Frontiers of surgical and catheter-based management of valvular heart disease

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. Mitral regurgitation has become a frontier in cardiovascular research and clinical practice1 with the development of the MitraClip® and with or without the recently introduced Cardioband®1–3 and balloon-expandable mitral valves4 that all can be implanted with catheter-based techniques. Indeed, a number of patients with mitral regurgitation are considered unsuitable for surgery because of impaired left ventricular ejection fraction (LVEF) or comorbidities among other causes, as also acknowledged by the most recent ESC Guidelines.5 Indeed, functional mitral regurgitation frequently is accompanied by heart failure and is associated with poor prognosis.6 Valvular surgery proved to be inferior to optimized medical therapy, cardiac resynchronization therapy, long-term ventricular assist devices, or cardiac transplantation. The recent COAPT7 and MITRA-FR trials8 tested the safety and efficacy of MitraClip® in such patients with unfortunately divergent results. Bernard Prendergast and colleagues from the St. Thomas Hospital in London, UK carefully discuss the lessons from both trials in their Viewpoint entitled ‘Mitral regurgitation in heart failure: time for a rethink’.9 They argue that careful echocardiographic screening of heart failure patients before and after the instigation of optimal medical treatment is essential to identify suitable candidates and the optimal timing of transcatheter interventions. Whilst the results of MITRA-FR indicate that those with advanced LV dilatation do not respond to MitraClip, those of COAPT demonstrate that earlier treatment is beneficial with moderate LV dilatation and severe mitral regurgitation. Further studies are required to determine whether patients with marked LV dilatation and severe mitral regurgitation might benefit from edge-to-edge repair, since they were under-represented in MITRA-FR and excluded from COAPT. In their original research article ‘Causes and mechanisms of isolated mitral regurgitation in the community: clinical context and outcome’, Maurice Enriquez-Sarano and colleagues from the Mayo Clinic in Rochester, Minnesota define the hitherto unknown spectrum of the aetiology or mechanism of mitral regurgitation in their Olmsted community and their clinical characteristics and outcomes.10 In total, 727 patients with a median age of 73 years and an LVEF of 49% were included. Mitral regurgitation was functional in two-thirds and organic in one-third. Functional mitral regurgitation was linked to LV remodelling in 38% and atrial dilatation in 27%. Those with functional mitral regurgitation with remodelling were younger than those with enlarged atria only, more likely to be males, less likely to have atrial fibrillation, and obviously have a lower LVEF. The dominant mechanism was Type-I with normal valve movement in 38%, Type-II with excessive valve movement in 25%, Type-IIIa with diastolic restricted movement in diastole in 3%, and Type-IIIb with restricted movement in systole in 34%. Mortality was increased compared with the general population in those with LV remodelling, with a hazard ratio of 3.45 and less so in those with atrial enlargement, i.e. 1.88, and organic mitral regurgitation, i.e. 1.83. Heart failure was frequent, particularly in those with LV remodelling. Thus, moderate or severe mitral regurgitation in the community displays considerable heterogeneity of aetiology and mechanism. Functional mitral regurgitation dominates, mostly in those with LV remodelling or an enlarged left atrium, and they have excess mortality and heart failure with preserved or reduced LVEF. As patients in the community are undertreated, as recently also reported for European countries,11 clinical trials tailored to specific mitral regurgitation causes and mechanisms are warranted. The manuscript is accompanied by an Editorial by Victoria Delgado and Jeroen Bax from the Leiden University Medical Center in the Netherlands.12 Recurrent mitral regurgitation is quite common after surgical repair of functional mitral regurgitation,13 but may also occur with MitraClip®.14 However, its impact on long-term survival remains poorly defined. In their article entitled ‘Impact of recurrent mitral regurgitation after mitral valve repair for functional mitral regurgitation: long-term analysis of competing outcomes’, Jerry Braun and colleagues from the Leiden University Medical Center in Leiden, The Netherlands studied mortality-adjusted recurrence rates, their clinical impact, and its determinants in 261 patients with ischaemic heart disease.15 The incidence of recurrent mitral regurgitation of grade 2 or greater was 9.6% at 1 year, 20.3% at 5 years, and 27.6% at 10 years. The respective survival was 85.8, 67.3, and 46.1%. Age, pre-operative NYHA class III or IV, and renal failure were independently associated with a three-fold increased mortality. Female gender, history of ST-segment elevation myocardial infarction (STEMI), pre-operative QRS duration ≥120 ms, higher pre-operative mitral regurgitation grade, and a greater LV end-systolic volume were independently associated with an increased risk of recurrent mitral regurgitation. Thus, surgical mitral valve repair for functional ischaemic mitral regurgitation is associated with an increasing incidence of recurrent mitral regurgitation over time. Recurrent mitral regurgitation at any moment after surgery is independently associated with an increased mortality. These findings are put into context in a thought-provoking Editorial by Piergiorgio Tozzi from the Centre Hospitalier Universitaire Vaudois CHUV in Lausanne, Switzerland.16 In addition to mitral regurgitation, aortic stenosis is the most frequent valvular abnormality, particularly in the elderly and in those with high blood pressure.17,18 Transcatheter aortic valve implantation or TAVI is an established therapy for patients with severe aortic stenosis at high or intermediate surgical risk19 and possibly soon also those at low risk.20 The ECG often changes after TAVI,21 but the clinical impact of new-onset left bundle branch block remains uncertain. In their Fast Track ‘New-onset left bundle branch block after transcatheter aortic valve replacement is associated with adverse long-term clinical outcomes in intermediate-risk patients: an analysis from the PARTNER II trial’ Tamim M. Nazif and colleagues from the Columbia University Medical Center in New York, USA investigated this issue.22 Among 1179 intermediate-risk patients, new-onset left bundle branch block occurred in 15%. Such patients were similar to controls except for both more frequent diabetes and SAPIEN 3 rather than SAPIEN XT valve use. At 2 years, new left bundle branch block was associated with all-cause mortality of 19.3% compared with 10.8%, cardiovascular mortality of 16.2% vs. 6.5%, and more frequent rehospitalization and pacemaker implantation. By multivariable analysis, new left bundle branch block remained an independent predictor of 2-year all-cause (hazard ratio 1.98) and cardiovascular (hazard ratio 2.66) mortality. New left bundle branch block was also associated with worse LVEF at follow-up. Thus, in intermediate-risk patients, new left bundle branch block occurs not uncommonly and is associated with adverse outcomes, including all-cause and cardiovascular mortality, rehospitalization, pacemaker implantation, and worsened LV systolic function, findings that are further discussed in an Editorial by Marina Urena from the Hôpital Bichat – Claude-Bernard in Paris, France.23 TAVI and also MitraClip® had initially been considered primarily in elderly and high-risk patients who often are frail.24,25 In their article ‘Frailty and related outcomes in patients undergoing transcatheter valve therapies in a nationwide cohort’,26 Harun Kundi and colleagues from the Beth Israel Deaconess Medical Center in Boston, USA analysed the prevalence and outcomes of frail individuals undergoing TAVI using the Hospital Frailty Risk Score. Of the 3746 patients, 11.6% underwent transcatheter mitral valve repair and 88.4% TAVI. In the transcatheter mitral valve repair and TAVI groups, about half were defined as low risk for frailty (score <5), ∼40% as intermediate risk (score 5–15), and ∼10% as high risk (score >15). One-year mortality of transcatheter mitral valve repair was 13% in low-risk, 30% in intermediate-risk, and 41% in high-risk patients (Figure 1). In TAVI patients, 1-year mortality rates were 8% in low-risk, 18% in intermediate-risk, and 30% in high-risk patients. Thus, the Hospital Frailty Risk Score allows for the identification of elderly individuals undergoing transcatheter valve therapies at greater risk of short- and long-term mortality. The practical implications of these results are further discussed in an Editorial by Jonathan N. Townend from the University Hospital Birmingham in the UK.27 The distribution of the Hospital Frailty Risk Score and its association with 1-year mortality in the transcatheter mitral valve repair and transcatheter aortic valve replacement populations using restricted cubic spline plots. The vertical red dashed lines show thresholds for categorizing patients as low frailty risk (score <5), intermediate frailty risk (score 5–15), or high frailty risk (score >15). Since there were very few patients with a Hospital Frailty Risk Score of >30, those patients are classified into a single group. (from Kundi H, Popma JJ, Reynolds MR, Strom JB, Pinto DS, Valsdottir LR, Shen C, Choi E, Yeh RW. Frailty and related outcomes in patients undergoing transcatheter valve therapies in a nationwide cohort. See pages 2231–2239) Endocarditis is an important complication after transcatheter and surgical valve interventions.28,29 even in those considered at moderate risk.30 In left-sided infective endocarditis, a large vegetation >10 mm is associated with increased mortality, yet it is unknown whether, in the acute phase, surgery or medical therapy provides better survival. In their article entitled ‘The association between vegetation size and surgical treatment on 6-month mortality in left-sided infective endocarditis’, Emil Loldrup Fosbøl and colleagues from the Rigshospitalet in Copenhagen, Denmark assessed this open question.31 Of the 1006 patients with left-sided infective endocarditis, 42% had a vegetation size <10 mm and 58% a size of >10 mm. Embolic events occurred in 28% and 44%, respectively. Large vegetations were associated with higher 6-month mortality of 25% vs. 19% (Figure 2). However, after propensity matching, the association with mortality persisted, but only in those with large vegetation managed medically, with a hazard ratio of 1.86, rather than surgically (hazard ratio 1.01). Thus, left-sided infective endocarditis with vegetation size >10 mm is associated with increased mortality. Survival of surgically managed large vegetations was similar to those with smaller vegetations, a finding that is put into practical context in an Editorial by Gilbert Habib from the Hopital Timone in Marseille, France.32 Risk of death by vegetation size and surgical treatment. There were 11 patients missing data for 6 months follow-up for mortality and these were excluded (one among those with the vegetation ≤10 mm who underwent surgery, two among those with the vegetation >10 mm who underwent surgery, two among those with the vegetation ≤10 mm who did not undergo surgery, and six among those with the vegetation >10 mm who did not undergo surgery) (from Fosbøl EL, Park LP, Chu VH, Athan E, Delahaye F, Freiberger T, Lamas C, Miro JM, Strahilevitz J, Tribouilloy C, Durante-Mangoni E, Pericas JM, Fernández-Hidalgo N, Nacinovich F, Rizk H, Barsic B, Giannitsioti E, Hurley JP, Hannan MM, Wang A, for the ICE-PLUS Investigators. The association between vegetation size and surgical treatment on 6-month mortality in left-sided infective endocarditis. See pages 2243–2251). Pulmonary valvular disease is much less frequent than diseases of other cardiac valves, but particularly prevalent in patients with congenital heart disease.33,34 In their article ‘Acute and midterm outcomes of the post-approval MELODY Registry: a multicentre registry of transcatheter pulmonary valve implantation’,35 Johannes Nordmeyer and colleagues from the Deutsches Herzzentrum Berlin in Germany report data of the MELODY Registry. Overall, 845 patients of 21 years of age underwent transcatheter pulmonary valve implantation with the Melody valve™ and were followed up for 6 years. Death or further surgical or interventional treatments occurred in 0.5, 1.2, and 2.0%, respectively. Acutely, the transvalvular pressure gradient and the percentage of patients with pulmonary regurgitation grade 2 or more improved from 37 to 13 mmHg and 47% to 1%, respectively. Post-procedural events occurred in 4.2% per person per year and infective endocarditis in 2.3% per person per year, and resulted in significant morbidity and nine deaths. In multivariable Cox proportional hazard models, the transvalvular pressure gradient was associated with a hazard ratio of 1.21 for the composite endpoint and risk with a hazard ratio of 1.17 for infective endocarditis. Thus, transcatheter pulmonary valve implantation with the Melody valve™ is safe and effective in a large cohort of congenital heart disease patients under ´real-world´ conditions, but infective endocarditis remains a concern. These results are further discussed in an Editorial by Lars Sondergaard from the Rigshospitalet in Copenhagen, Denmark.36 The issue is further complemented by a Discussion Forum. In their contribution ‘Optimizing confidence in systematic reviews through registration and bias minimization’, Hessam Kashani and colleagues from the University of Manitoba College of Medicine in Winnipeg, Canada comment on the article ‘Restrictive compared with liberal red cell transfusion strategies in cardiac surgery: a meta-analysis’37,38 by C, David Mazer and colleagues from the University of Toronto, who respond properly to the comments.39 The editors hope that readers of this issue of the European Heart Journal will find it interesting. With thanks to Amelia Meier-Batschelet for help with compilation of this article.