Michael J. Mack M.D.

Gaudino, M., D. J. Angiolillo, A. Di Franco, D. Capodanno, F. Bakaeen, M. E. Farkouh, S. E. Fremes, D. Holmes, L. N. Girardi, S. Nakamura, S. J. Head, S. J. Park, M. Mack, P. W. Serruys, M. Ruel, G. W. Stone, D. Y. Tam, M. Vallely and D. P. Taggart (2019). “Stroke After Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention: Incidence, Pathogenesis, and Outcomes.” J Am Heart Assoc 8(13): e013032. Epub 2019 Jun 27.

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Stroke carries high short‐ and long‐term mortality and significantly adversely affects quality of life after both CABG and PCI. In an era in which practice guidelines endorse fully informing patients of the available treatment options and actively including them in the decision‐making process, defining the risk of stroke, both acute and long term, and its clinical implications is of paramount importance. CABG carries higher perioperative risk of stroke but provides greater long‐term freedom from recurrent ischemic coronary events and better survival, especially in the patients with most severe disease.2 Percutaneous revascularization is feasible in many patients and is associated with relatively low stroke rates, but this benefit needs to weighed against the higher rates of long‐term mortality and myocardial infarction, particularly in some categories of patients with diabetes mellitus and/or extensive multivessel disease. Indeed, better understanding the size of an injury deriving from a stroke with the 2 available revascularization approaches and the significance of silent brain lesions or neurocognitive changes that may occur would inform the decision‐making process. However, data on these measures (e.g., serial brain imaging) are lacking. A number of measures can be considered to reduce neurological risk in patients undergoing revascularization. For surgery, pre‐ and intraoperative screening of the ascending aorta and optimization of cerebral perfusion pressure based on continuous monitoring are important measures to minimize stroke risk. The use of the anaortic technique has the potential to minimize stroke risk during CABG. Given its technical complexity, specific training is required, ideally in the context of a new CABG subspecialty. Other technical advancements (e.g., embolic protection) warrant investigation to reduce the perioperative risk of stroke in patients undergoing CABG. For PCI, the reduction in mortality and bleeding—with some data also showing a reduction in peri-procedural stroke—associated with radial access potentially makes this approach the vascular access of choice. Regardless of vascular access, operator experience and competency play key roles in minimizing catheter‐induced trauma to the aortic wall and cerebral embolization. Other important measures include optimal anticoagulation and avoidance of air embolism with adequate flushing and connections to the manifold. Routine use of manual thrombectomy in ST‐segment–elevation myocardial infarction should be avoided; if required, adequate catheter engagement should be maintained to avoid embolization of thrombotic material. Finally, IABP and hemodynamic support devices in general should be used with caution, particularly in patients with diffuse atherosclerotic aortic disease. (Excerpt from text, p. e013032, 8-9; no abstract available.)

Badhwar, V., M. Alkhouli, M. J. Mack, V. H. Thourani and G. Ailawadi (2019). “A pathoanatomic approach to secondary functional mitral regurgitation: Evaluating the evidence.” J Thorac Cardiovasc Surg 158(1): 76-81.

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As evidence to support transcatheter and surgical management of functional secondary mitral regurgitation evolves, targeting therapy to pathoanatomic grade may improve outcomes and the evidence . . . Surgical repair indeed has its niche role in pathoanatomically suitable disease and MV replacement has its place for symptom resolution, although randomized investigation has not been performed to clearly identify survival benefit. Transcatheter repair will clearly have an expanding role in SMR, but successes in some patients and failures in others highlight the need for clarity in how to identify the ideal patients to receive optimal benefit from this modality. Transcatheter MV replacement is undergoing active investigation, but anatomic limitations of LV outflow tract obstruction and annular size may limit its widespread application. Due to the spectrum of structural cardiac disease that accompanies SMR, not all patients can be managed in the same manner and therapy should be tailored . . . In light of the accumulated knowledge from the surgical and transcatheter literature, a simplified pathoanatomic classification scheme of SMR that incorporates the key categories of annular dilatation, LV dysfunction/dilatation and leaflet tethering is proposed. This scoring system may aid in assessing SMR features in outpatient clinics and echocardiography laboratories ( Table 2 ) and assist in tailoring the pathoanatomy to possible therapeutic options based on comorbid risk. This intuitive schema may be useful for future prospective investigation as well as for retrospective examination of both the MITRA-FR echocardiograms as well as the COAPT trial core lab echocardiograms to ascertain if this simple categorization predicts short- and long-term success in transcatheter MV repair. (Excerpts from text, p. 76, 79-80; no abstract available.)

Stone, G. W., N. J. Weissman and M. J. Mack (2019). “Transcatheter Mitral-Valve Repair in Patients with Heart Failure. Reply.” N Engl J Med 380(20): 1980-1981.

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The authors reply: Crestanello et al. question the apparently low forward stroke volume calculated from the total left ventricular stroke volume, which was determined by applying Simpson’s method to two-dimensional biplane echocardiographic measurements and using an assumed regurgitant volume. The actual mean forward stroke volume in the COAPT trial as measured with Doppler was 51 ml, and the regurgitant volume as measured with the use of the PISA (proximal isovelocity surface area) method was 59 ml, values that are consistent with severe mitral regurgitation. There are several reasons for the discrepancies from Crestanello’s theoretical extrapolation, in which two-dimensional and Doppler data are combined, the most important being the substantial underestimation of left ventricular volume (and stroke volume), as determined by two-dimensional echocardiography with the use of Simpson’s rule, especially in patients with dilated ventricles, such as those enrolled in the COAPT trial. Drake et al. posit that a lack of imaging guidance resulted in a high rate of recurrence of mitral regurgitation after surgical repair with a downsized annuloplasty ring in the trial conducted by the Cardiothoracic Surgical Trials Network. That trial used detailed echocardiographic analysis to gauge patient suitability for inclusion. A post hoc subanalysis defined the anatomical features shown on echocardiography that were predictive of a durable surgical repair. Ongoing, detailed echocardiographic analyses in the COAPT trial will further delineate the anatomical features that predict favorable outcomes after transcatheter mitral-leaflet approximation. We do agree that image-guided assessment is essential to the identification of a responder population and that in the future it may direct patient-specific intervention (leaflet repair, annuloplasty, or valve replacement). What Garbi and Lancellotti term valvular heart failure secondary to mitral regurgitation, Grayburn et al. designate as disproportionate mitral regurgitation and Carabello calls tertiary mitral regurgitation. Regardless of the nomenclature, we agree that relative to the MITRA-FR trial, the COAPT trial investigators enrolled a greater proportion of patients in whom prognosis was dictated more by the severity of mitral regurgitation than by the degree of left ventricular dysfunction — a major reason why patients in the COAPT trial, but not those in the MITRA-FR trial, benefited from transcatheter mitral-valve repair. We further agree that reduction in left atrial pressure (and volume) was probably responsible for many of the clinical benefits associated with transcatheter mitral-valve repair in the COAPT trial. Mitral-valve replacement offers the potential for greater reduction in mitral regurgitation than transcatheter mitral-valve repair. Whether the procedure will provide sufficiently greater clinical effectiveness warranting a potentially more complex and complicated procedure is uncertain and can only be addressed by means of adequately powered randomized trials. Finally, Kalavrouziotis et al. are incorrect in stating that enrollment in the COAPT trial was “supervised” by the sponsor. Rather, investigators at each site determined whether screened patients met prespecified enrollment criteria, a determination that was then confirmed by a physician-led, sponsor-independent, central eligibility committee and echocardiographic core laboratory. We believe that practitioner fidelity to the inclusion and exclusion criteria used in the COAPT trial should lead to duplication of our results in the real world. (Text of authors’ reply to several letters in the same issue of NEJM; see also authors’ original article, Stone, G. W., J. Lindenfeld, W. T. Abraham, S. Kar, D. S. Lim, J. M. Mishell, B. Whisenant, P. A. Grayburn, M. Rinaldi, S. R. Kapadia, V. Rajagopal, I. J. Sarembock, A. Brieke, S. O. Marx, D. J. Cohen, N. J. Weissman and M. J. Mack (2018). “Transcatheter Mitral-Valve Repair in Patients with Heart Failure.” N Engl J Med 379(24): 2307-2318.)

Webb, J. G., D. J. Murdoch, M. C. Alu, A. Cheung, A. Crowley, D. Dvir, H. C. Herrmann, S. K. Kodali, J. Leipsic, D. C. Miller, P. Pibarot, R. M. Suri, D. Wood, M. B. Leon and M. J. Mack (2019). “3-Year Outcomes After Valve-in-Valve Transcatheter Aortic Valve Replacement for Degenerated Bioprostheses: The PARTNER 2 Registry.” J Am Coll Cardiol 73(21): 2647-2655.

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BACKGROUND: Transcatheter aortic valve replacement (TAVR) for degenerated surgical bioprosthetic aortic valves is associated with favorable early outcomes. However, little is known about the durability and longer-term outcomes associated with this therapy. OBJECTIVES: The aim of this study was to examine late outcomes after valve-in-valve TAVR. METHODS: Patients with symptomatic degeneration of surgical aortic bioprostheses at high risk (>/=50% major morbidity or mortality) for reoperative surgery were prospectively enrolled in the multicenter PARTNER (Placement of Aortic Transcatheter Valves) 2 valve-in-valve and continued access registries. Three-year clinical and echocardiographic follow-up was obtained. RESULTS: Valve-in-valve procedures were performed in 365 patients. The mean age was 78.9 +/- 10.2 years, and the mean Society of Thoracic Surgeons score was 9.1 +/- 4.7%. At 3 years, the overall Kaplan-Meier estimate of all-cause mortality was 32.7%. Aortic valve re-replacement was required in 1.9%. Mean transaortic gradient was 35.0 mm Hg at baseline, decreasing to 17.8 mm Hg at 30-day follow-up and 16.6 mm Hg at 3-year follow-up. Baseline effective orifice area was 0.93 cm(2), increasing to 1.13 and 1.15 cm(2) at 30 days and 3 years, respectively. Moderate to severe aortic regurgitation was reduced from 45.1% at pre-TAVR baseline to 2.5% at 3 years. Importantly, moderate or severe mitral and tricuspid regurgitation also decreased (33.7% vs. 8.6% [p < 0.0001] and 29.7% vs. 18.8% [p = 0.002], respectively). Baseline left ventricular ejection fraction was 50.7%, increasing to 54.7% at 3 years (p < 0.0001), while left ventricular mass index was 136.4 g/m(2), decreasing to 109.1 g/m(2) at 3 years (p < 0.0001). New York Heart Association functional class improved, with 90.4% in class III or IV at baseline and 14.1% at 3 years (p < 0.0001), and Kansas City Cardiomyopathy Questionnaire overall score increased (43.1 to 73.1; p < 0.0001). CONCLUSIONS: At 3-year follow-up, TAVR for bioprosthetic aortic valve failure was associated with favorable survival, sustained improved hemodynamic status, and excellent functional and quality-of-life outcomes. (The PARTNER II Trial: Placement of Aortic Transcatheter Valves II - PARTNER II - Nested Registry 3/Valve-in-Valve [PII NR3/ViV]; NCT03225001).

Roberts, W. C., P. A. Grayburn, S. R. Lander, D. M. Meyer and S. A. Hall (2019). “Effect of Progressive Left Ventricular Dilatation on Degree of Mitral Regurgitation Secondary to Mitral Valve Prolapse.” Am J Cardiol 123(11): 1887-1888.

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Described herein is a 71-year-old man who at age 61 was found by echocardiogram to have severe mitral regurgitation (MR) from mitral valve prolapse. During the subsequent 9 years the MR progressively lessened as his left ventricular cavity dilated and his ejection fraction progressively fell such that just before orthotopic heart transplantation the degree of MR was no longer severe, and the prolapse of the mitral leaflets had disappeared. This report describes this unique patient.