Volume 47, Issue 11

European Heart Journal Issue at a Glance, Volume forty seven, issue eleven. Focus issue Valvular Heart Disease by Editor in Chief Professor Filippo Craya Read to you by Morgan Bryan. Valvular Heart Disease Challenges and Opportunity This focus issue on valvular heart disease starts with a State of the Art Review article entitled Valvular Heart Failure, Evolving Pharmacological Approaches, by Kieran Docherty from the University of Glasgow in the United Kingdom.

The author notes that heart failure, or HF and valvular heart disease, or VHD, are intricately linked. the development of symptomatic HF or asymptomatic left ventricular or L V dysfunction in patients with significant VHD should trigger an assessment for the suitability for definitive valvular intervention.

Whilst no medical therapies slow the progression of primary VHD, Evidence-based HF therapies have been demonstrated to have favorable remodelling effects in patients with secondary functional regurgitant lesions. and are important adjuncts in the management of HF in patients with primary valvular disease. This review provides an overview of the evidence for medical therapy to prevent progression of VHD and to prevent or treat established HF in patients with primary and secondary valve disease.

Treatment of patients with HF with reduced ejection fraction, or HEFREF, and secondary ventricular mitral regurgitation, or SMR, is complex. Secondary mitral regurgitation is a consequence of LV remodeling and contributes to HF progression by worsening ventricle overload. In a state-of-the-art review article entitled Heart failure with reduced ejection fraction and ventricular secondary mitral regurgitation a holistic approach.

Mariana Adamo and colleagues from the University of Brescia in Italy are Summarize current knowledge about management of HEFREF and ventricular SMR, including the entire patient pathway, i.e., diagnosis, treatment, and follow-up. The focus is mainly on the effects of guideline directed medical therapy, or GDMT, And cardiac resynchronization therapy, or CRT, on SMR, as well as on the effects of successful mitral transcatheter edge-to-edge repair, or MTIR, on GDMT.

Optimal management of patients with Hefref and SMR requires the integration of multiple competencies, assessing the interplay of GDMT for HefREF Devices and mitral MTR. Both GDMT and CRT can reduce SMR severity. However, GDMT may not be tolerated in patients with HEFREF who develop hypotension and worsening kidney function following uptitration.

On the other hand, a successful M-Tier can increase forward stroke volume and blood pressure and improve kidney perfusion so that GDMT may be better tolerated after rather than before this procedure. Thus, similarly to CRT, MTIR may serve as an enabling therapy for GDMT. Notably, catheter ablation for atrial fibrillation and coronary revascularization may have a role in very selected patients.

Last but not least, patients with HEFREF and SMR remain at high risk of clinical events even after successful MTR. Thus, careful follow-up and continuous implementation of GDMT remain a major priority both before and after any intervention.

Atrial functional mitral regurgitation, or AFMR, commonly affects elderly and frail individuals. There is growing interest in M-tier as well as in tricuspid tier. However, the prognostic impact of M-tier for AFMR has not been investigated. In a Fast Track Congress article entitled Transcatheter edge-to-edge repair versus medical therapy in atrial functional mitral regurgitation, a propensity score-based comparison from the Ocean Mitral and Reveal AFMR registries.

Tomohro Kanako and colleagues from the Junatendo University Graduate School of Medicine in Tokyo, Japan. Conduct a comprehensive investigation into the association between MTR and prognosis in patients with AFMR. By integrating data from two large-scale Japanese AFMR registries and using appropriate statistical methods.

Patients with AFMR who underwent MTR were selected from the Ocean Mitral Registry and medically managed controls were selected from the Reveal AFMR registry using an identical AFMR definition. The primary end point was a composite of all cause mortality and HF hospitalization. The secondary end point was all cause mortality. A total of 1081 patients female with moderate or severe AFMR were included. Of whom 441 underwent M-tier, and 640 remained on medical treatment.

Overlap weighting based on the propensity score yielded well-balanced baseline characteristics. where M tier was associated with a lower incidence of the primary hazard ratio, or HR zero point six five, P equaling point zero four four, and secondary endpoints, HR 0.58, P equaling.

In an exploratory subgroup analysis, favorable outcomes were much better in patients with less than or equal to mild residual AFMR after TIA while event rates in those with greater than or equal to moderate residual AFMR were comparable with those in the medication group. As sensitivity analyses, inverse probability of treatment weighting, propensity score matching, and multivariable cox regression all confirmed favorable associations of TIR with both endpoints.

The authors conclude that in real-world data, TIER for patients with moderate or severe AFMR was associated with a lower incidence of adverse events compared with medical treatment. The manuscript is accompanied by an editorial by Benedict MacDonagh, Simon Redwood, and Tiffany Patterson from Guy's and St Thomas' NHS Foundation Trust in London in the United Kingdom.

The authors note that this study, although limited by its observational and retrospective nature, is the first to examine hard clinical endpoints in the management of AFMR with MTIR. Increasingly, MR severity in AFMR is associated with worse outcomes, with excess five-year mortality as high as 50% compared with age-matched controls.

In AFMR, HF hospitalizations are higher, and LV diastolic function and pulmonary artery systolic pressures are significantly worse when compared with a ventricular MR cohort. The Transcatheter versus Surgical Mitral valve repair in patients with HF and secondary mitral regurgitation, or Matterhorn trial, demonstrated non-inferiority of M tier to mitral valve surgery in patients with SMR with a reduction in adverse events in the M tier group.

Interestingly, a post hoc analysis of the Matterhorn, which examined the subgroups of AFMR patients, also demonstrated lower event rates with M-Tear when compared with surgical treatment. The role of GDMT in AFMR is poorly understood, and more trial data are needed. The Dapogly flows in effect on functional mitral regurgitation and myocardial remodeling, or deformed trial, Examine the role of dapoglyflosin in both ventricular MR and AFMR patients.

demonstrating a reduction in MRG at three months when Dapoglyflosin was used in addition to GDMT. The ongoing sacubitral valsartin in HF with preserved ejection fraction and secondary mitral valve regurgitation, or PRASE MR trial, also aims to assess the addition of saccubitral valsartin in HF with at least moderate MR.

Invasive treatments, such as catheter ablation, to achieve rhythm control for atrial fibrillation, have been shown to be beneficial in AFMR patients with lower recurrence of MR atrial remodeling and a suggestion of improved clinical outcomes. However, data are limited to retrospective studies with further ongoing work in this area.

It is therefore essential that we better understand this cohort of patients, including the optimal treatment strategies, in addition to the transcatheter interventions. Certainly for M-tier, AFMR is the final frontier.

Pregnancy is an important sex-specific risk factor. In women with a prosthetic heart valve, pregnancy is considered high risk, primarily due to the need for effective anticoagulation. However, data on the relationship between anticoagulation practices and pregnancy outcomes are very limited. In a clinical research article entitled Pregnancy with a Prosthetic Heart Valve, Thrombosis and Bleeding, the ESC EORP Registry of Pregnancy and Cardiac Disease 3.

Johanna von der Zonder and colleagues from the University Medical Center Rotterdam in the Netherlands are Discuss how to better characterize pregnancy outcomes and compare maternal and perinatal outcomes between different anticoagulation regimens. The Registry of Pregnancy and Cardiac Disease is a global registry that prospectively enrolled pregnancies in women with a prosthetic heart valve between January 2018 and April 2023.

Detailed data on anticoagulation, including dosage and monitoring, and cardiovascular, pregnancy and perinatal outcomes were collected. In total, six hundred and thirteen pregnancies were included, of which four hundred and eleven pregnancies were in women with a mechanical valve, and two hundred and two were in women with a biological valve.

The chance of an uncomplicated pregnancy with a live birth in women with a mechanical valve was 54%, compared with 79% in women with a biological valve, P being less than point zero zero one. Thromboembolic and hemorrhagic complications most frequently occurred when low molecular weight heparin, or LMWH based regimens, were used. Valve thrombosis occurred in six percent of women, and a prosthetic valve in the mitral position was associated with valve thrombosis, odds ratio three point three.

A thromboembolic event occurred in 10% of women with anti-10A monitoring and in 21% of women without. Fetal death occurred in 20% of all pregnancies. The authors conclude that more favorable outcomes were found in women with a biological valve compared with a mechanical valve. In women with a mechanical valve, the use of LMWH is associated with an increased risk of thromboembolic complications. A mitroprosthetic valve is a predictor of valve thrombosis.

The benefit cannot be confirmed or refuted, in terms of reduced thromboembolic events, from using anti-10A level monitoring in women on LMWH. The manuscript is accompanied by an editorial by Juli de Becher, Lorna Swann, and Anne Marie Valente from the Gens University Hospital in Belgium, the Golden Jubilee NHS University Hospital in Glasgow in the United Kingdom.

and Harvard Medical School, Boston, Massachusetts, USA The authors highlight that an important message from this study is that significant regional disparities exist. With women with an MHV in high income countries, or HICs, experiencing a lower rate of uncomplicated pregnancies, forty three percent Compared with those in low and middle income countries or LMICs, fifty seven percent. Where anticoagulation regimens are typically more frequently based on vitamin K antagonists or VKAs.

Implying that VKAs are a safer option would be wrong, as the discrepancy may also relate to differences in the underlying disease spectrum, healthcare accessibility, anti-coagulation monitoring, and reporting practices. The regional variability observed in this study highlights the complexities of anticoagulation management and the need for more tailored, resource sensitive approaches to care.

Despite clear evidence that routine-planned cesarean section does not improve maternal outcomes in women with cardiovascular disease, and may in fact be associated with adverse fetal outcomes. The cesarean section rate remains high in this study. More than half of the women underwent cesarean section. This trend is concerning as cesarean deliveries in this population are associated with increased risk of hemorrhagic and thrombotic complications.

These findings underscore the need for stronger advocacy around vaginal delivery as the preferred mode of delivery in most women with prosthetic valves, unless specific obstetric and cardiac indications dictate otherwise.

Aortic stenosis may be managed differently in women and men, but evidence remains limited. sex specific characteristics and outcomes of low to intermediate risk patients assigned to transcatheter aortic valve implantation or TAVI Or Surgical Aortic Valve Replacement from the Dedicate DZHK6 trial are described. In a clinical research article entitled Sex specific outcomes after transcatheter or surgical treatment of aortic valve stenosis, the dedicate DZHK six trial.

Sabine Bleitzifer and colleagues from the Ruhr University of Germany describe sex specific periprocedural characteristics and outcomes of low to intermediate risk patients undergoing Tavi or Savar. The Dedicate DZHK six trial demonstrated non inferiority for the primary outcome of all cause death or stroke at one year. Sex specific effects were evaluated in this predefined descriptive subgroup analysis. A total of 1,394 patients, 43% women, were included.

Women were older and at higher operative risk. Median Society of Thoracic Surgeons risk score two point one percent versus one point five percent, P being less than point zero zero one. All cause death or stroke at one year was 5.2% in the Tavi versus eleven point five percent in the Savar group four six in women. and five point four percent versus nine point zero percent six one in men.

At one year after Tavi vs. Savar, the All caused death occurred in two point six percent versus six point seven per cent HR zero point four one in women and two point six per cent versus five point nine per cent HR zero point four four in men. Stroke occurred in two point six percent versus six point two percent in women and three point one percent versus three point six percent HR zero point eight nine in men.

The authors conclude that among patients with severe aortic stenosis at low to intermediate risk. TAVI is non inferior to SAVAR for the primary outcome in women and men, with lower event rates in patients assigned to TAVI. Women were at particular risk for early complications, irrespective of the assigned treatment, and at increased stroke risk after Savar. The manuscript is accompanied by an editorial by Tomazzo Gori and Hendrik Traeder from the University Medical Centre of Mainz in Germany.

The authors underscore that a key contributor to the observed sex disparities is women's smaller aortic valve annulus, which not only complicates the technical aspects of valve replacement procedure but also increases the risk of patient prosthesis mismatch or PPM. The latter occurs when the prosthetic valve area is too small relative to the patient's body surface area, an issue more common in women that leads to higher transvalvular gradients and worse postoperative hemodynamics.

This anatomical challenge may contribute to explain the increased rates of early complications and poor short term outcomes in women after both TAVI and SAVAR. Unlike TAVI, surgical aortic valve replacement theoretically allows for aortic root enlargement during the operation. Creating the opportunity to implant a larger prosthetic valve and thereby significantly reducing the risk of PPM.

However, in common clinical practice, root enlargement is performed infrequently, even in female patients at high risk due to anatomical size constraints. In the landmark Rea trial, which was exclusively designed to assess outcomes in women, no patient randomized to SAVA underwent surgical root enlargements. This underutilization of a proven technique starkly illustrates a system level gap.

Even when evidence and expertise are available, women are often not afforded optimal anatomical correction, perpetuating sex-based disparities in outcomes. With this background, the Dedicate DZHK6 trial provides further information on the ongoing discussion. Taking into account all the above considerations and the other limitations correctly acknowledged by the authors, the implication we derive from the present interesting publication is as follows.

Equal outcome does not imply equal journey, as it appears that the choice of therapeutic strategy or sav has a greater impact on women than men.

There are limited data on mortality in patients with moderate mixed aortic valve disease or MAVD. Defined as the combination of moderate aortic stenosis or AS and moderate aortic regurgitation or AR. Consequently, current guidelines lack specific recommendations for aortic valve replacement or AVR in this population. In a clinical research article entitled

Outcomes of moderate mixed aortic valve stenosis and regurgitation. Pila Lopez Santhi and colleagues from the Leiden University Medical Center in the Netherlands Aim to compare survival between moderate MAVD and isolated severe AS or severe AR. and to evaluate the impact of symptoms or left ventricular ejection fraction less than 50%, as current criteria for AVR in severe AS or AR.

Overall, one thousand nine hundred and twenty six patients were included from four centers, five hundred and twenty seven with moderate MAVD, four hundred and thirteen with severe AR, and nine hundred and eighty six with severe AS. The primary endpoint was all-course mortality. Over a median follow-up of 7.2 years, 748 patients died.

After adjusting for clinical and echocardiographic variables, moderate MAVD patients showed ten-year survival similar to those with severe AS, but worse than those with severe AR. Sixty-two per cent, fifty-five per cent, and seventy-nine per cent, respectively, P being less than point zero zero one. Symptomatic moderate MAVD patients showed adjusted mortality comparable with those with symptomatic severe AS.

while asymptomatic, moderate MAVD patients had adjusted mortality similar to those with severe AR, symptomatic and asymptomatic. Moderate MAVD patients with LVEF less than fifty percent had adjusted mortality comparable with patients with severe AS with LVEF less than fifty percent. While those with LVF greater than or equal to fifty percent showed mortality similar to those with severe AR, regardless of LV dysfunction.

The authors conclude that in moderate MAVD, the presence of symptoms or LVF less than fifty percent is is associated with increased mortality comparable with isolated severe AS under similar conditions. Therefore, patients with moderate MAVD should benefit from AVR in the presence of symptoms or LV dysfunction. The manuscript is accompanied by an editorial by Vidushe Yogesharan and Catherine Otto from the University of Washington School of Medicine in Seattle, Washington, USA.

The authors conclude that for patients with MAVD and symptoms or LV dysfunction, once other potential causes have been excluded, It can be concluded that adding moderate AR to moderate AS equals severe aortic valve disease for that individual. As for patients with severe AS or severe AR, Valve intervention may be appropriate in these patients, with similar considerations in shared decision making for the choice of prosthetic valve type and route of implantation.

Clinical management of patients with combined moderate AS and moderate AR remains challenging. As always, we should listen to the patient look at the valve.

This issue is also complemented by two discussion forum contributions. In a contribution entitled Is it all about mitral annular disjunction? Rohit Jawa, Luka Christin, and Francesca Delling from the University of California, San Francisco, California, USA, comment on the recently published paper entitled Mitral annular disjunction and mitral valve prolapse long term risk of ventricular arrhythmias after surgery by Clara Lodin et al from the Karolinska Institut in Stockholm, Sweden.

In another contribution entitled Concomitant surgical burden in Raya Implications for interpreting the primary endpoint. Pradip Narayana from Narayana Health in Kolkata, India. Comment on the recent published paper entitled Transcatheter versus Surgical Aortic Valve Replacement in Women, The Rhea Trial, by Didier Jetje et al. from the Clinique Pasteur in Toulouse, France. The editors hope that this issue of the European Heart Journal will be of interest to its listeners.