Does Vitamin D Provide Added Benefit to Antihypertensive Therapy in Reducing Left Ventricular Hypertrophy Determined by Cardiac Magnetic Resonance?

BACKGROUND: Left ventricular hypertrophy (LVH) and vitamin D deficiency have been linked to hypertension (HTN) and cardiovascular disease, particularly in African Americans (AAs). Our objective was to determine if the addition of vitamin D to antihypertensive therapy would lead to greater regression of LV mass index (LVMI) as determined by cardiac magnetic resonance (CMR) after 1 year in vitamin D deficient AA patients with uncontrolled HTN and LVH. METHODS: This study was a randomized, double-blind, placebo-controlled, single-center study. AA patients with HTN (systolic blood pressure [BP] >160 mm Hg), increased LVMI, and vitamin D deficiency (<20 ng/ml) were randomized. All patients received antihypertensive therapy combined with biweekly 50,000 IU vitamin D3 (vitamin D group, n = 55) or placebo (placebo group, n = 58). RESULTS: At 1 year, there were no statistical differences between the vitamin D and placebo groups in LVMI (-14.1 ± 14.6 vs. -16.9 ± 13.1 g/m2; P = 0.34) or systolic BP (-25.6 ± 32.1 vs. -25.7 ± 25.6 mm Hg; P = 0.99) reduction, respectively. Serum vitamin D levels increased significantly in the vitamin D group compared with placebo (12.7 ± 2.0 vs. 1.8 ± 8.2 ng/ml; P < 0.001). CONCLUSIONS: In this high-risk cohort of AAs we did not find an association between vitamin D supplementation and differential regression of LVMI or reduction in systolic BP. However, our study suffered from a small sample size with low statistical power precluding a definitive conclusion on the therapeutic benefit of vitamin D in such patients. CLINICAL TRIALS REGISTRATION: Trial Number NCT01360476. Full trial protocol is available from corresponding author.

Point-of-care echocardiography of the right heart improves acute heart failure risk stratification for low-risk patients: The REED-AHF prospective study.

OBJECTIVES: Validated acute heart failure (AHF) clinical decision instruments (CDI) insufficiently identify low-risk patients meriting consideration of outpatient treatment. While pilot data show that tricuspid annulus plane systolic excursion (TAPSE) is associated with adverse events, no AHF CDI currently incorporates point-of-care echocardiography (POCecho). We evaluated whether TAPSE adds incremental risk stratification value to an existing CDI. METHODS: Prospectively enrolled patients at two urban-academic EDs had POCechos obtained before or <1 h after first intravenous diuresis, positive pressure ventilation, and/or nitroglycerin. STEMI and cardiogenic shock were excluded. AHF diagnosis was adjudicated by double-blind expert review. TAPSE, with an a priori cutoff of ≥17 mm, was our primary measure. Secondary measures included eight additional right heart and six left heart POCecho parameters. STRATIFY is a validated CDI predicting 30-day death/cardiopulmonary resuscitation, mechanical cardiac support, intubation, new/emergent dialysis, and acute myocardial infarction or coronary revascularization in ED AHF patients. Full (STRATIFY + POCecho variable) and reduced (STRATIFY alone) logistic regression models were fit to calculate adjusted odds ratios (aOR), category-free net reclassification index (NRIcont ), ΔSensitivity (NRIevents ), and ΔSpecificity (NRInonevents ). Random forest assessed variable importance. To benchmark risk prediction to standard of care, ΔSensitivity and ΔSpecificity were evaluated at risk thresholds more conservative/lower than the actual outcome rate in discharged patients. RESULTS: A total of 84/120 enrolled patients met inclusion and diagnostic adjudication criteria. Nineteen percent experiencing the primary outcome had higher STRATIFY scores compared to those event free (233 vs. 212, p = 0.009). Five right heart (TAPSE, TAPSE/PASP, TAPSE/RVDD, RV-FAC, fwRVLS) and no left heart measures improved prediction (p < 0.05) adjusted for STRATIFY. Right heart measures also had higher variable importance. TAPSE ≥ 17 mm plus STRATIFY improved prediction versus STRATIFY alone (aOR 0.24, 95% confidence interval [CI] 0.06-0.91; NRIcont  0.71, 95% CI 0.22-1.19), and specificity improved by 6%-32% (p < 0.05) at risk thresholds more conservative than the standard-of-care benchmark without missing any additional events. CONCLUSIONS: TAPSE increased detection of low-risk AHF patients, after use of a validated CDI, at risk thresholds more conservative than standard of care.

Right ventricular dysfunction in acute heart failure from emergency department to discharge: Predictors and clinical implications.

BACKGROUND: Among acute heart failure (AHF) inpatients, right ventricular dysfunction (RVD) predicts clinical outcomes independent of left ventricular (LV) dysfunction. Prior studies have not accounted for congestion severity, show conflicting findings on echocardiography (echo) timing, and excluded emergency department (ED) patients. We describe for the first time the epidemiology, predictors, and outcomes of RVD in AHF starting with earliest ED treatment. METHODS: Point-of-care echo and 10-point lung ultrasound (LUS) were obtained in 84 prospectively enrolled AHF patients at two EDs, ≤1 h after first intravenous diuresis, vasodilator, and/or positive pressure ventilation (PPV). Echo and LUS were repeated at 24, 72, and 168 h, unless discharged sooner (n = 197 exams). RVD was defined as <17 mm tricuspid annulus plane systolic excursion (TAPSE), our primary measure. To identify correlates of RVD, a multivariable linear mixed model (LMM) of TAPSE through time was fit. Possible predictors were specified a priori and/or with p ≤ 0.1 difference between patients with/without RVD. Data were standardized and centered to facilitate comparison of relative strength of association between predictors of TAPSE. Survival curves for a 30-day death or AHF readmission primary outcome were assessed for RVD, LUS severity, and LVEF. A multivariable generalized linear mixed model (GLMM) for the outcome was used to adjust RVD for LVEF and LUS. RESULTS: 46% (n = 39) of patients at ED arrival showed RVD by TAPSE (median 18 mm, interquartile range 13-23). 18 variables with p ≤ 0.1 unadjusted difference with/without RVD, and 12 a priori predictors of RVD were included in the multivariable LMM model of TAPSE through time (R2 = 0.76). Missed antihypertensive medication (within 7 days), ED PPV, chronic obstructive pulmonary disease history, LVEF, LUS congestion severity, and right ventricular systolic pressure (RVSP) were the strongest multivariable predictors of RVD, respectively, and the only to reach statistical significance (p < 0.05). 30-day death or AHF readmission was associated with RVD at ED arrival (hazard ratio {HR} 3.31 {95%CI: 1.28-8.53}, p = 0.009), ED to discharge decrease in LUS (HR 0.11 {0.01-0.85}, p < 0.0001 for top quartile Δ), but not LVEF (quartile 2 vs. 1 HR 0.78 {0.22-2.68}, 3 vs. 1 HR 0.55 {0.16-1.92}, 4 vs. 1 HR 0.32 {0.09-1.22}, p = 0.30). The area under the receiver operating curve on GLMM for the primary outcome by TAPSE (p = 0.0012), ΔLUS (p = 0.0005), and LVEF (p = 0.8347) was 0.807. CONCLUSION: In this observational study, RVD was common in AHF, and predicted by congestion on LUS, LVEF, RVSP, and comorbidities from ED arrival through discharge. 30-day death or AHF-rehospitalization was associated with RVD at ED arrival and ΔLUS severity, but not LVEF.

Preliminary development of a questionnaire measuring patient views of participation in clinical trials.

OBJECTIVE: This study aimed to develop a questionnaire for measuring patient perceptions of participating in clinical trials. Development was based on earlier research on patient views of involvement in medical care and a literature review. Patients were recruited from an ongoing clinical trial focused on cardiovascular illness and from an outpatient psychiatry department. Factor analysis was conducted on a pilot version of the questionnaire in 2016 and on a revised version in 2017. RESULTS: A total of 53 patients were recruited for the pilot study and 55 were recruited for the main study, substantially below the goal of 100 participants. Factor analysis revealed six factors measuring aspects of patients' perceptions of participating in clinical trials, including motivation, risks and benefits, the nature of the trial itself, and practical considerations, such as cost and convenience. Inter-scale correlations ranged between 0.06 and 0.64, indicating acceptable scale independence. Reliability scores (Cronbach's alphas) ranged from 0.62 to 0.85. Factor analysis results were somewhat unstable, with shared variance for several items across scales. This is likely due to the small sample sizes. In larger, more diverse patient samples, this questionnaire can be useful for measuring and incorporating patients' views into the design and execution of clinical trials.

Changes in speckle-tracking-derived mechanical dispersion index are associated with 30-day readmissions in acute heart failure.

BACKGROUND: The objective of the present study was to evaluate the relationship between speckle-tracking-derived parameters left ventricular (LV) mechanical dispersion index (MDI), defined as the standard deviation of the time-to-peak longitudinal strain of all segments analyzed of the LV, and global longitudinal strain (GLS) and 30-day post-discharge outcomes (death and readmission to the hospital) in patients with acute heart failure (AHF). METHODS: We performed a prospective observational study of selected emergency department patients with a primary diagnosis of AHF. Point-of-care echocardiograms were performed at baseline (prior to, or concurrent with the initiation of treatment) and 23 h post-enrollment. Offline speckle-tracking analysis was utilized to calculate GLS and MDI. The primary outcome was 30-day readmissions. RESULTS: A total of 31 patients were included, 13 of whom were readmitted within 30 days. Patients who were not readmitted to the hospital experienced an average relative improvement in MDI of 24% from baseline to 23 h (84 ms to 64 ms), while patients who were readmitted experienced an average relative worsening in MDI of 6% (66 ms to 70 ms) from baseline to 23 h. CONCLUSIONS: MDI has promise as a treatment response variable in admitted patients with AHF; however, further study is needed.

Three-dimensional echocardiography in acute heart failure: Can and should we do it in the emergency department?

Despite its proven superiority over two-dimensional transthoracic echocardiography (2DTTE) for left ventricular (LV) volumes and ejection fraction, clinical use of 3DTTE remains very limited in the acute setting. 3DTTE may have significant clinical advantages in the assessment of acute heart failure. Further exploration of 3DTTE utilization may help in more precise assessment of the regional wall-motion abnormalities, early identification of acute ischemic from nonischemic LV dysfunction with a more precise approach to the AHF management. The use of other measures, especially the right ventricular and the left atrial assessment, and 3D strain methodology may further expand the potential future utility of 3DTTE in patients with new-onset HF.