Clinical Composite Score Research Articles

Daily adjunctive therapy with vitamin D3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia

Immunotherapy using vitamin D (vitD3 ) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD3 + PBA enhanced clinical recovery from pulmonary tuberculosis (TB). A randomized controlled trial was conducted in Addis Ababa, Ethiopia. Patients with smear-positive or smear-negative TB received daily oral supplementation with 5000 IU vitD3 and 2 × 500 mg PBA or placebo for 16 weeks, together with 6-month chemotherapy. Primary end-point: reduction of a clinical composite TB score at week 8 compared with baseline using modified intention-to-treat (mITT, n = 348) and per-protocol (n = 296) analyses. Secondary end-points: primary and modified TB scores (week 0, 4, 8, 16, 24), sputum conversion, radiological findings and plasma 25(OH)D3 concentrations. Most subjects had low baseline plasma 25(OH)D3 levels that increased gradually in the vitD3 + PBA group compared with placebo (P < 0.0001) from week 0 to 16 (mean 34.7 vs. 127.4 nmol L-1 ). In the adjusted mITT analysis, the primary TB score was significantly reduced in the intervention group at week 8 (-0.52, 95% CI -0.93, -0.10; P = 0.015) while the modified TB score was reduced at week 8 (-0.58, 95% CI -1.02, -0.14; P = 0.01) and 16 (-0.34, 95% CI -0.64, -0.03; P = 0.03). VitD3 + PBA had no effect on longitudinal sputum-smear conversion (P = 0.98). Clinical adverse events were more common in the placebo group (24.3%) compared with the vitD3 + PBA group (12.6%). Daily supplementation with vitD3 + PBA may ameliorate clinical TB symptoms and disease-specific complications, while the intervention had no effect on bacterial clearance in sputum.

Circulating microRNA miR-21-5p, miR-150-5p and miR-30e-5p correlate with clinical status in late onset myasthenia gravis

There are no biomarkers for late onset myasthenia gravis (LOMG; onset >50 years). We evaluated circulating microRNA in a discovery cohort of 4 LOMG patients and 4 healthy controls and in a prospective diagnostic validation cohort of 73 LOMG patients (48 male) with longitudinal follow-up samples. In immunosuppression naïve patients, levels of miRNAs miR-150-5p, miR-21-5p and miR-30e-5p decreased in parallel with clinical improvement after initiation of immunosuppression and their levels positively correlated with the clinical MG composite score. Levels of miR-150-5p and miR-21-5p were lower in patients with ocular compared to generalized LOMG. Circulating miR-150-5p, miR-21-5p and miR-30e-5p correlate with the clinical course in LOMG.

Will His Bundle Pacing Make Cardiac Resynchronization Therapy Obsolete?

Although permanent cardiac pacing successfully restores a physiological heart rate in patients with atrioventricular block, it has become apparent in recent years that chronic right ventricular (RV) pacing can lead to serious adverse consequences such as adverse ventricular remodeling and heart failure. Algorithms that minimize RV pacing for patients with sinus node dysfunction or intermittent atrioventricular block are in widespread use to avoid the problems associated with chronic RV pacing. However, in patients with advanced atrioventricular block, high percentages of ventricular pacing are unavoidable. One approach to this problem is cardiac resynchronization therapy (CRT), in which a left ventricular lead in the coronary sinus paces simultaneously or near-simultaneously with an RV lead to allow more coordinated activation of the ventricles and avoid dyssynchrony. The BLOCK HF study (Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block) showed that such an approach in patients with atrioventricular block and baseline left ventricular dysfunction (left ventricular ejection fraction [EF] ≤50% and New York Heart Association [NYHA] class I–III) led to better outcomes than RV pacing, including less adverse ventricular remodeling, a lower incidence of heart failure events, and better clinical composite scores.1 CRT has also proven to be valuable in patients with systolic heart failure without atrioventricular block but with evidence of conduction system disease manifested as a prolonged QRS duration, usually left bundle-branch block. Multiple trials …

Utility of dual-source computed tomography in cardiac resynchronization therapy—DIRECT study

Dual-source computed tomography (CT) can evaluate left ventricular (LV) dyssynchrony, myocardial scar, and coronary venous anatomy in patients undergoing cardiac resynchronization therapy (CRT). We aimed to determine whether dual-source CT predicts clinical CRT outcomes and reduces intraprocedural time. In this prospective study, 54 patients scheduled for CRT (mean age 63 ± 11 years; 74% men) underwent preprocedural CT to assess their venous anatomy as well as CT-derived dyssynchrony metrics and myocardial scar. Based on 1:1 randomization, the implanting physician had preimplant knowledge of the venous anatomy in half the patients. In blinded analyses, we measured time to maximal wall thickness and inward wall motion to determine (1) CT global and segmental dyssynchrony and (2) concordance of lead location to regional LV mechanical contraction. End points were 6-month CRT response measured using heart failure clinical composite score and 2-year major adverse cardiac events (MACE). There were 72% CRT responders and 17% with MACE. Two wall motion dyssynchrony indices-global wall motion and opposing anteroseptal-inferolateral wall motion-predicted MACE (P < .01). Lead location concordant to regions of maximal wall thickness was associated with less MACE (P < .01). No CT dyssynchrony metrics predicted 6-month CRT response (P = NS for all). Myocardial scar (43%), posterolateral wall scar (28%), and total scar burden did not predict outcomes (P = NS for all). Preknowledge of coronary venous anatomy by CT did not reduce implant or fluoroscopy time (P = NS for both). Two CT dyssynchrony metrics predicted 2-year MACE, and LV lead location concordant to regions of maximal wall thickness was associated with less MACE. Other CT factors had little utility in CRT.

Endocardial left ventricular pacing across the interventricular septum for cardiac resynchronization therapy: Clinical results of a pilot study

Cardiac resynchronization therapy (CRT) is an effective treatment for selected patients with heart failure, but it can be limited by the inability to place the left ventricular (LV) lead via the coronary sinus. The purpose of this study was to develop an alternative approach, placing the LV lead endocardially via an interventricular septal puncture, and to assess the feasibility and safety of this technique. All patients were anticoagulated with warfarin (international normalized ratio 2.5-3.5). A superior approach ventricular transseptal puncture using radiofrequency energy was performed. An active fixation pacing lead was delivered to the mapped site of latest electrical activation on the endocardial LV. Twenty patients were recruited, 15 with failed transvenous LV lead placement and 5 nonresponders to CRT. Mean (±SD) age was 67±12, with 80% male, QRS duration 157 ± 14 ms, ischemic etiology 45%, New York Heart Association functional class 2.9 ± 0.4, and LV ejection fraction 28% ± 7%. The procedure was successful in all, with no serious complications. Clinical composite score improved at 6 months in 65% and worsened in 35%. LV ejection fraction improved >5% in 88%, from 28% ± 7% to 41% ± 9%. Six-minute walking distance improved >10% in 64%, from 248 ± 125 m to 316 ± 109 m. One patient suffered a lacunar ischemic stroke after 5 months with partial neurological recovery, associated with labile international normalized ratios. After 2.0 ± 1.0 years of follow-up, 3 patients died (2 pneumonia, 1 heart failure), and 2 patients suffered transient ischemic attacks. LV endocardial pacing via interventricular septal puncture in patients for whom standard CRT is not possible is similarly effective and durable, with significant but potentially acceptable risks.

Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 × 2 factorial, double-blind, randomised controlled trial

Standard treatment for thyroid eye disease is with systemic corticosteroids. We aimed to establish whether orbital radiotherapy or antiproliferative immunosuppression would confer any additional benefit. CIRTED was a multicentre, double-blind, randomised controlled trial with a 2 × 2 factorial design done at six centres in the UK. Adults with active moderate-to-severe thyroid eye disease associated with proptosis or ocular motility restriction were recruited to the trial. Patients all received a 24 week course of oral prednisolone (80 mg per day, reduced to 20 mg per day by 6 weeks, 10 mg per day by 15 weeks, and 5 mg per day by 21 weeks) and were randomly assigned via remote computerised randomisation to receive either radiotherapy or sham radiotherapy and azathioprine or placebo in a 2 × 2 factorial design. Randomisation included minimisation to reduce baseline disparities in potential confounding variables between trial interventions. Patients and data analysts were masked to assignment, whereas trial coordinators (who monitored blood results), pharmacists, and radiographers were not. The radiotherapy dose was 20 Gy administered to the retrobulbar orbit in ten to 12 fractions over 2 to 3 weeks. Azathioprine treatment was provided for 48 weeks at 100-200 mg per day (dispensed as 50 mg tablets), depending on bodyweight (100 mg for <50 kg, 150 mg 50-79 kg, 200 mg for ≥80 kg). The primary outcomes were a binary composite clinical outcome score and an ophthalmopathy index at 48 weeks, and a clinical activity score at 12 weeks. The primary analysis was based on the intention-to-treat allocation and safety was assessed in all participants. This study is registered with ISRCTN, number 22471573. Between Feb 15, 2006, and Oct 3, 2013, 126 patients were recruited and randomly assigned to groups: 31 patients to radiotherapy plus azathioprine, 31 to sham radiotherapy and azathioprine, 32 to radiotherapy and placebo, and 32 to sham radiotherapy and placebo. Outcome data were available for 103 patients (54 for sham radiotherapy vs 49 for radiotherapy and 53 for placebo vs 50 for azathioprine), of whom 84 completed their allocated treatment of radiotherapy or sham radiotherapy and 57 continued to take azathioprine or placebo up to 48 weeks. There was no interaction betweeen azathioprine and radiotherapy (pinteraction=0·86). The adjusted odds ratio (ORadj) for improvement in the binary clinical composite outcome measure was 2·56 (95% CI 0·98-6·66, p=0·054) for azathioprine and 0·89 (0·36-2·23, p=0·80) for radiotherapy. In a post-hoc analysis of patients who completed their allocated therapy the ORadj for improvement was 6·83 (1·66-28·1, p=0·008) for azathioprine and 1·32 (0·30-4·84, p=0·67) for radiotherapy. The ophthalmopathy index, clinical activity score, and numbers of adverse events (161 with azathioprine and 156 with radiotherapy) did not differ between treatment groups. In both groups, the most common adverse events were mild infections. No patients died during the study. In patients receiving oral prednisolone for 24 weeks, radiotherapy did not have added benefit. We also did not find added benefit for addition of azathioprine in the primary analysis; however, our conclusions are limited by the high number of patients who withdrew from treatment. Results of post-hoc analysis of those who completed the assigned treatment suggest improved clinical outcome at 48 weeks with azathioprine treatment. National Eye Research Centre, Above and Beyond, and Moorfields Eye Charity.

Sleep Apnea in Patients Hospitalized With Acute Ischemic Stroke: Underrecognition and Associated Clinical Outcomes.

To evaluate clinical recognition of sleep apnea and related outcomes in patients hospitalized with acute ischemic stroke. A retrospective study of all patients hospitalized with acute ischemic stroke from April 2008 to December 2014. The primary predictor and outcome variables were sleep apnea and hospital mortality, respectively. Secondary outcomes were mechanical ventilation, hospital length of stay, and the survivor's functional level by the modified Rankin scale. A sensitivity multivariate regression analysis included the propensity score for cardiovascular comorbidities and sleep apnea. Of 989 patients, 190 (19%) were considered to have sleep apnea. Only 42 patients (22%) received any treatment for sleep apnea during the hospital stay. Despite higher prevalence of cardiovascular comorbidities, the patients with sleep apnea had lower hospital mortality, 1% versus 5.6% in patients without sleep apnea (odds ratio [OR] 0.18; 95% confidence interval [CI], 0.03-0.58, P = .002). Only the National Institutes of Health Stroke Scale (NIHSS) and the Glasgow coma scale (GCS) were significant predictors of adjusted hospital mortality (OR 1.06, 95% CI 1.01-1.11, P = .01 and OR 0.61, 95% CI 0.51-0.69, P ≤ .001, respectively). A composite clinical propensity score for sleep apnea and cardiovascular comorbidities was significantly associated with decreased mortality, independent to either NIHSS (OR 0.11, 95% CI 0.017-0.71; P = .02) or GCS (OR 0.07, 95% CI 0.01-0.52; P = .01). Prevalence of sleep apnea in our study was low, likely because of clinical underrecognition. Despite having more cardiovascular disease, the patients with acute stroke and sleep apnea had less severe neurological injury and lower unadjusted mortality than those without a history of sleep apnea.

What Is the Relationship Between a Preclerkship Portfolio Review and Later Performance in Clerkships?

Medical educators struggle to find effective ways to assess essential competencies such as communication, professionalism, and teamwork. Portfolio-based assessment provides one method of addressing this problem by allowing faculty reviewers to judge performance, as based on a longitudinal record of student behavior. At the Feinberg School of Medicine, the portfolio system measures behavioral competence using multiple assessments collected over time. This study examines whether a preclerkship portfolio review is a valid method of identifying problematic student behavior affecting later performance in clerkships. The authors divided students into two groups based on a summative preclerkship portfolio review in 2014: students who had concerning behavior in one or more competencies and students progressing satisfactorily. They compared how students in these groups later performed on two clerkship outcomes as of October 2015: final grades in required clerkships, and performance on a clerkship clinical composite score. They used Mann-Whitney tests and multiple linear regression to examine the relationship between portfolio review results and clerkship outcomes. They used USMLE Step 1 to control for knowledge acquisition. Students with concerning behavior preclerkship received significantly lower clerkship grades than students progressing satisfactorily (P = .002). They also scored significantly lower on the clinical composite score (P < .001). Regression analysis indicated concerning behavior was associated with lower clinical composite scores, even after controlling for knowledge acquisition. The results show a preclerkship portfolio review can identify behaviors that impact clerkship performance. A comprehensive portfolio system is a valid way to measure behavioral competencies.

Clinical impact of an additional left ventricular lead in cardiac resynchronization therapy nonresponders: The V3 trial

Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF), but is limited by a substantial proportion of nonresponders. We hypothesized that adding a second left ventricular (LV) lead to deliver a triple-site CRT (V3 CRT) may improve clinical status of CRT nonresponders. We assessed the feasibility and safety of adding a second LV lead to CRT nonresponders and its clinical impact. Eighty-four recipients of a CRT system and considered as nonresponders as per clinical composite score (CCS) were enrolled in this multicenter study. They were randomized to the V3 arm (implantation of an additional LV lead; n = 43) or control arm (no change; n= 41). Implant success rate, incidence of severe adverse events, CCS, and secondary clinical and echocardiographic end points were evaluated at 12 and 24 months. Positioning of a second LV lead was successful at first (40of 44 - 90.9%) or second (4 of 44 - 9.09%) attempt. The perioperative complication rate (infection, system explant, pneumothorax, and hematoma) was high (procedures or system-related complications for 9 patients- 20.4%). After 24 months, 35 systems (79.5%) were working properly. The multinomial logistic regression model showed that V3 treatment had no significant influence (P = .27) on the CCS, number of HF hospitalizations, time to first HF hospitalization, New York Heart Association class, and LV ejection fraction at 12 and 24 months. Although addition of a second LV lead in CRT nonresponders is feasible with a high success rate, this approach is associated with a significant rate of severe adverse events and does not provide significant long-term clinical benefits (ClinicalTrials.gov Identifier No. NCT01059175).

The role of interventricular conduction delay to predict clinical response with cardiac resynchronization therapy

Pacing at sites with late electrical activation or greater interventricular delay is associated with improvement in measures of cardiac resynchronization therapy (CRT) response, primarily reverse remodeling. However, little is known about whether such lead positions improve heart failure (HF) clinical outcomes. The purpose of this study was to assess the association between interventricular electrical delay and HF clinical outcomes. The Pacing Evaluation-Atrial SUpport Study was a multicenter randomized trial of patients undergoing CRT-defibrillator implantation. Interventricular delay was measured as the unpaced right ventricle-left ventricle (RV-LV) interval in sinus rhythm. The HF clinical composite score was the primary end point. In addition, the time to first HF hospitalization or death was measured and events were adjudicated by a blinded core laboratory. The cohort was divided at the median RV-LV interval into short (<67 ms) and long (≥67 ms) subgroups. In addition, receiver operating characteristic curves were constructed to identify the optimal cutoff of the RV-LV interval and spline analysis was performed to assess RV-LV interval as a continuous variable. A total of 1342 patients were included in this study. The clinical composite score at 1 year differed between groups, with more patients improving and fewer patients worsening in the long RV-LV group (P = .014). The time to first HF hospitalization or mortality also differed with a lower risk of an event in the long RV-LV group (hazard ratio 0.62; P = .002). Multivariate analysis showed that RV-LV time (hazard ratio 0.71; P = .038) and sex were independent predictors of this outcome. Baseline interventricular delay is a strong independent predictor of clinical response to CRT.

Optimizationof coronary sinus lead placement targeted to the longest right-to-left delay in patients undergoing cardiac resynchronization therapy: The Optimal Pacing SITE 2 (OPSITE 2) acute study and protocol.

Left ventricular (LV) lead positioning at the site of delayed electrical activation is associated with better response to cardiac resynchronization therapy (CRT). We hypothesized that a long electrical conduction delay between right ventricular (RV) and coronary sinus (CS) leads during RV pacing (RLD index) is correlated with a better clinical outcome METHODS AND RESULTS: RLD is measured intraprocedurally, during RV pacing, as the time interval between the intracardiac electrograms of RV and CS leads. Initially, we did a prove-of-concept, feasibility, acute study in 97 patients who underwent CRT implantation. The CS lead position was assessed in the 40° right anterior oblique and 40° left anterior oblique views and assigned to one of 11 prespecified segments of a schematic eyeball depiction of the LV walls. Acute outcomes were QRS width during biventricular (BIV) pacing. The longest RLD were found in the basal and mid lateral segments; these accounted for 82% and 78%, respectively, of the total QRS width (%RLD). %RLD was inversely correlated with BIV-paced QRS (P=0.0001). A similar slope was present either in the 78 patients with preserved atrioventricular (AV) conduction and in the 19 without AV conduction (-0.34vs-0.27, P=0.7). We showed that RLD can be used to guide lead placement at the time of CRT implantation and that it is correlated with BIV-QRS width, an indirect predictor of clinical outcome. Based on these findings we started the prospective, multicenter Optimal Pacing SITE 2 (OPSITE 2) trial with the objective to demonstrate a relationship between RLD and clinical outcomes assessed as death, hospitalization for heart failure, New York Heart Association class, and clinical composite score. The protocol is provided.

Vitamin D3 repletion versus placebo as adjunctive treatment of heart failure patient quality of life and hormonal indices: a randomized, double-blind, placebo-controlled trial

BackgroundVitamin D status may influence heart failure (HF) patient outcomes by affecting b-type natriuretic peptide (BNP), parathyroid hormone (PTH), and enhancing cardiac contractility. Vitamin D deficiency is associated with morbidity and mortality in HF patients. The objective of this study was to determine if vitamin D3 at a comparatively high dose would replete 25-hydroxyvitamin D (25(OH)D) stores, improve BNP, PTH, cardiopulmonary function, reduce inflammatory markers, and improve quality of life (QOL) in HF patients.MethodsThis was a 6 month, parallel group, double-blind, placebo-controlled, single clinic center, randomized trial of supplemental vitamin D3 using a dose of 10,000 IU daily or placebo in 40 vitamin D deficient or insufficient (25(OH)D level ≤ 32 ng/ml) patients with stable New York Heart Association Class II-III HF in a specialty cardiology clinic. All variables were measured at baseline and 6 months. Values between the two treatment groups were assessed using Student’s t-test or Mann-Whitney Test. Univariate analysis of covariance was conducted to adjust for variance in baseline 25(OH)D.ResultsAll results were adjusted for baseline 25(OH)D. The change in BNP from baseline was ∆ +30 ± 950 pg/ml for treatment vs. placebo ∆ +400 ± 1900 pg/ml, p = 0.003. 25(OH)D serum levels rose by 49 ± 32 ng/ml in the treatment group vs 4 ± 10 ng/ml in the placebo group, p < 0.001. PTH and exercise chronotropic response index improved in the treatment group vs placebo group, respectively, but both were attenuated by adjustment ((∆-20 ± 20 pg/ml vs ∆ + 7 ± 53 pg/ml respectively (p = 0.01, adjusted p = 0.07)) and (∆ + 0.13 ± 0.26 vs. ∆-0.03 ± 02.9 respectively, p < 0.01, adjusted p = 0.17)). Other measured cardiopulmonary parameters remained unchanged. High sensitivity C-reactive protein (hsCRP) remained unchanged for women, but improved for men (∆-2 ± 4 treatment versus ∆2 ± 5 mg/L placebo, p = 0.05). QOL scores, including composite overall and clinical summary scores significantly improved in treatment compared to placebo (∆ + 10 ± 15 versus −6 ± 15, p < 0.01 and ∆ + 8 ± 14 versus −8 ± 18, p = 0.01, respectively).ConclusionsRepletion of 25(OH)D may improve QOL in HF patients and may help to normalize BNP, PTH, and hsCRP.Trial registrationClinicaltrials.gov, Trial Registration Number: NCT01636570, First registered 3 July 2012.

Clinical Features and Outcomes of Patients With Tubercular Uveitis Treated With Antitubercular Therapy in the Collaborative Ocular Tuberculosis Study (COTS)–1

Eradication of systemic tuberculosis (TB) has been limited by neglected populations and the HIV pandemic. Whereas ocular TB often presents as uveitis without any prior evidence of systemic TB, the existing uncertainty in the diagnosis of TB uveitis may perpetuate missed opportunities to address systemic TB. To examine the clinical features of TB uveitis and the associations with response to antitubercular therapy (ATT). This retrospective multinational cohort study included patients from 25 ophthalmology referral centers diagnosed with TB uveitis and treated with ATT from January 1, 2004, through December 31, 2014, with a minimum follow-up of 1 year. Treatment failure, defined as a persistence or recurrence of inflammation within 6 months of completing ATT, inability to taper oral corticosteroids to less than 10 mg/d or topical corticosteroid drops to less than 2 drops daily, and/or recalcitrant inflammation necessitating corticosteroid-sparing immunosuppressive therapy. A total of 801 patients (1272 eyes) were studied (mean [SD] age, 40.5 [14.8] years; 413 [51.6%] male and 388 [48.4%] female; 577 [73.6%] Asian). Most patients had no known history (498 of 661 [75.3%]) of systemic TB. Most patients had bilateral involvement (471 of 801 [58.8%]). Common clinical signs reported include vitreous haze (523 of 1153 [45.4%]), retinal vasculitis (374 of 874 [42.8%]), and choroidal involvement (419 of 651 [64.4%]). Treatment failure developed in 102 of the 801 patients (12.7%). On univariate regression analysis, the hazard ratios (HRs) associated with intermediate uveitis (HR, 2.21; 95% CI, 1.07-4.55; P = .03), anterior uveitis (HR, 2.68; 95% CI, 1.32-2.35; P = .006), and panuveitis (HR, 3.28; 95% CI, 1.89-5.67; P < .001) were significantly higher compared with posterior distribution. The presence of vitreous haze had a statistically significant association (HR, 1.95; 95% CI, 1.26-3.02; P = .003) compared with absence of vitreous haze. Bilaterality had an associated HR of 1.50 (95% CI, 0.96-2.35) compared with unilaterality (HR, 1 [reference]), although this finding was not statistically significant (P = .07). On multivariate Cox proportional hazards regression analysis, the presence of vitreous haze had an adjusted HR of 2.98 (95% CI, 1.50-5.94; P = .002), presence of snow banking had an adjusted HR of 3.71 (95% CI, 1.18-11.62; P = .02), and presence of choroidal involvement had an adjusted HR of 2.88 (95% CI, 1.22-6.78; P = .02). A low treatment failure rate occurred in patients with TB uveitis treated with ATT. Phenotypes and test results are studied whereby patients with panuveitis having vitreous and choroidal involvement had a higher risk of treatment failure. These findings are limited by retrospective methods. A prospectively derived composite clinical risk score might address this diagnostic uncertainty through holistic and standardized assessment of the combinations of clinical features and investigation results that may warrant diagnosis of TB uveitis and treatment with ATT.

History of Sleep Apnea and Cardiovascular Disease May Portend Improved Mortality in Patients With Acute Ischemic Stroke

SESSION TITLE: Sleep, Heart, Brain, and More SESSION TYPE: Original Investigation Slide PRESENTED ON: Tuesday, October 31, 2017 at 11:00 AM - 12:15 PM PURPOSE: Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia (IH). History of OSA has been previously associated with improved outcomes after myocardial infarction suggesting ischemic preconditioning (IP) in these patients. We hypothesized that patients with history of OSA and cardiovascular disease would have better survival rates and outcomes after presentation with acute ischemic stroke (AIS), possibly due to IP. METHODS: We conducted a retrospective chart review of all hospitalized patients with AIS from Apirl 2008 to December 2014 at a tertiary medical center. We abstracted baseline demographic characteristics, pertinent clinical variables including: coronary artery disease (CAD), congestive heart failure (CHF), hypertension (HTN), hyperlipidemia (HL), diabetes mellitus (DM), known diagnosis or clinical suspicion for sleep apnea, admission National Institutes of Health Stroke Scale (NIHSS) score, and the worst Glasgow Coma Scale (GCS) score during the hospitalization. We assessed the significance of the sleep apnea and the above cardiovascular comorbidities by creating a composite propensity score for these conditions in a multivariate logistic regression analysis. The primary outcome was hospital mortality. RESULTS: A total of 994 patients suffered AIS within the study period. The majority of patients were white (86%), of female sex (52%), with a median age of 75 years (IQR 63, 85). The overall mortality was 5%. The median NIHSS was 5 (IQR 2, 10) and median worst GCS was 15 (13, 15). There were 190 (19%) patients with confirmed or suspected sleep apnea. Of all clinical variables, in univariate analysis only sleep apnea was significantly “protective” of hospital mortality (OR 0.18; 95% CI 0.03-0.58; p= 0.02), but not when adjusted by NIHSS or GCS. However, a composite clinical propensity score for sleep apnea, CAD, CHF, HTN, HL and DM was significantly associated with mortality independent to either NIHSS (range OR 0.11, 95% CI 0.017-0.71; p= 0.02) or the worst GCS during hospitalization (range OR 0.07, 95% CI 0.01-0.52; p= 0.01), which are well established neurological predictors of adverse outcome in patients with AIS. CONCLUSIONS: A composite clinical propensity score for sleep apnea and cardiovascular disease is a significant negative predictor of mortality in patients with AIS, independent of well-established neurological positive predictors (NIHSS and GCS). Our results could be in part supported by the theory of ischemic preconditioning of the brain in these patients. CLINICAL IMPLICATIONS: The presence of sleep apnea and other cardiovascular risk factors and comorbidities may need to be taken into account for more accurate assessment and mortality prediction in patients with AIS. Future studies are needed to confirm these findings. DISCLOSURE: The following authors have nothing to disclose: David Alejos, Nura Festic, Vikas Bansal, Emir Festic No Product/Research Disclosure Information

SY6-5 - Adaptive CRT Algorithm—Reducing the Non-Responder in CRT Recipients With Left Bundle Branch Block and QRS 120–150 ms

Background: Efficacy of the cardiac resynchronization therapy (CRT) in patients with left bundle branch block (LBBB), but QRS duration of 120–150 ms is still limited. Adaptive CRT algorithm had shown to be more effective in patients with preserved AV conduction but the impact of the Adaptive CRT algorithm in patients with different QRS duration remains uncertain. Methods: Patients with LBBB and preserved AV conduction enrolled in the Adaptive CRT trial, randomized study comparing the aCRT or echo-optimized CRT (control group), were used in this analysis. Endpoints for this analysis were clinical composite score (CCS) at 6 months post-implant and time to first heart failure (HF) hospitalization or death. Results: Among the 199 patients, 80 patients (40%) had a baseline QRS of 120–150 ms. In this subgroup, a greater proportion of aCRT patients had an improved CCS (79% vs 50%) at 6 months compared to the control group (P = .03). There was also a trend toward a lower risk of death or HF hospitalization (hazard ratio: 0.53; 95% CI: 0.24–1.15; P = .10) in aCRT group compared to the control arm. In the wide QRS subgroup, the efficacy was comparable in both treatment arms. Conclusion: Adaptive CRT was associated with improved patient outcomes over echo-optimized bi-ventricular CRT in patients with preserved AV conduction, LBBB, and QRS of 120–150 ms.

Past, present, and future of acute heart failure clinical trials-a high-risk population in search of a strategy.

Past, present, and future of acute heart failure clinical trials-a high-risk population in search of a strategy.

Three-dimensional interlead distance predicts response and outcomes after cardiac resynchronization therapy

Approximately one-third of patients do not respond favourably to cardiac resynchronization therapy (CRT). A longer distance between ventricular leads may improve response. To study the impact of the true three-dimensional interlead distance (ILD) on outcomes. Consecutive patients undergoing CRT device implantation were included prospectively. Interlead separation was measured from postprocedural anterior-posterior and lateral chest X-rays. The three-dimensional ILD was calculated using the Pythagorean theorem. Response to CRT was defined using a composite clinical score at 6 months. Forty-two patients were included (mean age 70±9 years; QRS duration 154±31ms; left ventricular ejection fraction 26±7%; 50% ischaemic). At 6 months, 71% of patients were considered to be responders. Responders had a significantly longer ILD (108±17 vs. 87±21mm; P=0.002). When the ILD was corrected for cardiac size, the optimal cut-off value was ≥ 0.53 for predicting response (sensitivity 83%, specificity 75%, area under the curve 0.84; P=0.0002). Similar results were obtained in a historical retrospective cohort. The use of proximal electrodes on the left ventricular lead was associated with a longer ILD in 95% of patients, compared with more distal pacing configurations. In the total cohort of 74 patients (median follow-up, 420 days), those with an indexed ILD ≥ 0.53 had a 70% reduction in risk of hospitalization for heart failure (P=0.004). Longer three-dimensional ILD corrected for cardiac size measured on chest radiographs can accurately predict response to CRT and outcomes. This simple variable may be used to identify optimal lead placement and pacing configuration during CRT implantation.

Rationale and design of the AdaptResponse trial: a prospective randomized study of cardiac resynchronization therapy with preferential adaptive left ventricular-only pacing.

The AdaptResponse trial is designed to test the hypothesis that preferential adaptive left ventricular‐only pacing with the AdaptivCRT® algorithm reduces the incidence of the combined endpoint of all‐cause mortality and intervention for heart failure (HF) decompensation, compared with conventional cardiac resynchronization therapy (CRT), among patients with a CRT indication, left bundle branch block (LBBB) and normal atrioventricular (AV) conduction. The AdaptResponse study is a prospective, randomized, controlled, single‐blinded, multicentre, clinical trial (ClinicalTrials.gov Identifier: NCT02205359), conducted at up to 200 centres worldwide. Following enrolment and baseline assessment, eligible subjects will be implanted with a CRT system containing the AdaptivCRT algorithm, and randomized in a 1:1 fashion to either a treatment (‘AdaptivCRT’) or control (‘Conventional CRT’) group. The study is designed to observe a primary endpoint in 1100 patients (‘event‐driven’) and approximately 3000 patients will be randomized. The primary endpoint is the composite of all‐cause mortality and intervention for HF decompensation; secondary endpoints include all‐cause mortality, intervention for HF decompensation, clinical composite score (CCS) at 6 months, atrial fibrillation, quality of life measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), health outcome measured by the EQ‐5D instrument, all‐cause readmission after a HF admission, and cost‐effectiveness. The AdaptResponse clinical trial is powered to assess clinical endpoints and is expected to provide definitive evidence on the incremental utility of AdaptivCRT‐enhanced CRT systems.

Rationale and design of a randomized trial to assess the safety and efficacy of MultiPoint Pacing (MPP) in cardiac resynchronization therapy: The MPP Trial.

Although the majority of Class III congestive heart failure (HF) patients treated with cardiac resynchronization therapy (CRT) show a clinical benefit, up to 40% of patients do not respond to CRT. This paper reports the design of the MultiPoint Pacing (MPP) trial, a prospective, randomized, double-blind, controlled study to evaluate the safety and efficacy of CRT using MPP compared to standard biventricular (Bi-V) pacing. A maximum of 506 patients with a standard CRT-D indication will be enrolled at up to 50 US centers. All patients will be implanted with a CRT-D system (Quartet LV lead Model 1458Q with a Quadra CRT-D, Abbott) that can deliver both MPP and Bi-V pacing. Standard Bi-V pacing will be activated at implant. At 3months postimplant, patients in whom the echocardiographic parameters during MPP are equal or better than during Bi-V pacing are randomized (1:1) to either an MPP or Bi-V arm. The primary safety endpoint is freedom from system-related complications at 9months. Each patient's response to CRT will be evaluated using a heart-failure clinical composite score, consisting of a change in NYHA functional class, patient global assessment score, HF events, and cardiovascular death. The primary efficacy endpoint is the proportion of responders in the MPP arm compared with the Bi-V arm between 3 and 9months. This trial seeks to evaluate whether MPP via a single quadripolar LV lead improves hemodynamic and clinical responses to CRT, both in clinical responders and nonresponders.

The Impact of the PR Interval in PatientsReceiving Cardiac Resynchronization Therapy: Results From the REVERSE Study.

This study sought to evaluate the impact of baseline PR interval on cardiac resynchronization therapy (CRT) outcomes in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) study. The baseline electrocardiogram has important prognostic value to determine response to CRT. Specifically, QRS duration and morphology are strong predictors of response and outcomes; however, the prognostic importance of the PR interval is less clear. REVERSE was a double-blinded, randomized study of CRT in mild heart failure (HF). The primary endpoint was the analysis of patients in sinus rhythm (n= 582) of the time-to-first HF hospitalization or death during the 2-year randomized period of the trial. In addition, the long-term impact of PR interval was assessed in the cohort actively on CRT during the pre-planned 5-year follow-up. Subjects were analyzed by PR interval, grouped by the median (180 ms) in 20-ms bins or as a continuous variable depending on the analysis performed. Secondary endpoints included the clinical composite score and echocardiographic measures of reverse remodeling. During the randomized phase of the study, CRT had similar effectiveness for both PR<180 ms (hazard ratio [HR]: 0.34) and PR >180 ms (HR: 0.57) subgroups (interaction p= 0.33). Similar results were observed when PR intervalwas grouped in 20-ms bins or treated as a continuous variable. In multivariable analysis of the long-term follow-up, left bundle branch block morphology, New York Heart Association functional class, HF etiology, and QRS duration, but not PR interval, predicted HF hospitalization or death. Baseline PR interval does not affect clinical outcomes or reverse remodeling with CRT in mild HF. (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction [REVERSE]; NCT00271154).