John Ehrlinger

Unexpected Abrupt Increase in Left Ventricular Assist Device Thrombosis

BACKGROUND We observed an apparent increase in the rate of device thrombosis among patients who received the HeartMate II left ventricular assist device, as compared with preapproval clinical-trial results and initial experience. We investigated the occurrence of pump thrombosis and elevated lactate dehydrogenase (LDH) levels, LDH levels presaging thrombosis (and associated hemolysis), and outcomes of different management strategies in a multi-institutional study. METHODS We obtained data from 837 patients at three institutions, where 895 devices were implanted from 2004 through mid-2013; the mean (±SD) age of the patients was 55±14 years. The primary end point was confirmed pump thrombosis. Secondary end points were confirmed and suspected thrombosis, longitudinal LDH levels, and outcomes after pump thrombosis. RESULTS A total of 72 pump thromboses were confirmed in 66 patients; an additional 36 thromboses in unique devices were suspected. Starting in approximately March 2011, the occurrence of confirmed pump thrombosis at 3 months after implantation increased from 2.2% (95% confidence interval [CI], 1.5 to 3.4) to 8.4% (95% CI, 5.0 to 13.9) by January 1, 2013. Before March 1, 2011, the median time from implantation to thrombosis was 18.6 months (95% CI, 0.5 to 52.7), and from March 2011 onward, it was 2.7 months (95% CI, 0.0 to 18.6). The occurrence of elevated LDH levels within 3 months after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within the weeks before diagnosis. Thrombosis was managed by heart transplantation in 11 patients (1 patient died 31 days after transplantation) and by pump replacement in 21, with mortality equivalent to that among patients without thrombosis; among 40 thromboses in 40 patients who did not undergo transplantation or pump replacement, actuarial mortality was 48.2% (95% CI, 31.6 to 65.2) in the ensuing 6 months after pump thrombosis. CONCLUSIONS The rate of pump thrombosis related to the use of the HeartMate II has been increasing at our centers and is associated with substantial morbidity and mortality.

Learning curves for transfemoral transcatheter aortic valve replacement in the PARTNER‐I trial: Success and safety

To identify number of cases needed to maximize device success and minimize adverse events after transfemoral transcatheter aortic valve replacement (TF‐TAVR), and determine if adverse events were linked to the technical performance learning curve.

Learning curves for transfemoral transcatheter aortic valve replacement in the PARTNER-I trial: Technical performance.

To assess technical performance learning curves of teams performing transfemoral transcatheter aortic valve replacement (TF‐TAVR).

Aortic Dissection in Patients With Bicuspid Aortic Valve-Associated Aneurysms.

BACKGROUND Data regarding the risk of aortic dissection in patients with bicuspid aortic valve and large ascending aortic diameter are limited, and appropriate timing of prophylactic ascending aortic replacement lacks consensus. Thus our objectives were to determine the risk of aortic dissection based on initial cross-sectional imaging data and clinical variables and to isolate predictors of aortic intervention in those initially prescribed serial surveillance imaging. METHODS From January 1995 to January 2014, 1,181 patients with bicuspid aortic valve underwent cross-sectional computed tomography (CT) or magnetic resonance imaging (MRI) to ascertain sinus or tubular ascending aortic diameter greater than or equal to 4.7 cm. Random Forest classification was used to identify risk factors for aortic dissection, and among patients undergoing surveillance, time-related analysis was used to identify risk factors for aortic intervention. RESULTS Prevalence of type A dissection that was detected by imaging or was found at operation or on follow-up was 5.3% (n = 63). Probability of type A dissection increased gradually at a sinus diameter of 5.0 cm--from 4.1% to 13% at 7.2 cm--and then increased steeply at an ascending aortic diameter of 5.3 cm--from 3.8% to 35% at 8.4 cm--corresponding to a cross-sectional area to height ratio of 10 cm(2)/m for sinuses of Valsalva and 13 cm(2)/m for the tubular ascending aorta. Cross-sectional area to height ratio was the best predictor of type A dissection (area under the curve [AUC] = 0.73). CONCLUSIONS Early prophylactic ascending aortic replacement in patients with bicuspid aortic valve should be considered at high-volume aortic centers to reduce the high risk of preventable type A dissection in those with aortas larger than approximately 5.0 cm or with a cross-sectional area to height ratio greater than approximately 10 cm(2)/m.

Insights Into Timing, Risk Factors, and Outcomes of Stroke and Transient Ischemic Attack After Transcatheter Aortic Valve Replacement in the PARTNER Trial (Placement of Aortic Transcatheter Valves)

Background—Prior studies of stroke and transient ischemic attack (TIA) after transcatheter aortic valve replacement (TAVR) are limited by reporting and follow-up variability. This is a comprehensive analysis of time-related incidence, risk factors, and outcomes of these events. Methods and Results—From April 2007 to February 2012, 2621 patients, aged 84±7.2 years, underwent transfemoral (TF; 1521) or transapical (TA; 1100) TAVR in the PARTNER trial (Placement of Aortic Transcatheter Valves; as-treated), including the continued access registry. Stroke and TIA were identified by protocol and adjudicated by a Clinical Events Committee. Within 30 days of TAVR, 87 (3.3%) patients experienced a stroke (TF 58 [3.8%]; TA 29 [2.7%]; P=0.09), 85% within 1 week. Instantaneous stroke risk peaked on day 2, then fell to a low prolonged risk of 0.8% by 1 to 2 weeks. Within 30 days, 13 (0.50%) patients experienced a TIA (TF 10 [0.67%]; TA 3 [0.27%]; P>0.17). Stroke and TIA were associated with lower 1-year survival than expected (TF 47% after stroke versus 82%, and 64% after TIA versus 83%; TA 53% after stroke versus 80%, and 64% after TIA versus 83%). Risk factors for early stroke after TA-TAVR included more postdilatations, pure aortic stenosis without regurgitation, and possibly more pacing runs, earlier date of procedure, and no dual antiplatelet therapy; high pre-TAVR aortic peak gradient was a risk factor for stroke early after TF-TAVR. Conclusions—Risk of stroke or TIA is highest early after TAVR and is associated with increased 1-year mortality. Modifications of TAVR, emboli-prevention devices, and better intraprocedural pharmacological protection may mitigate this risk. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

Impact of Present-on-admission Indicators on Risk-adjusted Hospital Mortality Measurement

Background:Benchmarking performance across hospitals requires proper adjustment for differences in baseline patient and procedural risk. Recently, a Risk Stratification Index was developed from Medicare data, which used all diagnosis and procedure codes associated with each stay, but did not distinguish present-on-admission (POA) diagnoses from hospital-acquired diagnoses. We sought to (1) develop and validate a risk index for in-hospital mortality using only POA diagnoses, principal procedures, and secondary procedures occurring before the date of the principal procedure (POARisk) and (2) compare hospital performance metrics obtained using the POARisk model with those obtained using a similarly derived model which ignored the timing of diagnoses and procedures (AllCodeRisk). Methods:We used the 2004–2009 California State Inpatient Database to develop, calibrate, and prospectively test our models (n = 24 million). Elastic net logistic regression was used to estimate the two risk indices. Agreement in hospital performance under the two respective risk models was assessed by comparing observed-to-expected mortality ratios; acceptable agreement was predefined as the AllCodeRisk-based observed-to-expected ratio within ±20% of the POARisk-based observed-to-expected ratio for more than 95% of hospitals. Results:After recalibration, goodness of fit (i.e., model calibration) within the 2009 data was excellent for both models. C-statistics were 0.958 and 0.981, respectively, for the POARisk and AllCodeRisk models. The AllCodeRisk-based observed-to-expected ratio was within ±20% of the POARisk-based observed-to-expected ratio for 89% of hospitals, which was slightly lower than the predefined limit of agreement. Conclusion:Consideration of POA coding meaningfully improved hospital performance measurement. The POARisk model should be used for risk adjustment when POA data are available.

Outcomes in Nonagenarians Undergoing Transcatheter Aortic Valve Replacement in the PARTNER-I Trial

BACKGROUND This study describes short-term and mid-term outcomes of nonagenarian patients undergoing transfemoral or transapical transcatheter aortic valve replacement (TAVR) in the Placement of Aortic Transcatheter Valve (PARTNER)-I trial. METHODS From April 2007 to February 2012, 531 nonagenarians, mean age 93 ± 2.1 years, underwent TAVR with a balloon-expandable prosthesis in the PARTNER-I trial: 329 through transfemoral (TF-TAVR) and 202 transapical (TA-TAVR) access. Clinical events were adjudicated and echocardiographic results analyzed in a core laboratory. Quality of life (QoL) data were obtained up to 1 year post-TAVR. Time-varying all-cause mortality was referenced to that of an age-sex-race-matched US population. RESULTS For TF-TAVR, post-procedure 30-day stroke risk was 3.6%; major adverse events occurred in 35% of patients; 30-day paravalvular leak was greater than moderate in 1.4%; median post-procedure length of stay (LOS) was 5 days. Thirty-day mortality was 4.0% and 3-year mortality 48% (44% for the matched population). By 6 months, most QoL measures had stabilized at a level considerably better than baseline, with Kansas City Cardiomyopathy Questionnaire (KCCQ) 72 ± 21. For TA-TAVR, post-procedure 30-day stroke risk was 2.0%; major adverse events 32%; 30-day paravalvular leak was greater than moderate in 0.61%; and median post-procedure LOS was 8 days. Thirty-day mortality was 12% and 3-year mortality 54% (42% for the matched population); KCCQ was 73 ± 23. CONCLUSIONS A TAVR can be performed in nonagenarians with acceptable short- and mid-term outcomes. Although TF- and TA-TAVR outcomes are not directly comparable, TA-TAVR appears to carry a higher risk of early death without a difference in intermediate-term mortality. Age alone should not preclude referral for TAVR in nonagenarians.

Probability of atrial fibrillation after ablation: Using a parametric nonlinear temporal decomposition mixed effects model

Atrial fibrillation is an arrhythmic disorder where the electrical signals of the heart become irregular. The probability of atrial fibrillation (binary response) is often time varying in a structured fashion, as is the influence of associated risk factors. A generalized nonlinear mixed effects model is presented to estimate the time-related probability of atrial fibrillation using a temporal decomposition approach to reveal the pattern of the probability of atrial fibrillation and their determinants. This methodology generalizes to patient-specific analysis of longitudinal binary data with possibly time-varying effects of covariates and with different patient-specific random effects influencing different temporal phases. The motivation and application of this model is illustrated using longitudinally measured atrial fibrillation data obtained through weekly trans-telephonic monitoring from an NIH sponsored clinical trial being conducted by the Cardiothoracic Surgery Clinical Trials Network.

Biatrial Maze Procedure versus Pulmonary Vein Isolation for Atrial Fibrillation during Mitral Valve Surgery: New Analytical Approaches and Endpoints

Objective: To use novel statistical methods for analyzing the effect of lesion set on (long‐standing) persistent atrial fibrillation (AF) in the Cardiothoracic Surgical Trials Network trial of surgical ablation during mitral valve surgery (MVS). Methods: Two hundred sixty such patients were randomized to MVS + surgical ablation or MVS alone. Ablation was randomized between pulmonary vein isolation and biatrial maze. During 12 months postsurgery, 228 patients (88%) submitted 7949 transtelephonic monitoring (TTM) recordings, analyzed for AF, atrial flutter (AFL), or atrial tachycardia (AT). As previously reported, more ablation than MVS‐alone patients were free of AF or AF/AFL at 6 and 12 months (63% vs 29%; P < .001) by 72‐hour Holter monitoring, without evident difference between lesion sets (for which the trial was underpowered). Results: Estimated freedom from AF/AFL/AT on any transmission trended higher after biatrial maze than pulmonary vein isolation (odds ratio, 2.31; 95% confidence interval, 0.95‐5.65; P = .07) 3 to 12 months postsurgery; estimated AF/AFL/AT load (ie, proportion of TTM strips recording AF/AFL/AT) was similar (odds ratio, 0.90; 95% confidence interval, 0.57‐1.43; P = .6). Within 12 months, estimated prevalence of AF/AFL/AT by TTM was 58% after MVS alone, and 36% versus 23% after pulmonary vein isolation versus biatrial maze (P < .02). Conclusions: Statistical modeling using TTM recordings after MVS in patients with (long‐standing) persistent AF suggests that a biatrial maze is associated with lower AF/AFL/AT prevalence, but not a lower load, compared with pulmonary vein isolation. The discrepancy between AF/AFL/AT prevalence assessed at 2 time points by Holter monitoring versus weekly TTM suggests the need for a confirmatory trial, reassessment of definitions for failure after ablation, and validation of statistical methods for assessing atrial rhythms longitudinally.

Characterizing

We consider