A case of delayed malposition of a CoreValve device causing obstruction of coronary ostia is described. Nine months after the original implant, the patient developed an acute coronary syndrome and was readmitted to hospital. Angiogram demonstrated an ostial stenosis of both the left main stem and the right coronary ostia, which were filled by a paravalvular leakage of the bioprosthesis. Gated computed tomography scan with 3D reconstruction showed valve malposition with cusps situated 14 mm above the ostium of the right coronary and the presence of fibrous and calcific agglomerations associated to one of the cusp causing a tight stenosis of the left ostium. Computed tomography scan is a crucial imaging technique in the transcatheter aortic valve replacement field and in this case enabled us to identify an interesting phenomenon of fibrosis/calcification originating at the level of the misplaced valve, which was actually the triggering cause of the coronary obstruction. Considering the reported need for more accurate investigations regarding the predictors of negative outcomes and the selection of transcatheter aortic valve replacement candidates, the use of cardiac-gated computed tomography should be stimulated and promoted as a valuable aid for the diagnosis and further clinical decision making in those patients.
The authors reported no conflicts of interest.The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.Okuno and colleagues1Okuno T. Praz F. Kassar M. Biaggi P. Mihalj M. Killing M. et al.Surgical versus transcatheter repair for secondary mitral regurgitation: a propensity score matched cohorts comparison.J Thorac Cardiovasc Surg. July 27, 2021; ([Epub ahead of print]. https://doi.org/10.1016/j.jtcvs.2021.07.029)Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar reported 2-year outcomes comparing surgical repair with restrictive mitral annuloplasty (RMA) versus transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation (SMR). It highlights contradictions in the 2020 American Heart Association/American College of Cardiology (AHA/ACC) guidelines for the indication for TEER in SMR was Class IIb with level of evidence B-R.2Otto C.M. Nishimura R.A. Bonow R.O. Carabello B.A. Erwin III, J.P. Gentile F. et al.2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines.J Am Coll Cardiol. 2021; 77: 450-500Crossref PubMed Scopus (249) Google Scholar In that study of 202 patients, the investigators compared propensity-matched surgical versus transcatheter repair for SMR with a report published immediately after the presentation of new AHA/ACC guidelines. After 2 years' follow-up, although the investigators found no significant difference in survival (P = .909), they recorded superiority in RMA with coronary revascularization versus TEER for decreasing mitral regurgitation (MR), improving ventricular ejection fraction, and reducing New York Heart Association functional class III or IV.1Okuno T. Praz F. Kassar M. Biaggi P. Mihalj M. Killing M. et al.Surgical versus transcatheter repair for secondary mitral regurgitation: a propensity score matched cohorts comparison.J Thorac Cardiovasc Surg. July 27, 2021; ([Epub ahead of print]. https://doi.org/10.1016/j.jtcvs.2021.07.029)Abstract Full Text Full Text PDF PubMed Scopus (10) Google ScholarLeft ventricular remodeling predicts poor prognosis in ischemic myocardial disease and is reversible with recovery of viable myocardium.3Nappi F. Lusini M. Spadaccio C. Nenna A. Covino E. Acar C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation.J Am Coll Cardiol. 2016; 67: 2334-2346Crossref PubMed Scopus (127) Google Scholar,4Nappi F. Spadaccio C. Nenna A. Lusini M. Fraldi M. Acar C. et al.Is subvalvular repair worthwhile in severe ischemic mitral regurgitation? Subanalysis of the papillary muscle approximation trial.J Thorac Cardiovasc Surg. 2017; 153: 286-295Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar Cardiothoracic Surgical Trials Network trial subanalyses included 75% of patients receiving concomitant coronary artery bypass grafting surgery, eliminating the possibility of improvement in regional wall motion for 25% of patients.4Nappi F. Spadaccio C. Nenna A. Lusini M. Fraldi M. Acar C. et al.Is subvalvular repair worthwhile in severe ischemic mitral regurgitation? Subanalysis of the papillary muscle approximation trial.J Thorac Cardiovasc Surg. 2017; 153: 286-295Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar,5Goldstein D. Moskowitz A.J. Gelijns A.C. Ailawadi G. Parides M.K. Perrault L.P. et al.Two-year outcomes of surgical treatment of severe ischemic mitral regurgitation.N Engl J Med. 2016; 374: 344-353Crossref PubMed Scopus (538) Google Scholar Subannular procedure combined with RMA have been superior to RMA alone in both ischemic and nonischemic cardiomyopathy in other studies.3Nappi F. Lusini M. Spadaccio C. Nenna A. Covino E. Acar C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation.J Am Coll Cardiol. 2016; 67: 2334-2346Crossref PubMed Scopus (127) Google Scholar,6Pausch J. Sequeira Gross T. Müller L. von Stumm M. Kloth B. Reichenspurner H. et al.Subannular repair for functional mitral regurgitation type IIIb in patients with ischaemic versus dilated cardiomyopathy.Eur J Cardiothorac Surg. 2021; 60: 122-130Crossref PubMed Scopus (6) Google Scholar,7Harmel E. Pausch J. Gross T. Petersen J. Sinning C. Kubitz J. et al.Standardized subannular repair improves outcomes in type IIIb functional mitral regurgitation.Ann Thorac Surg. 2019; 108: 1783-1792Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar In a papillary muscle approximation (PMA) randomized trial, 96 patients with severe chronic ischemic mitral regurgitation underwent complete surgical myocardial revascularization associated with either isolated RMA or PMA + RMA over a 5-year follow-up. Left ventricular end-diastolic diameter improved at 5-year follow-up (5.8 ± 4.1 mm and −0.2 ± 2.3 mm, respectively; P < .001), maintaining the benefit achieved immediately postoperatively with freedom from major adverse cardiac and cerebrovascular events (P = .004)3Nappi F. Lusini M. Spadaccio C. Nenna A. Covino E. Acar C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation.J Am Coll Cardiol. 2016; 67: 2334-2346Crossref PubMed Scopus (127) Google Scholar (Figure 1). TEER use in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) study did not reveal an improvement of left ventricular remodeling (left ventricular end-diastolic volume/mL, 194.4 ± 69.2 mL vs 192.2 ± 76.5 mL),8Nappi F. Antoniou G.A. Nenna A. Michler R. Benedetto U. Avtaar Singh S.S. et al.Treatment options for ischemic mitral regurgitation: a meta-analysis.J Thorac Cardiovasc Surg. 2022; 163: 607-622.e14Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar,9Stone G.W. Lindenfeld J. Abraham W.T. Kar S. Lim D.S. Mishell J.M. et al.Transcatheter mitral-valve repair in patients with heart failure.N Engl J Med. 2018; 379: 2307-2318Crossref PubMed Scopus (1415) Google Scholar although patients who underwent TEER had sustained 3-year improvements in MR severity, quality-of-life measures, and functional capacity compared with those who received guideline-directed medical therapy (GDMT) at 3 years' follow-up.10Mack M.J. Lindenfeld J. Abraham W.T. Kar S. Lim D.S. Mishell J.M. et al.3-year outcomes of transcatheter mitral valve repair in patients with heart failure.J Am Coll Cardiol. 2021; 77: 1029-1040Crossref PubMed Scopus (57) Google Scholar The benefit of TEER over GDMT was confirmed among 58 patients primarily managed with alone who crossed-over receiving TEER. For the subsequent composite rate of mortality or hospitalization for cardiac failure, hospitalization for cardiac failure was reduced compared with GDMT alone (P = .006).10Mack M.J. Lindenfeld J. Abraham W.T. Kar S. Lim D.S. Mishell J.M. et al.3-year outcomes of transcatheter mitral valve repair in patients with heart failure.J Am Coll Cardiol. 2021; 77: 1029-1040Crossref PubMed Scopus (57) Google ScholarFigure 1Composite cardiac end point. The composite end point of the rate of major adverse cardiac or cerebrovascular events (MACCEs) included cardiac death, stroke, subsequent mitral valve surgery, rehospitalization, and an increase in New York Heart Association functional class of 1 or more. Vertical marks indicate that a patient's data were censored at that point. At 5 years, there were no significant between = group differences with respect to the composite end point of MACCE, with 45 events in the restrictive annuloplasty (RA) group and 34 events in the papillary muscle approximation (PMA) group (left). However, the incidence of MACCE was significantly reduced in the PMA group during the last year of follow-up (right).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Okuno and colleagues1Okuno T. Praz F. Kassar M. Biaggi P. Mihalj M. Killing M. et al.Surgical versus transcatheter repair for secondary mitral regurgitation: a propensity score matched cohorts comparison.J Thorac Cardiovasc Surg. July 27, 2021; ([Epub ahead of print]. https://doi.org/10.1016/j.jtcvs.2021.07.029)Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar revealed that restrictive mitral annuloplasty was superior to TEER at 2 years as a secondary end point. Evidence from randomized controlled trials (RCTs) proved that RMA had higher MR recurrence rates at 2 and 5 years' follow-up (58.8% and 55.9%, respectively).3Nappi F. Lusini M. Spadaccio C. Nenna A. Covino E. Acar C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation.J Am Coll Cardiol. 2016; 67: 2334-2346Crossref PubMed Scopus (127) Google Scholar,5Goldstein D. Moskowitz A.J. Gelijns A.C. Ailawadi G. Parides M.K. Perrault L.P. et al.Two-year outcomes of surgical treatment of severe ischemic mitral regurgitation.N Engl J Med. 2016; 374: 344-353Crossref PubMed Scopus (538) Google Scholar Suitability for RMA should include smaller preoperative left ventricular end systolic diameter and reduced apical tethering of the leaflets. Seventy-four patients from the Cardiothoracic Surgical Trials Network trial with severe ischemic mitral regurgitation with no persistent or recurrent MR after RMA recorded significantly smaller left ventricles at 2 years' follow-up compared with patients with recurrent MR post-RMA alone (43 ± 26 mL/m2 vs 63 ± 27 mL/m2). Left ventricular end systolic volume was significantly lower compared with patients managed with mitral valve replacement (61 ± 39 mL/m2).5Goldstein D. Moskowitz A.J. Gelijns A.C. Ailawadi G. Parides M.K. Perrault L.P. et al.Two-year outcomes of surgical treatment of severe ischemic mitral regurgitation.N Engl J Med. 2016; 374: 344-353Crossref PubMed Scopus (538) Google ScholarIn the PMA trial, double-level repair achieved geometric restitution by normalization of 3 measures: anteroposterior annular dilation, tenting area, and interpapillary muscle distance. The goal is to address both the valvular and ventricular features of secondary MR (Carpentier class IIIb).3Nappi F. Lusini M. Spadaccio C. Nenna A. Covino E. Acar C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation.J Am Coll Cardiol. 2016; 67: 2334-2346Crossref PubMed Scopus (127) Google Scholar,4Nappi F. Spadaccio C. Nenna A. Lusini M. Fraldi M. Acar C. et al.Is subvalvular repair worthwhile in severe ischemic mitral regurgitation? Subanalysis of the papillary muscle approximation trial.J Thorac Cardiovasc Surg. 2017; 153: 286-295Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar,6Pausch J. Sequeira Gross T. Müller L. von Stumm M. Kloth B. Reichenspurner H. et al.Subannular repair for functional mitral regurgitation type IIIb in patients with ischaemic versus dilated cardiomyopathy.Eur J Cardiothorac Surg. 2021; 60: 122-130Crossref PubMed Scopus (6) Google Scholar,7Harmel E. Pausch J. Gross T. Petersen J. Sinning C. Kubitz J. et al.Standardized subannular repair improves outcomes in type IIIb functional mitral regurgitation.Ann Thorac Surg. 2019; 108: 1783-1792Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar The fundamental role of papillary muscles is also focused on by Kainuma and colleagues.11Kainuma S. Funatsu T. Kondoh H. Yokota T. Maeda S. Shudo Y. et al.Beneficial effects of restrictive annuloplasty on subvalvular geometry in patients with functional mitral regurgitation and advanced cardiomyopathy.J Thorac Cardiovasc Surg. 2018; 156: 630-638.e1Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Kainuma and colleagues11Kainuma S. Funatsu T. Kondoh H. Yokota T. Maeda S. Shudo Y. et al.Beneficial effects of restrictive annuloplasty on subvalvular geometry in patients with functional mitral regurgitation and advanced cardiomyopathy.J Thorac Cardiovasc Surg. 2018; 156: 630-638.e1Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar recorded that the use of restrictive mitral annuloplasty alone only partially alleviated the tethering of leaflet, which instead significantly favored a reduction in tethering and interpapillary muscles distance. The latter was the main determinant of MR recurrence. These beneficial effects could be mainly attributed to post-RMA reverse left ventricular remodeling leading to a reduction in interpapillary muscle distance (31 ± 6 mm to 25 ± 5 mm), potentially offsetting the negative effect of increasing posterior leaflet angle.11Kainuma S. Funatsu T. Kondoh H. Yokota T. Maeda S. Shudo Y. et al.Beneficial effects of restrictive annuloplasty on subvalvular geometry in patients with functional mitral regurgitation and advanced cardiomyopathy.J Thorac Cardiovasc Surg. 2018; 156: 630-638.e1Abstract Full Text Full Text PDF PubMed Scopus (14) Google ScholarPMA is more suitable than TEER in patients with SMR due to nonischemic cardiomyopathy (Carpentier class I) where annular dilation, lateral displacement of anterior and posterior papillary muscle, symmetrical tethering with apical tenting of anterior leaflet, and central jet were prevalent. Patients with severe left ventricular dilation and moderate-to-severe MR had poorer outcomes both in the small group of patients in the COAPT8Nappi F. Antoniou G.A. Nenna A. Michler R. Benedetto U. Avtaar Singh S.S. et al.Treatment options for ischemic mitral regurgitation: a meta-analysis.J Thorac Cardiovasc Surg. 2022; 163: 607-622.e14Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar and in Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary Mitral Regurgitation12Iung B. Armoiry X. Vahanian A. Boutitie F. Mewton N. Trochu J.-N. et al.Percutaneous repair or medical treatment for secondary mitral regurgitation: outcomes at 2 years.Eur J Heart Fail. 2019; 21: 1619-1627Crossref PubMed Scopus (124) Google Scholar trials. These patients had similar features of proportionate MR and did not respond favorably to TEER (Table 1).13Packer M. Grayburn P.A. New evidence supporting a novel conceptual framework for distinguishing proportionate and disproportionate functional mitral regurgitation.JAMA Cardiol. 2020; 5: 469-475Crossref PubMed Scopus (58) Google ScholarTable 1Randomized clinical trial (RCT) reporting secondary mitral regurgitation (SMR)First author or Study acronymType of studyNo. of patientsTreatmentMean follow-up (y)Criteria for SMRFindingsHarmel, 20197Harmel E. Pausch J. Gross T. Petersen J. Sinning C. Kubitz J. et al.Standardized subannular repair improves outcomes in type IIIb functional mitral regurgitation.Ann Thorac Surg. 2019; 108: 1783-1792Abstract Full Text Full Text PDF PubMed Scopus (19) Google ScholarProspective101RMA (50)RMA + PMR (51)1•Ischemic cardiomyopathy 100%•Average LVEDD >60 mm; LVEF <40%•EROA >0.2 cm2Better improvement of left ventricular remodeling in PMR groupMR > 2+ more common among patients with RMABetter survival in RMA + PMRStone, 20189Stone G.W. Lindenfeld J. Abraham W.T. Kar S. Lim D.S. Mishell J.M. et al.Transcatheter mitral-valve repair in patients with heart failure.N Engl J Med. 2018; 379: 2307-2318Crossref PubMed Scopus (1415) Google ScholarCOAPTRCT614TEER (302)GDMT (312)2•Ischemic cardiomyopathy 62.5%•Average LVEDV 192 mL; LVEF 31% ± 9% (18% LVEF >40%)•MR grade 3 or 4•EROA mean value 0.41 cm2; 14% EROA <0.3 cm2; 41% ≥ 0.4 cm2Lower rate of unplanned hospitalization in TEER with disproportionate SMR. Slight improvement of LVEDV/mL/min (from 194.4 ± 37.4-192.2 ± 76.5)Iung, 201912Iung B. Armoiry X. Vahanian A. Boutitie F. Mewton N. Trochu J.-N. et al.Percutaneous repair or medical treatment for secondary mitral regurgitation: outcomes at 2 years.Eur J Heart Fail. 2019; 21: 1619-1627Crossref PubMed Scopus (124) Google ScholarMITRA FrRCT306TEER (152)GDMT (154)1•Ischemic cardiomyopathy 62.5%•Average LVEDV 252 mL 33% ± 7% (all LVEF ≤40%)•EROA mean value 0.31 cm2•50% EROA <0.3 cm2; 16% ≥ 0.4 cm2No difference in unplanned hospitalization rate and death between TEER vs GDMT. Slight improvement of LVEDV/mL/min (from 136.2 ± 37.4-134.2 ± 37)Nappi, 20168Nappi F. Antoniou G.A. Nenna A. Michler R. Benedetto U. Avtaar Singh S.S. et al.Treatment options for ischemic mitral regurgitation: a meta-analysis.J Thorac Cardiovasc Surg. 2022; 163: 607-622.e14Abstract Full Text Full Text PDF PubMed Scopus (13) Google ScholarPMA trialRCT96RMA (48)RMA plus PMA (48)5•Ischemic cardiomyopathy 100%•Coronary artery disease with or without the need for coronary revascularization•Average value LVEDD 62 mm LVEF 42%•MR grade 3 or 4•EROA> 0.2 cm2 or regurgitant volume >30 mL∗European Society of Cardiology guidelines.•EROA mean value 0.34 cm2Lower rate of unplanned hospitalization in PMA group. Better improvement of LVEDD in PMA (62.7 ± 3.4-56.5 ± 5.7) vs RMA (61.4 ± 3.7-60.6 ± 4.6). Lower incidence of recurrent MR in the PMA group (27% vs 55.9%)Goldstein, 20165Goldstein D. Moskowitz A.J. Gelijns A.C. Ailawadi G. Parides M.K. Perrault L.P. et al.Two-year outcomes of surgical treatment of severe ischemic mitral regurgitation.N Engl J Med. 2016; 374: 344-353Crossref PubMed Scopus (538) Google ScholarCTSNRCT251MVR (125)RMA (126)2•Ischemic cardiomyopathy 100%•Average value LVESV 63.4 mL; LVEF 40%•MR grade 4•EROA ≥0.4 cm2 with tethering•Eligible for surgical repair and replacement of mitral valve•Coronary artery disease with or without the need for coronary revascularizationBetter improvement of LVESVI in MVR (52.6 ± 27.7 mL vs 60.6 ± 39.0 mL). Better improvement of LVESVI in RMA with smaller LV (43 ± 26 mL/m2 vs 63 ± 27 mL/m2). Higher incidence of recurrent MR in the RMA (58.8% vs 3.8%)RMA, Restrictive mitral annuloplasty; PMR, papillary muscle relocation; LVEDD, left ventricular end-diastolic diameter LVEF, left ventricular ejection fraction; EROA, effective regurgitant orifice area; MR, mitral regurgitation; COAPT, Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation; TEER, transcatheter edge-to-edge repair; GDMT, guide-direct medical therapy; LVEDV, left end-diastolic volume; MITRA Fr, Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation; PMA trial, papillary muscle approximation trial; CTSN, Cardiothoracic Surgical Trials Network; MVR, mitral valve replacement; LVESI, left end-systolic volume index.∗ European Society of Cardiology guidelines. Open table in a new tab All 5 AHA/ACC recommendations were classified as level of evidence B-R or B-NR, indicating moderate quality of studies. The available literature lacks RCTs designed with a large number of enrolled patients that include candidates receiving TEER, mitral valve replacement, or mitral valve repair with or without a subvalvular procedure. ACC/AHA guidelines reference 2 TEER-based RCTs with 3-year outcomes that are reported only for the COAPT trial,9Stone G.W. Lindenfeld J. Abraham W.T. Kar S. Lim D.S. Mishell J.M. et al.Transcatheter mitral-valve repair in patients with heart failure.N Engl J Med. 2018; 379: 2307-2318Crossref PubMed Scopus (1415) Google Scholar and the analysis of the new pathophysiological framework of the pathomechanism for SMR.10Mack M.J. Lindenfeld J. Abraham W.T. Kar S. Lim D.S. Mishell J.M. et al.3-year outcomes of transcatheter mitral valve repair in patients with heart failure.J Am Coll Cardiol. 2021; 77: 1029-1040Crossref PubMed Scopus (57) Google Scholar None of these recommendations are based on reports with 5 years' follow-up.2Otto C.M. Nishimura R.A. Bonow R.O. Carabello B.A. Erwin III, J.P. Gentile F. et al.2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines.J Am Coll Cardiol. 2021; 77: 450-500Crossref PubMed Scopus (249) Google Scholar For double-level repair, there currently is no solid evidence supported by more than 1 RCT, or meta-analysis of moderate-quality RCTs, that allows recommending this procedure.Although the results of the Multicenter Randomized, Controlled Study to Assess Mitral Valve Reconstruction for Advanced Insufficiency of Functional or Ischemic Origin14A Multicenter, randomized, controlled study to assess mitral vAlve reconsTrucTion for advancEd insufficiency of functional or iscHemic ORigiN (MATTERHORN). ClinicalTrials.gov identifier: NCT02371512.https://clinicaltrials.gov/ct2/show/NCT02371512Date accessed: March 8, 2022Google Scholar randomized study are awaited, other RCTs have demonstrated the efficacy of using novel devices. None of these are directed toward manipulating the papillary muscles by either an approximation or a relocation procedure.In the Edwards Pascal Transcatheter Mitral Valve Repair System Study RCT (N = 124), the Pascal system (Edwards Lifesciences) was implanted in patients enrolled for treatment of functional, degenerative, and mixed etiology. The Pascal transcatheter valve repair system and the MitraClip system (Abbott, Abbott Park, Ill) were compared in patients with both functional and degenerative MR. Evidence from the Edwards Pascal Transcatheter Mitral Valve Repair System Study recorded a high rate of survival, with a significant rate of reduction in heart failure-related hospitalization with reverse positive left ventricular remodeling at 1 and 2 years' follow-up.15Praz F. Spargias K. Chrissoheris M. Büllesfeld L. Nickenig G. Deuschl F. et al.Compassionate use of the PASCAL 536 transcatheter mitral valve repair system for patients with severe mitral regurgitation: a multicentre, prospective, 537 observational, first-in-man study.Lancet. 2017; 390: 773-780Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar, 16Lim D.S. Kar S. Spargias K. Kipperman R.M. O'Neill W.W. Ng M.K.C. et al.Transcatheter valve repair for patients with mitral regurgitation: 30-day results of 539 the CLASP study.JACC Cardiovasc Interv. 2019; 12: 1369-1378Crossref PubMed Scopus (91) Google Scholar, 17Webb J.G. Hensey M. Szerlip M. Schafer U. Cohen G.N. Kar S. et al.1-year outcomes for transcatheter repair in patients with mitral regurgitation 541 from the clasp study.JACC Cardiovasc Interv. 2020; 13: 2344-2357Crossref PubMed Scopus (31) Google Scholar, 18Edwards PASCAL CLASP IID/IIF Pivotal Clinical Trial (CLASP IID/IIF). ClinicalTrials.gov identifier: NCT03706833.https://clinicaltrials.gov/ct2/show/NCT03706833Date accessed: March 8, 2022Google ScholarAdditional multicenter RCTs designed with a minimum of 5-year follow-up enrolling patients to undergo either TEER or double-level repair should be encouraged. The authors reported no conflicts of interest.The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest. The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest. Okuno and colleagues1Okuno T. Praz F. Kassar M. Biaggi P. Mihalj M. Killing M. et al.Surgical versus transcatheter repair for secondary mitral regurgitation: a propensity score matched cohorts comparison.J Thorac Cardiovasc Surg. July 27, 2021; ([Epub ahead of print]. https://doi.org/10.1016/j.jtcvs.2021.07.029)Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar reported 2-year outcomes comparing surgical repair with restrictive mitral annuloplasty (RMA) versus transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation (SMR). It highlights contradictions in the 2020 American Heart Association/American College of Cardiology (AHA/ACC) guidelines for the indication for TEER in SMR was Class IIb with level of evidence B-R.2Otto C.M. Nishimura R.A. Bonow R.O. Carabello B.A. Erwin III, J.P. Gentile F. et al.2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines.J Am Coll Cardiol. 2021; 77: 450-500Crossref PubMed Scopus (249) Google Scholar In that study of 202 patients, the investigators compared propensity-matched surgical versus transcatheter repair for SMR with a report published immediately after the presentation of new AHA/ACC guidelines. After 2 years' follow-up, although the investigators found no significant difference in survival (P = .909), they recorded superiority in RMA with coronary revascularization versus TEER for decreasing mitral regurgitation (MR), improving ventricular ejection fraction, and reducing New York Heart Association functional class III or IV.1Okuno T. Praz F. Kassar M. Biaggi P. Mihalj M. Killing M. et al.Surgical versus transcatheter repair for secondary mitral regurgitation: a propensity score matched cohorts comparison.J Thorac Cardiovasc Surg. July 27, 2021; ([Epub ahead of print]. https://doi.org/10.1016/j.jtcvs.2021.07.029)Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Left ventricular remodeling predicts poor prognosis in ischemic myocardial disease and is reversible with recovery of viable myocardium.3Nappi F. Lusini M. Spadaccio C. Nenna A. Covino E. Acar C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation.J Am Coll Cardiol. 2016; 67: 2334-2346Crossref PubMed Scopus (127) Google Scholar,4Nappi F. Spadaccio C. Nenna A. Lusini M. Fraldi M. Acar C. et al.Is subvalvular repair worthwhile in severe ischemic mitral regurgitation? Subanalysis of the papillary muscle approximation trial.J Thorac Cardiovasc Surg. 2017; 153: 286-295Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar Cardiothoracic Surgical Trials Network trial subanalyses included 75% of patients receiving concomitant coronary artery bypass grafting surgery, eliminating the possibility of improvement in regional wall motion for 25% of patients.4Nappi F. Spadaccio C. Nenna A. Lusini M. Fraldi M. Acar C. et al.Is subvalvular repair worthwhile in severe ischemic mitral regurgitation? Subanalysis of the papillary muscle approximation trial.J Thorac Cardiovasc Surg. 2017; 153: 286-295Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar,5Goldstein D. Moskowitz A.J. Gelijns A.C. Ailawadi G. Parides M.K. Perrault L.P. et al.Two-year outcomes of surgical treatment of severe ischemic mitral regurgitation.N Engl J Med. 2016; 374: 344-353Crossref PubMed Scopus (538) Google Scholar Subannular procedure combined with RMA have been superior to RMA alone in both ischemic and nonischemic cardiomyopathy in other studies.3Nappi F. Lusini M. Spadaccio C. Nenna A. Covino E. Acar C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation.J Am Coll Cardiol. 2016; 67: 2334-2346Crossref PubMed Scopus (127) Google Scholar,6Pausch J. Sequeira Gross T. Müller L. von Stumm M. Kloth B. Reichenspurner H. et al.Subannular repair for functional mitral regurgitation type IIIb in patients with ischaemic versus dilated cardiomyopathy.Eur J Cardiothorac Surg. 2021; 60: 122-130Crossref PubMed Scopus (6) Google Scholar,7Harmel E. Pausch J. Gross T. Petersen J. Sinning C. Kubitz J. et al.Standardized subannular repair improves outcomes in type IIIb functional mitral regurgitation.Ann Thorac Surg. 2019; 108: 1783-1792Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar In a papillary muscle approximation (PMA) randomized trial, 96 patients with severe chronic ischemic mitral regurgitation underwent complete surgical myocardial revascularization associated with either isolated RMA or PMA + RMA over a 5-year follow-up. Left ventricular end-diastolic diameter improved at 5-year follow-up (5.8 ± 4.1 mm and −0.2 ± 2.3 mm, respectively; P < .001), maintaining the benefit achieved immediately postoperatively with freedom from major adverse cardiac and cerebrovascular events (P = .004)3Nappi F. Lusini M. Spadaccio C. Nenna A. Covino E. Acar C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation.J Am Coll Cardiol. 2016; 67: 2334-2346Crossref PubMed Scopus (127) Google Scholar (Figure 1). TEER use in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) study did not reveal an improvement of left ventricular remodeling (left ventricular end-diastolic volume/mL, 194.4 ± 69.2 mL vs 192.2 ± 76.5 mL),8Nappi F. Antoniou G.A. Nenna A. Michler R. Benedetto U. Avtaar Singh S.S. et al.Treatment options for ischemic mitral regurgitation: a meta-analysis.J Thorac Cardiovasc Surg. 2022; 163: 607-622.e14Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar,9Stone G.W. Lindenfeld J. Abraham W.T. Kar S. Lim D.S. Mishell J.M. et al.Transcatheter mitral-valve repair in patients with heart failure.N Engl J Med. 2018; 379: 2307-2318Crossref PubMed Scopus (1415) Google Scholar although patients who underwent TEER had sustained 3-year improvements in MR severity, quality-of-life measures, and functional capacity compared with those who received guideline-directed medical therapy (GDMT) at 3 years' follow-up.10Mack M.J. Lindenfeld J. Abraham W.T. Kar S. Lim D.S. Mishell J.M. et al.3-year outcomes of transcatheter mitral valve repair in patients with heart failure.J Am Coll Cardiol. 2021; 77: 1029-1040Crossref PubMed Scopus (57) Google Scholar The benefit of TEER over GDMT was confirmed among 58 patients primarily managed with alone who crossed-over receiving TEER. For the subsequent composite rate of mortality or hospitalization for cardiac failure, hospitalization for cardiac failure was reduced compared with GDMT alone (P = .006).10Mack M.J. Lindenfeld J. Abraham W.T. Kar S. Lim D.S. Mishell J.M. et al.3-year outcomes of transcatheter mitral valve repair in patients with heart failure.J Am Coll Cardiol. 2021; 77: 1029-1040Crossref PubMed Scopus (57) Google Scholar Okuno and colleagues1Okuno T. Praz F. Kassar M. Biaggi P. Mihalj M. Killing M. et al.Surgical versus transcatheter repair for secondary mitral regurgitation: a propensity score matched cohorts comparison.J Thorac Cardiovasc Surg. July 27, 2021; ([Epub ahead of print]. https://doi.org/10.1016/j.jtcvs.2021.07.029)Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar revealed that restrictive mitral annuloplasty was superior to TEER at 2 years as a secondary end point. Evidence from randomized controlled trials (RCTs) proved that RMA had higher MR recurrence rates at 2 and 5 years' follow-up (58.8% and 55.9%, respectively).3Nappi F. Lusini M. Spadaccio C. Nenna A. Covino E. Acar C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation.J Am Coll Cardiol. 2016; 67: 2334-2346Crossref PubMed Scopus (127) Google Scholar,5Goldstein D. Moskowitz A.J. Gelijns A.C. Ailawadi G. Parides M.K. Perrault L.P. et al.Two-year outcomes of surgical treatment of severe ischemic mitral regurgitation.N Engl J Med. 2016; 374: 344-353Crossref PubMed Scopus (538) Google Scholar Suitability for RMA should include smaller preoperative left ventricular end systolic diameter and reduced apical tethering of the leaflets. Seventy-four patients from the Cardiothoracic Surgical Trials Network trial with severe ischemic mitral regurgitation with no persistent or recurrent MR after RMA recorded significantly smaller left ventricles at 2 years' follow-up compared with patients with recurrent MR post-RMA alone (43 ± 26 mL/m2 vs 63 ± 27 mL/m2). Left ventricular end systolic volume was significantly lower compared with patients managed with mitral valve replacement (61 ± 39 mL/m2).5Goldstein D. Moskowitz A.J. Gelijns A.C. Ailawadi G. Parides M.K. Perrault L.P. et al.Two-year outcomes of surgical treatment of severe ischemic mitral regurgitation.N Engl J Med. 2016; 374: 344-353Crossref PubMed Scopus (538) Google Scholar In the PMA trial, double-level repair achieved geometric restitution by normalization of 3 measures: anteroposterior annular dilation, tenting area, and interpapillary muscle distance. The goal is to address both the valvular and ventricular features of secondary MR (Carpentier class IIIb).3Nappi F. Lusini M. Spadaccio C. Nenna A. Covino E. Acar C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation.J Am Coll Cardiol. 2016; 67: 2334-2346Crossref PubMed Scopus (127) Google Scholar,4Nappi F. Spadaccio C. Nenna A. Lusini M. Fraldi M. Acar C. et al.Is subvalvular repair worthwhile in severe ischemic mitral regurgitation? Subanalysis of the papillary muscle approximation trial.J Thorac Cardiovasc Surg. 2017; 153: 286-295Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar,6Pausch J. Sequeira Gross T. Müller L. von Stumm M. Kloth B. Reichenspurner H. et al.Subannular repair for functional mitral regurgitation type IIIb in patients with ischaemic versus dilated cardiomyopathy.Eur J Cardiothorac Surg. 2021; 60: 122-130Crossref PubMed Scopus (6) Google Scholar,7Harmel E. Pausch J. Gross T. Petersen J. Sinning C. Kubitz J. et al.Standardized subannular repair improves outcomes in type IIIb functional mitral regurgitation.Ann Thorac Surg. 2019; 108: 1783-1792Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar The fundamental role of papillary muscles is also focused on by Kainuma and colleagues.11Kainuma S. Funatsu T. Kondoh H. Yokota T. Maeda S. Shudo Y. et al.Beneficial effects of restrictive annuloplasty on subvalvular geometry in patients with functional mitral regurgitation and advanced cardiomyopathy.J Thorac Cardiovasc Surg. 2018; 156: 630-638.e1Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Kainuma and colleagues11Kainuma S. Funatsu T. Kondoh H. Yokota T. Maeda S. Shudo Y. et al.Beneficial effects of restrictive annuloplasty on subvalvular geometry in patients with functional mitral regurgitation and advanced cardiomyopathy.J Thorac Cardiovasc Surg. 2018; 156: 630-638.e1Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar recorded that the use of restrictive mitral annuloplasty alone only partially alleviated the tethering of leaflet, which instead significantly favored a reduction in tethering and interpapillary muscles distance. The latter was the main determinant of MR recurrence. These beneficial effects could be mainly attributed to post-RMA reverse left ventricular remodeling leading to a reduction in interpapillary muscle distance (31 ± 6 mm to 25 ± 5 mm), potentially offsetting the negative effect of increasing posterior leaflet angle.11Kainuma S. Funatsu T. Kondoh H. Yokota T. Maeda S. Shudo Y. et al.Beneficial effects of restrictive annuloplasty on subvalvular geometry in patients with functional mitral regurgitation and advanced cardiomyopathy.J Thorac Cardiovasc Surg. 2018; 156: 630-638.e1Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar PMA is more suitable than TEER in patients with SMR due to nonischemic cardiomyopathy (Carpentier class I) where annular dilation, lateral displacement of anterior and posterior papillary muscle, symmetrical tethering with apical tenting of anterior leaflet, and central jet were prevalent. Patients with severe left ventricular dilation and moderate-to-severe MR had poorer outcomes both in the small group of patients in the COAPT8Nappi F. Antoniou G.A. Nenna A. Michler R. Benedetto U. Avtaar Singh S.S. et al.Treatment options for ischemic mitral regurgitation: a meta-analysis.J Thorac Cardiovasc Surg. 2022; 163: 607-622.e14Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar and in Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary Mitral Regurgitation12Iung B. Armoiry X. Vahanian A. Boutitie F. Mewton N. Trochu J.-N. et al.Percutaneous repair or medical treatment for secondary mitral regurgitation: outcomes at 2 years.Eur J Heart Fail. 2019; 21: 1619-1627Crossref PubMed Scopus (124) Google Scholar trials. These patients had similar features of proportionate MR and did not respond favorably to TEER (Table 1).13Packer M. Grayburn P.A. New evidence supporting a novel conceptual framework for distinguishing proportionate and disproportionate functional mitral regurgitation.JAMA Cardiol. 2020; 5: 469-475Crossref PubMed Scopus (58) Google Scholar RMA, Restrictive mitral annuloplasty; PMR, papillary muscle relocation; LVEDD, left ventricular end-diastolic diameter LVEF, left ventricular ejection fraction; EROA, effective regurgitant orifice area; MR, mitral regurgitation; COAPT, Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation; TEER, transcatheter edge-to-edge repair; GDMT, guide-direct medical therapy; LVEDV, left end-diastolic volume; MITRA Fr, Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation; PMA trial, papillary muscle approximation trial; CTSN, Cardiothoracic Surgical Trials Network; MVR, mitral valve replacement; LVESI, left end-systolic volume index. All 5 AHA/ACC recommendations were classified as level of evidence B-R or B-NR, indicating moderate quality of studies. The available literature lacks RCTs designed with a large number of enrolled patients that include candidates receiving TEER, mitral valve replacement, or mitral valve repair with or without a subvalvular procedure. ACC/AHA guidelines reference 2 TEER-based RCTs with 3-year outcomes that are reported only for the COAPT trial,9Stone G.W. Lindenfeld J. Abraham W.T. Kar S. Lim D.S. Mishell J.M. et al.Transcatheter mitral-valve repair in patients with heart failure.N Engl J Med. 2018; 379: 2307-2318Crossref PubMed Scopus (1415) Google Scholar and the analysis of the new pathophysiological framework of the pathomechanism for SMR.10Mack M.J. Lindenfeld J. Abraham W.T. Kar S. Lim D.S. Mishell J.M. et al.3-year outcomes of transcatheter mitral valve repair in patients with heart failure.J Am Coll Cardiol. 2021; 77: 1029-1040Crossref PubMed Scopus (57) Google Scholar None of these recommendations are based on reports with 5 years' follow-up.2Otto C.M. Nishimura R.A. Bonow R.O. Carabello B.A. Erwin III, J.P. Gentile F. et al.2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines.J Am Coll Cardiol. 2021; 77: 450-500Crossref PubMed Scopus (249) Google Scholar For double-level repair, there currently is no solid evidence supported by more than 1 RCT, or meta-analysis of moderate-quality RCTs, that allows recommending this procedure. Although the results of the Multicenter Randomized, Controlled Study to Assess Mitral Valve Reconstruction for Advanced Insufficiency of Functional or Ischemic Origin14A Multicenter, randomized, controlled study to assess mitral vAlve reconsTrucTion for advancEd insufficiency of functional or iscHemic ORigiN (MATTERHORN). ClinicalTrials.gov identifier: NCT02371512.https://clinicaltrials.gov/ct2/show/NCT02371512Date accessed: March 8, 2022Google Scholar randomized study are awaited, other RCTs have demonstrated the efficacy of using novel devices. None of these are directed toward manipulating the papillary muscles by either an approximation or a relocation procedure. In the Edwards Pascal Transcatheter Mitral Valve Repair System Study RCT (N = 124), the Pascal system (Edwards Lifesciences) was implanted in patients enrolled for treatment of functional, degenerative, and mixed etiology. The Pascal transcatheter valve repair system and the MitraClip system (Abbott, Abbott Park, Ill) were compared in patients with both functional and degenerative MR. Evidence from the Edwards Pascal Transcatheter Mitral Valve Repair System Study recorded a high rate of survival, with a significant rate of reduction in heart failure-related hospitalization with reverse positive left ventricular remodeling at 1 and 2 years' follow-up.15Praz F. Spargias K. Chrissoheris M. Büllesfeld L. Nickenig G. Deuschl F. et al.Compassionate use of the PASCAL 536 transcatheter mitral valve repair system for patients with severe mitral regurgitation: a multicentre, prospective, 537 observational, first-in-man study.Lancet. 2017; 390: 773-780Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar, 16Lim D.S. Kar S. Spargias K. Kipperman R.M. O'Neill W.W. Ng M.K.C. et al.Transcatheter valve repair for patients with mitral regurgitation: 30-day results of 539 the CLASP study.JACC Cardiovasc Interv. 2019; 12: 1369-1378Crossref PubMed Scopus (91) Google Scholar, 17Webb J.G. Hensey M. Szerlip M. Schafer U. Cohen G.N. Kar S. et al.1-year outcomes for transcatheter repair in patients with mitral regurgitation 541 from the clasp study.JACC Cardiovasc Interv. 2020; 13: 2344-2357Crossref PubMed Scopus (31) Google Scholar, 18Edwards PASCAL CLASP IID/IIF Pivotal Clinical Trial (CLASP IID/IIF). ClinicalTrials.gov identifier: NCT03706833.https://clinicaltrials.gov/ct2/show/NCT03706833Date accessed: March 8, 2022Google Scholar Additional multicenter RCTs designed with a minimum of 5-year follow-up enrolling patients to undergo either TEER or double-level repair should be encouraged. Surgical versus transcatheter repair for secondary mitral regurgitation: A propensity score–matched cohorts comparisonThe Journal of Thoracic and Cardiovascular SurgeryPreviewTo compare the efficacy and clinical outcomes of transcatheter edge-to-edge mitral valve repair (TMVr) and surgical mitral valve repair (SMVr) among patients with secondary mitral regurgitation (SMR). Full-Text PDF Reply: The perfect decision with imperfect information: Pitfalls of generalizing to many what we know of few?JTCVS OpenVol. 10PreviewSecondary mitral regurgitation (SMR) remains a problem that affects many. The publication of 2 randomized controlled trials ontranscatheter edge-to-edge repair (TEER) for SMR with conflicting outcomes were followed with the designation of TEER as a IIa indication in the treatment of SMR alongside surgical mitral valve repair with reductive annuloplasty (RMA) plus revascularization in the American Heart Association/American College of Cardiology guidelines.1-3 The final word on the best management of SMR is far from written. Full-Text PDF Open Access
Domenico De Berardis, Michele Fornaro, Laura Orsolini, Luigi Olivieri, Francesco Nappi, Gabriella Rapini, Federica Vellante, Cosimo Napoletano, Nicola Serroni, and Massimo Di Giannantonio. Clin Psychopharmacol Neurosci 2018;16:505-7. https://doi.org/10.9758/cpn.2018.16.4.505
Micro-RNAs have been recently investigated in preclinical and clinical research as regulators of valvulopathies pathogenesis, diagnostic biomarkers and therapeutical targets. Evidences from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse, aortic leaflet fusion and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes or different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address mi-RNAs over or under-representation. In this review we discuss the fundamental intracellular homeostatic and cardiogenetic pathways regulated by mi-RNAs leading to defects in mitral and aortic valves, congenital heart diseases and the possible therapeutical strategies targeting them. Mi-RNAs inhibitors comprise antisense oligonucleotides and sponge vectors while mi-RNA mimics, mi-RNA expression vectors and small molecules are possible practical strategies to increase their activity. Advantages and technical limitations, including instability and complex pharmacokinetics are also presented. Novel strategies, such as nanoparticles and liposomes, are conclusively described to improve knowledge on these molecules delivery and establish future personalized treatment directions.
Aortic dissection is a clinicopathological entity caused by rupture of the intima leading to a high mortality if not treated. Over time, diagnostic and investigative methods, antihypertensive therapy, and early referrals have resulted in improving outcomes according to registry data. Some data has also emerged from recent studies suggesting a link between Human Cytomegalovirus (HCMV) infection and aortic dissection. Furthermore, the use of microRNAs have also become increasingly widespread in the literature. These have been noted to play a role in aortic dissections with elevated levels noted in studies as early as 2017. This review aims to provide a broad and holistic overview of the role of miRNAs, while studying the role of HCMV infection in the context of aortic dissections. The role of long non-coding RNAs, circular RNAs and microRNAs are explored to identify changes in expression during aortic dissections. The use of such biomarkers may one day be translated into clinical practice to allow early detection and prognostication of outcomes and drive preventative and therapeutic options in the future.
