Publications by Year: 2020

OBJECTIVE: The Appropriate Use Criteria (AUC) has been used to identify individuals who are likely to benefit from percutaneous coronary intervention (PCI) for stable ischaemic heart disease. However, whether physicians reliably grade PCI appropriateness and whether AUC categories stratify symptomatic improvement in real-world practice are unclear.

METHODS: Patient-reported outcomes measures (PROMs) for angina (Seattle Angina Questionnaire (SAQ-7)), dyspnoea (Rose Dyspnea Scale (RDS)) and depression (Patient Health Questionnaire-2 (PHQ-2)) were collected on patients undergoing elective coronary angiography at an academic medical centre. Retrospectively, two physicians independently determined PCI appropriateness by the AUC criteria.

RESULTS: Inter-rater agreement on appropriateness was moderate (κ=0.48, 95% CI 0.32 to 0.63). Of PCI procedures evaluated, 57 (47.1%) were appropriate (A-PCI), 62 (51.2%) were maybe appropriate (MA-PCI) and 2 (1.6%) were rarely appropriate. At baseline, A-PCI compared with MA-PCI patients had worse RDS scores (2.0 vs 1.2, p=0.01). At 30 days, the change in SAQ-7 summary score was similar between groups (A-PCI vs MA-PCI, +27.1 vs +20.7, p=0.11). The mean change in RDS score was greater in A-PCI than MA-PCI (-1.0 vs -0.5, p for group by time interaction=0.03). PHQ-2 scores were similar and did not improve at 30 days.

CONCLUSION: In patients undergoing PCI with PROMs collected before and 30 days after PCI, similar improvements in angina were observed regardless of appropriateness. Inter-rater agreement on PCI appropriateness was only moderate. Use of PROMs may improve reliability of physician assessments of PCI appropriateness.

BACKGROUND: Whether passively collected data can substitute for adjudicated outcomes to reproduce the magnitude and direction of treatment effect observed in cardiovascular clinical trials is not well known.

METHODS: We linked adults ≥65 years of age in the HiR (US CoreValve Pivotal High Risk) and SURTAVI trials (Surgical or Transcatheter Aortic Valve Replacement in Intermediate-Risk Patients) to 100% Medicare inpatient claims, January 1, 2011, to December 31, 2016. Primary (eg, death and stroke) and secondary trial end points were compared across treatment arms (eg, transcatheter aortic valve replacement [TAVR] versus surgical aortic valve replacement [SAVR]) using trial-adjudicated outcomes versus outcomes derived from claims at 1 year (HiR) or 2 years (SURTAVI).

RESULTS: Among 600 linked HiR participants (linkage rate, 80.0%), the rate of the trial's primary end point of all-cause mortality occurred in 13.7% of patients receiving TAVR and 16.4% of patients receiving SAVR at 1 year by using both trial data (hazard ratio, 0.84 [95% CI, 0.65-1.09]; P=0.33) and claims data (hazard ratio, 0.86 [95% CI, 0.66-1.11]; P=0.34; interaction P value=0.80). Noninferiority of TAVR relative to SAVR was seen by using both trial- and claims-based outcomes (Pnoninferiority<0.001 for both). Among 1005 linked SURTAVI trial participants (linkage rate, 60.5%), the trial's primary end point was 12.9% for TAVR and 13.1% for SAVR using trial data (hazard ratio, 1.08 [95% CI, 0.79-1.48]; P=0.90), and 11.3% for TAVR and 12.5% for SAVR patients using claims data (hazard ratio, 1.02 [95% CI, 0.73-1.41]; P=0.58; interaction P value=0.89). TAVR was noninferior to SAVR when compared using both trial and claims (Pnoninferiority<0.001 for both). Rates of procedural secondary outcomes (eg, aortic valve reintervention, pacemaker rates) were more closely concordant between trial and claims data than nonprocedural outcomes (eg, stroke, bleeding, cardiogenic shock).

CONCLUSIONS: In the HiR and SURTAVI trials, ascertainment of trial primary end points using claims reproduced both the magnitude and direction of treatment effect in comparison with adjudicated event data, but nonfatal and nonprocedural secondary outcomes were not as well reproduced. Use of claims to substitute for adjudicated outcomes in traditional trial treatment comparisons may be valid and feasible for all-cause mortality and certain procedural outcomes but may be less suitable for other end points.

To evaluate the relation of aortic regurgitation (AR) pressure half-time (PHT) on transthoracic echocardiography (TTE) and all-cause mortality, we screened 118,647 baseline TTE reports from 2000 to 2017, to identify patients with any AR and PHT data. Patients with infective endocarditis or previous aortic valve replacement were excluded. The relation of baseline PHT on time to all-cause mortality was evaluated using Cox regression. A total of 2,653 patients were included (73.1 ± 14.3 years; 53.8% female; PHT, 530 ± 162 ms). Patients with shorter PHTs more frequently had 3-4+ AR (PHT ≤ 200 ms vs > 500 ms, 17.9% vs 0.6%, p < 0.0001). Diastolic parameters (E/e', E/A ratio, mitral valve deceleration time, and pulmonary artery systolic pressure) all significantly correlated with PHT (all p < 0.05). Over a median (IQR) follow-up of 8 (4 to 11 years), there were 799 (30.1%) deaths at a median (IQR) of 1.9 (0.4 to 4.3) years. On a univariate basis, a PHT ≤ 320 ms or > 750 ms was significantly related to increased mortality, even amongst those with nonsevere AR. After multivariable adjustment (in particular for E/e'), PHT was no longer significantly related to death. In conclusion, in this large, single center, retrospective study, AR PHT was not independently related to mortality. While a PHT ≤ 320 ms was associated with increased mortality in patients without severe AR, this relation was no longer significant after adjusting for diastolic functional variables. Thus, a PHT ≤ 320 ms in patients without significant AR may indicate prognostically-relevant diastolic dysfunction.

OBJECTIVES: The aim of this study was to evaluate the performance of administrative claims in ascertaining trial clinical events committee-adjudicated outcomes in the U.S. CoreValve studies.

BACKGROUND: Real-world data offer tremendous opportunity to improve outcome ascertainment in clinical trials. However, little is known about the validity of outcomes ascertained using real-world data to capture trial endpoints.

METHODS: Patients enrolled in 3 pivotal trials and 2 pre-market continued-access studies evaluating transcatheter aortic valve replacement were linked to Medicare fee-for-service inpatient claims. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa agreement statistic of claims to detect clinical endpoints and procedural complications in trial patients were calculated.

RESULTS: Claims accurately identified trial-adjudicated deaths (sensitivity, specificity, PPV, and NPV all >99.6%; kappa 1.00). Claims had good performance in identifying trial-adjudicated permanent pacemaker implantation (sensitivity 92.2%, specificity 99.1%, PPV 96.1%, NPV 98.2%, kappa 0.93) and aortic valve reintervention (sensitivity 84.4%, specificity 99.6%, PPV 69.1%, NPV 99.8%, kappa 0.76). Claims had more modest performance in ascertaining trial-adjudicated myocardial infarction (sensitivity 63.6%, specificity 97.2%, PPV 29.9%, NPV 99.3%, kappa 0.39) and acute kidney injury (sensitivity 70.2%, specificity 85.4%, PPV 38.2%, NPV 95.7%, kappa 0.41) and the poorest performance for identifying trial-adjudicated bleeding events (sensitivity 86.4%, specificity 36.8%, PPV 35.0%, NPV 86.3%, kappa 0.16).

CONCLUSIONS: Compared with trial-adjudicated outcomes, claims data performed well in ascertaining death and outcomes with procedural billing codes and more modestly in identifying other outcomes. Claims may be cautiously and selectively used to augment data collection in future cardiovascular device trials.

BACKGROUND: Ultrasound enhancing agents (UEAs) are routinely used to improve transthoracic echocardiographic (TTE) image quality, yet anticipation of UEA need is a barrier to their use.

METHODS: Structured report data from 171,509 consecutive TTE studies in 97,515 patients who underwent TTE imaging from January 26, 2000, to September 20, 2018, were analyzed. Trends in UEA use and suboptimal image quality were examined. Among outpatients (92,291 TTE examinations, n = 56,479), the data set was randomly split into a 75% derivation sample and a 25% validation sample. Logistic regression was used to model the composite of either UEA receipt or suboptimal image quality (two or more nonvisualized segments) using only variables available at the start of the TTE examination. Model performance was tested in the validation sample.

RESULTS: A total of 4,444 TTE examinations (2.6%) in 3,827 patients (3.9%) involved UEAs, and 28,468 TTE examinations (16.6%) in 21,994 patients (22.5%) were suboptimal. UEA use increased over the observation period. Among TTE studies with suboptimal image quality, UEA use was lower in women (P < .0001). Among outpatients referred for TTE imaging, older age, greater weight, and higher heart rate best predicted UEA use or suboptimal image quality. Model performance in the validation sample was excellent (C statistic = 0.74 [95% CI, 0.73-0.75]; calibration slope = 1.11 [95% CI, 1.06-1.15]).

CONCLUSIONS: In this large, single-center, retrospective study, UEA use remained substantially below rates of suboptimal image quality, despite increases over time. Among outpatients, a simple prediction rule using three routinely collected variables available before TTE image acquisition predicted potential benefit from UEAs with high accuracy. If confirmed in other cohorts, this rule may be used to identify patients who may benefit from intravenous placement for UEA administration before TTE image acquisition, thus potentially improving work-flow efficiency.

BACKGROUND: Patients with symptomatic and asymptomatic heart failure undergoing noncardiac surgery may benefit from the haemodynamic profile of etomidate. However, the safety of etomidate in this population is unknown. We examined anaesthesiologist variation in etomidate use and assessed its safety using an instrumental variable approach to account for differences in treatment selection.

METHODS: A retrospective cohort study of 19 714 patients with heart failure undergoing noncardiac surgery at two tertiary care institutions from January 2006 to December 2017 was performed. The proportion of etomidate use among 294 anaesthesiologists was examined and adjusted risk differences (aRD) for in-hospital and 30-day mortality were calculated using physician preference for etomidate as an instrumental variable.

RESULTS: Etomidate was used in 14.3% (2821/19 714) of patients. Preference for etomidate varied substantially among individual anaesthesiologists with the lowest and highest quartile users using etomidate in 0-4.7% and 20.4-66.7% of their own heart failure patients, respectively. The adjusted instrumental variable analysis showed no significant differences in the risk of in-hospital (aRD -0.2%; 95% confidence interval, -2.4%-1.9%; P=0.83) or 30 day mortality (aRD 0.2%; 95% confidence interval, -2.5%-2.9%; P=0.90). Anaesthesiologists with higher preferences for etomidate were more experienced (greater heart failure and total case volume) than anaesthesiologists with lower preferences for etomidate.

CONCLUSIONS: We found substantial variability in anaesthesiologists' preference for etomidate for use in patients with heart failure undergoing noncardiac surgery. There was no association between etomidate use and in-hospital or 30-day mortality. Etomidate is not inferior to other currently used options for induction of general anaesthesia in patients with heart failure.

BACKGROUND: Limited data exist on the differential ability of variables on transthoracic echocardiogram (TTE) to predict heart failure (HF) readmission across the spectrum of left ventricular (LV) systolic function.

METHODS: We linked 15 years of TTE report data (1/6/2003-5/3/2018) at Beth Israel Deaconess Medical Center to complete Medicare claims. In those with recent HF, we evaluated the relationship between variables on baseline TTE and HF readmission, stratified by LVEF.

RESULTS: After excluding TTEs with uninterpretable diastology, 5,900 individuals (mean age: 76.9 years; 49.1% female) were included, of which 2545 individuals (41.6%) were admitted for HF. Diastolic variables augmented prediction compared to demographics, comorbidities, and echocardiographic structural variables (p < 0.001), though discrimination was modest (c-statistic = 0.63). LV dimensions and eccentric hypertrophy predicted HF in HF with reduced (HFrEF) but not preserved (HFpEF) systolic function, whereas LV wall thickness, NT-proBNP, pulmonary vein D- and Ar-wave velocities, and atrial dimensions predicted HF in HFpEF but not HFrEF (all interaction p < 0.10). Prediction of HF readmission was not different in HFpEF and HFrEF (p = 0.93).

CONCLUSIONS: In this single-center echocardiographic study linked to Medicare claims, left ventricular dimensions and eccentric hypertrophy predicted HF readmission in HFrEF but not HFpEF and left ventricular wall thickness predicted HF readmission in HFpEF but not HFrEF. Regardless of LVEF, diastolic variables augmented prediction of HF readmission compared to echocardiographic structural variables, demographics, and comorbidities alone. The additional role of medication adherence, readmission history, and functional status in differential prediction of HF readmission by LVEF category should be considered for future study.