The Year in Cardiology 2018: Valvular Heart Disease

In 2018, the publications on valvular heart disease (VHD) addressed all topics—epidemiology, diagnosis, therapy, and predictors of outcome—but were dominated by studies focusing on transcatheter treatment. Regarding mitral regurgitation (MR) two pivotal studies investigating transcatheter edge-to-edge repair for secondary MR as well as early clinical experience with transcatheter mitral valve replacement (TMVR) were published. Regarding aortic stenosis (AS) there is a clear trend towards the expansion of indications for transcatheter aortic valve implantation (TAVI) to intermediate and low-risk groups, bicuspid aortic valve (BAV) and failed surgically implanted bioprostheses. Tricuspid valve (TV) disease is a growing clinical problem associated with high morbidity and mortality. Isolated TV surgery has a high risk and is currently performed in a minority of patients. Novel therapies using the edge-to-edge approach or annuloplasty are being investigated. Transcatheter aortic valve implantation is rapidly evolving, and implantation numbers are steeply increasing. In Germany where all procedures are mandatorily registered in a quality control programme, more than 15 000 TAVI procedures were performed in 2016. The number more than tripled since 2011, while isolated surgical aortic valve replacement (SAVR) remained relatively stable with approximately 10 000 per year being performed now much less frequently than TAVI (Figure 1). Complication rates and mortality decreased continuously with overall in-hospital mortality being in 2016 for the first time similar for TAVI (2.6%) and SAVR (2.9%) despite the different risk profile of both patient groups.1 Expanding adoption of TAVI across the risk strata is widespread both in Europe and the USA. Based on SURTAVI, Sapien3 Intermediate Risk and PARTNER 2A the safety and efficacy was established for intermediate risk and following the NOTION study the concept showed promising results for low-risk patients.2 Importantly, surgical risk scales used for both approaches tend to overestimate mortality for TAVI patients in all the risk strata even taking into consideration that low-risk patients undergoing TAVI are younger than SAVR (Figure 2). The recent FDA-approved low-risk TAVR trial prospectively studied the outcomes of transfemoral TAVI in the low-risk group (STS-PROM ≤3%) and compared the results to historical controls from the Society of Thoracic Surgeons (STS) database. No mortality and strokes at 30 days, low risk of paravalvular regurgitation as well as permanent pacemaker implantation (PPI) rates similar to SAVR were reported, however, frailty was an exclusion criterium.3 A sub-analysis of the randomized controlled SURTAVI trial evaluating patients with STS-PROM <3% suggested that TAVI may achieve superior early clinical outcomes compared with SAVR.4 These findings support the need for an adequately powered randomized trial to compare TAVI with SAVR in patients at low operative risk. Apparently, in such a population with assumingly longer life expectancy, there is a clear need for data on the long-term durability because no follow-up beyond 2 years has so far been published for this population. Ongoing trials such as PARTNER3, Evolut R Low Risk and NOTION 2 with follow-up of 5–10 years will provide more data with this regard. Currently available long-term durability data for transcatheter aortic valves although promising are unfortunately limited by the poor survival of the high-risk early populations. Eltchaninoff et al.5 reported an incidence of structural valve deterioration of 3.2% and bioprosthetic valve failure of 0.58% at 8 years using the new European consensus definition. Holy et al.6 estimated from their series that the rate of bioprosthetic valve failure at 8 years was 7.9% for the actuarial and 4.5% for the actual analysis. However, long-term durability will remain one of the key concerns until we have more solid data. Numbers of procedures (A) and in-hospital mortality (B) related to transvascular transcatheter aortic valve implantation, transapical TAVI, and isolated surgical aortic valve replacement. Data from the German Institute for Quality Assurance and Transparency in Healthcare (IQTIG) report. Reprinted with permission from Gaede et al.,1 combining Figures 1 and 3. Different performance of surgical risk scores in surgical aortic valve replacement and transcatheter aortic valve implantation patients across the risk strata. Reprinted from Tarantini et al.2 One of the other concerns beyond durability is the need for PPI which is in most reports higher with TAVI than with SAVR. A recent systematic review demonstrated the highly variable risk of PPI (2.3–36.1%) due to new onset conduction abnormalities after TAVI.7 The risk tended to be lower after balloon-expandable than self-expandable valves. Procedural factors, such as the depth of implantation, predilatation, distribution of calcifications, and pre-existing conduction abnormalities were important risk factors for PPI. The possible long-term impact of even mild paravalvular leak (PVL) and the necessity of access to coronary arteries in patients with long life expectancy must also be considered. Severe periprocedural complications of TAVI requiring emergent cardiac surgery (mainly annular rupture, ventricular perforation, and valve embolization) are rare but remain approximately 1%8 to 2%.9 Early mortality remains high in such cases. Nevertheless, given these life-threatening complications, the 30-day survival rate exceeding 50% underlines the importance of an experienced and well-attuned heart team providing immediate access to surgical bailout procedures. One-year mortality remains high (78%). These numbers may also indicate that on-site cardiac surgery alone is not sufficient and the setup for emergency conversion requires further improvement. Complication rates and early mortality decrease with increasing procedure volume. In an analysis of German national quality assurance data, in-hospital mortality varied highly (0–16.7%) and was on average markedly higher with 5.6 ± 5.0% in hospitals performing <50 transfemoral TAVIs annually compared with 2.4 ± 1.0% with rather consistent results (range 0.5–3.7%) in hospitals with ≥200 procedures per year.10 These studies support the recommendation of performing TAVI in heart valve centres with departments of cardiac surgery on-site and sufficiently high volumes.8 Impact on the healthcare resources utilization is an important issue given the epidemiology of AS and currently expanding indications for TAVI. The estimated number of TAVI candidates in Europe under current indications exceeds 114 000 per year and assuming low-risk indication is accepted this number may increase to 177 00011 (Figure 3). The estimated number of transcatheter aortic valve implantation candidates in Europe under current indications (A) and projected numbers after accepting low-risk indication (B). Reprinted from Durko et al. 11 Aortic stenosis and coronary artery disease (CAD) have common risk factors, and clinically overt CAD is present in approximately half of the patients undergoing TAVI or SAVR. Coronary artery disease impacts the outcomes of TAVI, but data are still lacking for recommendations whether and when to perform percutaneous coronary intervention—before, during, or after TAVI.12 The usefulness of invasive physiological assessment of CAD significance in severe AS is also unclear due to the hypertrophy, increased end-diastolic pressure and impaired function of the microvasculature. However, recent data suggest that both fractional flow reserve as well as an instantaneous valve-free ratio (iFR) have good correlation with ischaemic burden in SPECT and might be useful in clinical decision making about the revascularization strategy before aortic valve intervention.13 In most centres, the revascularization is limited to large proximal vessels, but the completeness of revascularization can have a prognostic impact, and use of the residual SYNTAX score could improve the risk stratification.12 , 14 Transcatheter treatment of severe BAV stenosis is associated with procedural challenges related to large volume and asymmetrically distributed calcifications, large aortic annulus, the presence of calcified raphe, and coexisting aortopathy. Such anatomy increases the risk of non-uniform valve expansion, under-expansion, aortic root injury, and PVL. Despite that, given the high prevalence of BAV in the population TAVI procedures are increasingly done in this population. Data from the German TAVI registry including 1424 patients showed reassuring clinical outcomes with similar 30-day mortality as in TV. In patients with BAV, there was, however, a higher rate of PVL while pacemaker implantation was less frequent.15 Transcatheter valve-in-valve (ViV) implantation has become an accepted alternative to redo surgery in patients with surgical bioprosthetic valve failure and should be considered depending on surgical risk, valve type and size (IIa, level of evidence C recommendation).16 The STS/ACC registry provided reassuring data on the safety of ViV. Such patients should have a meticulous follow-up with echocardiography because the post-procedural gradients are higher than for native valve TAVI (16 mmHg vs. 9 mmHg; P < 0.001). The follow-up in this study was limited to 1 year.17 Coronary obstruction following ViV procedures occurred in 2.3% patients enrolled in the Valve-in-Valve International Data (VIVID) Registry and was more frequent in stented bioprostheses with externally mounted leaflets and stentless biological valves as well as in patients with a virtual transcatheter valve to coronary ostium distance measured by computed tomography below 4 mm.18 Delayed coronary obstruction is an infrequent (0.22%) complication of TAVI (more often in ViV procedures and with self-expanding valves) but related to a high risk of death and myocardial infarction. ViV is challenging in small surgical prostheses because of a high post-procedural gradient, and new concepts, such as using the high-pressure inflation of non-compliant balloon and fracturing of the prosthetic valve ring are evaluated.19 The antithrombotic regimen after TAVI remains a matter of debate and results of randomized controlled trials are still awaited. In patients who required oral anticoagulation with vitamin K antagonists (VKA) for atrial fibrillation, an observational study reported significantly less major, and life-threatening bleeding complications on VKA therapy only compared with those with additional single (SAPT) or dual antiplatelet therapy (DAPT). This difference was not outweighed by a reduction of embolic events thus favouring VKA monotherapy.20 In a propensity-matched analysis comparing SAPT and DAPT in 1210 patients, at 30 days, VARC mortality, major vascular complications, and major bleedings were significantly lower in the SAPT group without a difference in prosthetic heart valve dysfunction after TAVI with a balloon-expandable valve favouring aspirin monotherapy when no anticoagulation is indicated.21 Data from the FRANCE-TAVI registry, on the other hand, showed that VKA are related to less bioprosthetic valve dysfunction in short-term follow-up.22 More research is required to define the optimal antithrombotic treatment after TAVI. There are currently no convincing data that all patients with severe AS who have normal left ventricular function and are asymptomatic by history and during exercise testing may benefit from early valve replacement and current guidelines, therefore, recommend watchful waiting for these patients unless they present with particular risk factors.16 Retrospective analyses reporting a benefit from early surgery were mainly driven by the fact that a considerable number of patients did not undergo surgery in the conservative group when developing indications for intervention, mainly symptoms. This suggests that the worse outcome in the conservative group was primarily due to nonadherence to the guidelines. A retrospective cohort study including 300 patients with asymptomatic severe AS appears to support this assumption.23 Nonadherent patients had significantly higher mortality and rate of hospital admission for heart failure (HF), while they underwent less frequently SAVR during follow-up. A recent analysis of the Heart Valve Clinic International Database reported that in asymptomatic patients with severe AS left ventricular (LV) ejection and aortic were associated with increased and mortality that this population may benefit from early valve but more data will be required for solid the indications for surgery in asymptomatic severe A new recommendation was that SAVR should be considered when surgical risk is and patients present with severe The impact of on long-term outcome was reported more in a study including more than patients with severe AS the also no longer the recommendation that surgery may be considered in asymptomatic patients with an increase in mmHg on This was on concerns and new studies this et did not a difference in survival asymptomatic patients on exercise with or without increase severe AS on the long-term to other heart et al. of no cardiac left ventricular left atrial or mitral valve or TV and ventricular One-year mortality increased continuously from to The of cardiac was associated with increased mortality after aortic valve replacement These data more the importance of of myocardial with impact on long-term outcome of AS has been a for a long However, to this into remains et al. studied patients with severe AS undergoing SAVR. with and volume were performed as well as with volume but not and with volume was also associated with worse and both the of patients at In patients with 1 year after did not while and myocardial In a study of patients with severe AS undergoing SAVR or TAVI, on was associated with mortality these studies provide important new whether we should asymptomatic patients with severe AS for early of to the of surgery can still not be from currently available data. with low flow low AS remain a challenging as well as of these patients not only have AS but other of myocardial data suggest that cardiac is associated disease one should et al. performed cardiac prospectively on patients who underwent TAVI to for cardiac patients These patients had and lower more severe and lower ejection These findings even more importance in the of a recent randomized controlled trial that in patients with was associated with in mortality and and the in and quality of life as compared with The prevalence of aortic regurgitation is approximately in patients years and increases with to current guidelines, aortic valve surgery is in severe patients are or asymptomatic patients present with of the or with aortic In patients with surgical risk transcatheter remains an however, due to the of and to of the the procedural challenges TAVI results less and associated with higher rates of PVL and data suggest that TAVI using and is in high surgical risk patients with A registry including patients showed less post-procedural with new valves. was a of The burden of MR is increasing with The data on the of MR vs. AS is In a study from the prevalence of MR was higher than of but the European and demonstrated that MR was the most frequent after the AS et al. at In a cohort isolated MR was common and associated with mortality and frequent in all patient even in those with normal and low Despite these poor only a small minority of patients underwent mitral surgery for and for secondary even in a with all of and treatment available and This suggests that in a population there might be a need for treatment for this and of in the of patients with MR were addressed in a European Based on an including and and cardiac from European systematic was for the early of therapy was and therapy in while of therapy was frequently not in secondary for were in most patients with MR but were frequent for secondary These important for MR was reported to be associated with mortality in patients with and to be a of long-term mortality after for clinical ratio P P optimal therapy and This was most in patients with Heart and and These findings suggest that repair of MR might be more in patients in the valve has the impact on the and is the associated with the of the the other hand, there is a of data on the long-term of surgical mitral valve repair on the clinical outcomes of secondary The widespread use of transcatheter edge-to-edge repair using the in patients with secondary MR was on registry data safety and clinical outcomes MR and and ventricular The efficacy was, however, lower for secondary than for MR and the predictors of outcomes were low and , There has been that the of transcatheter repair of secondary MR in clinical can only be in randomized clinical and two of these were now published enrolled patients with severe secondary and who were on and cardiac therapy as were to additional therapy or The procedure was performed with a low complication rate and high had MR Nevertheless, there was no difference for the or for at vs. for and conservative vs. vs. in both and was similar at The study has the of a randomized trial with follow-up the and that is an The is that a of follow-up data on outcome and at were The analyses in this trial showed no of this therapy across The of the for Heart with study enrolled patients with ischaemic and and or severe secondary MR and were despite of and as by were to the procedure or alone showed a reduction of the of due to at 2 years vs. P < with the number to to one of There was also a reduction of mortality at 2 vs. P < and of the quality of of and reduction of secondary There were the and with to the size vs. and of follow-up for vs. The in was all for and in of death from or for Regarding the of MR volume vs. and as well as of vs. and This in on average end-diastolic volume vs. and less severe MR ± 10 vs. ± 15 while was similar ± vs. ± the rate in was good compared with observational tended to be even higher in the the strategy was different with evaluating current treatment in patient in the and more approach in trial which could in the in the control in the these may have remains unclear the results of the two trials could so More studies will be required to this and the patient that a benefit from valve repair in secondary MR The and trials will the of this in secondary of outcomes in (A) and (B) Reprinted with permission from et and et In to edge-to-edge annuloplasty to achieve results in the secondary MR by the of the mitral and the of the leaflets using implanted by the A recent study by et al. the safety and efficacy of the Valve in patients with and secondary The rate was and in patients a reduction of and MR mild or less in-hospital and at 1 The rate was in 1 periprocedural complications and and were in the first cohort patients. This alone or in with edge-to-edge repair the long-term clinical outcomes further reduction of MR requires not only the the leaflets or alone but of both approaches or implantation of the The early experience was with valve and but the of the and reported by et al. Transcatheter mitral valve replacement with self-expandable transapical valve with leaflets in patients with high or operative risk and in providing was also with no periprocedural strokes or The trial which is to will provide important data for this A approach the use of transapical is to improve the In severe of asymptomatic patients with and no atrial or remains a matter of et al. prospectively such patients with a watchful waiting strategy for a of 8 with the and a population survival and early survival rates were even in the study population. was still after 10 These data support watchful However, has to be that these patients had follow-up in an and the results may only be in such a The concept of implantation of balloon-expandable valves in risk patients with severe mitral annular was on series and et al. reported follow-up of patients enrolled in in the rate was high and to there was mortality related to obstruction in of patients such an approach need to be further and is Tricuspid regurgitation is a clinical problem in Europe approximately 300 000 patients There is a growing of this disease and of regurgitation has an impact on and key risk factors for have been (Figure is accepted that TV repair during valve is in of mortality, however, increasing number of patients with MR have also In such transcatheter repair on not the TV and is in the of The concept of or transcatheter TV repair using the has been and This approach requires with and during the transcatheter such as repair or approach or two TAVI implanted the in have been with promising early results of in high risk The of patients are on a and have and the impact of repair requires further The Tricuspid Valve registry high-risk patients with transcatheter and showed procedural and reduction of predictors of the vs. of regurgitation (A) and survival to the rate of of regurgitation (B). Reprinted with permission from et only secondary coexisting with the disease of other valves remains a clinical but also isolated TV disease which an increased risk of mortality and increasing Isolated TV surgery is associated with a high risk mortality of and not time despite the growing number of surgical to the key is patient the current the most be high surgical risk patients without ventricular failure and has to be that for secondary similar to secondary only with worse outcome has been demonstrated while remains whether reduction by can improve regurgitation (PVL) is an complication of surgical valve replacement requiring repair in of cases. surgery is associated with risk. Transcatheter is a treatment after exclusion of in patients with However, data on the periprocedural and long-term outcomes were on the using the PVL for the assessment of disease data and of prosthetic valve remains A study including patients with of the of and assessment of in this and the importance of early in the to of low due to valve implantation was not a of but surgical used during implantation , The incidence of in the is estimated to be The risk factors of mortality in patients are the history of prosthetic and history of valve data from the of risk factors in and high-risk in to the population. There was a increase of risk in these populations. The risk factors for in risk group were an and the risk of was higher than the population but lower than in high-risk , In a in stable who had on the left of the heart by or for at 10 with were to or to to oral treatment. The outcome of mortality, embolic or of occurred in vs. of to oral treatment. These findings could have major impact on clinical may after of is associated with increased morbidity and mortality. treatment is in this remains In a trial including patients with valve replacement or repair procedure at 1 year before a artery pressure still mmHg with a and were to or for The was a clinical score combining hospital admission for in and patient on had a significantly worse outcome that this treatment be for this patient There is a growing of the burden of and the adoption of invasive treatment will be expanding to new and of and TV are in high risk and patients but will need to more challenges than aortic valve due to the more and variable of reports from from from the reports from from from from the