Cardiology

Grayburn, P.A., Packer, M., Sannino, A. and Stone, G.W. (2020). “Disproportionate secondary mitral regurgitation: myths, misconceptions and clinical implications.” Heart Nov 24;heartjnl-2020-316992. [Epub ahead of print.].

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Secondary (functional) mitral regurgitation (SMR) most commonly arises secondary to left ventricular (LV) dilation/dysfunction. The concept of disproportionately severe SMR was proposed to help explain the different results of two randomised trials of transcatheter edge-to-edge mitral valve repair (TEER) versus medical therapy. This concept is based on the fact that effective regurgitant orifice area (EROA) depends on LV end-diastolic volume (LVEDV), ejection fraction, regurgitant fraction and the velocity-time integral of SMR. This review focuses on the haemodynamic framework underlying the concept and the myths and misconceptions arising from it. Each component of EROA/LVEDV is prone to measurement error which can result in misclassification of individual patients. Moreover, EROA is typically measured at peak systole rather than its mean value over the duration of MR. This can result in physiologically impossible values of EROA or regurgitant volume. Although the EROA/LVEDV ratio (1) emphasises that grading MR severity needs to consider LV size and function and (2) helps explain the different outcomes between COAPT and MITRAFR, there are important factors that are not included. Among these are left atrial compliance, LV pressure and ejection fraction, pulmonary hypertension, right ventricular function and tricuspid regurgitation. Because medical therapy can reduce LV volumes and improve both LV function and SMR severity, the key to patient selection is forced titration of neurohormonal antagonists to the target doses that have been proven in clinical trials (along with cardiac resynchronisation when appropriate). Patients who continue to have symptomatic severe SMR after doing so should be considered for TEER.

Kandzari, D.E., Kirtane, A.J., Windecker, S., Latib, A., Kedhi, E., Mehran, R., Price, M.J., Abizaid, A., Simon, D.I., Worthley, S.G., Zaman, A., Choi, J.W., Caputo, R., Kanitkar, M., McLaurin, B., Potluri, S., Smith, T., Spriggs, D., Tolleson, T., Nazif, T., Parke, M., Lee, L.C., Lung, T.H. and Stone, G.W. (2020). “One-Month Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention With Zotarolimus-Eluting Stents in High-Bleeding-Risk Patients.” Circ Cardiovasc Interv 13(11): e009565.

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BACKGROUND: Despite treatment guidance endorsing shortened dual antiplatelet therapy (DAPT) duration in high bleeding risk (HBR) patients after drug-eluting stents, limited evidence exists to support these recommendations. The present study was designed to examine the safety and effectiveness of 1-month DAPT duration following percutaneous coronary intervention with zotarolimus-eluting stents in HBR patients. METHODS: Onyx ONE Clear was a prospective, multicenter, nonrandomized study evaluating the safety and effectiveness of 1-month DAPT followed by single antiplatelet therapy in HBR patients undergoing percutaneous coronary intervention with Resolute Onyx drug-eluting stents. The primary analysis of cardiac death or myocardial infarction between 1 month and 1 year was performed in the prespecified one-month clear population of patients pooled from the Onyx ONE US/Japan study and Onyx ONE randomized controlled trial. One-month clear was defined as DAPT adherence and without major adverse events during the first month following percutaneous coronary intervention. RESULTS: Among patients enrolled in Onyx ONE US/Japan (n=752) and Onyx ONE randomized controlled trial (n=1018), 1506 patients fulfilled one-month clear criteria. Mean HBR characteristics per patient was 1.6 with 44.7% having multiple risks. By 2 months and 1 year, respectively, 96.9% and 89.3% of patients were taking single antiplatelet therapy. Between 1 month and 1 year, the rate of the primary end point was 7.0%. The 1-sided upper 97.5% CI was 8.4%, less than the performance goal of 9.7% (P<0.001). CONCLUSIONS: Among HBR patients who were event free before DAPT discontinuation at 1 month, favorable safety and effectiveness through 1 year support treatment with Resolute Onyx drug-eluting stents as part of an individualized strategy for shortened DAPT duration following percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier NCT03647475.

Xenogiannis, I., Alaswad, K., Krestyaninov, O., Khelimskii, D., Khatri, J.J., Choi, J.W., Jaffer, F.A., Patel, M., Mahmud, E., Doing, A.H., Dattilo, P., Koutouzis, M., Tsiafoutis, I., Uretsky, B., Jefferson, B.K., Patel, T., Jaber, W., Samady, H., Sheikh, A.M., Yeh, R.W., Tamez, H., Elbaruny, B., Love, M.P., Abi Rafeh, N., Maalouf, A., Fadi, A.J., Toma, C., Shah, A.R., Chandwaney, R.H., Omer, M., Megaly, M.S., Vemmou, E., Nikolakopoulos, I., Rangan, B.V., Garcia, S., Abdullah, S., Banerjee, S., Burke, M.N., Karmpaliotis, D. and Brilakis, E.S. (2020). “Impact of adherence to the hybrid algorithm for initial crossing strategy selection in chronic total occlusion percutaneous coronary intervention.” Rev Esp Cardiol (Engl Ed) Nov 12;S1885-5857(20)30410-2. [Epub ahead of print.].

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INTRODUCTION AND OBJECTIVES: The hybrid algorithm was designed to assist with initial and subsequent crossing strategy selection in chronic total occlusion (CTO) percutaneous coronary interventions (PCIs). However, the success of the initially selected strategy has received limited study. METHODS: We examined the impact of adherence to the hybrid algorithm recommendation for initial CTO crossing technique selection in 4178 CTO PCIs from a large multicenter registry. RESULTS: The initial crossing strategy was concordant with the hybrid algorithm recommendation in 1833 interventions (44%). Patients in the concordant group had a similar age to those in the discordant group but a lower mean J-CTO score (2.0 ± 1.4 vs 2.8 ± 1.1; P < .01). The concordant group showed higher technical success with the first crossing strategy (68% vs 48%; P < .01) and higher overall technical success (88% vs 83%; P < .01) with no difference in the incidence of in-hospital major adverse events (1.8% vs 2.3%; P = .26). In multivariable analysis, after adjustment for age, prior myocardial infarction, prior PCI, prior coronary artery bypass grafting, J-CTO score, and scheduled CTO PCI, nonadherence to the hybrid algorithm was independently associated with lower technical success of the initial crossing strategy (odds ratio, 0.55; 95% confidence interval, 0.48-0.64; P < .01). CONCLUSIONS: Adherence to the hybrid algorithm for initial crossing strategy selection is associated with higher CTO PCI success but similar in-hospital major adverse cardiac events.

Brinkman, W.T. (2020). “The Details Matter in Open TAAA Surgery.” Ann Thorac Surg Dec 3;S0003-4975(20)32051-8. [Epub ahead of print.].

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Background: The present study was done to examine the incidence, predictors, and impact of early gastrointestinal complications (GICs) after open thoracoabdominal aortic aneurysm (TAAA) repair. Methods: We retrospectively analyzed data from 3,587 open TAAA repairs performed at our center during 1986-2019. We used univariate analyses and multivariable logistic regression to identify risk factors associated with GICs including bleeding, ischemia, obstruction, and acute pancreatitis. Adverse event was defined as operative death or persistent stroke, paraplegia, paraparesis, or renal failure necessitating dialysis. Results: GICs developed after 213 repairs (5.9%). GICs less often developed after extent I repair than after repairs that involved infrarenal abdominal aortic segments (ie, extent II-IV repairs; p = 0.003). Patients who developed GICs more often underwent endarterectomy, stenting, or bypass of visceral arteries (51.2% vs 42.2%; p = 0.01). Use of selective visceral perfusion did not differ between groups. Patients who developed GICs had higher rates of operative mortality (34.3% vs 6.6%) and adverse event (44.1% vs 13.2%) and had longer hospitalization (29 d vs 11 d) (p < 0.001 for all). Independent predictors of GICs included incidental splenectomy, rupture, non–extent I repair, older age, and longer aortic cross-clamp time. Short-, mid-, and long-term survival were poorer in patients who developed GICs (p < 0.001). Conclusions: Although uncommon, early GICs after open TAAA repair are associated with significant short- and long-term morbidity and mortality. Development of perioperative strategies to mitigate these complications is warranted.

Packer, M., Butler, J., Filippatos, G., Zannad, F., Ferreira, J.P., Zeller, C., Brueckmann, M., Jamal, W., Pocock, S. and Anker, S.D. (2020). “Design of a Prospective Patient-Level Pooled Analysis of Two Parallel Trials of Empagliflozin in Patients With Established Heart Failure.” Eur J Heart Fail Nov 30. [Epub ahead of print.].

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The EMPEROR-Reduced trial demonstrated that empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with a reduced ejection fraction, and the EMPEROR-Preserved trial is currently evaluating the effect of the drug on the same endpoint in patients with an ejection fraction > 40%. However, neither the trial was designed to have adequate statistical power to evaluate the effects of empagliflozin and dapagliflozin on major adverse renal outcomes or on mortality. Herein we describe the design of a prospective individual patient-level pooled analysis of two large-scale trials with empagliflozin (EMPEROR-Reduced and EMPEROR-Preserved) in patients with heart failure across the spectrum of ejection fraction. The trials were carried out in parallel using the same administrative structure and committees, randomization procedure, schedule of study visits and adjudication criteria and similar groups of investigators and case report forms. The two component trials specified the same primary and key secondary endpoints and used an identical hierarchical testing procedure, which included a pooled analysis of the two trials as a key component of the hierarchy. Consequently, the pooled analysis has been prospectively assigned a false positive error rate, which is conditional on one or both trials first achieving success on their primary and one or both key secondary endpoints. The pooled analysis has its own statistical plan with its own endpoints, and this plan was finalized before either trial had begun recruitment of patients into either study. The primary endpoint of the pooled analysis is a composite of serious adverse renal outcomes, defined by chronic dialysis, renal transplantation and a profound or sustained decrease in glomerular filtration rate. All-cause and cardiovascular mortality are specified as secondary endpoints. The planned pooled analysis has an unusually high degree of statistical rigor that will allow it to address important questions that cannot be fully addressed by the individual trials.