between groups in patients’ ability to name complications of percutaneous coronary intervention, among patients who identified either death or bleeding as a potential complication, more patients in the PREDICT group recalled being informed of their estimated risk of that complication (death: 85% versus 62%, RR 1.37, 95% CI 1.03 to 1.82; bleeding: 92% versus 71%, RR 1.28, 95% CI 1.06 to 1.56). Conclusions—In this preliminary, single-center experience, individualized consent forms with patient-specific risks were associated with improved participation in the consent process, reduced anxiety, and better risk recall. PREDICT is one potential strategy for improving the current practice of obtaining informed consent for percutaneous coronary intervention.

Rapid Estimation of Left Ventricular Function Using Echocardiographic Speckle-Tracking of Mitral Annular Displacement

BACKGROUND Left ventricular (LV) ejection fraction (EF) by transthoracic two-dimensional echocardiography is time-intensive and highly dependent on image quality. Mitral annular displacement (MAD) qualitatively correlates with EF and can be measured in patients with poor image quality and dropout. The authors hypothesized that speckle-tracking echocardiography (STE)-derived MAD could quantify EF accurately and tested this hypothesis using cardiac magnetic resonance (CMR) as a reference. METHODS One hundred eighteen patients undergoing clinical transthoracic echocardiography were screened, and 110 whose mitral annuli was sufficiently well-defined irrespective of LV endocardial visualization underwent CMR within 6 days (85 of 110 in 1 day). Reference CMR EF values were obtained using standard methodology. STE was used to track annular motion throughout the cardiac cycle in the apical 2-chamber and 4-chamber views. To establish the relationship between MAD and CMR EF and to obtain a formula to estimate EF from MAD, regression analysis was performed in a study group of 60 patients with a wide range of EFs. This formula was then used in an independent test group of 50 patients by comparing estimated MAD EF against CMR EF values using Pearsons correlation and Bland-Altman analyses. RESULTS In the study group, STE MAD correlated highly with CMR EF and resulted in a formula relating MAD to EF. In the test group, estimated EF correlated well with CMR EF (4-chamber, R(2) = 0.64; 2-chamber, R(2) = 0.55), with near-zero bias and acceptable limits of agreement. Intraobserver and interobserver variability were between 5.8% and 12.7%. CONCLUSIONS STE MAD is a clinically useful tool for quick, easy, robust, and accurate estimates of EF irrespective of LV endocardial definition.

A novel molecular signature for elevated tricuspid regurgitation velocity in sickle cell disease

RATIONALE An increased tricuspid regurgitation jet velocity (TRV > 2.5 m/s) and pulmonary hypertension defined by right heart catheterization both independently confer increased mortality in sickle cell disease (SCD). OBJECTIVES We explored the usefulness of peripheral blood mononuclear cell-derived gene signatures as biomarkers for an elevated TRV in SCD. METHODS Twenty-seven patients with SCD underwent echocardiography and peripheral blood mononuclear cell isolation for expression profiling and 112 patients with SCD were genotyped for single-nucleotide polymorphisms. MEASUREMENTS AND MAIN RESULTS Genome-wide gene and miRNA expression profiles were correlated against TRV, yielding 631 transcripts and 12 miRNAs. Support vector machine analysis identified a 10-gene signature including GALNT13 (encoding polypeptide N-acetylgalactosaminyltransferase 13) that discriminates patients with and without increased TRV with 100% accuracy. This finding was then validated in a cohort of patients with SCD without (n = 10) and with pulmonary hypertension (n = 10, 90% accuracy). Increased TRV-related miRNAs revealed strong in silico binding predictions of miR-301a to GALNT13 corroborated by microarray analyses demonstrating an inverse correlation between their expression. A genetic association study comparing patients with an elevated (n = 49) versus normal (n = 63) TRV revealed five significant single-nucleotide polymorphisms within GALNT13 (P < 0.005), four trans-acting (P < 2.1 × 10(-7)) and one cis-acting (P = 0.6 × 10(-4)) expression quantitative trait locus upstream of the adenosine-A2B receptor gene (ADORA2B). CONCLUSIONS These studies validate the clinical usefulness of genomic signatures as potential biomarkers and highlight ADORA2B and GALNT13 as potential candidate genes in SCD-associated elevated TRV.

Mechanistic Insights and Characterization of Sickle Cell Disease Associated Cardiomyopathy

Background—Cardiovascular disease is an important cause of morbidity and mortality in sickle cell disease (SCD). We sought to characterize sickle cell cardiomyopathy using multimodality noninvasive cardiovascular testing and identify potential causative mechanisms. Methods and Results—Stable adults with SCD (n=38) and healthy controls (n=13) prospectively underwent same day multiparametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator first pass myocardial perfusion, and late gadolinium enhancement imaging), transthoracic echocardiography, and applanation tonometry. Compared with controls, patients with SCD had severe dilation of the left ventricle (124±27 vs 79±12 mL/m2), right ventricle (127±28 vs 83±14 mL/m2), left atrium (65±16 vs 41±9 mL/m2), and right atrium (78±17 vs 56±17 mL/m2; P<0.01 for all). Patients with SCD also had a 21% lower myocardial perfusion reserve index than control subjects (1.47±0.34 vs 1.87±0.37; P=0.034). A significant subset of patients with SCD (25%) had evidence of late gadolinium enhancement, whereas only 1 patient had evidence of myocardial iron overload. Diastolic dysfunction was present in 26% of patients with SCD compared with 8% in controls. Estimated filling pressures (E/e′, 9.3±2.7 vs 7.3±2.0; P=0.0288) were higher in patients with SCD. Left ventricular dilation and the presence of late gadolinium enhancement were inversely correlated to hepatic T2* times (ie, hepatic iron overload because of frequent blood transfusions; P<0.05 for both), whereas diastolic dysfunction and increased filling pressures were correlated to aortic stiffness (augmentation pressure and index, P<0.05 for all). Conclusions—Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some patients myocardial fibrosis, abnormal perfusion reserve, diastolic dysfunction, and only rarely myocardial iron overload. Left ventricular dilation and myocardial fibrosis are associated with increased blood transfusion requirements, whereas left ventricular diastolic dysfunction is predominantly correlated with increased aortic stiffness. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01044901.

Geometric Assessment of Regional Left Ventricular Remodeling by Three-Dimensional Echocardiographic Shape Analysis Correlates with Left Ventricular Function

BACKGROUND Left ventricular (LV) volumes and ejection fraction derived from two-dimensional echocardiography are two measures of adverse LV remodeling, which predict survival in patients with systolic heart failure. However, the geometric assumptions and image foreshortening that can occur with two-dimensional echocardiography reduces measurement accuracy and thus predictive value. By its nature, three-dimensional (3D) echocardiography allows the entire LV shape to be studied, providing a methodology to examine LV remodeling through LV curvature on a global and regional scale. The aim of this study was to correlate changes in global and regional LV shape to LV ejection fraction. METHODS Full-volume, 3D transthoracic echocardiographic studies of the left ventricle were performed in 106 consecutive patients with either normal left ventricles (n = 59) or cardiomyopathies (n = 47). Customized software (QLAB) was used to extract segmented 3D LV endocardial shells at end-systole and end-diastole and to analyze these shells to determine global and regional LV shape analysis. Independent t tests were used for intergroup comparisons, and linear regression was used to correlate regional shape changes with systolic performance. RESULTS Derivation and analysis of the 3D LV shells was possible in all patients. Patients with dilated cardiomyopathy had significantly smaller curvature values, indicating rounder global LV shape throughout the cardiac cycle. Regional analysis identified a loss of septal and apical curvatures in these patients. Systolic apical mean curvature was well correlated with LV ejection fraction (r = 0.89). CONCLUSIONS This is the first study to demonstrate that regional remodeling measured by regional 3D LV curvature correlates well with LV function. As well, this methodology is independent of the geometric assumptions that limit the predictive value of two-dimensional echocardiographic measures of LV remodeling. Overall, this is a novel tool that may have applications in the assessment and prediction of outcomes of different forms of dilated cardiomyopathy.

Implementing an innovative consent form: The PREDICT experience

BackgroundIn the setting of coronary angiography, generic consent forms permit highly variable communication between patients and physicians. Even with the existence of multiple risk models, clinicians have been unable to readily access them and thus provide patients with vague estimations regarding risks of the procedure.MethodsWe created a web-based vehicle, PREDICT, for embedding patient-specific estimates of risk from validated multivariable models into individualized consent documents at the point-of-care. Beginning August 2006, outpatients undergoing coronary angiography at the Mid America Heart Institute received individualized consent documents generated by PREDICT. In February 2007 this approach was expanded to all patients undergoing coronary angiography within the four Kansas City hospitals of the Saint Lukes Health System. Qualitative research methods were used to identify the implementation challenges and successes with incorporating PREDICT-enhanced consent documents into routine clinical care from multiple perspectives: administration, information systems, nurses, physicians, and patients.ResultsMost clinicians found usefulness in the tool (providing clarity and educational value for patients) and satisfaction with the altered processes of care, although a few cardiologists cited delayed patient flow and excessive patient questions. The responses from administration and patients were uniformly positive. The key barrier was related to informatics.ConclusionThis preliminary experience suggests that successful change in clinical processes and organizational culture can be accomplished through multidisciplinary collaboration. A randomized trial of PREDICT consent, leveraging the accumulated knowledge from this first experience, is needed to further evaluate its impact on medical decision-making, patient compliance, and clinical outcomes.

Mechanistic insights and characterization of cardiomyopathy due to Sickle Cell Disease

Summary We sought to characterize the features of sickle cell cardiomyopathy and to identify causative mechanisms using comprehensive cardiac magnetic resonance, echocardiography, and arterial tonometry. We found that sickle cell cardiomyopathy is characterized by 4-chamber dilation, myocardial fibrosis, abnormal myocardial perfusion reserve, diastolic dysfunction, and only rarely myocardial iron overload. Left ventricular dilation and myocardial fibrosis are associated with increased blood transfusion requirements; where as, diastolic dysfunction is due to increased aortic stiffness. Background Cardiovascular disease is an important cause of morbidity and mortality in adults with sickle cell disease (SCD). We sought to characterize the features of SCD cardiomyopathy and to identify causative mechanisms. Methods Stable adults with SCD (n=38) and matched controls (n=13) were prospectively recruited to undergo 1) multiparametric cardiovascular magnetic resonance (CMR) (i. e. steady state free precession cine, regadenoson first pass myocardial perfusion, phase sensitive inversion recovery late gadolinium enhancement (LGE), and myocardial and hepatic multi-echo time (TE) single breathhold T2* imaging), 2) echocardiography (TTE), and 3) applanation tonometry (pulse wave analysis). Chamber size and function were measured from CMR using method of disks. Myocardial perfusion reserve index (MPRi) was calculated from time intensity curves generated from first pass perfusion images as the stress to rest ratio of mid-ventricular myocardium upslope (normalized by the left ventricular cavity upslope). LGE was considered present if the signal intensity (SI) was >5 standard deviations above normal remote myocardium and if seen in 2 consecutive slices or 2 imaging planes. Myocardial and hepatic T2* times were calculated using the formula ΔTE/ ln(SI TE2/SI TE1). Presence of diastolic dysfunction (DD) was determined using American Society of Echocardiography criteria. Aortic augmentation index was determined using standard tonometry methods.