Gaurav Singal

Pre-Capillary Pulmonary Hypertension and Right Ventricular Dilation Predict Clinical Outcome in Cardiac Resynchronization Therapy

OBJECTIVES This study examined the prognostic significance of pre- and post-capillary components of pulmonary hypertension (PH) in patients receiving cardiac resynchronization therapy (CRT). BACKGROUND PH is common in patients with left ventricular systolic dysfunction (LVSD) receiving CRT. The impact of PH subtype on clinical outcome in CRT is unknown. METHODS The study population consisted of 101 patients (average age 66 ± 13 years, left ventricular ejection fraction 0.23 ± 0.07, and New York Heart Association functional class 3.2 ± 0.4) who underwent right heart catheterization in the 6 months before CRT. PH was defined as a mean pulmonary artery pressure ≥25 mm Hg; a significant pre-capillary contribution to elevated mean pulmonary artery pressure was defined as a transpulmonary gradient (TPG) ≥12 mm Hg. Clinical endpoints were assessed at 2 years and included all-cause mortality and a composite of death, left ventricular assist device, or cardiac transplantation. RESULTS Patients with TPG ≥12 mm Hg were more likely to experience all-cause mortality (hazard ratio [HR]: 3.2; 95% confidence interval [CI]: 1.3 to 7.4; p = 0.009) and the composite outcome (HR: 3.0; 95% CI: 1.4 to 6.3; p = 0.004) compared with patients with TPG <12 mm Hg. After multivariate adjustment for hemodynamic, clinical, and echocardiographic variables, only TPG ≥12 mm Hg and baseline right ventricular (RV) dilation (RV end-diastolic dimension >42 mm) were associated with the composite clinical outcome (p = 0.05 and p = 0.04, respectively). CONCLUSIONS High TPG PH and RV dilation are independent predictors of adverse outcomes in patients with LVSD who are receiving CRT. RV pulmonary vascular dysfunction may be a therapeutic target in select patients receiving CRT.

Enhancing the Prediction of 30-Day Readmission After Percutaneous Coronary Intervention Using Data Extracted by Querying of the Electronic Health Record

Background—Early readmission after percutaneous coronary intervention is an important quality metric, but prediction models from registry data have only moderate discrimination. We aimed to improve ability to predict 30-day readmission after percutaneous coronary intervention from a previously validated registry-based model. Methods and Results—We matched readmitted to non-readmitted patients in a 1:2 ratio by risk of readmission, and extracted unstructured and unconventional structured data from the electronic medical record, including need for medical interpretation, albumin level, medical nonadherence, previous number of emergency department visits, atrial fibrillation/flutter, syncope/presyncope, end-stage liver disease, malignancy, and anxiety. We assessed differences in rates of these conditions between cases/controls, and estimated their independent association with 30-day readmission using logistic regression conditional on matched groups. Among 9288 percutaneous coronary interventions, we matched 888 readmitted with 1776 non-readmitted patients. In univariate analysis, cases and controls were significantly different with respect to interpreter (7.9% for cases and 5.3% for controls; P=0.009), emergency department visits (1.12 for cases and 0.77 for controls; P<0.001), homelessness (3.2% for cases and 1.6% for controls; P=0.007), anticoagulation (33.9% for cases and 22.1% for controls; P<0.001), atrial fibrillation/flutter (32.7% for cases and 28.9% for controls; P=0.045), presyncope/syncope (27.8% for cases and 21.3% for controls; P<0.001), and anxiety (69.4% for cases and 62.4% for controls; P<0.001). Anticoagulation, emergency department visits, and anxiety were independently associated with readmission. Conclusions—Patient characteristics derived from review of the electronic health record can be used to refine risk prediction for hospital readmission after percutaneous coronary intervention.

Mutational Landscapes of Smoking-Related Cancers in Caucasians and African Americans: Precision Oncology Perspectives at Wake Forest Baptist Comprehensive Cancer Center

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high mutational load. These tumors are characterized by high-frequency mutations in TP53, DNA damage repair genes (BRCA2 and ATM), and chromatin remodeling genes (the lysine methyltransferases KMT2D or MLL2, and KMT2C or MLL3). These tobacco-related cancers also exhibit augmented tumor heterogeneities. Smoking related genetic mutations were validated by The Cancer Genome Atlas dataset that includes 2,821 cases with known smoking status. The Wake Forest and The Cancer Genome Atlas cohorts (431 and 7,991 cases, respectively) revealed a significantly increased mutation rate in the TP53 gene in the African-American subgroup studied. Both cohorts also revealed 5 genes (e.g. CDK8) significantly amplified in the African-American population. Conclusions: These results provide strong evidence that tobacco is a major cause of genomic instability and heterogeneity in cancer. TP53 mutations and key oncogene amplifications emerge as key factors contributing to cancer outcome disparities among different racial/ethnic groups.

Renal Response in Patients with Chronic Kidney Disease Predicts Outcome Following Cardiac Resynchronization Therapy.

Chronic kidney disease (CKD) severity is associated with increased morbidity and mortality in congestive heart failure. There is a paucity of data regarding renal improvement after cardiac resynchronization therapy (CRT) and its potential impact on clinical outcomes, especially in patients with severe CKD.

Usefulness and consequences of cardiac resynchronization therapy in dialysis-dependent patients with heart failure.

Cardiac resynchronization therapy (CRT) is often deferred in dialysis-dependent patients with heart failure (HF) because of a perceived lack of benefit and potentially higher risks, although the outcomes associated with CRT in dialysis have not been reported. We therefore studied our centers experience with CRT in dialysis-dependent patients. We constructed a descriptive assessment of these patients (n = 15) and performed a case-control analysis matching for age, gender, bundle branch morphology, diabetes mellitus, cardiomyopathy origin, and β-blocker and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. Baseline and 6-month echocardiograms were assessed for evidence of reverse remodeling. No periprocedural or long-term complications were observed among dialysis patients. Heterogenous improvement in ejection fraction (+3.1 ± 9.2%) was noted and 2 patients derived absolute improvements of 8% and 22%, respectively. Dialysis patients demonstrated the following 3-year event rates: HF hospitalization, 31%; all-cause hospitalization, 100%; mortality, 73%; and HF hospitalization or death, 82%. In the case-control analysis, controls demonstrated superior reverse remodeling (+9.2 ± 9.5% increase in ejection fraction), decreased mortality (73% vs 44%, p = 0.038), and all-cause hospitalizations (76% vs 100%, p = 0.047), with no difference in HF hospitalizations (p = 0.39), compared with dialysis patients. In conclusion, at our center, the dialysis-dependent patients with HF who underwent CRT implantation did so safely and no serious complications were observed. Certain dialysis patients demonstrated compelling improvement after device implantation. Compared with matched controls, dialysis patients were at increased risk for adverse events and worsened echocardiographic outcomes.

How can we best use electronic data to find and treat the critically ill

1. Chan PS, Jain R, Nallmothu BK, et al: Rapid response teams: A systematic review and meta-analysis. Arch Intern Med 2010; 170:18–26 2. DeVita MA, Smith GB, Adam SK, et al: “Identifying the hospitalised patient in crisis”—A consensus conference on the afferent limb of rapid response systems. Resuscitation 2010; 81:375–382 3. Wunderink RG, Diederich ER, Caramez MP, et al: Rapid reponse team-triggered procalcitonin measurement predicts infectious intensive care unit transfers. Crit Care Med 2012; 40:2090–2095 4. Jensen JU, Hein L, Lundgren B, et al; for The

A web-based patient tool for preventive health: preliminary report.

Background: The Internet is a promising medium for engaging the community in preventive care and health promotion, particularly among those who do not routinely access health care. Objective: The authors pilot-tested a novel website that translates evidence-based preventive health guidelines into a patient health education tool. The web-based tool allows individuals to enter their health risk factors and receive a tailored checklist of recommended preventive health services based on up-to-date guidelines from the US Preventive Services Task Force and the Advisory Committee on Immunization Practices. Methods: The authors conducted surveys and in-depth interviews among a purposive sample of adults from an urban African American community who pilot-tested the website in a standardized setting. Interviews were designed to assess the usability, navigability, and content of the website and capture patient perceptions about its educational value and usefulness. Each interview was audiotaped, transcribed, and examined using the constant comparative method. Results: Twenty-five participants piloted the tool: 96% found it easy to use and 64% reported learning something new. Many participants reported that, in addition to improving clinical preventive care (the intended purpose), the website could serve as a stand-alone tool to improve self-awareness and motivate behavior change. Conclusions: A web-based tool designed to translate preventive health guidelines for the community may serve the dual purpose of improving the delivery of preventive health care and encouraging health promotion. The website developed here is publicly available for use by practitioners and the community.