Lee, Kerry L.

Background: Evaluation of obese patients with suspected CAD is challenging because obesity is a CV risk factor, but adiposity itself may mimic symptoms of CAD and reduce the accuracy of diagnostic testing. Optimal testing strategies in obese patients are not known. Methods: Patients with stable symptoms suggestive of cardiac ischemia from the PROMISE trial (n=9230) were classified according to BMI. Providers specified a functional test modality prior to stratified randomization to functional (stress testing) or anatomical (CTA) testing. We assessed relationships between BMI, physician’s preference of functional test, test positivity and results of catheter angiography (cath) using logistic regression. Results: Providers were more likely to choose SPECT over other functional tests as BMI increased (OR 1.04 per unit increase in BMI above 27, p<0.001). In patients with BMI ≥ 35 vs. < 35, the rate of positivity with CTA was similar (10% vs. 12%; see Table). The same was true for stress echo and stress ECG (positivity 8-13%, p>0.8 for both). In contrast, SPECT was significantly more likely to be positive in those with BMI ≥ 35 vs. <35 (18% vs. 13%; p=0.001). The likelihood of finding obstructive CAD at cath did not differ with BMI ≥ 35 vs. <35 in patients having CTA (59% vs. 52%, p=0.22), but among SPECT patients, positivity was only 29% with BMI ≥ 35 compared to 52% with BMI < 35 (p=0.005; Table). Conclusions: Increasing levels of obesity were associated with stronger physician preference for SPECT over other noninvasive tests. In patients receiving SPECT, higher levels of obesity were associated with a higher rate of positive results, but a lower cath yield for obstructive CAD. In contrast, in patients receiving CTA, positivity rates and cath yield did not vary by BMI. Obesity appears to significantly influence provider decision-making with regard to noninvasive test choice, probability of abnormal test results and probability of finding obstructive disease at cath.

Background Women with atrial fibrillation (AF) demonstrate more AF‐related symptoms and worse quality of life (QOL). Whether increased use of ablation in women reduces sex‐related QOL differences is unknown. Sex‐related outcomes for ablation versus drug therapy was a prespecified analysis in the CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial. Methods and Results Symptoms were assessed periodically over 60 months with the Mayo AF‐Specific Symptom Inventory (MAFSI) frequency score, and QOL was assessed with the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary and component scores. Women had lower baseline QOL scores than men (mean AFEQT scores 55.9 and 65.6, respectively). Ablation patients improved more than drug therapy patients with similar treatment effect by sex: AFEQT 12‐month mean adjusted treatment difference in women 6.1 points (95% CI, 3.5–8.6) and men 4.9 points (95% CI, 3.0–6.9). Participants with baseline AFEQT summary scores <70 had greater QOL improvement, with a mean treatment difference at 12 months of 7.6 points for women (95% CI, 4.3–10.9) and 6.4 points for men (95% CI, 3.3–9.4). The mean adjusted difference in MAFSI frequency score between women randomized to ablation versus drug therapy at 12 months was −2.5 (95% CI, −3.4 to −1.6); for men, the difference was −1.3 (95% CI, −2.0 to −0.6). Conclusions Compared with drug therapy for AF, ablation resulted in more QOL improvement in both sexes, primarily driven by improvements in those with lower baseline QOL. Ablation did not eliminate the AF‐related QOL gap between women and men. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00911508.

Background: In the CABANA trial (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation), catheter ablation did not significantly reduce the primary end point of death, disabling stroke, serious bleeding, or cardiac arrest compared with drug therapy by intention-to-treat, but did improve the quality of life and freedom from atrial fibrillation recurrence. In the heart failure subgroup, ablation improved both survival and quality of life. Cost-effectiveness was a prespecified CABANA secondary end point. Methods: Medical resource use data were collected for all CABANA patients (N=2204). Costs for hospital-based care were assigned using prospectively collected bills from US patients (n=1171); physician and medication costs were assigned using the Medicare Fee Schedule and National Average Drug Acquisition Costs, respectively. Extrapolated life expectancies were estimated using age-based survival models. Quality-of-life adjustments were based on EQ-5D–based utilities measured during the trial. The primary outcome was the incremental cost-effectiveness ratio, comparing ablation with drug therapy on the basis of intention-to-treat, and assessed from the US health care sector perspective. Results: Costs in the first 3 months averaged $20 794±SD 1069 higher with ablation compared with drug therapy. The cumulative within-trial 5-year cost difference was $19 245 (95% CI, $11 360–$27 170) and the lifetime mean cost difference was $15 516 (95% CI, –$2963 to $35,512) higher with ablation than with drug therapy. The drug therapy arm accrued an average of 12.5 life-years (LYs) and 10.7 quality-adjusted life-years (QALYs). For the ablation arm, the corresponding estimates were 12.6 LYs and 11.0 QALYs. The incremental cost-effectiveness ratio was $57 893 per QALY gained, with 75% of bootstrap replications yielding an incremental cost-effectiveness ratio < $100 000 per QALY gained. With no quality-of-life/utility adjustments, the incremental cost-effectiveness ratio was $183 318 per LY gained. Conclusions: Catheter ablation of atrial fibrillation was economically attractive compared with drug therapy in the CABANA Trial overall at present benchmarks for health care value in the United States on the basis of projected incremental QALYs but not LYs alone.

Abstract Aims Influence of atrial fibrillation (AF) type on outcomes seen with catheter ablation vs. drug therapy is incompletely understood. This study assesses the impact of AF type on treatment outcomes in the Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA). Methods and results CABANA randomized 2204 patients ≥65 years old or &lt;65 with at least one risk factor for stroke to catheter ablation or drug therapy. Of these, 946 (42.9%) had paroxysmal AF (PAF), 1042 (47.3%) had persistent AF (PersAF), and 215 (9.8%) had long-standing persistent AF (LSPAF) at baseline. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Symptoms were measured with the Mayo AF-Specific Symptom Inventory (MAFSI), and quality of life was measured with the Atrial Fibrillation Effect on Quality of Life (AFEQT). Comparisons are reported by intention to treat. Compared with drug therapy alone, catheter ablation produced a 19% relative risk reduction in the primary endpoint for PAF {adjusted hazard ratio [aHR]: 0.81 [95% confidence interval (CI): 0.50, 1.30]}, and a 17% relative reduction for PersAF (aHR: 0.83, 95% CI: 0.56, 1.22). For LSPAF, the ablation relative effect was a 7% reduction (aHR: 0.93, 95% CI: 0.36, 2.44). Ablation was more effective than drug therapy at reducing first AF recurrence in all AF types: by 51% for PAF (aHR: 0.49, 95% CI: 0.39, 0.62), by 47% for PersAF (aHR: 0.53, 95% CI: 0.43,0.65), and by 36% for LSPAF (aHR 0.64, 95% CI 0.41,1.00). Ablation was associated with greater improvement in symptoms, with the mean difference between groups in the MAFSI frequency score favouring ablation over 5 years of follow-up in all subgroups: PAF had a clinically significant −1.9-point difference (95% CI: −1.2 to −2.6); PersAF a −0.9 difference (95% CI: −0.2 to −1.6); LSPAF a clinically significant difference of −1.6 points (95% CI: −0.1 to −3.1). Ablation was also associated with greater improvement in quality of life in all subgroups, with the AFEQT overall score in PAF patients showing a clinically significant 5.3-point improvement (95% CI: 3.3 to 7.3) over drug therapy alone over 5 years of follow-up, PersAF a 1.7-point difference (95% CI: 0.0 to 3.7), and LSPAF a 3.1-point difference (95% CI: -1.6 to 7.8). Conclusion Prognostic treatment effects of catheter ablation compared with drug therapy on the primary and major secondary clinical endpoints did not differ consequentially by AF subtype. With regard to decreases in AF recurrence and improving quality of life, ablation was more effective than drug therapy in all three AF type subgroups. ClinicalTrials.gov Identifier NCT00911508

Background. ICD implantation for primary prevention of sudden death in patients with ischemic cardiomyopathy and left ventricular dysfunction is well established. However debate exists between the relationship between ischemia and the proarrhythmic state. Persistent ischemia may counter antiarrhythmic (AA) drug and/or device efficacy. Furthermore, the extent to which revascularization mitigates this influence of ischemia on efficacy is unknown. Methods . 704 patients enrolled in the MUSTT trial were studied. Ischemia was determined by the presence of angina within 6 weeks of enrollment and ≥ 2 reversible thallium defects. Revascularization was characterized as CABG or PTCA within 1 year of enrollment or the use of thrombolytics with the sentinal myocardial infarction (MI). We compared groups who were randomized to background medical treatment (BG Rx) verses those who were randomized to AA drug therapy in addition to EP testing (EP AARx). Results . 507 (81%) patients had ≤2 vessel CAD, whereas the remaining 19% had 3 vessel disease. 268 patients reported angina within 6 weeks of study enrollment. Thallium imaging revealed 0–1 defects in 458 (65%) and ≥2 in another 246 (35%). Those with ≥ 2 defects on Thallium and angina within 6 weeks of device implant had a significantly lower 5-year freedom from mortality in the EP AARx and BG Rx cohorts (Table ). Patients with EP AARx had an 8% lower mortality than those with BG Rx therapy alone if they received thrombolytics. However, if they did not receive thrombolytics, their mortality rate was 5% higher than the BG Rx group. Conclusion . Outcomes are worse in patients on antiarrhythmic therapy with ischemic factors compared to those on background therapy alone, particularly in the setting of recent angina. A proarrhythmic effect from antiarrhythmic drug therapy in patients with ischemia may underlie the higher mortality. ICD therapy mitigates the negative long-term effect of ischemia on mortality in those treated with AA therapy. Five Year Freedom from Mortality

Objectives To test the relationship between increasing severity of obesity, calculated risk and observed outcomes. Methods Patients with symptoms suggestive of coronary artery disease (CAD) (n=10 003) were stratified according to body mass index (BMI). We compared risk factors, pooled risk scores and physicians’ perception of risk. Cox regression tested the association between BMI and (1) presence of obstructive CAD and (2) composite clinical endpoints (death, cardiovascular death, unstable angina hospitalisation and myocardial infarction). Results BMI was ≥30 kg/m2 in 48% of patients and ≥35 in 20%. Increasingly obese patients were younger, female and non-smoking but with higher prevalence of hypertension, diabetes, black race and sedentary lifestyle. Pooled risk estimates of CAD were highest in those with mid-range BMI. In contrast, physicians’ estimation of the likelihood of significant CAD based on clinical impression increased progressively with BMI. For a 10% increase in the Diamond-Forrester probability of CAD, the adjusted OR for obstructive CAD was 1.5 (95% CI 1.4 to 1.5) in patients with BMI <35, but only 1.2 (95% CI 1.1 to 1.3) in those with BMI ≥35 (interaction p<0.001). Framingham Risk Score increased across increasing BMI categories. However, there was a strong and consistent inverse relationship between degree of obesity and all three composite clinical endpoints over a median 25 months of follow-up. Conclusions Despite perceptions of higher risk and higher risk scores, increasingly obese patients had obstructive CAD less frequently than predicted and had fewer adverse clinical outcomes. There is a need for risk assessment tools and guidelines that account for obesity. Trial registration number NCT01174550.