Weintraub, William S.

Abstract Background and Aims A simple diagnostic method able to reliably exclude left main (LM) coronary artery disease (CAD) or LMCAD-equivalent would expand implementation of an initial non-invasive strategy in patients with chronic coronary syndrome (CCS). This study assessed the diagnostic utility of an approach using clinical and ECG stress testing (EST) variables in excluding LMCAD/LMCAD-equivalent in CCS patients. Methods In a multicentre case-control study, CCS patients undergoing invasive coronary angiography (CAG) after a maximal EST were evaluated. Cases were patients with angiographic ≥ 50% LM stenosis or ≥70% stenosis of both proximal left anterior descending and proximal circumflex arteries, matched with similar patients without them (controls) in a 1:3 ratio. A risk model developed through logistic regression was internally and externally validated. Results Three hundred and thirty-five cases were matched with 797 controls. The model area under the curve (AUC) was .78. Assuming LMCAD prevalence of 5% and a misclassification cost ratio of 1:100 (ratio of cost of performing CAG in a control to cost of not performing CAG in a case), negative predictive value was 98.2%. Thus, CAG could be safely avoided in 41% of patients, missing one LMCAD/LMCAD-equivalent diagnosis for every 58 CAGs safely spared in patients without them. Conclusions Among CCS patients, LMCAD/LMCAD-equivalent can be excluded with high negative predictive value through a model based on clinical and EST parameters, allowing initial non-invasive management of most patients able to exercise. This approach is potentially useful particularly in communities where access to computed tomography coronary angiography is limited.

Importance Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. Objective To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. Design, Setting, and Participants A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. Exposures Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. Main Outcomes and Measures The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy–related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. Results Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro–B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate ( P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). Conclusions and Relevance These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. Trial Registration ClinicalTrials.gov Identifier: NCT01915615

Background: One month following a myocardial infarction (MI), more than a third of older adults (age ≥65 years) are frail as demonstrated by slow gait speed (≤ 0.65 m/sec). The prognostic significance of frailty in a cardiovascular population in terms of future health states is unknown. Methods: The TRIUMPH longitudinal registry enrolled 1314 older adults (age ≥65 years) following an acute MI from 24 US centers. Gait speed (m/sec) was determined at one month (to allow for acute recovery) in 329 patients with in-home follow up. Using averages of 3 timed walks over 15-feet, patients were stratified by gait speed into 2 groups: slow (<0.65m/sec) and preserved (≥0.65m/sec). One year basic (mobility, self care) and instrumental activities of daily living (ADL) (phone, meds, travel, money), physical function score (SF12 PCS), quality of life (Seattle Angina Questionnaire (SAQ)), and mortality were assessed. Results: Slow gait speed was present in 38% (N=126) of older adults at 1 month. At 1 year, despite similar survival, frail adults were much more likely to need help with basic and instrumental (ADL), and had lower physical function and quality of life (QOL) compared to non-frail adults. ( table ) Slower gait speed remained a significant predictor of worse physical function at 1 year after adjustment for baseline physical function (p=0.013). Conclusions: Frailty is common in older adults following an MI, and those with frailty are at substantial risk for continued impairment over time. Understanding the mechanisms or reversibility of this vulnerable state would contribute to optimization of independence and quality of life among older adults with cardiovascular disease. Frailty Post MI and 1 Year Outcomes Frail (Gait <0.65m/sec)N=126 Not Frail (Gait ≥0.65m/sec)N=203 P value Mobility ADL (% need help) 45 23 <0.001 Self-Care ADL (% need help) 11 4 <0.001 Instrumental ADLs (% need help) 36 19 0.003 Physical Function (PCS) 39.2 ± 12.0 47.2 ± 9.7 <0.001 SAQ Quality of Life (QOL) 88.0 ± 15.9 91.3 ± 12.1 0.061 Mortality (%) 5.6 4.5 NS

Background Assessing hospital quality in the performance of carotid endarterectomy ( CEA ) requires appropriate risk adjustment across hospitals with varying case mixes. The aim of this study was to develop and validate a prediction model to assess the risk of in‐hospital stroke or death after CEA that could aid in the assessment of hospital quality. Methods and Results Patients from National Cardiovascular Data Registry (NCDR)'s Carotid Artery Revascularization and Endarterectomy (CARE) Registry undergoing CEA without acute evolving stroke from 2005 to 2013 were included. In‐hospital stroke or death was modeled using hierarchical logistic regression with 20 candidate variables and accounting for hospital‐level clustering. Internal validation was achieved with bootstrapping; model discrimination and calibration were assessed. A total of 213 (1.7%) primary end point events occurred during 12 889 procedures. Independent predictors of stroke or death included age, prior peripheral artery disease, diabetes mellitus, prior coronary artery disease, having a symptomatic carotid lesion, having a contralateral carotid occlusion, or having New York Heart Association Class III or IV heart failure. The model was well calibrated and demonstrated moderate discriminative ability (c‐statistic 0.65). The NCDR CEA score was then developed to support simple, prospective risk quantification in the clinical setting. Conclusions The NCDR CEA score, comprising 7 clinical variables, predicts in‐hospital stroke or death after CEA . This model can be used to estimate hospital risk‐adjusted outcomes for CEA and to assist with the assessment of hospital quality.

Background Although an inverse relation between physician caseload and complications has been conclusively demonstrated for several surgical procedures, such data are lacking for percutaneous coronary intervention, and the ACC/AHA guidelines requiring ≥75 cases per year for operator “competency” are considered by some physicians to be arbitrary. Methods and Results From quality-controlled databases at five high-volume centers, models predictive of death and the composite outcome of death, Q-wave infarction, or emergency bypass surgery were developed from 12 985 consecutively treated patients during 1993 through 1994. Models had moderate to high discriminative capacity (area under ROC curves, 0.65 to 0.85), were well calibrated, and were not overfitted by standard tests. These models were used for risk adjustment, and the relations between both yearly caseload and years of interventional experience and the two adverse outcome measures were explored for all 38 physicians with ≥30 cases per year. The average physician performed a mean±SD of 163±24 cases per year and had been practicing angioplasty for 8±5 years. Risk-adjusted measures of both death and the composite adverse outcome were inversely related to the number of cases each operator performed annually but bore no relation to total years of experience. Both adverse outcomes were more closely related to the logarithm of caseload (for death, r =.37, P =.01; for death, Q-wave infarction, or bypass surgery, r =.58, P <.001) than to linear caseload. Conclusions In this analysis, high-volume operators had a lower incidence of major complications than did lower-volume operators, but the difference was not consistent for all operators. If these data are validated, their implications for hospital, physician, and payer policy will require exploration.

Background— Restenosis after implantation of coronary artery stents remains a significant clinical problem. We undertook a randomized, double-blind, placebo-controlled trial to determine whether cilostazol, a drug that suppresses intimal proliferation, would reduce renarrowing in patients after stent implantation in native coronary arteries. Methods and Results— We assigned 705 patients who had successful coronary stent implantation to receive, in addition to aspirin, cilostazol 100 mg BID or placebo for 6 months; clopidogrel 75 mg daily was administered to all patients for 30 days. Restenosis was determined by quantitative coronary angiography at 6 months. The minimal luminal diameter at 6 months for cilostazol-treated patients was 1.77 mm for the analysis segment (stent plus 5-mm borders) compared with 1.62 mm in the placebo group ( P =0.01). Restenosis, defined as ≥50% narrowing, occurred in 22.0% of patients in the cilostazol group and in 34.5% of the placebo group ( P =0.002), a 36% relative risk reduction. Restenosis was significantly lower in cilostazol-treated diabetics (17.7% versus 37.7%, P =0.01) and in those with small vessels (23.6% versus 35.2%, P =0.02), long lesions (29.9% versus 46.6%, P =0.04), and left anterior descending coronary artery site (19.3% versus 39.8%, P =0.001). There was no difference in bleeding, rehospitalization, target-vessel revascularization, myocardial infarction, or death. Conclusions— Treatment with the drug cilostazol resulted in a significantly larger minimal luminal diameter and a significantly lower binary restenosis rate compared with placebo-treated patients. These favorable effects were apparent in patients at high risk for restenosis.