Cardiology

Piccini, J. P., A. Ahlsson, P. Dorian, M. A. Gillinov, P. R. Kowey, M. J. Mack, C. A. Milano, L. P. Perrault, J. S. Steinberg, N. H. Waldron, L. M. Adams, D. B. Bharucha, M. F. Brin, W. G. Ferguson and S. Benussi (2021). “Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation – The NOVA Study.” Am Heart J Oct 20;S0002-8703(21)00366-5. [Epub ahead of print].

Full text of this article.

BACKGROUND: Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in 2 clinical studies of cardiac surgery patients, without new safety observations. METHODS: The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety. CONCLUSION: The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

Thuijs, D., P. Davierwala, M. Milojevic, S. V. Deo, T. Noack, A. P. Kappetein, P. W. Serruys, F. W. Mohr, M. C. Morice, M. J. Mack, L. Ståhle, N. J. Verberkmoes, D. R. Holmes and S. J. Head (2021). “Long-term survival after coronary bypass surgery with multiple versus single arterial grafts.” Eur J Cardiothorac Surg Oct 7;ezab392. [Epub ahead of print].

Full text of this article.

OBJECTIVES: This study sought to evaluate the long-term differences in survival between multiple arterial grafts (MAG) and single arterial grafts (SAG) in patients who underwent coronary artery bypass grafting (CABG) in the SYNTAX study. METHODS: The present analysis included the randomized and registry-treated CABG patients (n = 1509) from the SYNTAX Extended Survival study (SYNTAXES). Patients with only venous (n = 42) or synthetic grafts (n = 1) were excluded. The primary end point was all-cause death at the longest follow-up. Multivariable Cox regression was used to adjust for differences in baseline characteristics. Sensitivity analysis using propensity matching with inverse probability for treatment weights was performed. RESULTS: Of the 1466 included patients, 465 (31.7%) received MAG and 1001 (68.3%) SAG. Patients receiving MAG were younger and at lower risk. At the longest follow-up of 12.6 years, all-cause death occurred in 23.6% of MAG and 40.0% of SAG patients [adjusted hazard ratio (HR) 0.74, 95% confidence interval (CI) (0.55-0.98); P = 0.038], which was confirmed by sensitivity analysis. MAG in patients with the three-vessel disease was associated with significant lower unadjusted and adjusted all-cause death at 12.6 years [adjusted HR 0.65, 95% CI (0.44-0.97); P = 0.033]. In contrast, no significance was observed after risk adjustment in patients with the left main disease, with and without diabetes, or among SYNTAX score tertiles. CONCLUSIONS: In the present post hoc analysis of all-comers patients from the SYNTAX trial, MAG resulted in markedly lower all-cause death at 12.6-year follow-up compared to a SAG strategy. Hence, this striking long-term survival benefit of MAG over SAG encourages more extensive use of multiple arterial grafting in selected patients with reasonable life expectancy. TRIAL REGISTRATION: SYNTAXES ClinicalTrials.gov reference: NCT03417050; SYNTAX ClinicalTrials.gov reference: NCT00114972.

Mack, M., J. D. Carroll, V. Thourani, S. Vemulapalli, J. Squiers, P. Manandhar, G. M. Deeb, W. Batchelor, H. C. Herrmann, D. J. Cohen, G. Hanzel, T. Gleason, A. Kirtane, N. Desai, K. Guibone, K. Hardy, J. Michaels, J. M. DiMaio, B. Christensen, S. Fitzgerald, C. Krohn, R. G. Brindis, F. Masoudi and J. Bavaria (2021). “Transcatheter Mitral Valve Therapy in the United States: A Report from the STS/ACC TVT Registry.” Ann Thorac Surg Oct 21;S0003-4975(21)01408-9. [Epub ahead of print].

Full text of this article.

Data for nearly all patients undergoing transcatheter edge-to-edge repair (TEER) and transcatheter mitral valve replacement (TMVR) with an approved device in the United States is captured in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. All data submitted for TEER or TMVR between 2014 and March 31, 2020, are reported. A total of 37,475 patients underwent a mitral transcatheter procedure, including 33,878 TEER and 3,597 TMVR. Annual procedure volumes for TEER have increased from 1,152 per year in 2014 to 10,460 per year in 2019 at 403 sites and for TMVR from 84 per year to 1,120 per year at 301 centers. Mortality rates have decreased for TEER at 30 days (5.6%-4.1%) and 1 year (27.4%-22.0%). Early off-label use data on TMVR in mitral valve-in-valve therapy led to approval by the U.S. Food and Drug Administration in 2017, and the 2019 30-day mortality rate was 3.9%. Overall improvements in outcomes over the last 6 years are apparent. (STS/ACC TVT Registry Mitral Module; NCT02245763).

Ihdayhid, A. R., J. Leipsic, R. T. Hahn, P. Pibarot, V. Thourani, R. Makkar, S. Kodali, M. Russo, S. Kapadia, Y. Chen, M. Mack, J. Webb, J. Bax, M. B. Leon and P. Blanke (2021). “Impact of Annular Oversizing on Paravalvular Regurgitation and Valve Hemodynamics: New Insights From PARTNER 3.” JACC Cardiovasc Interv 14(19): 2158-2169.

Full text of this article.

OBJECTIVES: This study sought to investigate the impact of computed tomography (CT)-based area and perimeter oversizing on the incidence of paravalvular regurgitation (PVR) and valve hemodynamics in patients treated with the SAPIEN 3 transcatheter heart valve (THV). BACKGROUND: The incremental value of considering annular perimeter or left ventricular outflow tract measurements and the impact of THV oversizing on valve hemodynamics are not well defined. METHODS: The PARTNER 3 (Placement of Aortic Transcatheter Valves 3) trial included 495 low-surgical-risk patients with severe aortic stenosis who underwent THV implantation. THV sizing was based on annular area assessed by CT. Area- and perimeter-based oversizing was determined using systolic annular CT dimensions and nominal dimensions of the implanted THV. PVR, effective orifice area, and mean gradient were assessed on 30-day transthoracic echocardiography. RESULTS: Of 485 patients with available CT and echocardiography data, mean oversizing was 7.9 ± 8.7% for the annulus area and 2.1 ± 4.1% for the perimeter. A very low incidence of ≥moderate PVR (0.6%) was observed, including patients with minimal annular oversizing. Incidence of ≥mild PVR and need for procedural post-dilatation were inversely related to the degree of oversizing. For patients with annular dimensions suitable for 2 THV sizes, the larger THV with both area and perimeter oversizing was associated with the lowest incidence of ≥mild PVR (12.0% vs 43.4%; P < 0.0001). Left ventricular outflow tract area oversizing was not associated with PVR. THV prosthesis size, rather than degree of oversizing, had greatest impact on effective orifice area and mean gradient. CONCLUSIONS: In low-surgical-risk patients, a low incidence of ≥moderate PVR was observed, including patients with minimal THV oversizing. The degree of prosthesis oversizing had the greatest impact on reducing mild PVR and incidence of post-dilatation, without impacting valve hemodynamics. In selected patients with annular dimensions in between 2 valve sizes, the larger THV device oversized to both the annular area and perimeter reduced PVR and optimized THV hemodynamics.

Gibson, C. M., M. J. Mack, V. T. Lee, D. J. Schneider, F. W. Sellke, E. M. Ohman, V. H. Thourani, G. Doros, H. Kroger, D. E. Cutlip and E. N. Deliargyris (2021). “Rationale and Design of the Safe and Timely Antithrombotic Removal – Ticagrelor (STAR-T) Trial: A Prospective, Multi-center, Double-blind, Randomized Controlled Trial Evaluating Reductions in Postoperative Bleeding with Intraoperative Removal of Ticagrelor by the DrugSorb™-ATR Device in Patients Undergoing Cardiothoracic Surgery within 48hrs from Last Ticagrelor Dose.” Am Heart J Nov 1; S0002-8703(21)00442-7. [Epub ahead of print].

Full text of this article.

Ticagrelor is often administered to patients with acute coronary syndromes. However, when these patients require urgent or emergent cardiothoracic (CT) surgery the presence of ticagrelor significantly increases surgical bleeding. The goal of the current trial is to evaluate the effectiveness and safety of the DrugSorb™-ATR hemoadsorption device for the intraoperative removal of ticagrelor to reduce postoperative bleeding in the above patient population. The Safe and Timely Antithrombotic Removal – Ticagrelor (STAR-T) Trial is a multi-center, double-blind, randomized, controlled trial enrolling patients who require cardiothoracic surgery on cardiopulmonary bypass (CPB) within 48 hours of last ticagrelor dose. Subjects will be randomized 1:1 to receive either the DrugSorb™-ATR device or an identical sham device during CPB. The study will enroll up to 120 subjects at 20 U.S centers, and the primary outcome is the composite of fatal perioperative bleeding, moderate/severe/massive bleeding according to the Universal Definition of Perioperative Bleeding in Cardiac Surgery (UDPB), and 24hr chest tube drainage. The components of the composite are hierarchically ranked according to clinical significance and the primary analysis will utilize the Win Ratio method. Percent change in ticagrelor levels before and after CPB (drug removal) will be the key secondary endpoint. An independent Clinical Events Committee will adjudicate all clinical endpoints including safety endpoints relating to postoperative thrombotic events. Subjects will be followed through 30 days after the index operation. The results from STAR-T, if positive, will potentially support FDA clearance of the device.