Adjustment For Baseline Predictors Research Articles

In-depth phenotypic characterisation of myocardial fibrosis by cardiovascular magnetic resonance predicts sudden cardiac death in coronary heart disease: a long-term prospective outcome study

Abstract Background Prospective studies harnessing late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) afford the potential to non-invasively characterise the phenotypic substrate for sudden cardiac death (SCD) and simultaneously interrogate its mechanistic drivers. Purpose To assess the utility of infarct characterisation by CMR, including scar microstructure analysis, to predict SCD in prospectively investigated patients with coronary heart disease (CHD). Methods Patients with stable CHD were prospectively recruited into a registry between August 2009 and January 2016. The primary outcome for this study was SCD or aborted SCD. Patients with a secondary prevention implantable cardioverter defibrillator (ICD) indication were excluded. All patients had CMR with LGE imaging. Infarct quantification (core scar and peri-infarct zone [PIZ]) was performed by an independent level 3 CMR reader. Outcome events were adjudicated by a panel of cardiologists blinded to the CMR data. To investigate fibrosis microstructure, bespoke computational image processing algorithms were applied to the LGE images in order to extract specific morphological and texture related features. Results Of 437 patients (mean age 64, mean left ventricular ejection fraction [LVEF] 47%, 91% with LGE) followed for a median of 6.3 years, 49 patients (11.2%) experienced the primary outcome. Patients with higher PIZ mass had an increased risk of the primary outcome (10-year risk 0.7%, 24.0% and 37.8% for patients with PIZ mass <5.66g, 5.66–12.28g and ≥12.29g respectively, P<0.001; figure 1a). On univariable analysis, an increase in PIZ mass and core infarct mass was associated with an increased risk of the primary outcome (per gram: HR 1.12, 95% CI 1.09–1.15, P<0.001 and HR 1.05, 95% CI 1.04–1.06, P<0.001 respectively). PIZ mass and core infarct mass remained independently associated with the primary outcome after adjustment for baseline predictors (per gram: HR 1.10, 95% CI 1.06–1.14, P<0.001 and HR 1.04, 95% CI 1.02–1.06, P<0.001 respectively) and together provided incremental value compared to conventional variables in predicting the endpoint (Harrell's C-statistic 0.76 to 0.82, figure 1b-c). Bespoke analysis of imaging data identified several shape-based scar metrics that associated with the primary outcome (figure 2). These included core infarct transmurality, radiality and interface length (the latter defining the core scar-PIZ boundary length), and the number of PIZ islets. Conclusions In this large prospective study of patients with stable CHD, both PIZ mass and core infarct mass independently predicted long-term SCD risk after adjusting for conventional predictors including LVEF. Reassuringly, minimal or absent LGE portended a comparatively low risk of SCD. Analysis of the scar microstructure identified several shape-based features that associated with SCD. These results highlight a potential avenue towards a more personalised approach to ICD implantation decisions. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Lung and Heart Institute, Imperial College London

Intraoperative Predictors of Long-term Outcomes After Radiofrequency Endometrial Ablation

Study ObjectiveTo identify intraoperative predictors of radiofrequency ablation (RFA) failure after adjusting for clinical risk factors. DesignA cohort study (Canadian Task Force II-2). SettingAn academic institution in the Upper Midwest. PatientsData were retrospectively collected from medical records of women who underwent RFA and who had a postprocedure gynecologic assessment between April 1998 and December 2011. InterventionsRFA. Measurements and Main ResultsThe primary outcome was RFA failure, which was defined as hysterectomy, repeat ablation, synechiolysis, or treatment with gonadotropin-releasing hormone analogue for postablation pain or bleeding. Cox proportional hazards regression was used to test the predictability of intraoperative variables on RFA failure with adjustment for baseline predictors. We created an RFA index to capture the procedure duration divided by the uterine surface area. One thousand one hundred seventy-eight women were eligible. The median age at ablation was 44 years (interquartile range, 40–48 years), and the median parity was 2 (interquartile range, 2–3). Dysmenorrhea and prior tubal ligation were reported in 37.1% and 37.2% of women, respectively. After adjustment for baseline characteristics, intraoperative predictors of failure were uterine sounding length >10.5 cm (adjusted hazard ratio [HR] = 2.58; 95% confidence interval [CI], 1.31–5.05), uterine cavity length >6 cm (adjusted HR = 2.06; 95% CI, 1.30–3.27), uterine width >4.5 cm (adjusted HR = 2.06; 95% CI, 1.29–3.28), surface area >25 cm2 (adjusted HR = 2.02; 95% CI, 1.26–3.23), procedure time <93 seconds (adjusted HR = 2.61; 95% CI, 1.25–5.47), and RFA index <3.6 (adjusted HR = 3.14; 95% CI, 1.70–5.77). ConclusionIntraoperative parameters are predictive of long-term adverse outcomes of RFA independent of patient clinical characteristics. Uterine length, procedure duration, and RFA index are associated with unfavorable outcomes and thus could be used to optimize postprocedure patient counseling.

An Evidence-Based Algorithm for the Use of B-Type Natriuretic Testing in Acute Coronary Syndromes

Measurable B-type natriuretic peptides (BNPs), which are largely produced by the left ventricle, include BNP and N-terminal prohormone BNP (NT-proBNP). These proteins are released by cardiomyocytes in response to wall tension and neurohumoral signals, and are established tools in the diagnosis and prognosis of heart failure (HF). We identified 32 articles for entry into evidence tables that presented original data on BNP and/or NT-proBNP in more than 100 patients with acute coronary syndromes (ACS) presenting with chest discomfort with or without dyspnea. Natriuretic peptide (NP) elevation was associated with older age, female sex, hypertension, diabetes, prior HF, prior ischemic heart disease, and reduced renal function. Clinical correlates of elevated blood NP levels included left main or 3-vessel coronary disease, lipid-rich plaques with large necrotic cores in proximal locations, large zones of myocardial ischemia or infarction, no-reflow and impaired perfusion after percutaneous intervention, reduced left ventricular ejection fraction, higher Killip classification, and the development of cardiogenic shock. All studies indicated that after adjustment for baseline predictors and clinical risk scores, elevated NP concentrations were independently predictive of the development of HF and all-cause mortality. In contrast, studies did not consistently demonstrate that NPs were predictive of myocardial infarction and rehospitalization for ACS. In addition to baseline measurement, there is consensus that repeat testing at 4 to 12 weeks and 6 to 12 months in follow-up is helpful in the anticipation of late cardiac sequelae and may assist in assessing prognosis and guiding management.

Associations of major bleeding and myocardial infarction with the incidence and timing of mortality in patients presenting with non-ST-elevation acute coronary syndromes: a risk model from the ACUITY trial

To evaluate the associations of myocardial infarction (MI) and major bleeding with 1-year mortality. Both MI and major bleeding predict 1-year mortality in patients presenting with acute coronary syndrome (ACS). However, the risk of each of these events on the magnitude and timing of mortality has not been well studied. A multivariable Cox regression model was developed relating 13 independent baseline predictors to 1-year mortality for 13 819 patients with moderate and high-risk ACS enrolled in the Acute Catheterization and Urgent Intervention Triage strategy trial. After adjustment for baseline predictors, Cox models with major bleeding and recurrent MI as time-updated covariates estimated the effect of these events on mortality hazard over time. Within 30 days of randomization, 705 patients (5.1%) had an MI, 645 (4.7%) had a major bleed; 524 (3.8%) died within a year. The occurrence of an MI was associated with a hazard ratio of 3.1 compared with patients not yet having an MI, after adjustment for baseline predictors. However, MI within 30 days markedly increased the mortality risk for the first 2 days after the event (adjusted hazard ratio of 17.6), but this risk declined rapidly post-infarct (hazard ratio of 1.4 beyond 1 month after the MI event). In contrast, major bleeding had a prolonged association with mortality risk (hazard ratio of 3.5) which remained fairly steady over time throughout 1 year. After accounting for baseline predictors of mortality, major bleeds and MI have similar overall strength of association with mortality in the first year after ACS. MI is correlated with a dramatic increase in short-term risk, whereas major bleeding correlates with a more prolonged mortality risk.

Adherence to Both Cotrimoxazole and Placebo is Associated with Improved Survival Among HIV-Infected Zambian Children

In the CHAP randomized placebo-controlled trial of cotrimoxazole prophylaxis in HIV-infected Zambian children conducted between 2001 and 2003, cotrimoxazole was associated with significant mortality reductions. In a secondary analysis we used Cox regression models to estimate the association between adherence measured by bottle weights and caregiver report and subsequent mortality in children surviving >28 days (n = 496, 153 deaths). Adherence was high and similar in both cotrimoxazole and placebo groups; adherence from bottle weights was 100% at 71% of visits, while caregivers reported 100% adherence at 79% of visits. Every 10% lower adherence to cotrimoxazole or placebo measured by bottle weights was associated with a 10-11% increase in mortality risk. Effects remained after adjustment for baseline predictors of survival and for current and recent change in primary caregiver. Caregiver-reported adherence was not associated with survival. The association between bottle-weight adherence to placebo and survival is likely capturing unmeasured caregiver effects, whose identification will be essential for quantifying the impact of antiretroviral therapy (ART) adherence on clinical outcomes in children.

Effect of Infectious Diseases on Outcome After Heart Transplant

To determine how often cardiac allograft recipients develop infectious diseases and how the infections affect these patients. We retrospectively studied 313 patients who underwent heart transplant at Mayo Clinic's site in Rochester, MN, from January 1, 1988, through June 30, 2006. In the early postoperative period (ie, period between heart transplant and discharge from the hospital), infectious diseases occurred in 70 (22%) of 313 patients but were not associated with 1-year mortality; the most commonly infected sites were the lungs (7%), bloodstream (6%), upper respiratory tract (5%), and urinary tract (4%). In the 18 years after transplant, the cumulative incidence of infectious diseases was 93%; the most common infectious complications were skin and soft tissue (63%), urinary tract (46%), cytomegalovirus (40%), lung (36%), upper respiratory tract (23%), and varicella zoster virus (15%) infections. After adjustment for baseline predictors, lung (hazard ratio [HR], 3.87; 95% confidence interval [CI], 2.49-6.02; P less than .001) and central nervous system (HR, 4.48; 95% CI, 1.75-11.46; P equals .002) infections were predictive of mortality. Serum creatinine levels (HR, 1.74; 95% CI, 1.07-2.81; P equals .02) and sirolimus use (HR, 2.72; 95% CI, 1.00-7.36; P equals .05) were predictive of lung infection. Death occurred during the study period in 95 (30%) of 313 patients, with a cumulative incidence of 71% at 18 years. The cause of death was infection in 17 (18%) of 95 patients. Early postoperative infectious complications are frequent in cardiac allograft recipients but are not associated with 1-year mortality. Lung and central nervous system infections are predictors of mortality.