Cardiology

Xenogiannis, I., D. Karmpaliotis, K. Alaswad, F. A. Jaffer, R. W. Yeh, M. Patel, E. Mahmud, J. W. Choi, M. N. Burke, A. H. Doing, P. Dattilo, C. Toma, A. J. C. Smith, B. Uretsky, O. Krestyaninov, D. Khelimskii, E. Holper, S. Potluri, R. M. Wyman, D. E. Kandzari, S. Garcia, M. Koutouzis, I. Tsiafoutis, J. J. Khatri, W. Jaber, H. Samady, B. K. Jefferson, T. Patel, J. W. Moses, N. J. Lembo, M. Parikh, A. J. Kirtane, Z. A. Ali, D. Doshi, P. Tajti, B. V. Rangan, S. Abdullah, S. Banerjee and E. S. Brilakis (2019). “Usefulness of Atherectomy in Chronic Total Occlusion Interventions (from the PROGRESS-CTO Registry).” Am J Cardiol Feb 11. [Epub ahead of print].

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There is limited data on the use of atherectomy during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We compared the clinical and procedural characteristics and outcomes of CTO PCIs performed with or without atherectomy in a contemporary multicenter CTO PCI registry. Between 2012 and 2018, 3,607 CTO PCIs were performed at 21 participating centers. Atherectomy was used in 117 (3.2%) cases: rotational atherectomy in 105 cases, orbital atherectomy in 8, and both in 4 cases. Patients in whom atherectomy was used, were older (68 +/- 8 vs 64 +/- 10 years, p <0.0001) and had higher Japan-chronic total occlusion score (3.0 +/- 1.2 vs 2.4 +/- 1.3, p <0.0001). CTO PCI cases in which atherectomy was used had similar technical (91% vs 87%, p=0.240) and procedural (90% vs 85%, p=0.159) success and in-hospital major adverse cardiac event (4% vs 3%, p=0.382) rates. However, atherectomy cases were associated with higher rates of donor vessel injury (4% vs 1%, p=0.031), tamponade requiring pericardiocentesis (2.6% vs 0.4%, p=0.012) and more often required use of a left ventricular assist device (9% vs 5%, p=0.031). Atherectomy cases were associated with longer procedural duration (196 [141, 247] vs 119 [76, 180] minutes, p <0.0001), and higher patient air kerma radiation dose (3.6 [2.5, 5.6] vs 2.8 [1.6, 4.7] Gray, p=0.001). In conclusion, atherectomy is currently performed in approximately 3% of CTO PCI cases and is associated with similar technical and procedural success and overall major adverse cardiac event rates, but higher risk for donor vessel injury and tamponade.

Reardon, M. J., T. E. Feldman, C. U. Meduri, R. R. Makkar, D. O’Hair, A. Linke, D. J. Kereiakes, R. Waksman, V. Babliaros, R. C. Stoler, G. J. Mishkel, D. G. Rizik, V. S. Iyer, T. G. Gleason, D. Tchetche, J. D. Rovin, T. Lhermusier, D. Carrie, R. W. Hodson, D. J. Allocco and I. T. Meredith (2019). “Two-Year Outcomes After Transcatheter Aortic Valve Replacement With Mechanical vs Self-expanding Valves: The REPRISE III Randomized Clinical Trial.” JAMA Cardiol Feb 27. [Epub ahead of print].

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Importance: To our knowledge, REPRISE III is the first large randomized comparison of 2 different transcatheter aortic valve replacement platforms: the mechanically expanded Lotus valve (Boston Scientific) and self-expanding CoreValve (Medtronic). Objective: To evaluate outcomes of Lotus vs CoreValve after 2 years. Design, Setting, and Participants: A total of 912 patients with high/extreme risk and severe, symptomatic aortic stenosis enrolled between September 22, 2014, and December 24, 2015, were randomized 2:1 to receive Lotus (607 [66.6%]) or CoreValve (305 [33.4%] at 55 centers in North America, Europe, and Australia. The first 2-year visit occurred on October 17, 2016, and the last was conducted on April 12, 2018. Clinical and echocardiographic assessments are complete through 2 years and will continue annually through 5 years. Main Outcomes and Measures: All-cause mortality and all-cause mortality or disabling stroke at 2 years. Other clinical factors included overall stroke, disabling stroke, repeated procedures, rehospitalization, valve thrombosis, and pacemaker implantation. Echocardiographic analyses included effective orifice area, mean gradient, and paravalvular leaks (PVLs). Results: Of 912 participants, the mean (SD) age was 82.8 (7.3) years, 465 (51%) were women, and the mean (SD) Society of Thoracic Surgeons predicted risk of mortality was 6.8% (4.0%). At 2 years, all-cause death was 21.3% with Lotus vs 22.5% with CoreValve (hazard ratio [HR], 0.94; 95% CI, 0.69-1.26; P = .67) and all-cause mortality or disabling stroke was 22.8% with Lotus and 27.0% with CoreValve (HR, 0.81; 95% CI, 0.61-1.07; P = .14). Overall stroke was 8.4% vs 11.4% (HR, 0.75; 95% CI, 0.48-1.17; P = .21); disabling stroke was more frequent with CoreValve vs Lotus (4.7% Lotus vs 8.6% CoreValve; HR, 0.53; 95% CI, 0.31-0.93; P = .02). More Lotus patients received a new permanent pacemaker (41.7% vs 26.1%; HR, 1.87; 95% CI, 1.41-2.49; P < .01) or had a valve thrombosis (3.0% vs 0.0%; P < .01) compared with CoreValve. More patients who received CoreValve experienced a repeated procedure (0.6% Lotus vs 2.9% CoreValve; HR, 0.19; 95% CI, 0.05-0.70; P < .01), valve migration (0.0% vs 0.7%; P = .05), or embolization (0.0% vs 2.0%; P < .01) than Lotus. Valve areas remained significantly larger and the mean gradient was lower with CoreValve than Lotus (valve area, mean [SD]: Lotus, 1.53 [0.49] cm2 vs CoreValve, 1.76 [0.51] cm2; P < .01; valve gradient, mean [SD]: Lotus, 13.0 [6.7] mm Hg vs 8.1 [3.7] mm Hg; P < .01). Moderate or greater PVL was more frequent with CoreValve (0.3% Lotus vs 3.8% CoreValve; P < .01) at 2 years. Larger improvements in New York Heart Association (NYHA) functional class were observed with Lotus compared with CoreValve (improved by >/=1 NYHA class: Lotus, 338 of 402 [84.1%] vs CoreValve, 143 of 189 [75.7%]; P = .01; improved by >/=2 NYHA classes: 122 of 402 [37.3%] vs 65 of 305 [21.3%]). Conclusions and Relevance: After 2 years, all-cause mortality rates, mortality or disabling stroke were similar between Lotus and CoreValve. Disabling stroke, functional class, valve migration, and PVL favored the Lotus arm whereas valve hemodynamics, thrombosis, and new pacemaker implantation favored the CoreValve arm. Trial Registration: clinicaltrials.gov Identifier: NCT02202434.

Zile, M. R., E. O’Meara, B. Claggett, M. F. Prescott, S. D. Solomon, K. Swedberg, M. Packer, J. J. V. McMurray, V. Shi, M. Lefkowitz and J. Rouleau (2019). “Effects of Sacubitril/Valsartan on Biomarkers of Extracellular Matrix Regulation in Patients With HFrEF.” J Am Coll Cardiol 73(7): 795-806.

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BACKGROUND: Myocardial fibrosis is an important pathophysiological mechanism underlying the development of heart failure (HF). Given the biochemical targets of sacubitril/valsartan, we hypothesized that circulating biomarkers reflecting the mechanisms that determine extracellular matrix (ECM) homeostasis, including collagen synthesis, processing, and degradation, are altered by sacubitril/valsartan in comparison to enalapril. OBJECTIVES: The purpose of this study was to examine the effects of sacubitril/valsartan on biomarkers of ECM homeostasis and the association between the rate of primary composite outcome (cardiovascular death or HF hospitalization) and these biomarkers. METHODS: Biomarkers at baseline (n = 2,067) and both baseline and 8 months after randomization (n = 1,776) included aldosterone, soluble ST2 (sST2), tissue inhibitor of matrix metalloproteinase (TIMP)-1, matrix metalloproteinase (MMP)-2, MMP-9, Galectin-3 (Gal-3), N-terminal propeptide of collagen I (PINP), and N-terminal propeptide of collagen III (PIIINP). The effects of sacubitril/valsartan on biomarkers were compared with enalapril. Baseline biomarker values and changes from baseline to 8 months were related to primary outcome. RESULTS: At baseline, the profibrotic biomarkers aldosterone, sST2, TIMP-1, Gal-3, PINP, and PIIINP were higher, and biomarkers associated with collagen degradation, MMP-2 and -9, were lower than published referent control values. Eight months after randomization, aldosterone, sST2, TIMP-1, MMP-9, PINP, and PIIINP had decreased more in the sacubitril/valsartan than enalapril group. At baseline, higher values of sST-2, TIMP-1, and PIIINP were associated with higher primary outcome rates. Changes from baseline to 8 months in sST-2 and TIMP-1 were associated with change in outcomes. CONCLUSIONS: Biomarkers associated with profibrotic signaling are altered in HF with reduced ejection fraction, sacubitril/valsartan significantly decreased many of these biomarkers, and these biomarkers have important prognostic value. These findings suggest that sacubitril/valsartan may reduce profibrotic signaling, which may contribute to the improved outcomes. (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure [PARADIGM-HF]; NCT01035255).

Zaidat, O. O., N. H. Mueller-Kronast, A. E. Hassan, D. C. Haussen, A. P. Jadhav, M. T. Froehler, R. Jahan, M. Ali Aziz-Sultan, R. P. Klucznik, J. L. Saver, F. R. Hellinger, Jr., D. R. Yavagal, T. L. Yao, R. Gupta, C. O. Martin, H. Bozorgchami, R. Kaushal, R. G. Nogueira, R. H. Gandhi, E. C. Peterson, S. Dashti, C. A. Given, 2nd, B. P. Mehta, V. Deshmukh, S. Starkman, I. Linfante, S. H. McPherson, P. Kvamme, T. J. Grobelny, M. S. Hussain, I. Thacker, N. Vora, P. R. Chen, S. J. Monteith, R. D. Ecker, C. M. Schirmer, E. Sauvageau, A. B. Chebl, C. P. Derdeyn, L. Maidan, A. Badruddin, A. H. Siddiqui, T. M. Dumont, A. Alhajeri, M. A. Taqi, K. Asi, J. Carpenter, A. Boulos, G. Jindal, A. S. Puri, R. Chitale, E. M. Deshaies, D. Robinson, D. F. Kallmes, B. W. Baxter, M. Jumaa, P. Sunenshine, A. Majjhoo, J. D. English, S. Suzuki, R. D. Fessler, J. Delgado-Almandoz, J. C. Martin and D. S. Liebeskind (2019). “Impact of Balloon Guide Catheter Use on Clinical and Angiographic Outcomes in the STRATIS Stroke Thrombectomy Registry.” Stroke 50(3): 697-704.

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Background and Purpose- Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods- STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0-2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, >/=2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, >/=2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results- Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P=0.001) and distal access catheter (83/235 [35%]; P=0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P<0.001) and distal access catheter (129/234 [55%]; P=0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P=0.007) and distal access catheter (113/218 [52%]; P=0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions- BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Vardeny, O., B. Claggett, J. Kachadourian, A. S. Desai, M. Packer, J. Rouleau, M. R. Zile, K. Swedberg, M. Lefkowitz, V. Shi, J. J. V. McMurray and S. D. Solomon (2019). “Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial.” Eur J Heart Fail.

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AIMS: To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. METHODS AND RESULTS: Overall, 8399 patients with New York Heart Association class II-IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics (n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post-randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on-treatment analysis. CONCLUSION: Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.