Technical and Clinical Outcomes After Transcatheter Edge-to-Edge Repair of Mitral Regurgitation in Male and Female Patients: Is Equality Achieved?

Currently, no clear impact of sex on short- and long-term survival following transcatheter edge-to-edge mitral valve repair (TEER) is evident, although no data are available on postprocedural life expectancy. Our aim was to assess sex-specific differences in outcomes of patients with mitral regurgitation (MR) treated by TEER. Short-term and 5-year outcomes in men and women undergoing TEER between 2011 and 2018 who were included in the large, multicenter, real-world MitraSwiss registry were analyzed. Outcomes were compared stratified by sex and according to MR cause (primary versus secondary). The impact of TEER on postprocedural life expectancy was estimated by relative survival analysis. Among 1142 patients aged 60 to 89 years, 39.8% were women. They were older, with fewer cardiovascular risk factors and lower functional capacity compared with men. Thirty-day mortality was higher in men than in women (3.3% versus 1.1%; odds ratio, 3.16 [95% CI, 1.16-10.7]; P=0.020). Five-year survival was comparable in both sexes (adjusted hazard ratio for 5-year mortality in men, 1.14 [95% CI, 0.90-1.44], P=0.275). Both men and women with either primary or secondary MR showed similar clinical efficacy over time. TEER provided high relative survival estimates among all groups, and fully restored predicted life expectancy in women with primary MR (5-year relative survival estimate, 97.4% [95% CI, 85.5-107.0]). TEER is not associated with increased short-term mortality in women, whereas 5-year outcomes are comparable between sexes. Moreover, TEER completely restored normal life expectancy in women with primary MR. A residual excess mortality persists in secondary MR, independently of sex

Long-Term Implications of Atrial Fibrillation in Patients With Degenerative Mitral Regurgitation

Background: Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery. Objectives: This study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term. Methods: Patients were enrolled in the MIDA (Mitral Regurgitation International Database) registry, which reported the consecutive, multicenter, international experience with DMR due to flail leaflets echocardiographically diagnosed. Results: Among 2,425 patients (age 67 \ub1 13 years; 71% male, 67% asymptomatic, ejection fraction 64 \ub1 10%), 1,646 presented at diagnosis with sinus rhythm (SR), 317 with paroxysmal AD, and 462 with persistent AF. Underlying clinical/instrumental characteristics progressively worsened from SR to paroxysmal to persistent AF. During follow-up, paroxysmal and persistent AF were associated with excess mortality (10-year survival in SR and in paroxysmal and persistent AF was 74 \ub1 1%, 59 \ub1 3%, and 46 \ub1 2%, respectively; p < 0.0001), that persisted 20 years post-diagnosis and independently of all baseline characteristics (p values <0.0001). Surgery (n = 1,889, repair 88%) was associated with better survival versus medical management, regardless of all baseline characteristics and rhythm (adjusted hazard ratio: 0.26; 95% confidence interval: 0.23 to 0.30; p < 0.0001) but post-surgical outcome remained affected by AF (10-year post-surgical survival in SR and in paroxysmal and persistent AF was 82 \ub1 1%, 70 \ub1 4%, and 57 \ub1 3%, respectively; p < 0.0001). Conclusions: AF is a frequent occurrence at DMR diagnosis. Although AF is associated with older age and more severe presentation of DMR, it is independently associated with excess mortality long-term after diagnosis. Surgery is followed by improved survival in each cardiac rhythm subset, but persistence of excess risk is observed for each type of AF. Our study indicates that detection of AF, even paroxysmal, should trigger prompt consideration for surgery

Genome-wide association study reveals novel genetic loci:a new polygenic risk score for mitral valve prolapse

AIMS: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder. METHODS AND RESULTS: We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors. CONCLUSION: We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-beta signalling molecules and spectrin beta. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention. KEY QUESTION: Expand our understanding of the genetic basis for mitral valve prolapse (MVP). Uncover relevant pathways and target genes for MVP pathophysiology. Leverage genetic data for MVP risk prediction. KEY FINDING: Sixteen genetic loci were significantly associated with MVP, including 13 novel loci. Interesting target genes at these loci included LTBP2, TGFB2, ALKP3, BAG3, RBM20, and SPTBN1. A risk score including clinical factors and a polygenic risk score, performed best at predicting MVP, with an area under the receiver operating characteristics curve of 0.677. TAKE-HOME MESSAGE: Mitral valve prolapse has a polygenic basis: many genetic variants cumulatively influence pre-disposition for disease. Disease risk may be modulated via changes to transforming growth factor-beta signalling, the cytoskeleton, as well as cardiomyopathy pathways. Polygenic risk scores could enhance the MVP risk prediction

Patients with Complex Chronic Diseases: Perspectives on Supporting Self-Management

A Complex Chronic Disease (CCD) is a condition involving multiple morbidities that requires the attention of multiple health care providers or facilities and possibly community (home)-based care. A patient with CCD presents to the health care system with unique needs, disabilities, or functional limitations. The literature on how to best support self-management efforts in those with CCD is lacking. With this paper, the authors present the case of an individual with diabetes and end-stage renal disease who is having difficulty with self-management. The case is discussed in terms of intervention effectiveness in the areas of prevention, addiction, and self-management of single diseases. Implications for research are discussed

Mitral regurgitation and dyspnoea: The expanding role of mitral effective regurgitant orifice among un-selected patients

Aims Mitral regurgitation is frequent in the general population and among suspected heart failure patients; however, to what extent it contributes to dyspnoea is unclear. We hypothesized mitral regurgitation to have a role in determining dyspnoea in unselected ambulatory patients. Methods Consecutive outpatients referred for echocardiography were retrospectively screened and included. We excluded patients with mitral stenosis or prosthesis, congenital heart disease, cardiac surgery (previous 6 months) and atrial fibrillation. Patients were classified into four dyspnoea grades based on how they perceived their disability. We assessed mitral regurgitation severity through the effective regurgitant orifice area (ERO). Results One hundred and fifty-four patients (58% men; age 67 +/- 14 years; mean ejection fraction 54 +/- 12%) formed the study population; 76 (49%) classified asymptomatic (grade I), 63 (41%) dyspnoea grade II and 15 (10%) grade III; none was in grade IV. Mitral regurgitation was present in 102 patients (66%): primary in 14 (14%) and secondary in 88 (86%); among grades I, II and III patients, mitral regurgitation was present in 35 (46%; ERO 0.05 +/- 0.10 cm(2)), 52 (82%; ERO 0.10 +/- 0.13 cm(2)) and 15 (100%; ERO 0.20 +/- 0.11 cm(2)) patients, respectively (P < 0.0001). After adjusting for clinical (age, hypertension, ischemic heart disease, chronic kidney injury, chronic pulmonary disease) and echocardiographic confounders (ejection fraction, E/e'), ERO remained associated with symptoms presence (grade I versus II - III;P = 0.01 andP = 0.03, respectively). Conclusion Among unselected heterogeneous ambulatory patients, mitral ERO was associated with the presence of dyspnoea and could therefore help in identifying symptomatic patients and in clinical characterization of patients with perceived dyspnoea

Cardiac imaging in anderson-fabry disease: past, present and future

Anderson-Fabrydisease is an X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-galactosidase A. This results in pathological accumulation of glycosphin-golipids in several tissues and multi-organ progressive dysfunction. The typical clinical phenotype of Anderson-Fabry cardiomyopathy is progressive hypertrophic cardiomyopathy associated with rhythm and conduction disturbances. Cardiac imaging plays a key role in the evaluation and management of Anderson-Fabry disease patients. The present review highlights the value and perspectives of standard and advanced cardiovascular imaging in Anderson-Fabry disease

Prevalence of patients with severely reduced aortic valve area and low gradient despite a preserved ejection fraction. Results from a cath-lab data base.

Prevalence of patients with severely reduced aortic valve area and low gradient despite a preserved ejection fraction. Results from a cath-lab data base

Mitral regurgitation, left atrial structural and functional remodelling and the effect on pulmonary haemodynamics

Aims To assess the association between mitral regurgitation (MR) and left atrial (LA) structural and functional remodelling and their effect on pulmonary haemodynamics. Methods and results Consecutive unselected patients undergoing comprehensive echocardiography were enrolled. Parameters of cardiac structure and function were obtained as well as mitral effective regurgitant orifice area (ERO) and estimation of pulmonary artery systolic pressure (PASP). Measures of LA structure [LA volume (LAV)] and function [peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS) and conduit strain (CS)] were also calculated. The study population included 102 patients (mean age 70 +/- 14 years, 42% women), with a mean ejection fraction of 52 +/- 13%. MR was classified as organic due to mitral valve prolapse in 14 patients (14%) and functional in 88 patients (86%). Mean ERO was 0.12 +/- 0.12 cm(2) and 86 patients (84%) had an ERO <= 0.2 cm(2). ERO was significantly associated with worse measures of LA structure and function. Despite the low burden of MR, the association remained significant after adjusting for clinical and echocardiographic confounders (beta: 3.7, P = 0.022 for LAV; beta: -3.0, P = 0.003 for PALS; beta: -1.8, P = 0.027 for PACS) and was significantly related with functional MR (P for interaction <0.001). ERO was also significantly associated with PASP, and measures of LA function (PALS and PACS) significantly modified this relationship (P for interaction <0.001). Conclusions Even a mild degree of MR contributes to LA remodelling and this relationship plays an active role in pulmonary circulation, suggesting a potential mechanism by which these parameters contribute to the development of heart failure

How to incorporate left atrial strain in the diagnostic algorithm of left ventricular diastolic dysfunction

The combination of early trans-mitral inflow and mitral annular tissue Doppler velocities (E/e ' ratio) is widely applied to noninvasively estimate left ventricular (LV) filling pressures. However, when E/e ' is between 8 and 14 its accuracy decreases substantially. Left atrial (LA) deformation analysis by speckle tracking echocardiography was recently proposed as an alternative approach to estimate LV filling pressures, but its role when E/e ' is between 8 and 14 has been under-investigated. We aimed to assess whether LA strain could help to identify elevated filling pressures in patients with E/e ' between 8 and 14. Among consecutive non-selected patients who underwent a comprehensive echocardiographic evaluation, we enrolled those with E/e ' ratio > 8 and <= 14. Exclusion criteria were: organic mitral valve disease or mitral surgery; presence of mitral regurgitation greater than moderate in severity; diseases associated with pre-capillary pulmonary hypertension; and undetectable systolic pulmonary artery pressure (PAP-S). Peak LA longitudinal (PALS) and contraction strain (PACS) values was obtained by averaging all segments, and by separately averaging segments measured in the 4-chamber and 2-chamber views. Seventy-six patients had E/e ' > 8 and <= 14 and formed the study cohort. Mean age 69 +/- 12 years, LV ejection fraction (LVEF) 54.5 +/- 11.2%, mean E/e ' 11.2 +/- 1.9, PAP-S 33 +/- 7 mmHg, PALS 31.6 +/- 11.7%. PALS was significantly associated to PAP-S after adjustment for LVEF, E/e ', septal LV longitudinal shortening velocity (s '), LA volume indexed (p = 0.002) and also for ASE/EACVI diastolic dysfunction classification (p = 0.0002). Furthermore, PALS but not ASE/EACVI diastolic dysfunction grading, resulted independently associated to New York Heart Association (NYHA) class (p = 0.0004). PALS is able to predict increased intra-cardiac pressure and NYHA class in patients characterized by E/e ' between 8 and 14. Therefore, we propose that PALS might be incorporated in a simplified diagnostic algorithm based on E/e ' classes

Mitral regurgitation, left atrial structural and functional remodelling and the effect on pulmonary haemodynamics

Aims: To assess the association between mitral regurgitation (MR) and left atrial (LA) structural and functional remodelling and their effect on pulmonary haemodynamics. Methods and results: Consecutive unselected patients undergoing comprehensive echocardiography were enrolled. Parameters of cardiac structure and function were obtained as well as mitral effective regurgitant orifice area (ERO) and estimation of pulmonary artery systolic pressure (PASP). Measures of LA structure [LA volume (LAV)] and function [peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS) and conduit strain (CS)] were also calculated. The study population included 102 patients (mean age 70 ± 14 years, 42% women), with a mean ejection fraction of 52 ± 13%. MR was classified as organic due to mitral valve prolapse in 14 patients (14%) and functional in 88 patients (86%). Mean ERO was 0.12 ± 0.12 cm2 and 86 patients (84%) had an ERO ≤0.2 cm2. ERO was significantly associated with worse measures of LA structure and function. Despite the low burden of MR, the association remained significant after adjusting for clinical and echocardiographic confounders (β: 3.7, P = 0.022 for LAV; β: −3.0, P = 0.003 for PALS; β: −1.8, P = 0.027 for PACS) and was significantly related with functional MR (P for interaction <0.001). ERO was also significantly associated with PASP, and measures of LA function (PALS and PACS) significantly modified this relationship (P for interaction <0.001). Conclusions: Even a mild degree of MR contributes to LA remodelling and this relationship plays an active role in pulmonary circulation, suggesting a potential mechanism by which these parameters contribute to the development of heart failure