Jiaxiang Gai

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 Acute Thrombogenicity for Metallic and Polymeric Bioabsorbable Scaffolds: Magmaris Versus Absorb in a Porcine Arteriovenous Shunt Model

Background— A comparison in acute thrombogenicity between the Magmaris sirolimus-eluting bioabsorbable magnesium scaffold and the Absorb bioresorbable vascular scaffold has not been performed. This study assessed acute thrombogenicity of Magmaris compared with Absorb and the Orsiro hybrid drug-eluting stent in a porcine arteriovenous shunt model. Methods and Results— An ex vivo porcine carotid jugular arteriovenous shunt was established and connected to SYLGARD tubing containing the Magmaris, Absorb, and Orsiro scaffolds/stents and allowed to run in the shunt for a maximum of 1 hour. Twelve shunts (2 shunt runs per pig) were run comparing the 3 scaffolds in alternating order. Nested generalized linear mixed models were used to compare variables between scaffold groups while adjusting for variability between shunt runs. Confocal fluorescent microscopy costaining CD61/CD42b demonstrated that both Magmaris (3.0%) and Orsiro (4.6%) had less platelet coverage of the total scaffold compared with Absorb (21.8%). Scanning electron microscopy demonstrated significantly less thrombus deposition to Magmaris as a percentage of the total scaffold compared with Absorb (5.0% versus 16.1%, P=0.02). Magmaris had significantly less PM-1–positive neutrophil and CD14-positive monocyte adherence compared with both Orsiro and Absorb. Orsiro had significantly less monocyte deposition compared with Absorb. Conclusions— Despite a similar scaffold strut thickness, the Magmaris sirolimus-eluting bioabsorbable magnesium scaffold was significantly less thrombogenic compared with the Absorb bioresorbable vascular scaffold in an ex vivo porcine arteriovenous shunt model. Further studies are needed to determine whether the reduced thrombogenicity of Magmaris will result in reductions in major cardiovascular events.

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 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.

The influence of lipid-containing plaque composition assessed by near-infrared spectroscopy on coronary lesion remodelling.

AIMS Vessel remodelling is commonly observed in coronary atherosclerosis, but factors influencing remodelling, such as plaque lipid content, remain poorly described. METHODS AND RESULTS Remodelling index (RI) was calculated as the ratio of lesion to proximal and distal references external membrane area and was categorized as follows: positive (PR; RI > 1.05), intermediate (IR; RI 0.95-1.05), and negative remodelling (NR; RI < 0.95). RI was studied by near-infrared spectroscopy (NIRS) as a function of lipid content metrics, including the maximal 4 mm lipid core burden index of the segment (maxLCBI4 mm) and intravascular ultrasound (IVUS) lesion plaque burden (PB). The authors further stratified the analysis according to obstructive (≥50%) and non-obstructive (<50%) lesions using quantitative coronary angiography. Receiver-operating characteristic curves were performed to describe the maxLCBI4 mm level associated with PR. From May 2012 to November 2014, 100 de novo lesions from 67 patients underwent simultaneous NIRS-IVUS. PR was found in 28% of the lesions. There was a positive linear correlation between RI and maxLCBI4 mm (ρ = 0.58; P < 0.001). Although PR lesions had a larger PB than NR or IR (P < 0.001), the correlation of RI with maxLCBI4 mm was stronger compared with plaque volume (ρ = 0.18; P = 0.07) and with per cent PB (ρ = 0.41; P < 0.001). This relationship remained significant for obstructive (ρ = 0.72; P < 0.001) and non-obstructive lesions (ρ = 0.48; P < 0.001). By receiver-operating characteristic curve analysis, values of maxLCBI4 mm ≥ 439 were predictive for PR (area under the curve = 0.79, 95% confidence interval: 0.69-0.89). CONCLUSION In vivo coronary lesion remodelling is positively correlated with lipid plaque content assessed by NIRS rather than simply PB. Thus, the use of NIRS can potentially aid in further stratifying vulnerable lesions.

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.

Effect of Bleeding Risk on Type of Stent Used in Patients Presenting With Acute Coronary Syndrome

Patients at high bleeding risk (HBR) are at increased risk of bleeding following percutaneous coronary intervention (PCI) with drug-eluting stents (DES) due to the need for longer dual antiplatelet duration. We sought to evaluate the likelihood of receiving DES during PCI in HBR populations and to characterize DES utilization trends over time. Consecutive patients who underwent PCI from April 2003 to September 2015 were identified. HBR is defined as patients fulfilling 1 or more of the HBR criteria: age ≥75 years, anticoagulation use at discharge, history of stroke, cancer in previous 3 years, glucocorticoid use, hemoglobin (Hgb) <11 g/dl, platelet count <100,000/mm3, or creatinine clearance (CCr) <40 ml/min. Multivariate analysis was performed to identify which variables predicted DES selection. There were 10,594 patients (41.6%) who the met HBR definition. When adjusting for known risk factors, HBR patients were less likely to receive a DES compared with non-HBR patients (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.54 to 0.62, p <0.001). A preprocedural Hgb <11 g/dl had the greatest association with choosing DES during PCI (OR 0.51, 95% CI 0.45 to 0.57, p <0.001). Within the HBR patients, having 3 or more HBR criteria versus <3 HBR criteria had lower likelihood of receiving a DES (OR 0.50, 95% CI 0.44 to 0.57, p <0.001). In conclusion, presence of HBR has a significant impact upon the decision to use DES.

Impact of restrictive versus obstructive pulmonary function patterns on mortality in patients undergoing transcatheter aortic valve implantation

BACKGROUND Pulmonary function tests to estimate force vital capacity (FVC) and forced expiratory volume in the first second (FEV1) have increasingly been used in patients evaluated for transcatheter aortic valve implantation (TAVI). The impact of obstructive versus restrictive lung disease on mortality remains unclear. The authors sought to identify differences in survival in patients with 2 distinct pulmonary function patterns (obstruction vs. restriction). METHODS The authors retrospectively analyzed all patients with abnormal FEV1 (lower than 80% of predicted) detected on the pulmonary function tests prior to TAVI from May 2011 to November 2014. Patients were divided into a group with obstructive pattern (FEV1/FVC<70% of predicted) and a group with restrictive pattern (FEV1/FVC>70% of predicted). Cox proportional hazards regression was used to explore the impact of FEV1 on mortality. RESULTS A total of 94 patients were included in this analysis. Forty-one percent (n=38) had obstructive pattern, and 59% (n=56) had restrictive pattern. FEV1 values were similar between both groups (43±19 vs. 42±26, p=0.89). Both groups had similar rates of in-hospital, 30-day, and 1-year mortality. FEV1 was not a correlate for 1-year mortality. Patients with pulmonary obstructive and restrictive patters had similar rates of mortality. Moreover, FEV1 value is not a correlate for 1-year mortality. CONCLUSION In the current era, the pattern on pulmonary function tests and FEV1 values should not influence the decision on whom to offer a transcatheter option for their severe valvular disease.