Baylor Heart and Vascular Institute

Desai, A. S., B. L. Claggett, M. Packer, M. R. Zile, J. L. Rouleau, K. Swedberg, V. Shi, M. Lefkowitz, R. Starling, J. Teerlink, J. J. McMurray and S. D. Solomon (2016). “Influence of sacubitril/valsartan (lcz696) on 30-day readmission after heart failure hospitalization.” J Am Coll Cardiol 68(3): 241-248.

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BACKGROUND: Patients with heart failure (HF) are at high risk for hospital readmission in the first 30 days following HF hospitalization. OBJECTIVES: This study sought to determine if treatment with sacubitril/valsartan (LCZ696) reduces rates of hospital readmission at 30-days following HF hospitalization compared with enalapril. METHODS: We assessed the risk of 30-day readmission for any cause following investigator-reported hospitalizations for HF in the PARADIGM-HF trial, which randomized 8,399 participants with HF and reduced ejection fraction to treatment with LCZ696 or enalapril. RESULTS: Accounting for multiple hospitalizations per patient, there were 2,383 investigator-reported HF hospitalizations, of which 1,076 (45.2%) occurred in subjects assigned to LCZ696 and 1,307 (54.8%) occurred in subjects assigned to enalapril. Rates of readmission for any cause at 30 days were 17.8% in LCZ696-assigned subjects and 21.0% in enalapril-assigned subjects (odds ratio: 0.74; 95% confidence interval: 0.56 to 0.97; p = 0.031). Rates of readmission for HF at 30-days were also lower in subjects assigned to LCZ696 (9.7% vs. 13.4%; odds ratio: 0.62; 95% confidence interval: 0.45 to 0.87; p = 0.006). The reduction in both all-cause and HF readmissions with LCZ696 was maintained when the time window from discharge was extended to 60 days and in sensitivity analyses restricted to adjudicated HF hospitalizations. CONCLUSIONS: Compared with enalapril, treatment with LCZ696 reduces 30-day readmissions for any cause following discharge from HF hospitalization.

Gandhi, S. S., J. V. Blas, S. Lee, J. F. Eidt and C. G. Carsten, 3rd (2016). “Nonoperative management of grade iii blunt thoracic aortic injuries.” J Vasc Surg: 2016 Jul 2022 [Epub ahead of print].

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OBJECTIVE: Blunt thoracic aortic injuries (BTAIs) have historically been treated with open surgery; thoracic endovascular aortic repair (TEVAR), however, is rapidly becoming the standard of care for all grades of injury. Previous studies have shown successful, conservative management of low-grade (I and II) BTAI, but limited literature exists regarding nonoperative management (NOM) for high-grade BTAI. The purpose of this study was to evaluate NOM for grade III BTAI compared with TEVAR. METHODS: There were 75 patients diagnosed with BTAI between January 2004 and June 2015. Of these, 40 were excluded for different grades of BTAI (17), death before any treatment (6), and need for urgent open repair (17). The remaining 35 patients were divided into two groups by treatment approach: NOM (n = 18) and TEVAR (n = 17). Primary end points were complications and mortality. The secondary end point was difference in pseudoaneurysm and aortic diameter measurements between groups. RESULTS: The groups of patients were similar in age, gender, Injury Severity Score, length of stay, in-hospital mortality, and hospital-associated complications. There were four TEVAR-related complications: graft involutions (2), type I endoleak (1), and distal embolization (1). All TEVAR-related complications required either an adjunctive procedure at the time of the primary procedure or an additional procedure. No patients from the NOM group required operative intervention. There were seven in-hospital mortalities: two in the TEVAR group (11.8%) and five in the NOM group (27.8%; P = .402). One death in the NOM group was related to aortic disease. Follow-up computed tomography imaging revealed similar aortic-related outcomes between groups, with a high proportion showing resolved or improved aortic injury (NOM, 87.5%; TEVAR, 92.9%; P = .674). Initial computed tomography imaging showed similar aortic diameters between groups. The average diameter of the aorta distal to the subclavian artery was 22.6 mm in the NOM group vs 22.8 mm in the TEVAR group (P = .85). The average maximum diameter of the pseudoaneurysm was 30.1 mm in the TEVAR group and 29.9 mm in the NOM group (P = .90). The average ratio of diameter of the pseudoaneurysm to diameter of the aorta distal to the subclavian artery was 1.32 for the TEVAR group and 1.33 for the NOM group (P = .85). CONCLUSIONS: The natural history of grade III BTAIs is not well described. This study suggests that observation and NOM of grade III BTAI may be a reasonable therapeutic option in selected patients. It also speaks to the need for further delineation of the natural history of this injury. Serial imaging and long-term follow-up are necessary to monitor the progression of the pseudoaneurysm.

Packer, M. (2016). “The room where it happens: A skeptic’s analysis of the new heart failure guidelines.” J Card Fail: 2016 Jul [Epub ahead of print].

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New heart failure guidelines have been issued during the past several months, both in the US and in Europe, in response to recent advances in and the approval of new drugs for the treatment of heart failure. Although guidelines documents are often viewed as authoritative and purely evidence-based, there are replete with meaningful (and inexplicable) inconsistencies, which derive from a review of the same body of scientific data by different groups. This satirical review highlights several examples of the entertaining foolishness of recent guideline documents in the good-natured hope that physicians will understand what the guidelines are, and more importantly, what they are not. Specifically, this paper describes the emergence of a new non-existent disease; the strange battle between two bradycardic drugs (digoxin and ivabradine); the confusion that reigns over the positioning and dosing of inhibitors of the renin-angiotensin system; and the special recommendations that have been issued for certain special populations. As Otto von Bismarck remarked, guideline deliberations are like sausages; it is better not to see them being made. Yet, even after they are ready for public view, we should be cautious. Practitioners who rely on them for clinical decision-making engage in an unnecessary form of self-deception; those who read them literally and adhere to them strictly do not practice evidence-based medicine; and those who delve into them in a search for the truth are destined to be disappointed.

Patel, A. N., T. D. Henry, A. A. Quyyumi, G. L. Schaer, R. D. Anderson, C. Toma, C. East, A. E. Remmers, J. Goodrich, A. S. Desai, D. Recker and A. DeMaria (2016). “Ixmyelocel-t for patients with ischaemic heart failure: A prospective randomised double-blind trial.” Lancet 387(10036): 2412-2421.

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BACKGROUND: Ixmyelocel-T is an expanded, multicellular therapy produced from a patient’s own bone marrow by selectively expanding two key types of bone marrow mononuclear cells: CD90+ mesenchymal stem cells and CD45+ CD14+ auto-fluorescent+ activated macrophages. Early phase clinical trials suggest that intramyocardial delivery of ixmyelocel-T might improve clinical, functional, symptomatic, and quality-of-life outcomes in patients with heart failure due to ischaemic dilated cardiomyopathy. We aimed to assess the safety and efficacy of catheter-based transendocardial injection of ixmyelocel-T cell therapy in patients with heart failure and reduced ejection fractions. METHODS: In this randomised, double-blind, placebo-controlled phase 2B trial (ixCELL-DCM), patients from 31 sites in North America with New York Heart Association class III or IV symptomatic heart failure due to ischaemic dilated cardiomyopathy, who had left ventricular ejection fraction 35% or less, an automatic implantable cardioverter defibrillator, and who were ineligible for revascularisation procedures were randomly assigned (1:1) to receive ixmyelocel-T or placebo at the time of bone marrow aspiration and followed for 12 months. Randomisation was done through an interactive (voice/web) response system. The pharmacist, treating physician, and coordinator at each site were unblinded, but the the follow-up team was completely blinded. The primary endpoint was a composite of all-cause death, cardiovascular admission to hospital, and unplanned clinic visits to treat acute decompensated heart failure based on the blinded adjudication of an independent clinical endpoint committee. Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01670981. FINDINGS: Between April 2, 2013, and Jan 28, 2015, 126 participants were randomly assigned to receive either ixmyelocel-T (n=66) or placebo (n=60). 114 (90%) patients comprised the modified intention-to-treat population and 109 (87%) patients were included in the per-protocol primary efficacy analysis (58 in the ixmyelocel-T group and 51 in the placebo group). The primary efficacy endpoint was observed in 47 patients: 50 events in 25 (49%) of 51 patients in the placebo group and 38 events in 22 (38%) of 58 patients in the ixmyelocel-T group, which represents a 37% reduction in cardiac events compared with placebo (risk ratio 0.63 [95% CI 0.42-0.97]; p=0.0344). 41 (75%) of 51 participants in the placebo group had serious adverse events versus 31 (53%) of 58 in the ixmyelocel-T group (p=0.0197). INTERPRETATION: To the best of our knowledge, ixCELL-DCM is the largest cell therapy study done in patients with heart failure so far. The transendocardial delivery of ixmyelocel-T in patients with heart failure and reduced ejection fraction due to ischaemic dilated cardiomyopathy resulted in a significant reduction in adjudicated clinical cardiac events compared with placebo leading to improved patient outcomes.

Cedars, A. M., S. Burns, E. L. Novak and A. P. Amin (2016). “Lesion-specific factors contributing to inhospital costs in adults with congenital heart disease.” Am J Cardiol 117(11): 1821-1825.

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The population of adults with congenital heart disease (ACHD) in the United States is growing rapidly with concomitant increases in care costs. We sought to define the variables having the greatest influence on annual cost of inpatient care in patients with ACHD in the United States. To do so, we conducted a retrospective analysis of admissions in patients >18 years old with a 3-digit International Classification of Disease, Ninth Revision, code of 745 to 747 from the State Inpatient Databases of Arkansas (2008 to 2010), California (2003 to 2012), Florida (2005 to 2012), Hawaii (2006 to 2010), Nebraska (2003 to 2011), and New York (2005 to 2012). We selected variables we believed would have the greatest effect on care costs and built a series of multivariable regression models grouping patients by congenital lesion to examine the relative contribution of the specified variables to total annual inpatient cost. We analyzed a total of 68,314 patients aged 57 +/- 18.6 years, 51% of whom were women. The multivariable regression model had an overall R(2) of 0.35. Readmission was responsible for 10.3% of annual inpatient cost among all patients with ACHD and had the greatest effect on inpatient care cost for each congenital lesion except Eisenmenger syndrome and conotruncal abnormalities, for both of which it was the second most significant contributor. Other major contributors to annual inpatient care costs included length of stay and operative procedures. In conclusion, rehospitalization is the most significant contributor to annual inpatient cost for individual patients with ACHD in the United States, regardless of underlying anatomy.