Dilated cardiomyopathy (DCM) is a prevalent cardiac disorder affecting 1 in 250-500 individuals, characterized by ventricular dilation and impaired systolic function, leading to heart failure and increased mortality, including sudden cardiac death. DCM arises from genetic and environmental factors, such as drug-induced, inflammatory, and viral causes, resulting in diverse yet overlapping phenotypes. Advances in precision medicine are revolutionizing DCM management by leveraging genetic and molecular profiling for tailored diagnostic and therapeutic approaches. This review highlights comprehensive diagnostic evaluations, genetic discoveries, and multi-omics approaches integrating genomic, transcriptomic, proteomic, and metabolomic data to enhance understanding of DCM pathophysiology. Innovative risk stratification methods, including machine learning, are improving predictions of disease progression. Despite these advancements, the current one-size-fits-all management strategy contributes to persistently high morbidity and mortality. Emerging targeted therapies, such as CRISPR/Cas9 genome editing, aetiology-specific interventions, and pharmacogenomics, are reshaping treatment paradigms. Precision medicine holds promise for optimizing DCM diagnosis, treatment, and outcomes, aiming to reduce the burden of this debilitating condition.

Ischaemic mitral regurgitation (IMR) results from dysfunctional myocardial remodelling, which portends a poor clinical prognosis. This study assessed the surgical treatment of IMR and its associations with clinical and echocardiographic outcomes in the context of 2014 reports suggesting non-surgical management of non-severe IMR.

Patients who underwent mitral valve (MV) procedures for IMR at Liverpool Hospital (Sydney, Australia) between 2008 and 2020 were included based on coronary disease and echocardiographic criteria. Data were obtained from patient records and linkage with the Australian Institute of Health and Welfare National Death Index. The primary outcome was the type of MV surgery performed in 2008-2014 and 2015-2020. Secondary outcomes were survival and freedom from combination of mortality and congestive heart failure (CHF) readmission, comparing MV repair and MV replacement and the outcomes for two periods by MV procedure.

Of 106 patients treated surgically for IMR, 78 had MV repair (59 in 2008-2014, 19 in 2015-2020) and 28 had MV replacement (14 in 2008-2014, 14 in 2015-2020). Patients were followed up for 7.2 years (interquartile range 5.2-9.1). Compared to 2008-2014, there was a reduced proportion of MV procedures for IMR (4.2% and 2.0%; p<0.001) and MV repair for IMR (80.8% and 57.6%; p=0.012) post-2014. Freedom from a combination of mortality and CHF readmission over 10 years was significantly better in the MV repair than in the MV replacement group (log rank p<0.001). Over 5 years, freedom from mortality and the combination of mortality and CHF readmission were similar in both periods (log rank p=0.675 and p=0.433). In the earlier period, freedom from combined outcome was better in the MV repair group than the MV replacement group (log rank p<0.001) but not different in the second period (log rank p=0.149). Mitral regurgitation recurrence was less in the later period (25.8% and 3.6%; p=0.013).

The proportion of MV procedures and MV repairs performed for IMR declined significantly after 2014, indicating a significant change in practice towards conservative surgical correction of IMR. The combined long-term outcomes were unchanged after the change in practice, but the incidence of mitral regurgitation recurrence was significantly improved.

The present study aimed to develop a comprehensive clinical- and echocardiography-based risk score for predicting cardiovascular (CV) adverse outcomes in patients with ischemic heart failure (IHF) and reduced left ventricular ejection fraction (LVEF).

This retrospective cohort study included 1341 hospitalized patients with IHF and LVEF < 50% at our hospital from 2009 to 2017. Cox regression models and nomogram were utilized to develop a comprehensive prediction model (C&E risk score) for CV mortality and CV-related events (hospitalization or death).

Over a median 26-month follow-up, CV mortality and CV events rates were 17.4% and 40.9%, respectively. The C&E risk score, incorporating both clinical and echocardiographic factors, demonstrated superior predictive performance for CV outcomes compared to models using only clinical or echocardiographic factors. Internal validation confirmed the stable predictive ability of the C&E risk score, with an AUC of 0.740 (95% CI 0.709-0.775, P < 0.001) for CV mortality and an AUC of 0.678 (95% CI 0.642-0.696, P < 0.001) for CV events. Patients were categorized into low-, intermediate-, and high-risk based on the C&E risk score, with progressively increasing CV mortality (5.3% vs. 14.6% vs. 31.9%, P < 0.001) and CV events (28.8% vs. 38.2% vs. 55.0%, P < 0.001). External validation also confirmed the risk score's prognostic efficacy within additional IHF patient datasets.

This study establishes and validates the novel C&E risk score as a reliable tool for predicting CV outcomes in IHF patients with reduced LVEF. The risk score holds potential for enhancing risk stratification and guiding clinical decision-making for high-risk patients.

Atrial fibrillation (AF) and left ventricular (LV) systolic dysfunction (LVSD) may be associated with function mitral and tricuspid regurgitation (FMR/FTR). Prior studies have largely assessed impact of MR on AF ablation outcomes in the presence of preserved LV ejection fraction.

This study sought to determine the impact of FMR on the outcomes of catheter ablation (CA) in patients with AF and LVSD.

We examined baseline clinical characteristics, CA outcomes, and change in echocardiographic parameters (FMR and FTR severity, LV and left atrial [LA] dimensions, LVEF) at baseline and 12 months in individuals with AF and LVSD with at least mild FMR undergoing CA. Patients with primary mitral valve disease were excluded.

235 patients (age 62.8 years,16.2% female, NYHA functional class III (Q1-Q3: II-III)) underwent CA and were categorized by FMR severity at baseline (mild n = 117; moderate/severe n = 118). Baseline characteristics were comparable irrespective of degree of FMR, other than lower LVEF (LVEF 29% [Q1-Q3: 22.8%-35.0%] vs 35% [Q1-Q3: 30.0%-41.0%]; P < 0.001) and increased tricuspid regurgitation in moderate/severe MR (22%) vs mild MR (8%, P < 0.001). LA size did not differ significantly across FMR groups (P = 0.233). At 12 months following CA, recurrent atrial arrhythmia occurred in 101 of 235 (43.0%) including 42.7% in mild vs 43.2% in moderate-to-severe MR (P = 0.940). The severity of FMR did not influence arrhythmia recurrence (OR: 1.15; 95% CI: 0.54-1.86; P = 0.601) nor LV recovery (OR: 1.07; 95% CI: 0.67-1.25; P = 0.153). After CA, 89% of those with significant FMR and 85% with significant FTR exhibited ≥1 grade reduction at 12 months. Change in LV dimensions was associated with MR responders (OR: 0.93; 95% CI: 0.87-0.99; P = 0.022) with a greater reduction in LV size at 12 months in MR improvement (-5.0 (Q1-Q3: -9.3 to -1.0) vs non-improvement -1.0 (Q1-Q3: -5.0 to 2.5), P = 0.004) whereas change in LA size was not (OR: 0.98; 95% CI: 0.97-1.03; P = 0.984).

In patients with AF and LVSD, the degree of FMR did not impact the success of ablation. There was a significant reduction in FMR and FTR at 12 months following CA. Patients with AF and LVSD should be strongly considered for AF ablation irrespective of the degree of mitral regurgitation.

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, with acute HF (AHF) or cardiogenic shock requiring rapid intervention to prevent fatal outcomes. Advances in temporary mechanical circulatory support (tMCS) devices have revolutionized the management of advanced HF, offering temporary, durable, and individualized support options. This manuscript reviews the pathophysiology and clinical presentation of AHF, the role of multi-disciplinary Heart Teams, and the growing importance of structured care networks in managing complex cases of HF. We explore the strategic deployment of tMCS in acute settings, device options, implications for patient outcomes, and current challenges in the field. This manuscript emphasizes the importance of team-based approaches and underscores the potential of tMCS devices in stabilizing patient haemodynamics, bridging to recovery or definitive therapy, and improving survival in patients facing high-risk HF.

The Cardiovascular Outcomes Assessment for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) risk score predicts the risk of death or hospitalization for heart failure within 2 years after transcatheter edge-to-edge repair (TEER) of mitral regurgitation (MR) using the MitraClip device. We performed an international validation of the score in patients who underwent TEER in Italian and Polish cardiology centers. Patients with severe functional MR who underwent TEER with MitraClip between March 2012 and July 2023 were included. Patients were categorized as COAPT-eligible or -noneligible based on the COAPT trial criteria. Clinical data were collected from medical records and the COAPT risk score was calculated for each patient. The primary end point was a composite of all-cause mortality and hospitalization for heart failure at the 2-year follow-up. Of 344 patients, 218 were COAPT-eligible (63%) and 126 were COAPT-noneligible (37%). A higher COAPT score correlated to increased risk of primary end point in the overall population (p <0.001) and COAPT-eligible (p = 0.020) and COAPT-noneligible groups (p = 0.042). The COAPT score had a poor predictive value for the primary end point in every group (area under the curve [AUC] ≤0.61 for all). It performed better in lower-risk patients (<4 points) than higher-risk patients (≥4 points) (AUC 0.658 vs AUC 0.523). The COAPT score was independently associated with an increased risk of primary end point in patients with <4 points (adjusted hazard ratio 1.338, 95% confidence interval 1.031 to 1.737, p = 0.028) but not those with higher score values. In conclusion, the COAPT risk score has a poor performance in COAPT-eligible and -noneligible patients with severe functional MR. The score performance depends on the patient baseline risk, with better accuracy in lower-risk patients.

The impact of functional mitral regurgitation and type 2 mellitus diabetes (T2DM) on left ventricular (LV) strain in nonischemic dilated cardiomyopathy (NIDCM) patients remains unclear.

To evaluate the impact of mitral regurgitation severity on LV strain, and explore additive effect of T2DM on LV function across varying mitral regurgitation severity levels in NIDCM patients.

Retrospective.

352 NIDCM (T2DM-) patients (49.1 ± 14.6 years, 67% male) (207, 85, and 60 no/mild, moderate, and severe mitral regurgitation) and 96 NIDCM (T2DM+) patients (55.2 ± 12.4 years, 77% male) (47, 30, and 19 no/mild, moderate, and severe mitral regurgitation).

3.0 T/balanced steady-state free precession sequence.

LV geometric parameters and strain were measured and compared among groups. Determinants of LV strain were investigated.

Student's t-test, Mann-Whitney U test, one-way ANOVA, Kruskal-Wallis test, univariable and multivariable linear regression. P < 0.05 was considered statistically significant.

LV GLPS and longitudinal PDSR decreased gradually with increasing mitral regurgitation severity in NIDCM patients with T2DM(GLPS: -5.7% ± 2.1% vs. -4.3% ± 1.6% vs. -2.6% ± 1.3%; longitudinal PDSR:0.5 ± 0.2 sec-1 vs. 0.4 ± 0.2 sec-1 vs. 0.3 ± 0.1 sec-1). NIDCM (T2DM+) demonstrated decreased GCPS and GLPS in the no/mild subgroup, reduced LV GCPS, GLPS, and longitudinal PDSR in the moderate subgroup, and reduced GRPS, GCPS, GLPS, and longitudinal PDSR in the severe subgroup compared with NIDCM (T2DM-) patients. Multivariable regression analysis identified that mitral regurgitation severity (β = -0.13, 0.15, and 0.25 for GRPS, GCPS, and GLPS) and the presence of T2DM (β = 0.14 and 0.13 for GCPS and GLPS) were independent determinants of LV strains in NIDCM patients.

Increased mitral regurgitation severity is associated with reduced LV strains in NIDCM patients with T2DM. The presence of T2DM exacerbated the decline of LV function across various mitral regurgitation levels in NIDCM patients, resulting in reduced LV strains.

Stage 3.

The assessment of left ventricular (LV) outflow velocity time integral (LVOT-VTI) has gained favor in the stratification of patients with heart failure (HF). We evaluated the prognostic significance of LVOT-VTI compared with the commonly used indices of LV outflow: cardiac index (CI) and stroke volume index (SVI), their reproducibility and cut-off values.

A total of 424 outpatients diagnosed with HF and LV systolic dysfunction (LV ejection fraction < 50%) underwent a Doppler echocardiographic examination, including the assessment of CI, SVI, and LVOT-VTI. The Bland-Altman analysis showed LVOT-VTI the most reproducible outflow index. The study follow-up duration was 3.5 years (interquartile range 1.6-6.5), at the end of which there were 94 cardiovascular deaths (29%). Cox regression univariate analysis showed that LVOT-VTI was the most predictive of the study end-point. The ratio of tricuspid annular displacement-to-pulmonary artery systolic pressure (TAPSE/PASP) (p < 0.0001), LVOT-VTI (p = 0.0011), and end-systolic volume index (p = 0.0036) independently predicted the study end-point. At receiver-operating characteristic (ROC) analysis, LVOT-VTI < 12.0 cm had the best sensitivity and specificity for predicting cardiovascular mortality. Reduced LV EF (p = 0.0011), raised BNP levels (p = 0.0053), and high LV filling pressure (p = 0.044) were associated with low LVOT-VTI in multivariate logistic regression analysis. Patients with low LVOT-VTI and TAPSE/PASP < 0.32 mm/mmHg exhibited the worst prognosis on Kaplan-Meier survival curves (p < 0.0001).

A LVOT-VTI < 12.0 cm represents the best predictor of the cardiovascular outcome and proved the most reproducible index of LV forward flow in patients with chronic HF and systolic dysfunction. The combination of impaired LVOT-VTI with TAPSE/PASP showed the worst survival.

This meta-analysis aims to assess the impact of pulmonary hypertension (PH) on the clinical prognosis of patients with moderate to severe mitral valve regurgitation (MR) undergoing transcatheter edge-to-edge mitral valve repair (TEER).

As of August 2024, relevant studies were identified through searches of the PubMed, Cochrane Library, Web of Science, and Embase databases. A comprehensive screening process was conducted, with quality assessment performed utilizing the Newcastle Ottawa Scale (NOS). Data analysis was carried out using Stata17.0 software, generating forest plots, funnel plots, Egger's test, and sensitivity analysis plots to analyze heterogeneity and publication bias. Odds ratios (OR) and standardized mean differences (SMD) were calculated for dichotomous and continuous variables, respectively, each presented with a 95% confidence interval (CI).

A total of 10 studies involving 28,404 patients were included, with all articles achieving a NOS score of ≥7. The outcome indicators were as follows: 2-year all-cause mortality [OR = 2.06, 95%CI(1.49, 2.84), p < 0.01, I 2 = 79.9%]; heart failure rehospitalization rate [OR = 1.56, 95%CI(1.29,1.76), p < 0.01, I 2 = 41.7%]; 30-day all-cause mortality [OR = 2.10, 95%CI(1.78,2.47), p < 0.01, I 2 = 0%]; cardiogenic mortality [OR = 2.00, 95%CI (1.61,2.49), p < 0.01, I 2 = 0%]; and length of hospital stay [OR = 0.17, 95%CI(0.14,0.20), p < 0.01, I 2 = 0%]. All outcome indicators demonstrated that the PH group had significantly worse outcomes compared to the non-PH group. Subgroup analyses were performed on outcome indicators with notable heterogeneity, focusing on PH measurement methods, PH diagnostic criteria, and the severity of PH. The results indicated that most combined subgroup outcomes were consistent with the overall findings and showed significantly reduced heterogeneity. The sources of heterogeneity are likely attributed to the methods of PH measurement, diagnostic criteria for PH, and the severity of PH.

Within two years after undergoing transcatheter edge-to-edge repair (TEER), patients with MR and PH experiecne significantly higher rates of all-cause mortality, 30-day all-cause mortality, heart failure readmissions, cardiogenic mortality, and longer hospital stays compared to those without PH.

https://inplasy.com/, identifier (INPLASY202480068).

Secondary mitral regurgitation (SMR) and tricuspid regurgitation (TR) are the most common valvular heart diseases in patients with heart failure (HF). Transcatheter edge-to-edge repair (TEER) devices designed for treating MR and TR have been successfully tested in randomized controlled trials, but methodological issues have often challenged their interpretation. This manuscript aimed to provide an overview of TEER registries on SMR and TR in HF, highlighting their key features, describing clinical characteristics and outcomes of patients receiving these devices, and exploring the available data limitations.

PubMed, Web of Science, and EMBASE were searched for registries reporting on TEER in SMR or TR. Registries were excluded if single-centre and with <100 patients. Twenty-six registries (46% prospective, 12% ongoing), including a total cohort of 18 925 patients, were retrieved for TEER in SMR, and six registries (50% retrospective, 33% ongoing) reported on the use of TEER for TR in a total cohort of 1412 patients. Limited geographical representativity outside North America and Europe, high number of missing values, and inconsistency in data reporting were the main existing evidence limitations.

Registries on TEER represent a key data source in a setting where it is difficult to conduct randomized controlled trials. However, limitations in design, patient characterization, and outcomes reporting restrain their use. A novel conceptual framework for future prospective TEER registries, as proposed in this document, might inform current practice, address relevant clinical questions and future trial design.

Mitral regurgitation (MR) is a common valvular disorder linked to high morbidity and mortality. For patients unsuitable for surgery, transcatheter mitral edge-to-edge repair (TEER) with the MitraClip® G4 system offers an alternative. This study aims to evaluate procedural, echocardiographic, functional, and quality of life (QoL) outcomes in patients who underwent TEER with the MitraClip® G4 system, along with possible predictors of New York Heart Association (NYHA) class I at 30 days and at 1 year.

Patients with moderate-to-severe (3+) or severe (4+) degenerative MR (DMR) or functional MR (FMR), classified as NYHA class III or IV, and who underwent TEER with the MitraClip® G4 system at our center between January 2021 and December 2023 were included.

A total of 83 patients [71% FMR, 66% male, median (IQR) age 70 (11) years] underwent TEER, with 100% procedural success. MR ≤ 2+ was achieved in 100% and 98% of patients at 30 days and 1 year, respectively. NYHA class I or II was achieved in 100% and 96.8% of patients at 30 days and 1 year, respectively. The Kansas City Cardiomyopathy Questionnaire (KCCQ) score improved from 51 ± 20 at baseline to 69 ± 15 at 30 days (p < 0.001) and 70.5 ± 15 at 1 year (p < 0.001). Lower baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) predicted achieving NYHA class I at 30 days (HR: 0.63, 95% CI: 0.41-0.95, p = 0.030), while lower European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) and NT-proBNP predicted it at 1 year [(HR: 0.50, 95% CI: 0.28-0.89, p = 0.019), (HR: 0.67, 95% CI: 0.44-0.99, p = 0.049), respectively].

The MitraClip® G4 system provides significant improvements in MR severity, functional class, and QoL. Lower NT-proBNP and EuroSCORE II were strong predictors of achieving optimal functional status (NYHA class I).

Mitral valve regurgitation (MR) is associated with worse outcomes in patients undergoing percutaneous coronary intervention (PCI). We sought to evaluate outcomes of Impella-supported high-risk PCI (HRPCI) patients according to MR severity.

Patients from the PROTECT III study undergoing Impella-supported HRPCI were stratified into 4 groups according to MR severity: No or trace MR, mild MR, moderate MR, and severe MR. Immediate PCI-related complications, major adverse cardiovascular and cerebrovascular events (MACCE: all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization) at 90 days and death at 1-year were assessed.

From March 2017 to March 2020, 631 patients who underwent Impella-supported HRPCI in the PROTECT III study had evaluable MR severity at baseline. Patients with severe MR had lower body mass indices, lower left ventricular ejection fractions (LVEFs), and were more frequently diagnosed with heart failure. The incidence of immediate PCI-related complications was similar between groups. Unadjusted 90-day MACCE and 1-year mortality rates were numerically higher in patients with severe MR compared to the other study groups yet without reaching statistical significance. In multivariable analyses, there was no significant association between the presence of severe MR for 90-day MACCE or 1-year mortality compared with other degrees of MR (adj. HR = 1.71, 95% CI [0.73, 3.98], p = 0.21; adj. HR = 1.79, 95% CI [0.86, 3.74], p = 0.12, respectively).

Impella-supported HRPCI patients with moderate or severe MR exhibited a higher prevalence of heart failure, lower LVEF, and longer hospital stays. Patients with severe MR showed numerically higher unadjusted rates of 90-day MACCE and 1-year mortality compared to other groups, however these differences did not reach statistical significance even after adjustment for potential confounders.

Trial Name: The Global cVAD Study (cVAD) ClinicalTrial.govIdentifier:NCT04136392 URL: https://clinicaltrials.gov/ct2/show/NCT04136392?term=cvad&draw=2&rank=2.

Significant secondary mitral regurgitation (SMR) is known to be associated with worse prognosis. However, data focusing specifically on moderate SMR and associated risk factors are lacking. In the present study, clinical and echocardiographic parameters associated with outcomes were evaluated in a large cohort of patients with moderate SMR.

Patients with moderate SMR were retrospectively included and stratified by New York Heart Association (NYHA) class and specific aetiology (atrial SMR (aSMR) or ventricular SMR (vSMR)) with a further classification of vSMR based on left ventricular ejection fraction (LVEF) ≥40% or <40%. The primary endpoint was all-cause mortality and the secondary endpoint was the composite of all-cause mortality and heart failure (HF) events.

Of the total 1061 patients with moderate SMR (age 69±11 years, 59% male) included, 854 (80%) were in NYHA class I-II and 207 (20%) were in NYHA class III-IV. Regarding the aetiology, 352 (33%) had aSMR and 709 (67%) had vSMR, of which 329 (46%) had LVEF ≥40% and 380 (54%) had LVEF <40%. During a median follow-up of 82 (IQR 55-115) months, 397 (37%) died and 539 (51%) patients had HF events or died. On multivariable analysis, NYHA class III-IV (HR 1.578; 95% CI 1.244 to 2.002, p<0.001) and SMR aetiology were independently associated with both endpoints. Specifically, compared to aSMR, vSMR with LVEF ≥40% had a HR of 1.528 (95% CI 1.108 to 2.106, p=0.010) and vSMR with LVEF <40% had a HR of 1.960 (95% CI 1.434 to 2.679, p<0.001). To further support these findings, patients were matched for (1) NYHA class and (2) SMR aetiology by propensity scores including age, sex, diabetes, chronic obstructive pulmonary disease, renal function, left atrial volume index, NYHA class (only for SMR aetiology matching), LVEF, SMR aetiology (only for NYHA class matching), tricuspid regurgitation severity and right ventricular pulmonary artery coupling index. After matching, NYHA class and SMR aetiology remained associated with both outcomes (for both: log rank p<0.050).

In patients with moderate SMR, distinction in SMR aetiology and assessment of symptoms are important independent determinants of outcome.

Secondary mitral regurgitation (MR) worsens in 10-15 % of heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). Transcatheter edge-to-edge repair (TEER) with Mitra-Clip (Abbot Vascular, Santa Clara, CA, USA) therapy is associated with improved survival and decreased rates of hospitalization for HF in selected patients with secondary MR. Data on TEER outcomes in CRT-non-responders are limited. The purpose of this meta-analysis was to evaluate outcomes of mitral TEER with Mitra-Clip in CRT-non-responders.

Cochrane, Scopus, MEDLINE, and EMBASE were searched for studies discussing outcomes of Mitra-Clip in CRT non-responders. Two reviewers were independently involved in screening studies and extracting relevant data. Individual study incidence rate estimates underwent logit transformation to calculate the weighted summary proportion under the random effect model.

A total of eight reports met the inclusion criteria (439 patients). Mitra-Clip improved MR grade to ≤2+ in 83.8 % and 86.8 % of CRT non-responders at six months and one year, respectively. Symptomatic improvement (New York Heart Association class ≤II) was also found in 71 % and 78.1 % of CRT non-responders at six months and one year, respectively. The pooled overall incidence estimates of mortality at 30 days, 6 months, 1 year, and 2 years were 3.6 %, 9.2 %, 17.8 %, and 25.9 %, respectively.

TEER with Mitra-Clip in patients with significant secondary MR who do not respond to CRT was associated with MR improvement, alleviation of symptoms, and mortality rates similar to those in the COAPT trial.

Secondary mitral regurgitation (MR) negatively affects prognosis in acutely decompensated heart failure (ADHF), but can be rapidly sensitive to changes in volume status and medical interventions. We sought to assess the evolution of secondary MR in patients hospitalized for ADHF and its prognostic implications.

We retrospectively enrolled 782 patients admitted for ADHF with at least two in-hospital echocardiographic evaluations of MR. We classified MR severity as none-mild or moderate-severe. Based on MR evolution, patients were divided into 'persistent moderate-severe MR', 'improved MR' (from moderate-severe to none-mild) and 'persistent none-mild MR'.

Four hundred and forty patients (56%) had moderate-severe MR at first evaluation, of whom 144 (33% of patients with baseline moderate-severe MR) had 'improved MR', while 296 (67%) had 'persistent moderate-severe MR'. Patients with improved MR had better clinical, laboratory and echocardiographic parameters of decongestion at discharge compared with those with persistent moderate-severe MR and showed a higher up-titration of recommended therapies. Left ventricular volume, ejection fraction and serum urea were the predictors of improved MR at multivariable analysis. After adjustment, no differences in 5-years survival (primary outcome) were observed according to baseline MR severity. When patients were stratified according to the in-hospital changes in MR severity, improved MR was associated with lower risk of 5-years mortality, compared with both persistent none-mild MR [hazard ratio (HR) = 0.505, P = 0.032] and persistent moderate-severe MR (HR = 0.556, P = 0.040).

The severity of MR frequently improved during hospitalization for ADHF; the extent and the changes in MR severity during the in-hospital stay identified distinct patient phenotypes, and seemed to portend different long-term outcomes, with higher 5-years survival associated with improvement in MR.

Cardiac resynchronization therapy (CRT) has emerged as a pivotal intervention in reducing functional mitral regurgitation (FMR), not only by enhancing global left ventricular (LV) systolic function but also by refining local myocardial synchronization. This study hypothesized that CRT-mediated synchronization of myocardial segments, particularly between papillary muscles, reduces FMR further, independent of the improvement of the LV systolic indices.

Eighteen patients with dilated cardiomyopathy and biventricular pacing were evaluated. Measurements included the rate of rise in LV systolic pressure (LV dP/dt), asynchrony indices, transmitral pressure differences, mitral regurgitation quantification and diastolic filling times during pacing and with pacemaker interruption. As LV dP/dt decreased while the pacemaker was interrupted, dobutamine infusion was administered to restore LV dP/dt to pacing levels. All parameters were reassessed to evaluate the impact of myocardial resynchronization on FMR, independent of LV systolic performance.  Results: LV dP/dt significantly decreased in 10 patients after pacemaker interruption (838±190 vs 444±72, p<0.01), with no significant change in eight patients (603±134 vs 592±156, p=0.679). Despite similar LV performance indices, biventricular pacing led to a statistically significant reduction in both effective regurgitant orifice area and regurgitant volume across all patients (p<0.001 and p=0.003, respectively).

CRT significantly reduces FMR in dilated cardiomyopathy patients with intraventricular delay independent of improvements in LV systolic performance indicators by resynchronization of the LV segments underlying the papillary muscles. Moreover, it may be the main determinant of the reduction in FMR in CRT, underscoring the need for further research into its mechanisms and therapeutic implications.

This article revisits the severity threshold for secondary mitral regurgitation (MR), focusing on insights and lessons from the RESHAPE-HF2 trial. It aims to challenge the traditional effective regurgitant orifice area (EROA) threshold of ≥0.40 cm2 used for intervention, suggesting that earlier intervention may benefit patients with lower EROA. It also explores how transcatheter edge-to-edge repair (TEER) improves outcomes in patients with secondary MR and assesses the impact of left ventricular (LV) remodeling on treatment success.

The RESHAPE-HF2 trial evaluated the use of TEER in patients with moderate-to-severe secondary MR, comparing outcomes in those with an EROA ≥0.2 cm2 and no extensive LV remodeling. TEER significantly reduced heart failure hospitalizations and improved quality of life in these patients. This supports the notion that patients with less severe MR, who still show symptoms despite optimal medical therapy, may benefit from earlier intervention. Comparisons with COAPT and MITRA-FR trials underscored the importance of selecting patients based on MR severity relative to LV dilatation.

The RESHAPE-HF2 trial highlights the need to reconsider the current EROA threshold for secondary MR intervention. TEER has shown to be beneficial even in patients with lower MR severity, suggesting that earlier intervention could improve outcomes. A more dynamic and integrated approach, considering both MR severity and LV remodeling, is essential for optimizing patient selection and treatment success.

Functional mitral regurgitation induces adverse effects on the left ventricle and the left atrium. Left atrial (LA) dilatation and reduced LA strain are associated with poor outcomes in heart failure (HF). Transcatheter edge-to-edge repair (TEER) of the mitral valve reduces heart failure hospitalization (HFH) and all-cause death in selected HF patients.

The aim of this study was to evaluate the impact of LA strain improvement 6 months after TEER on the outcomes of patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial.

The difference in LA strain between baseline and the 6-month follow-up was calculated. Patients with at least a 15% improvement in LA strain were labeled as "LA strain improvers." All-cause death and HFH were assessed between the 6- and 24-month follow-up.

Among 347 patients (mean age 71 ± 12 years, 63% male), 106 (30.5%) showed improvement of LA strain at the 6-month follow-up (64 [60.4%] from the TEER + guideline-directed medical therapy [GDMT] group and 42 [39.6%] from the GDMT alone group). An improvement in LA strain was significantly associated with a reduction in the composite of death or HFH between the 6-month and 24-month follow-up, with a similar risk reduction in both treatment arms (Pinteraction = 0.27). In multivariable analyses, LA strain improvement remained independently associated with a lower risk of the primary composite endpoint both as a continuous variable (adjusted HR: 0.94 [95% CI: 0.89-1.00]; P = 0.03) and as a dichotomous variable (adjusted HR: 0.49 [95% CI: 0.27-0.89]; P = 0.02). The best outcomes were observed in patients treated with TEER in whom LA strain improved.

In symptomatic HF patients with severe mitral regurgitation, improved LA strain at the 6-month follow-up is associated with subsequently lower rates of the composite endpoint of all-cause mortality or HFH, both after TEER and GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079).

The COAPT Trial was the first ever to demonstrate a survival benefit in treating functional mitral regurgitation (FMR). That was achieved through transcatheter mitral repair in selected patients. The exact proportion of patients fulfilling COAPT selection criteria in the real-world is unknown.

To assess the applicability of COAPT criteria in real world and its impact on patients' survival.

We assessed the clinical data and follow-up results of all consecutive patients admitted for FMR at our Department between January 2016 and May 2021 according to COAPT eligibility. COAPT eligibility was retrospectively assessed by a cardiac surgeon and a cardiologist.

Among 394 patients, 56 (14%) were COAPT eligible. The most frequent reasons for exclusion were MR ≤ 2 (22%), LVEF < 20% or >50% (19%), and non-optimized GDMT (21.3%). Among Non-COAPT patients, weighted 4-year survival was higher in patients who received MitraClip compared to those who were left in optimized medical therapy (91.5% confidence interval [CI: 0.864, 0.96] vs. 71.8% [CI: 0.509, 0.926], respectively, p = 0.027).

Only a minority (14%) of real-world patients with FMR referred to a tertiary hospital fulfilled the COAPT selection criteria. Among Non-COAPT patients, weighted 4-year survival was higher in patients who received MitraClip compared to those who were left in optimized medical therapy (91.5% [0.864, 0.96] vs. 71.8% [0.509, 0.926], respectively, p = 0.027).

This study aimed to evaluate the clinical significance of secondary mitral regurgitation (MR) in patients with heart failure with preserved ejection fraction (HFpEF).

We conducted a prospective study enrolling consecutively evaluated patients with HFpEF undergoing invasive haemodynamic exercise testing with simultaneous echocardiography. Compared to HFpEF without MR (n = 145, 79.7%), those with mild or moderate MR (n = 37, 20.3%) were older, more likely to be women, had more left ventricular (LV) systolic dysfunction, and more likely to have left atrial (LA) myopathy reflected by greater burden of atrial fibrillation, more LA dilatation, and poorer LA function. Pulmonary artery (PA) wedge pressure was higher at rest in HFpEF with MR (17 ± 5 mmHg vs. 20 ± 5 mmHg, p = 0.005), but there was no difference with exercise. At rest, only 2 (1.1%) patients had moderate MR, and none developed severe MR. Pulmonary vascular resistance was higher, and right ventricular (RV)-PA coupling was more impaired in patients with HFpEF and MR at rest and exercise. LV and LA myocardial dysfunction remained more severe in patients with MR during stress compared to those without MR, characterized by greater LA dilatation during all stages of exertion, lower LA emptying fraction and compliance, steeper and rightward-shifted LA pressure-volume relationships, and reduced LV longitudinal contractile function.

Patients with HFpEF and mild or moderate MR have more severe LV systolic dysfunction, LA myopathy, RV-PA uncoupling, and more severe pulmonary vascular disease. Mitral valve incompetence in this setting is a phenotypic marker of more advanced disease but is not a causal factor in development of HFpEF.

The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials.

The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF.

Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice.

This review offers an evidence-based analysis of established and emerging cardiovascular magnetic resonance (CMR) techniques used to assess the severity of primary mitral regurgitation (MR), identify adverse cardiac remodeling and its prognostic effect. The aim is to provide different insights regarding clinical decision-making and enhance the clinical outcomes of patients with MR.

Cardiac remodeling and myocardial replacement fibrosis are observed frequently in the presence of substantial LV volume overload, particularly in cases with severe primary MR. CMR serves as a useful diagnostic imaging modality in assessing mitral regurgitation severity, early detection of cardiac remodeling, myocardial dysfunction, and myocardial fibrosis, enabling timely intervention before irreversible damage ensues. Incorporating myocardial remodeling in terms of left ventricular (LV) dilatation and myocardial fibrosis with quantitative MR severity assessment by CMR may assist in defining optimal timing of intervention.

This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the diagnosis and management of valvular heart diseases with referring to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee sought to reflect national data on the topic of valvular heart diseases published to date through a systematic literature search based on validity and relevance. In the part II of this article, we intend to present recommendations for diagnosis and treatment of mitral valve disease and tricuspid valve disease.

The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction.

The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide).

The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12).

Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

Objectives: Mitral valve repair is the current standard approach for mitral valve regurgitation. However, patients suffering from functional mitral regurgitation have a significant risk of recurrent regurgitation. Adjustable mitral rings may provide a solution for this adverse event. Methods: A single-center, first-in-man clinical study was performed on patients suffering from mitral valve regurgitation. Patients were implanted with the study ring and followed for six months. A balloon catheter can be inserted into the study ring frame at any time after implantation and inflated independently in the areas P1, P2, or P3, which reduces the anterior-posterior diameter. Results: Five patients (75.4 ± 6.1 years; EuroSCORE II 2.1 ± 0.9%; three female) were successfully implanted. Mechanisms of mitral regurgitation were prolapse of the P2-segment in three patients and annular dilation in two patients. Surgical implantation according to the protocol was feasible and is described herein. Median cardiopulmonary bypass time and cross clamp time were 105 (118; 195) and 94 (90; 151) min, respectively. The median intensive care unit stay was 2 (2; 3) days. No perioperative, 30-day, or 6-month mortality was observed, and the repair was stable without residual or recurrent regurgitation ≥ grade 2. All patients reached the primary endpoint without device-related morbidity. Conclusions: Successful implantation was completed in five patients without device-related adverse events. Ring implantation was safe and feasible for all patients. The opportunity of post-implant adjustment to improve leaflet coaptation is a promising new therapeutic strategy that is assessed in a phase II study.

Heart failure (HF) is a complex medical condition characterized by both electrical and mechanical dyssynchrony. Both dyssynchrony mechanisms are intricately linked together, but the current guidelines for cardiac resynchronization therapy (CRT) rely only on the electrical dyssynchrony criteria, such as the QRS complex duration. This possible inconsistency may result in undertreating eligible individuals who could benefit from CRT due to their mechanical dyssynchrony, even if they fail to fulfill the electrical criteria. The main objective of this literature review is to provide a comprehensive analysis of the practical value of echocardiography for the assessment of left ventricular (LV) dyssynchrony using parameters such as septal flash and apical rocking, which have proven their relevance in patient selection for CRT. The secondary objectives aim to offer an overview of the relationship between septal flash and apical rocking, to emphasize the primary drawbacks and benefits of using echocardiography for evaluation of septal flash and apical rocking, and to offer insights into potential clinical applications and future research directions in this area. Conclusion: there is an opportunity to render resynchronization therapy more effective for every individual; septal flash and apical rocking could be a very useful and straightforward echocardiography resource.

Secondary mitral regurgitation (MR) is common in heart failure with reduced ejection fraction (HFrEF) and is associated with poor outcomes. However, there is little evidence regarding secondary MR in advanced HFrEF. Poor outcomes for MR intervention suggest a need for further risk stratification.

Patients were assessed with echocardiography, right heart catheterization (RHC), and cardiopulmonary exercise testing. Ventricular-secondary MR was identified by echocardiography and categorized as mild, moderate, or severe according to guidelines. RV ability to compensate for pulmonary pressure rise was assessed by RV-pulmonary artery (PA) coupling, calculated as ratio of tricuspid annular plane systolic excursion (TAPSE), and systolic pulmonary artery pressure (SPAP) (echocardiography for TAPSE and RHC for SPAP). Primary end-point was a composite of all-cause mortality, urgent heart transplantation, or mechanical circulatory support.

Four hundred and fifty-six patients with ventricular-secondary MR were followed up for a median of 2.39 years, with 237 reaching a primary end-point. Severe MR conferred a worse prognosis than mild or moderate ((hazard ratio) HR 2.6, p < 0.001). Right atrial pressure was predictive of survival. RV-PA uncoupling, defined as TAPSE/SPAP below median value of 0.37, was associated with reduced survival across all severities of MR (p < 0.001).

Ventricular-secondary MR is common and severity correlates with adverse prognosis in advanced heart failure. RV-PA uncoupling can improve risk stratification in all grades of MR severity, particularly with PA pressure determined invasively.

The assessment of ventricular secondary mitral regurgitation (v-SMR) severity through effective regurgitant orifice area (EROA) and regurgitant volume (RegVol) calculations using the proximal isovelocity surface area (PISA) method and the two-dimensional echocardiography volumetric method (2DEVM) is prone to underestimation. Accordingly, we sought to investigate the accuracy of the three-dimensional echocardiography volumetric method (3DEVM) and its association with outcomes in v-SMR patients.

We included 229 patients (70 ± 13 years, 74% men) with v-SMR. We compared EROA and RegVol calculated by the 3DEVM, 2DEVM, and PISA methods. The end point was a composite of heart failure hospitalization and death for any cause.

After a mean follow-up of 20 ±11 months, 98 patients (43%) reached the end point. Regurgitant volume and EROA calculated by 3DEVM were larger than those calculated by 2DEVM and PISA. Using receiver operating characteristic curve analysis, both EROA (area under the curve, 0.75; 95% CI, 0.68-0.81; P = .008) and RegVol (AUC, 0.75; 95% CI, 0.68-0.82; P = .02) measured by 3DEVM showed the highest association with the outcome at 2 years compared to PISA and 2DEVM (P < .05 for all). Kaplan-Meier analysis demonstrated a significantly higher rate of events in patients with EROA ≥ 0.3 cm2 (cumulative survival at 2 years: 28% ± 7% vs 32% ± 10% vs 30% ± 11%) and RegVol ≥ 45 mL (cumulative survival at 2 years: 21% ± 7% vs 24% ± 13% vs 22% ± 10%) by 3DEVM compared to those by PISA and 2DEVM, respectively. In Cox multivariable analysis, 3DEVM EROA remained independently associated with the end point (hazard ratio, 1.02, 95% CI, 1.00-1.05; P = .02). The model including EROA by 3DEVM provided significant incremental value to predict the combined end point compared to those using 2DEVM (net reclassification index = 0.51, P = .003; integrated discrimination index = 0.04, P = .014) and PISA (net reclassification index = 0.80, P < .001; integrated discrimination index = 0.06, P < .001).

Effective regurgitant orifice area and RegVol calculated by 3DEVM were independently associated with the end point, improving the risk stratification of patients with v-SMR compared to the 2DEVM and PISA methods.

The safety and effectiveness of the MitraClip device to treat functional mitral regurgitation (FMR) has been tested in previous clinical trials yielding somewhat heterogeneous results in heart failure (HF) patients. Over time, the MitraClip device system has been modified and clinical practice evolved to consider also less severely diseased HF patients with FMR for this therapeutic option. The RESHAPE-HF2 trial aims to assess the safety and effectiveness of the MitraClip device system on top of medical therapy considered optimal in the treatment of clinically significant FMR in symptomatic patients with chronic HF.

The RESHAPE-HF2 is an investigator-initiated, prospective, randomized, parallel-controlled, multicentre trial designed to evaluate the use of the MitraClip device (used in the most up-to-date version as available at sites) plus optimal standard of care therapy (device group) compared to optimal standard of care therapy alone (control group). Eligible subjects have signs and symptoms of HF (New York Heart Association [NYHA] class II-IV despite optimal therapy), and have moderate-to-severe or severe FMR, as confirmed by a central echocardiography core laboratory; have an ejection fraction between ≥20% and ≤50% (initially 15-35% for NYHA class II patients, and 15-45% for NYHA class III/IV patients); have been adequately treated per applicable standards, and have received appropriate revascularization and cardiac resynchronization therapy, if eligible; had a HF hospitalization or elevated natriuretic peptides (B-type natriuretic peptide [BNP] ≥300 pg/ml or N-terminal proBNP ≥1000 pg/ml) in the last 90 days; and in whom isolated mitral valve surgery is not a recommended treatment option. The trial has three primary endpoints, which are these: (i) the composite rate of total (first and recurrent) HF hospitalizations and cardiovascular death during 24 months of follow-up, (ii) the rate of total (i.e. first and recurrent) HF hospitalizations within 24 months, and (iii) the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire overall score. The three primary endpoints will be analysed using the Hochberg procedure to control the familywise type I error rate across the three hypotheses.

The RESHAPE-HF2 trial will provide sound evidence on the MitraClip device and its effects in HF patients with FMR. The recruitment was recently completed with 506 randomized patients.

The impact of mitral regurgitation (MR) in patients with advanced heart failure (HF) is poorly known. We aimed to evaluate the impact of MR on clinical outcomes of a real-world, contemporary, multicentre population with advanced HF.

The HELP-HF registry enrolled patients with HF and at least one "I NEED HELP" criterion, at four Italian centres between January 2020 and November 2021. The population was stratified by none/mild MR vs. moderate MR vs. severe MR. Outcomes of interest were all-cause, cardiovascular (CV) death, the composite of all-cause death or first HF hospitalization, first HF hospitalization and recurrent HF hospitalizations.

Among 1079 patients, 429 (39.8%) had none/mild MR, 443 (41.1%) had moderate MR and 207 (19.2%) had severe MR. Patients with severe MR were most likely to be inpatients, present with cardiogenic shock, need intravenous loop diuretics and inotropes/vasopressors, have lower ejection fraction and higher natriuretic peptides. Estimated rates of all-cause death, CV death, and the composite of all-cause death or first HF hospitalization at 1 year increased with increasing MR severity. Compared with no/mild MR, severe MR was independently associated with an increased risk of CV death (adjusted HR 1.61, 95% CI 1.04-2.51, p = 0.033) and recurrent HF hospitalizations (adjusted HR 1.49, 95% CI 1.08-2.06, p = 0.015), but not with and increased risk of all-cause death, first HF hospitalization and composite outcome.

In unselected patients with advanced HF, severe MR was common and independently associated with an increased risk of CV death and of recurrent HF hospitalizations.