Edward Koifman

Impact of triggering event in outcomes of stress-induced (Takotsubo) cardiomyopathy

Background: Takotsubo syndrome is also known as stress cardiomyopathy because of the regularity with which it has been associated with physical or emotional stress. Such stress may well be a “trigger” of the syndrome. Aims: This analysis was undertaken to describe our experience with this disorder and in particular to examine the effects of the underlying trigger on outcomes. Methods: We conducted a retrospective review of the medical records of 345 consecutive patients treated at our institution from 2006 to 2014. All presented with acute cardiac symptoms, a characteristic left ventricular contraction pattern (typical, atypical), and no major obstructive coronary artery disease. Patients were grouped based on their triggering event: (a) medical illness; (b) post-operative period; (c) emotional distress; or (d) no identified trigger. Baseline demographic characteristics, death in hospital, length of stay in hospital, and cardiac complications were abstracted from the patients’ medical records. Results: The mean±SD age of the population was 72±12 years and 91% were women. No significant difference in baseline characteristics was noted between the groups except for a higher prevalence of African Americans in the group with a medical illness. ST elevation was noted in 13.3% of patients and the average peak troponin level was 5±12 ng/dl. An inotropic drug was required in 49 (14.2%) patients, an intra-aortic balloon pump in 37 (10.7%) patients, and mechanical ventilation in 54 (15.7%) patients; 43.5% required treatment in the intensive care unit. Overall, 12 (3.5%) patients died. In only two (16.7%) patients was a there a direct cardiac cause of death. In those patients in whom the cardiac manifestations seemed to be triggered by a medical illness, the death rate was 7.1% and this was significantly higher than in the other groups (p=0.03). Medical illness (odds ratio=6.25, p=0.02) and ST elevation (odds ratio=5.71, p=0.04) were both significantly associated with death. Conclusions: Our study showed that different triggers for Takotsubo syndrome confer different prognoses, with medical illness conferring the worst prognosis. Overall, the in-hospital death rate was low and mostly related to non-cardiac death secondary to the underlying medical illness. Although an unidentified trigger was prevalent in a third of this population, efforts should be made to identify the triggering event to classify the risk group of patients with Takotsubo syndrome.

Comparison of Watchman device with new oral anti-coagulants in patients with atrial fibrillation: A network meta-analysis.

BACKGROUND New oral anticoagulants (NOAC) and the Watchman device represent an alternative to warfarin for stroke prophylaxis in atrial fibrillation (AF) patients. However, no studies compare these new treatments. We performed a network meta-analysis to indirectly compare Watchman and NOACs among AF patients. METHODS We performed a MEDLINE search for studies comparing warfarin with NOACs (dabigatran, rivaroxaban, apixaban and edoxaban) or Watchman in AF patients with reported clinical outcomes. Mixed treatment comparison model generation was performed to directly and indirectly compare NOACs, warfarin and Watchman. RESULTS 14 studies with 246,005 patients were included in the analysis, among which 124,823 were treated with warfarin, 120,450 were treated with NOACs and 732 had Watchman implanted. Mean age was 72 ± 9 years, 53% were male, and mean CHADS2 score was 2.1 ± 1.6. Both NOACs and Watchman were superior to warfarin in hemorrhagic stroke prevention (OR = 0.46 [0.30-0.82] and OR = 0.21 [0.05-0.99], respectively). NOACs significantly reduced total stroke (OR = 0.78 [0.58-0.96]) and major bleeding (OR = 0.78 [0.65-0.91]) compared with warfarin. Indirect comparison between NOAC and Watchman revealed no significant differences in outcomes, though there was a trend toward higher rates of ischemic stroke with Watchman compared with NOAC (OR 2.60 [0.60-13.96]) with the opposite findings with hemorrhagic stroke (OR = 0.44 [0.09-2.14]). CONCLUSIONS NOAC therapy was superior to warfarin for multiple outcomes while Watchman reduced hemorrhagic stroke. Further studies are needed to assess Watchman versus NOAC to optimize therapy for stroke prevention in AF patients.

Body mass index association with survival in severe aortic stenosis patients undergoing transcatheter aortic valve replacement

Conflicting results have been reported regarding impact of body mass index (BMI) on outcome of transcatheter aortic valve replacement (TAVR) patients. This study evaluates the impact of BMI on 1 year mortality in patients undergoing TAVR via the transfemoral (TF) access.

Clinical profiles and correlates of mortality in nonagenarians with severe aortic stenosis undergoing transcatheter aortic valve replacement.

BACKGROUND Transcatheter aortic valve replacement (TAVR) is the current standard for nonoperable and high-risk surgical patients with aortic stenosis, including those of advanced age. However, the clinical profiles, procedural characteristics, and outcomes of nonagenarians undergoing TAVR have not been thoroughly reported. METHODS A total of 654 patients (n = 107 >90 years old and n = 547 <90 years) with severe aortic stenosis undergoing TAVR were included in this analysis. Baseline characteristics, procedural variables, and in-hospital outcomes and complications at 30 days and 12 months were analyzed. RESULTS Overall, of the patients included, 46% were high risk and 53% inoperable. Although nonagenarians had a higher Society of Thoracic Surgeons score of 9.2 ± 4 (12.1 ± 4 vs 8.6 ± 4, P < .001), other factors were considerably lower in this group: diabetes (22% vs 36%, P = .008), hyperlipidemia (65% vs 83%, P < .001), prior coronary artery bypass (13% vs 39%, P < .001), and mean body mass index (24.5 ± 5 vs 28.1 ± 7 kg/m(2), P < .001). The correlates for 1-year mortality in nonagenarians were as follows: ≥moderate aortic insufficiency post-TAVR (hazard ratio [HR] 5.07, 95% CI 1.17-22, P = .03), pacemaker implantation after TAVR (HR 6.87, 95% CI 2.32-20.3, P = .001), and peripheral vascular disease (HR 2.35, 95% CI 1.03-5.38, P = .042). Mortality at 30 days (12.1% vs 7.1%, P = .07) and at 1 year (25% vs 21%, P = .35) was similar between groups. CONCLUSION Nonagenarians undergoing TAVR had a healthier clinical profile compared with younger patients. Age alone should not be a discriminatory factor when screening elderly patients with aortic stenosis because even the nonagenarians are doing well when compared with the younger elderly population. Transcatheter aortic valve replacement remains a viable option for the treatment of severe symptomatic aortic stenosis for the elderly regardless of their age.

Impact of Pre-Procedural Serum Albumin Levels on Outcome of Patients Undergoing Transcatheter Aortic Valve Replacement

Risk assessment for transcatheter aortic valve replacement (TAVR) patients is challenging, and surgical scores do not optimally correlate with outcome. The aim of this study was to assess the correlation between serum albumin and survival of patients with symptomatic severe aortic stenosis undergoing TAVR. Patients with severe aortic stenosis who underwent TAVR were categorized into 2 groups according to low and normal preprocedural serum albumin (<3.5 and ≥3.5 g/dl, respectively). The all-cause mortality rates at hospital discharge, at 30-day and 1-year follow-up were compared across the groups. Additionally, a Cox proportional-hazards model was generated to assess the independent effect of serum albumin at 1-year follow-up. Among 567 consecutive patients who underwent TAVR, 476 (84%) had documented preprocedural serum albumin measurements. Of these, 50% had low serum albumin levels, and 50% had normal serum albumin levels. Baseline and procedural characteristics, including age, gender, and transapical access, were similar among the groups. Prevalence of left ventricular ejection fraction<40% was higher in patients with low albumin (29% vs 20%, p=0.02), and risk assessment according to Society of Thoracic Surgeons score tended to be higher in the low-albumin group (10±4.7 vs 9.4±4.4, p=0.09). Patients presenting with low albumin had higher in-hospital mortality (11% vs 5%), as well as at 30-day (12% vs 6%, p=0.01) and 1-year (29% vs 19%, p=0.02) follow-up. Serum albumin was independently associated with 1-year mortality (adjusted hazard ratio per 0.1 g/dl decrease 1.64, 95% confidence interval 2.50 to 1.75, p=0.02), along with body mass index<20 kg/m2 (hazard ratio 1.89, 95% confidence interval 3.33 to 1.75, p=0.03). In conclusion, preprocedural serum albumin level and low body mass index are independently associated with mortality in patients who undergo TAVR. Patients with severe aortic stenosis and low albumin levels should undergo careful evaluation before and after TAVR.

Impact of transfemoral versus transapical access on mortality among patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

OBJECTIVE To compare early and late mortality of transfemoral (TF) and transapical (TA) transcatheter aortic valve replacement (TAVR) patients and assess predictors for mortality. BACKGROUND Studies have shown conflicting results regarding impact of access on outcome in severe aortic stenosis (AS) patients undergoing TAVR. METHODS AS patients undergoing TAVR between May 2007-December 2014 were included. Baseline demographic, clinical, and imaging parameters were compared according to access, and landmark analysis models were generated to assess outcomes and associated factors. RESULTS Among 648 severe AS patients undergoing TAVR, TF was used in 516 and TA in 132. Baseline characteristics between groups demonstrated lower body mass index, higher STS score, and rate of peripheral vascular disease among TA patients. Procedural complications were more common in the TA group, especially major bleeding (15% vs. 6%, p<0.001) and acute kidney injury >1 (8% vs. 1.4%, p<0.001). Landmark analysis demonstrated higher cumulative mortality rates at 30days among TA than TF patients (log-rank p<0.001), with similar mortality after 30days and up to 1-year (13% in both log-rank p=0.64). In a multivariate model, TA was an independent predictor of early mortality (HR=4.55 95% CI [12.5-1.6], p=0.003) along with pulmonary artery systolic pressure>60mmHg (HR=3.08 95% CI [7.37-1.29], p=0.01) and residual aortic regurgitation severity above mild (HR=3.99 95% CI [10.2-1.56], p=0.004). CONCLUSIONS Patients undergoing TAVR via TA have higher adjusted early mortality and similar late mortality rates compared to TF, despite higher risk profile.

Impact of Functional Versus Organic Baseline Mitral Regurgitation on Short- and Long-Term Outcomes After Transcatheter Aortic Valve Replacement

The impact of the specific etiology of mitral regurgitation (MR) on outcomes in the transcatheter aortic valve replacement (TAVR) population is unknown. This study aimed to evaluate the longitudinal changes in functional versus organic MR after TAVR in addition to their impact on survival. Consecutive patients who underwent TAVR from May 2007 to May 2015 who had baseline significant (moderate or greater) MR were included. Transthoracic echocardiography was used to evaluate the cohort at baseline, post-procedure, 30-day, 6-month, and 1-year follow-up. The primary outcomes included mortality at 30 days and 1 year. Longitudinal, mixed-model regression analyses were performed to assess the differences in the magnitude of longitudinal changes of MR, left ventricular (LV) ejection fraction, and New York Heart Association functional class. Seventy patients (44% men, mean 83 years) with moderate or greater MR at baseline (30 functional vs 40 organic) were included, with the functional group having a statistically significant mean younger age and higher rates of previous coronary artery bypass grafting. Kaplan-Meier cumulative mortality rates were similar: 30 days (10% vs 17.5%, unadjusted log-ranked p = 0.413) and 1 year (29.4% vs 23.2%, unadjusted log-ranked p = 0.746) in the functional versus organic MR groups, respectively. There were greater degrees of short- and long-term improvement in MR severity (slope difference p = 0.0008), LV ejection fraction (slope difference p = 0.0009), and New York Heart Association class (slope difference p = 0.0054) in the functional versus organic group. In conclusion, patients with significant functional versus organic MR who underwent TAVR have similar short- and long-term survival; nevertheless, those with a functional origin are more likely to have significant improvements in MR severity, LV-positive remodeling, and functional class. These findings may help strategize therapies for MR in patients with combined aortic and mitral valve disease who are undergoing TAVR.

Contemporary transcatheter aortic valve replacement with third-generation balloon-expandable versus self-expanding devices

OBJECTIVES To evaluate balloon-expandable and self-expanding third-generation transcatheter aortic valve replacement (TAVR) devices according to patient selection criteria and outcomes. BACKGROUND Two competing third-generation TAVR technologies are currently commercially available in the US. There are no published head-to-head comparisons of the relative performance of these two devices. METHODS 257 consecutive patients undergoing TAVR with a third-generation balloon-expandable (Edwards Sapien 3) or self-expanding device (Medtronic CoreValve Evolut R) at a single US medical center were included. Choice of TAVR device was at the discretion of the multidisciplinary Heart Team. Baseline clinical characteristics, echocardiographic and CT imaging, procedural and 30-day outcomes were prospectively collected. RESULTS 74 patients received a self-expanding valve (SEV) and 183 received a balloon-expandable valve (BEV). Patients selected for SEV were more frequently women, with lower body surface area and smaller calcified iliofemoral arteries. Three SEV patients required implantation of a second valve to successfully treat paravalvular leak. Only one BEV patient had moderate paravalvular regurgitation. There was no difference in the rate of stroke, major vascular complication or bleeding. Permanent pacemaker implantation rate was significantly higher with SEV (12.7% vs 4.7%, P = 0.49) and hospital length of stay was longer (8.3% vs 6.5%, P = 0.043), but 30-day mortality was comparable (1.4% vs 1.6%, P = 1.00). CONCLUSIONS Short-term outcomes were equivalent between the two technologies. Clinically significant paravalvular regurgitation was rare. SEV were more frequently selected in women and patients with challenging transfemoral access, but were associated with higher permanent pacemaker implantation rate and longer hospital length of stay.

Impact of right ventricular function on outcome of severe aortic stenosis patients undergoing transcatheter aortic valve replacement

Background Right ventricular (RV) dysfunction was shown to be associated with adverse outcomes in a variety of cardiac patients and is considered a risk factor for adverse outcome according to the updated Valve Academic Research Consortium criteria. Objective Our goal was to assess the impact of RV function at baseline on 1‐year mortality among patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods All patients with severe AS treated with TAVR from May 2007 to March 2015 at our center were included in the present study, and baseline and procedural characteristics were recorded for each patient. The patients were categorized according to RV function at baseline as assessed by current guidelines, and a comparison of mortality rates up to 1 year was performed. Results Among 650 patients, 606 had adequate echocardiogram quality and 146 (24%) had RV dysfunction. There were significant differences between the 2 groups, as patients with RV dysfunction were younger (81 ± 9 vs 84 ± 7 years, P = .01) and were more likely to be male (65% vs 42%, P < .001). In addition, patients with RV dysfunction had higher rates of prior myocardial infarction (26% vs 16%, P = .02) and atrial fibrillation (51% vs 39%, P = .02). Echocardiographic parameters demonstrated higher rates of left ventricular ejection fraction <40% (40% vs 18%, P < .001), tricuspid regurgitation above moderate (16% vs 9%, P = .04), and higher pulmonary artery systolic pressure (50 ± 17 vs 44 ± 16 mm Hg, P < .001) among patients with severe AS and RV dysfunction compared with patients with normal RV function. Despite the unfavorable cardiac function, patients with severe AS undergoing TAVR have similar functional class (P = .22) and mortality rates at 1 year (27% vs 23%, log‐rank P = .45). Conclusions Patients with severe AS and RV dysfunction have similar 1‐year mortality and functional class after TAVR to patients with normal RV function. The presence of RV dysfunction does not correlate with outcome in patients with severe AS.

Society of Thoracic Surgeons Score Variance Results in Risk Reclassification of Patients Undergoing Transcatheter Aortic Valve Replacement

Role of the Funder/Sponsor: The funding organization, in collaboration with the academic investigators, provided input on the design and conduct of the study; oversaw the collection and management of the data; and contributed to the preparation, review, and approval of the manuscript as well as the decision to submit the manuscript for publication. The funding organization had no role in the analysis or interpretation of the data. Additional Contributions: We thank Bradford Tuckfield, PhD, Berkadia, for his contributions to study conception and design, and Hae Nim (Sunny) Lee, BA, University of Pennsylvania, for her contributions to study conception and design and data analysis; they both received funding in part by grants from Humana during the conduct of the study. We also thank Joelle Friedman, MPA, University of Pennsylvania, for her help with acquisition of data; she was not compensated for her contributions. We also thank Humana Inc, especially Heather E. Pearce, RPh, George J. Spurlock, MBA, Peinie P. Young, PharmD, BCACP, Shannon Clark, MBA, Vicki L. Vogel, BA, and Tova Levin, MBA, for their administrative and technical support. As employees of Humana, they were compensated for their normal work. Trial Registration: Clinicaltrials.gov Identifier: NCT02411032. 1. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5): 487-497. 2. Strandbygaard U, Thomsen SF, Backer V. A daily SMS reminder increases adherence to asthma treatment: a three-month follow-up study. Respir Med. 2010;104(2):166-171. 3. Dai H, Milkman KL, Riis J. Put your imperfections behind you: Temporal landmarks spur goal initiation when they signal new beginnings. Psychol Sci. 2015;26(12):1927-1936. 4. Dai H, Milkman KL, Riis J. The fresh start effect: Temporal landmarks motivate aspirational behavior. Manage Sci. 2014;60(10):2563-2582. 5. Beshears J, Dai H, Milkman KL, Benartzi S. Framing the future: the risks of pre-commitment nudges and potential of fresh start messaging. Paper presented at: 36th Annual Conference of the Society for Judgment and Decision Making; November 21, 2015; Chicago, IL. 6. Shore S, Ho PM, Lambert-Kerzner A, et al. Site-level variation in and practices associated with dabigatran adherence. JAMA. 2015;313(14):1443-1450.