Citations

Background: Prophylactic exclusion of the left atrial appendage (LAA) is often performed during cardiac surgery ostensibly to reduce the risk of stroke. However, the clinical impact of LAA closure in humans remains inconclusive. Methods: Of 10 633 adults who underwent coronary artery bypass grafting and valve surgery between January 2000 and December 2005, 9792 patients with complete baseline characteristics, surgery procedure, and follow-up data were included in this analysis. A propensity score–matching analysis based on 28 pretreatment covariates was performed and 461 matching pairs were derived and analyzed to estimate the association of LAA closure with early postoperative atrial fibrillation (POAF) (atrial fibrillation ≤30 days of surgery), ischemic stroke, and mortality. Results: In the propensity-matched cohort, the overall incidence of POAF was 53.9%. In this group, the rate of early POAF among the patients who underwent LAA closure was 68.6% versus 31.9% for those who did not undergo the procedure ( P <0.001). LAA closure was independently associated with an increased risk of early POAF (adjusted odds ratio, 3.88; 95% confidence interval, 2.89–5.20), but did not significantly influence the risk of stroke (adjusted hazard ratio, 1.07; 95% confidence interval, 0.72–1.58) or mortality (adjusted hazard ratio, 0.92; 95% confidence interval, 0.75–1.13). Conclusions: After adjustment for treatment allocation bias, LAA closure during routine cardiac surgery was significantly associated with an increased risk of early POAF, but it did not influence the risk of stroke or mortality. It remains uncertain whether prophylactic exclusion of the LAA is warranted for stroke prevention during non–atrial fibrillation-related cardiac surgery.

Abstract Clinical trial Data and Safety Monitoring Boards (DSMBs) have a primary obligation of ensuring study participant safety, while maintaining trial integrity. The role of DSMBs is expanding, and ideally should include post-hoc reporting of deliberative processes related to clinically important safety issues or factors that could impact on future trial designs. We describe how the TOPCAT DSMB detected, investigated, and adjudicated an unexpectedly large renal adverse event signal midway through the trial, and offer general guidelines for dealing with similar unanticipated occurrences in future trials. The detection of a greater than expected incidence of deterioration in renal function, occurring in 6.1% of patients in the spironolactone arm compared with 3.9% in the placebo arm (P = 0.009), led to an in-depth DSMB review of associated study medication withdrawals and adverse events. The trial continued uninterrupted throughout the review, which reached the conclusions that spironolactone-associated renal dysfunction did not compromise overall patient safety or interfere with a perceived efficacy signal. Although no discrete mechanism for the spironolactone-associated renal adverse event signal was identified, likely possibilities are discussed. In clinical trials, DSMBs and co-ordinating centres should have the resources to detect, investigate, and adjudicate unexpected safety issues, with goals of ensuring patient safety and preserving the potential for detection of therapeutic effectiveness. In TOPCAT, spironolactone-associated renal dysfunction emerged as a potentially trial-threatening adverse event and, although clinically important, did not lead to compromise of patient safety, trial interruption, termination, or apparent loss of treatment effectiveness.

A 70-year-old man presented with recent onset, predominantly right-sided heart failure. Echocardiogram demonstrated features of hypertensive heart disease and was suggestive of, but non-diagnostic for, constrictive pericarditis (CP). CT demonstrated mild pericardial thickening. Right heart catheterisation showed elevation and equalisation of diastolic pressures in all cardiac chambers with early rapid filling, minimal ventricular interdependence, and no dissociation of intrathoracic and intracardiac pressures. While several features pointed towards CP, the minimal ventricular interdependence and no dissociation of intrathoracic and intracardiac pressures suggested other pathology. Diagnostic pericardiectomy was performed, after which the central venous pressure decreased from 22 to 12 mm Hg. Pathology revealed pericardial fibrosis. The patient experienced sustained resolution of his heart failure. A potential explanation for lack of CP criteria was the presence of hypertensive heart disease. CP needs to be considered when approaching patients with heart failure as diagnostic evaluation can be multifaceted and treatment curative.

Background While atrial fibrillation is a recognized risk factor for stroke, contemporary data on trends in stroke incidence after the diagnosis of atrial fibrillation are scarce. Methods and Results Olmsted County, MN residents with incident atrial fibrillation or atrial flutter (collectively referred to as AF ) from 2000 to 2010 were identified. Cox regression determined associations of year of AF diagnosis with ischemic stroke and transient ischemic attack ( TIA ) occurring through 2013. Among 3247 AF patients, 321 (10%) had an ischemic stroke/ TIA over a mean of 4.6 years (incidence rate [95% CI ] per 100 person‐years: 2.14 [1.91–2.38]). Two hundred thirty‐nine (7%) of 3265 AF patients experienced an ischemic stroke (incidence rate: 1.54 [1.35–1.75]). The risk of both outcomes remained unchanged over time after adjusting for demographics and comorbidities (hazard ratio [95% CI ] per year of AF diagnosis: 1.00 [0.96–1.04] for ischemic stroke/ TIA ; 1.01 [0.96–1.06] for ischemic stroke only). In analyses restricted to patients with prescription information, the rates of anticoagulation use did not change over time, reaching 50.8% at 1 year after AF diagnosis. Further adjustment for anticoagulation use did not alter the temporal trends in stroke incidence (hazard ratio [95% CI ] per year of AF diagnosis: 1.06 [0.97–1.15] for ischemic stroke/ TIA ; 1.08 [0.98–1.20] for ischemic stroke only). Conclusions Strokes/ TIA s are frequent after AF , occurring in 10% of patients after 5 years of follow‐up. The occurrence of stroke/ TIA did not decline over the last decade, which may be influenced by a leveling off of anticoagulation use. This concerning trend has major public health implications.

Background Whereas insurance status has been previously associated with care patterns, little is currently known about the association between Medicaid insurance and the clinical characteristics, treatment, or outcomes of patients with atrial fibrillation ( AF ). Methods and Results We used data from adults with AF enrolled in the Outcomes Registry for Better Informed Treatment of AF ( ORBIT ‐ AF ), a national outpatient registry conducted at 176 community, multispecialty sites. The primary outcome of interest was the proportion of patients prescribed any oral anticoagulation ( OAC ; warfarin or novel oral anticoagulants [ NOAC ]). Secondary outcomes of interest included the proportion of patients prescribed NOAC s (dabigatran or rivaroxaban); time in therapeutic range ( TTR ) for warfarin users, all‐cause mortality, stroke/systemic embolism, and major bleed. Of 10 133 patients, N=470 (4.6%) had Medicaid insurance. Medicaid patients were similarly likely to receive OAC at baseline (72.8% vs 76.3%; unadjusted P =0.079), but less likely to receive NOAC at baseline or follow‐up (12.1% vs 16.3%; unadjusted P =0.019). After risk adjustment, Medicaid status was associated with lower use of OAC at baseline among patients with high stroke risk (odds ratio [ OR ]=0.68; 95% CI =0.49, 0.94), but was not associated with OAC use overall ( OR =0.82; 95% CI =0.61, 1.09). Among warfarin users, median TTR was lower among Medicaid patients (60% vs 68%; P <0.0001; adjusted TTR difference, −2.9; 95% CI =−5.7, −0.2; P =0.04). Use of an NOAC over 2 years of follow‐up was not statistically different by insurance. Compared with non‐Medicaid patients, Medicaid patients had higher unadjusted rates of mortality, stroke/systemic embolism, and major bleeding; however, these differences were attenuated following adjustment for clinical characteristics. Conclusions In a contemporary AF cohort, use of OAC overall and use of NOAC s were not significantly lower among Medicaid patients relative to others. However, among warfarin users, Medicaid patients spent less time in therapeutic range compared with those with other forms of insurance.