Gabriel Brooks

Predicting Persistent Left Ventricular Dysfunction Following Myocardial Infarction : The PREDICTS Study

BACKGROUND Persistent severe left ventricular (LV) systolic dysfunction after myocardial infarction (MI) is associated with increased mortality and is a class I indication for implantation of a cardioverter-defibrillator. OBJECTIVES This study developed models and assessed independent predictors of LV recovery to >35% and ≥50% after 90-day follow-up in patients presenting with acute MI and severe LV dysfunction. METHODS Our multicenter prospective observational study enrolled participants with ejection fraction (EF) of ≤35% at the time of MI (n = 231). Predictors for EF recovery to >35% and ≥50% were identified after multivariate modeling and validated in a separate cohort (n = 236). RESULTS In the PREDICTS (PREDiction of ICd Treatment Study) study, 43% of patients had persistent EF ≤35%, 31% had an EF of 36% to 49%, and 26% had an EF ≥50%. The model that best predicted recovery of EF to >35% included EF at presentation, length of stay, prior MI, lateral wall motion abnormality at presentation, and peak troponin. The model that best predicted recovery of EF to ≥50% included EF at presentation, peak troponin, prior MI, and presentation with ventricular fibrillation or cardiac arrest. After predictors were transformed into point scores, the lowest point scores predicted a 9% and 4% probability of EF recovery to >35% and ≥50%, respectively, whereas profiles with the highest point scores predicted an 87% and 49% probability of EF recovery to >35% and ≥50%, respectively. CONCLUSIONS In patients with severe systolic dysfunction following acute MI with an EF ≤35%, 57% had EF recovery to >35%. A model using clinical variables present at the time of MI can help predict EF recovery.

Accuracy and Usability of a Self-Administered 6-Minute Walk Test Smartphone Application

Background—The 6-minute walk test (6MWT) independently predicts congestive heart failure severity, death, and heart failure hospitalizations, but must be administered in clinic by qualified staff on a premeasured course. As part of the Health eHeart Study, we sought to develop and validate a self-administered 6MWT mobile application (SA-6MWTapp) for independent use at home by patients. Methods and Results—We performed a validation study of an SA-6MWTapp in 103 participants. In phase 1 (n=52), we developed a distance-estimation algorithm for the SA-6MWTapp by comparing step counts from an Actigraph and measured distance on a premeasured 6MWT course with step counts and estimated distance obtained simultaneously from our SA-6MWTapp (best estimation algorithm, r=0.89 [95% confidence interval 0.78–0.99]). In phase 2, 32 participants (including those with congestive heart failure and pulmonary hypertension) used the SA-6MWTapp independently in clinic, and the distance estimated by the SA-6MWTapp was compared with the measured distance (r=0.83 [95% confidence interval 0.79–0.92]). In phase 3, 19 patients with congestive heart failure and pulmonary hypertension consecutively enrolled from clinic performed 3.2±1 SA-6MWTapp tests per week at home over 2 weeks. Distances estimated from the SA-6MWTapp during home 6MWTs were highly repeatable (coefficient of variation =4.6%) and correlated with in-clinic–measured distance (r=0.88 [95% confidence interval 0.87–0.89]). Usability surveys performed during the second (in-clinic) and third (at-home) phases demonstrated that the SA-6MWTapp was simple and easy to use independently. Conclusions—An SA-6MWTapp is easy to use and yields accurate repeatable measurements in the clinic and at home.

Reassessing Phase II Heart Failure Clinical Trials: Consensus Recommendations

The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue on the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17, 2016, represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions.

Measuring cardiac efficiency using PET/MRI

Heart failure (HF) is a complex syndrome that is projected by the American Heart Association to cost

Cardiac Magnetic Resonance Evaluation of Left Ventricular Myocardial Strain in Pulmonary Hypertension

160 billion by 2030. In HF, significant metabolic changes and structural remodeling lead to reduced cardiac efficiency. A normal heart is approximately 20-25% efficient measured by the ratio of work to oxygen utilization (1 ml oxygen = 21 joules). The heart requires rapid production of ATP where there is complete turnover of ATP every 10 seconds with 90% of ATP produced by mitochondrial oxidative metabolism requiring substrates of approximately 30% glucose and 65% fatty acids. In our preclinical PET/MRI studies in normal rats, we showed a negative correlation between work and the influx rate constant for 18FDG, confirming that glucose is not the preferred substrate at rest. However, even though fatty acid provides 9 kcal/gram compared to 4 kcal/gram for glucose, in HF the preferred energy source is glucose. PET/MRI offers the potential to study this maladapted mechanism of metabolism by measuring work in a region of myocardial tissue simultaneously with the measure of oxygen utilization, glucose, and fatty acid metabolism and to study cardiac efficiency in the etiology of and therapies for HF. MRI is used to measure strain and a finite element mechanical model using pressure measurements is used to estimate myofiber stress. The integral of strain times stress provides a measure of work which divided by energy utilization, estimated by the production of 11CO2 from intravenous injection of 11C-acetate, provides a measure of cardiac efficiency. Our project involves translating our preclinical research to the clinical application of measuring cardiac efficiency in patients. Using PET/MRI to develop technologies for studying myocardial efficiency in patients, provides an opportunity to relate cardiac work of specific tissue regions to metabolic substrates, and measure the heterogeneity of LV efficiency.

Evaluation of myocardial fibrosis by post gadolinium T1 measurement in patients with pulmonary hypertension.

RATIONALE AND OBJECTIVES We investigated the feasibility of detecting left ventricular (LV) cardiac magnetic resonance (CMR) strain abnormalities using feature-tracking in patients with pulmonary hypertension (PH). MATERIALS AND METHODS CMR was performed in 16 patients with all groups of PH and in 13 controls. Global and regional peak circumferential strains (%) (which have been shown to be robust by CMR), peak diastolic strain rate (%/s), and dyssynchrony index (ms) were quantified with feature-tracking software. Ventricular function and volumes were calculated from CMR, and right heart pressures were measured with catheterization. RESULTS Left ventricular ejection fraction (LVEF) was similar in patients (60.2% ± 11.0%) and controls (61.9% ± 4.5%), P = .150. Global LV peak circumferential strain was significantly different in patients compared to controls, -16.7 ± 2.8% vs -19.9 ± 1.8%, respectively (P = .001). The greatest difference in strain was seen in the LV septum, -11.6 ± 4.3% in patients vs -16.7 ± 4.0% in controls (P < .001). There was a significant association between septal strain and right ventricular end-diastolic volume index (P = .047) in patients with PH; however, there were no associations with pulmonary artery pressures or right ventricular ejection fraction. CONCLUSIONS Feature-tracking CMR can detect LV strain abnormalities in patients with PH and preserved or mildly depressed LVEF, with greatest abnormality in the septum. The association between septal strain and right ventricular end-diastolic volume index suggests that ventricular interdependence may be a mechanism of LV dysfunction in PH. Feature-tracking CMR may be useful for identification of LV dysfunction before LVEF significantly declines in patients with PH. The feasibility of detecting LV strain abnormalities in patients with PH shown by this study paves the way for a variety of future investigations into the applications of LV strain in this patient population.

Highly-accelerated self-gated free-breathing 3D cardiac cine MRI: validation in assessment of left ventricular function

Methods Patients (n=19) with a clinical diagnosis or imaging findings of pulmonary hypertension who underwent cardiac MR between 1/1/2009 and 9/30/2014 were identified. Controls (n=10) were referred for cardiac MR evaluation to rule out ARVD due to family history or palpitations, but with a normal cardiac MR examination. Both patients and controls underwent cardiac MR with delayed gadolinium enhancement. Post-contrast locklocker inversion recovery sequences were obtained approximately 15 minutes following administration of gadolinium. T1 values were measured in the ventricular septum by placing a region of interest (ROI) that was confined to the myocardium using a semiautomated method. Manual correction was used to adjust ROIs that included the blood-pool. Statistical analysis was performed using Kruskal-Wallis equality-of-populations rank test to compare the patient and control groups due to data skewness.