Cardiology

Alam, A., Mancini, D. and Hall, S. (2021). “Should Withdrawal Of Care Be Listed As A Cause Of Death?” Ann Thorac Surg Mar 19;S0003-4975(21)00534-8. [Epub ahead of print].

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In the latest INTERMACS report we were encouraged to read that despite the heart failure community implanting left ventricular assist devices (LVAD) in a sicker patient population, survival continues to improve. However, the frequent adverse events and the primary cause of death remain concerning. Major bleeding and infection continue to lead the adverse events profile with a declining rate of strokes. Interestingly, the report does not track incidence of right sided heart failure which had been included in prior annual INTERMACS reports. Furthermore, the report concludes that “withdrawal of care” is now the leading cause of death. [No abstract, excerpt from article].

Alam, A., Kobashigawa, J., Milligan, G.P. and Hall, S.A. (2021). “Evolution of Testing for Allograft Rejection After Orthotopic Heart Transplantation Without the Evolution of Guidelines and a Proposal for the Multidisciplinary Health-Team Approach.” Am J Cardiol Mar 19;S0002-9149(21)00254-X. [Epub ahead of print].

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Acute allograft rejection remains among the most common causes of morbidity and mortality, especially in the first year following orthotopic heart transplant with roughly 25% of patients having at least 1 episode of allograft rejection within this time period. Despite its prevalence and substantial clinical significance, accurate diagnosis often proves elusive. Endomyocardial biopsy (EMB) remains the gold standard in diagnosis of acute rejection,2 despite its inherent limitations of sampling bias, subjectivity, and false negatives are well known. This has prompted the use of an expanding array of diagnostic modalities such as cardiac magnetic resonance imaging, gene expression profiling, donor-derived cell free DNA (dd-cfDNA), and more recently, microarray biopsy technology known as the Molecular Microscope Diagnostic System (MMDx). Recommendations on the utility of some of these tests were provided in the latest guidelines on care of the heart transplant recipient published by the International Society of Heart and Lung Transplant in 2010, however, as the field has rapidly evolved, so must our approach to the care of these patients. [No abstract; excerpt from article].

Nazif, T.M., Moses, J., Sharma, R., Dhoble, A., Rovin, J., Brown, D., Horwitz, P., Makkar, R., Stoler, R., Forrest, J., Messé, S., Dickerman, S., Brennan, J., Zivadinov, R., Dwyer, M.G. and Lansky, A.J. (2021). “Randomized Evaluation of TriGuard 3 Cerebral Embolic Protection After Transcatheter Aortic Valve Replacement: REFLECT II.” JACC Cardiovasc Interv 14(5): 515-527.

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OBJECTIVES: The REFLECT II (Randomized Evaluation of TriGuard 3 Cerebral Embolic Protection After Transcatheter Aortic Valve Implantation) trial was designed to investigate the safety and efficacy of the TriGUARD 3 (TG3) cerebral embolic protection in patients undergoing transcatheter aortic valve replacement. BACKGROUND: Cerebral embolization occurs frequently following transcatheter aortic valve replacement and procedure-related ischemic stroke occurs in 2% to 6% of patients at 30 days. Whether cerebral protection with TriGuard 3 is safe and effective in reducing procedure-related cerebral injury is not known. METHODS: This prospective, multicenter, single-blind, 2:1 randomized (TG3 vs. no TG3) study was designed to enroll up to 345 patients. The primary 30-day safety endpoint (Valve Academic Research Consortium-2 defined) was compared with a performance goal (PG). The primary hierarchical composite efficacy endpoint (including death or stroke at 30 days, National Institutes of Health Stroke Scale score worsening in hospital, and cerebral ischemic lesions on diffusion-weighted magnetic resonance imaging at 2 to 5 days) was compared using the Finkelstein-Schoenfeld method. RESULTS: REFLECT II enrolled 220 of the planned 345 patients (63.8%), including 41 roll-in and 179 randomized patients (121 TG3 and 58 control subjects) at 18 US sites. The sponsor closed the study early after the U.S. Food and Drug Administration recommended enrollment suspension for unblinded safety data review. The trial met its primary safety endpoint compared with the PG (15.9% vs. 34.4% (p < 0.0001). The primary hierarchal efficacy endpoint at 30 days was not met (mean scores [higher is better]: -8.58 TG3 vs. 8.08 control; p = 0.857). A post hoc diffusion-weighted magnetic resonance imaging analysis of per-patient total lesion volume above incremental thresholds showed numeric reductions in total lesion volume >500 mm(3) (-9.7%) and >1,000 mm(3) (-44.5%) in the TG3 group, which were more pronounced among patients with full TG3 coverage: -51.1% (>500 mm(3)) and -82.9% (>1,000 mm(3)). CONCLUSIONS: The REFLECT II trial demonstrated that the TG3 was safe compared with a historical PG but did not meet its pre-specified primary superiority efficacy endpoint.

Kirtane, A.J., Stoler, R., Feldman, R., Neumann, F.J., Boutis, L., Tahirkheli, N., Toelg, R., Othman, I., Stein, B., Choi, J.W., Windecker, S., Yeh, R.W., Dauerman, H.L., Price, M.J., Underwood, P., Allocco, D., Meredith, I. and Kereiakes, D.J. (2021). “Primary Results of the EVOLVE Short DAPT Study: Evaluation of 3-Month Dual Antiplatelet Therapy in High Bleeding Risk Patients Treated With a Bioabsorbable Polymer-Coated Everolimus-Eluting Stent.” Circ Cardiovasc Interv Mar 1;CIRCINTERVENTIONS120010144. [Epub ahead of print]. Circinterventions120010144.

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BACKGROUND: Prolonged dual antiplatelet therapy (DAPT) after percutaneous coronary intervention is associated with increased bleeding, despite a reduced incidence of ischemic events. The SYNERGY everolimus-eluting stent is a thin-strut platinum-chromium stent that elutes everolimus from a thin abluminal layer of bioabsorbable polymer. These design elements may facilitate rapid endothelialization and enable shorter-duration DAPT. METHODS: EVOLVE Short DAPT prospectively evaluated the safety of 3-month DAPT in high bleeding risk patients treated with the SYNERGY everolimus-eluting stent, enrolling 2009 patients at 110 global sites. Patients with acute myocardial infarction or complex lesions were excluded. After percutaneous coronary intervention, patients were required to take DAPT (aspirin+P2Y(12) inhibitor) for 3 months, except those on chronic anticoagulation in whom aspirin was optional. Patients free of events (stroke, myocardial infarction, revascularization, and stent thrombosis) who discontinued P2Y(12) inhibitor at 3 months, but continued aspirin, and had at least 1 year of follow-up or an end point event were included in the primary analysis. Two powered coprimary end points were (1) death/myocardial infarction compared with a historical control and (2) study stent-related definite/probable stent thrombosis compared to a performance goal. RESULTS: The analysis population consisted of 1487 patients. The adjusted rate of death/myocardial infarction between 3 and 15 months was 5.6% among patients receiving 3-month DAPT versus 5.7% patients in the 12-month DAPT control (propensity adjusted difference=-0.12%; 97.5% upper bound=1.63% which was less than the prespecified margin of 2.52; P(non-inferiority)=0.0016). The rate of study stent-related stent thrombosis between 3-15 months was 0.2% in the 3-month DAPT group (97.5% upper bound=0.63%; P=0.0005 for comparison to 1% performance goal). CONCLUSIONS: Favorable rates of ischemic outcomes were observed among selected high bleeding risk patients undergoing percutaneous coronary intervention with the SYNERGY everolimus-eluting stent who tolerated 3 months of P2Y(12) inhibitor and then discontinued it, supporting the safety of abbreviated DAPT with this stent platform. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02605447.

Fam, N.P., von Bardeleben, R.S., Hensey, M., Kodali, S.K., Smith, R.L., Hausleiter, J., Ong, G., Boone, R., Ruf, T., George, I., Szerlip, M., Näbauer, M., Ali, F.M., Moss, R., Bapat, V., Schnitzler, K., Kreidel, F., Ye, J., Deva, D.P., Mack, M.J., Grayburn, P.A., Peterson, M.D., Leon, M.B., Hahn, R.T. and Webb, J.G. (2021). “Transfemoral Transcatheter Tricuspid Valve Replacement With the EVOQUE System: A Multicenter, Observational, First-in-Human Experience.” JACC Cardiovasc Interv 14(5): 501-511.

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OBJECTIVES: The purpose of this observational first-in-human experience was to investigate the feasibility and safety of the EVOQUE tricuspid valve replacement system and its impact on short-term clinical outcomes. BACKGROUND: Transcatheter tricuspid intervention is a promising option for selected patients with severe tricuspid regurgitation (TR). Although transcatheter leaflet repair is an option for some, transcatheter tricuspid valve replacement (TTVR) may be applicable to a broader population. METHODS: Twenty-five patients with severe TR underwent EVOQUE TTVR in a compassionate-use experience. The primary outcome was technical success, with NYHA (NYHA) functional class, TR grade, and major adverse cardiac and cerebrovascular events assessed at 30-day follow-up. RESULTS: All patients (mean age 76 ± 3 years, 88% women) were at high surgical risk (mean Society of Thoracic Surgeons risk score 9.1 ± 2.3%), with 96% in NYHA functional class III or IV. TR etiology was predominantly functional, with mean tricuspid annular diameter of 44.8 ± 7.8 mm and mean tricuspid annular plane systolic excursion of 16 ± 2 mm. Technical success was 92%, with no intraprocedural mortality or conversion to surgery. At 30-day follow-up, mortality was 0%, 76% of patients were in NYHA functional class I or II, and TR grade was ≤2+ in 96%. Major bleeding occurred in 3 patients (12%), 2 patients (8%) required pacemaker implantation, and 1 patient (4%) required dialysis. CONCLUSIONS: This first-in-human experience evaluating EVOQUE TTVR demonstrated high technical success, acceptable safety, and significant clinical improvement. Larger prospective studies are needed to confirm durability and safety and the impact on long-term clinical outcomes.