Papillary Muscle Maneuvers: Pathophysiology-based Approach in Secondary Mitral Regurgitation.

The treatment of secondary mitral regurgitation (SMR) remains challenging despite the implementation of modern heart failure medication and established catheter-based techniques. Only a subgroup of SMR patients benefit from mitral valve (MV) intervention, and the long-term prognostic benefit of different therapeutic approaches in SMR remains controversial. A literature search was conducted through PubMed and Embase databases to identify relevant studies addressing the pathophysiological background for papillary muscle maneuvers in SMR and currently available surgical techniques. Furthermore, the studies evaluating patients' selection criteria for papillary muscle maneuvers were specifically considered. Articles were selected based on quality and relevance. Over the last two decades, papillary muscle maneuvers have evolved as a pathophysiology-based treatment strategy to address left ventricular (LV) remodeling in SMR. In particular, patients with severe leaflet tenting and moderate heart failure phenotype seem to benefit most from papillary muscle maneuvers that improve LV geometry and thereby the durability of MV repair. We conclude that papillary muscle maneuvers are an evolving pathophysiology-based treatment strategy of ventricular SMR which target papillary muscle displacement due to LV remodeling.

Association of Mitral Valve Geometry at CT with Secondary Mitral Regurgitation after Transcatheter Aortic Valve Replacement in Patients with Aortic Regurgitation.

Background: The improvement rate and predictors of secondary mitral regurgitation in patients with aortic regurgitation undergoing transcatheter aortic valve replacement (TAVR) remain unclear. This study aimed to identify predictors of persistent moderate to severe secondary mitral regurgitation after TAVR in patients with aortic regurgitation by assessing mitral valve geometry with computed tomography (CT). Methods: This retrospective cohort study reviewed 242 consecutive patients with aortic regurgitation who underwent TAVR between May 2014 and December 2022. Patients with primary or less than moderate mitral regurgitation were excluded. Mitral annular dimensions (area, perimeter, anteroposterior, intercommissural, and trigone-to-trigone diameter), mitral valve tenting geometry (mitral valve tenting area [MVTA] and mitral valve tenting height [MVTH]), and papillary muscle displacement were systematically measured at CT. Mitral regurgitation improvement was assessed at 3 months after TAVR by echocardiography. Logistic regression was performed to explore the association of mitral valve geometry with mitral regurgitation improvement after TAVR. Results: A total of 75 patients (mean age, 74 ± 7 years; 32.0% female) with moderate to severe secondary mitral regurgitation were included in the final analysis. Mitral regurgitation improved in 49 patients and remained unchanged in 26 patients. Mitral annular dimensions, including area, perimeter, anteroposterior, and intercommissural diameter, were associated with mitral regurgitation improvement. MVTA and MVTH were risk factors for sustained mitral regurgitation. In addition, QRS duration > 120 ms and atrial fibrillation had an impact on the mitral regurgitation improvement. Mitral annular area (odds ratio [OR], 1.41; 95% confidence interval [CI]: 1.05, 1.90; p = 0.02) and MVTA (OR, 7.24; 95% CI: 1.72, 30.44; p = 0.007) were independent predictors of persistent secondary mitral regurgitation after TAVR. Conclusions: Mitral annular area and MVTA were independent predictors of persistent secondary mitral regurgitation after TAVR.

Changes in Left Ventricular Function and Outcomes After Trancatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.

Background: Transcatheter edge-to-edge repair (TEER) improved outcomes in patients with heart failure (HF) and severe secondary mitral regurgitation (SMR) compared with guideline-directed medical therapy (GDMT) alone regardless of the severity of baseline left ventricular ejection fraction (LVEF). The study aimed to evaluate the effect of early changes in LVEF after TEER and GDMT alone in patients with HF and severe SMR. Methods: Within the COAPT trial, we evaluated outcomes according to changes in LVEF from baseline to 30 days. The primary outcome was all-cause death or HF hospitalization (HFH) between 30 days and 2 years. Results: Among 432 patients with paired echocardiographic data, 182 (42.1%) had increased LVEF (LVEF change 6.0% ± 4.9%) and 250 (57.9%) had a decrease or no change in LVEF (LVEF change -6.6% ± 5.6%) from baseline to 30 days. LVEF at 30 days increased more frequently with GDMT alone compared with TEER plus GDMT (51.4% vs 33.0%; P = .0001). Between 30 days and 2 years, there were no significant differences in death or HFH in the increase LVEF and the decrease LVEF groups (58.8% vs 51.4%; multivariable-adjusted HR, 0.97; 95% CI, 0.87-1.08; P = .59). TEER plus GDMT reduced the 30-day to 2-year rate of death or HFH compared with GDMT alone consistently in patients with increase LVEF and decrease LVEF (Pint = 0.75). Conclusions: Among patients with HF and severe SMR, early improvements in LVEF were more frequent with GDMT alone compared with TEER plus GDMT but were not associated with subsequent outcomes at 2 years. TEER reduced death or HFH during 2-year follow-up irrespective of early LVEF changes.

Secondary Mitral Regurgitation and Transcatheter Mitral Valve Therapies: Do They Have a Role in Advanced Heart Failure with Reduced Ejection Fraction?

Transcatheter mitral valve repair should be considered for patients with severe secondary mitral regurgitation with symptomatic heart failure with reduced ejection fraction for symptom improvement and survival benefit. Patients with a higher severity of secondary mitral regurgitation relative to the degree of left ventricular dilation are more likely to benefit from transcatheter mitral valve repair. A multidisciplinary Heart Team should participate in patient selection for transcatheter mitral valve therapy.

Impact of heart failure severity on the mortality benefit of mitral transcatheter edge-to-edge valve repair.

BACKGROUND: To assess the interaction between heart failure (HF) severity and optimal reduction of secondary mitral regurgitation (SMR) on mortality in patients undergoing transcatheter edge-to-edge repair (M-TEER). METHODS AND RESULTS: Among 1656 patients included in the Italian Society of Interventional Cardiology (GIse) registry Of Transcatheter treatment of mitral valve regurgitaTiOn (GIOTTO) 984 had SMR and complete data on advanced HF. Advanced HF was defined as NYHA class III or IV, left ventricular ejection fraction ≤ 30%, and > 1 HF hospitalization during the last 12 months. Optimal M-TEER was defined as residual SMR ≤ 1 + at discharge. One hundred sixteen patients (11.8%) had advanced HF. Achievement of an optimal SMR reduction was similar in patients with and without advanced HF (65% and 60% respectively). Advanced HF was an independent predictor of 2-year all-cause death (adjusted HR 1.52, 95% CI 1.09-2.10). Optimal M-TEER, as compared to a no-optimal M-TEER, was associated with a reduced risk of death both in patients with advanced (HR 0.55, 95% CI 0.32-0.97; p = 0.039) and no-advanced HF (HR 0.59, 95% CI 0.46-0.78; p < 0.001; p = 0.778 for interaction). CONCLUSIONS: Advanced HF is associated with poor outcome in patients undergoing M-TEER. However, an optimal SMR reduction reduces the risk of 2-year mortality regardless of HF severity.

Guideline-Directed Medical Therapy and Survival After TEER for Secondary Mitral Regurgitation With Right Ventricular Impairment.

BACKGROUND: Right ventricular impairment is common among patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation (SMR). Adherence to guideline-directed medical therapy (GDMT) for heart failure is poor in these patients. OBJECTIVES: The aim of this study was to evaluate the impact of GDMT on long-term survival in this patient cohort. METHODS: Within the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) international registry, we selected patients with SMR and right ventricular impairment (tricuspid annular plane systolic excursion ≤17 mm and/or echocardiographic right ventricular-to-pulmonary artery coupling <0.40 mm/mm Hg). Titrated guideline-directed medical therapy (GDMTtit) was defined as a coprescription of 3 drug classes with at least one-half of the target dose at the latest follow-up. The primary outcome was all-cause mortality at 6 years. RESULTS: Among 1,213 patients with SMR and right ventricular impairment, 852 had complete data on medical therapy. The 123 patients who were on GDMTtit showed a significantly higher long-term survival vs the 729 patients not on GDMTtit (61.8% vs 36.0%; P < 0.00001). Propensity score-matched analysis confirmed a significant association between GDMTtit and higher survival (61.0% vs 43.1%; P = 0.018). GDMTtit was an independent predictor of all-cause mortality (HR: 0.61; 95% CI: 0.39-0.93; P = 0.02 for patients on GDMTtit vs those not on GDMTtit). Its association with better outcomes was confirmed among all subgroups analyzed. CONCLUSIONS: In patients with right ventricular impairment undergoing transcatheter edge-to-edge repair for SMR, titration of GDMT to at least one-half of the target dose is associated with a 40% lower risk of all-cause death up to 6 years and should be pursued independent of comorbidities.

Association of Secondary Mitral Regurgitation and Right Ventricular Dysfunction among Patients with Non-Ischemic Cardiomyopathy.

AIMS: The association between secondary mitral regurgitation (MR) and right ventricular (RV) dysfunction in heart failure patients with non-ischemic cardiomyopathy (NICM) is unclear. Hence, our objective was to study the association between secondary MR and the occurrence of RV dysfunction among patients with NICM using cardiac magnetic resonance (CMR). METHODS AND RESULTS: Patients with NICM were enrolled in a prospective observational registry between 2008-2019. CMR was used to quantify MR severity along with RV function. RV dysfunction was defined as RV ejection fraction <45%. The outcome of the study was a composite event of all-cause death, heart transplantation, or left ventricular assist device implantation at follow-up. In the study cohort of 241 patients, RV dysfunction (RVEF < 45%) was present in 148 (61%). In comparison to patients without RV dysfunction, those with RV dysfunction had higher median MR volume (23 ml [IQR 16-31ml] vs 18 ml [IQR 12-25 ml], P=0.002) and MR fraction (33% [IQR 25-43%] vs 22% [IQR 15-29%], P<0.001). Furthermore, secondary MR was independently associated with RV dysfunction: MR volume ≥ 24ml (OR 3.21, 95% CI 1.26-8.15, P= 0.01) and MR fraction≥ 30% (OR 5.46, 95% 2.23-13.35, P=0.002). Increasing RVEF (every 1% increase) was independently associated with lower risk of adverse events (HR 0.98, 95% 0.95, 1.00, P=0.047). CONCLUSIONS: In patients with NICM, the severity of secondary MR is associated with an increased prevalence of RV dysfunction. RV dysfunction is not only associated with the severity of LV dysfunction, but also with the severity of secondary MR.

Left Atrium: A New Prognostic Marker and Therapeutic Target in Secondary Mitral Regurgitation?

Mitral regurgitation (MR) is one of the most common valvular abnormalities worldwide and can be subdivided into primary and secondary causes. Atrial MR consists of a novel type of secondary MR (SMR), most often observed in patients with AF and heart failure with preserved ejection fraction. The main pathophysiological mechanism of atrial MR is mitral valve annular dilatation. Recently published studies have highlighted the clinical significance of left atrium (LA) evaluation in the early diagnosis and prognosis of patients with primary MR. However, there are little data regarding the role of the LA in SMR. The present literature review aims to elucidate the use of the echocardiographic parameters regarding LA evaluation in the prognosis prediction and therapeutic strategy of patients with SMR.

Prevalence and prognostic significance of malnutrition in patients with secondary mitral regurgitation undergoing transcatheter edge-to-edge repair.

BACKGROUND: Malnutrition is associated with poor prognosis in several cardiovascular diseases; however, its role in patients with secondary mitral regurgitation (SMR) is poorly known. AIMS: To evaluate the impact of nutritional status, assessed using different scores, on clinical outcomes in patients with SMR undergoing transcatheter edge-to-edge repair (TEER) in a real-world setting. METHODS: A total of 658 patients with SMR and complete nutritional data were identified from the MIVNUT registry. Nutritional status has been assessed using controlling nutritional status index (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI) scores. Outcomes of interest were all-cause mortality and all-cause mortality or heart failure (HF) hospitalization. RESULTS: Any malnutrition grade was observed in 79.4%, 16.7%, and 47.9% of patients by using CONUT, PNI, and GNRI, respectively, while moderate to severe malnutrition was noted in 24.7%, 16.7%, and 25.6% of patients, respectively. At a median follow-up of 2.2 years, 212 patients (32.2%) died. Moderate-severe malnutrition was associated with a higher rate of all-cause mortality (HR: 2.46 [95% CI: 1.69-3.58], HR: 2.18 [95% CI: 1.46-3.26], HR: 1.97 [95% CI: 1.41-2.74] for CONUT, PNI, and GNRI scores, respectively). The combined secondary endpoint of all-cause mortality and HF rehospitalization occurred in 306 patients (46.5%). Patients with moderate-severe malnutrition had a higher risk of the composite endpoint (HR: 1.56 [95% CI: 1.20-2.28], HR: 1.55 [95% CI: 1.01-2.19], HR: 1.36 [95% CI: 1.02-1.80] for CONUT, PNI, and GNRI scores, respectively). After adjustment for multiple confounders, moderate-severe malnutrition remained independently associated with clinical outcomes. CONCLUSIONS: Moderate-severe malnutrition was common in patients with SMR undergoing TEER. It was independently associated with poor prognosis regardless of the different scores used.

Left Atrial Improvement in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 Evolving Concept of Secondary Mitral Regurgitation Phenotypes: Lessons From the M-TEER Trials.

Conflicting results from 2 randomized clinical trials of transcatheter mitral valve edge-to-edge repair in secondary mitral regurgitation (SMR) have led to the recognition that SMR is a heterogeneous disease entity presenting with different functional and morphological phenotypes. This review summarizes the current knowledge on SMR caused primarily by atrial secondary mitral regurgitation (aSMR) and ventricular SMR pathology. Although aSMR is generally characterized by severe left atrial enlargement in the setting of preserved left ventricular anatomy and function, different patterns of mitral annular distortion cause different phenotypes of aSMR. In ventricular SMR, the relation of SMR severity to left ventricular dilation as well as the degree of pulmonary hypertension and right ventricular dysfunction are important phenotypic characteristics, which are key for a better understanding of prognosis and treatment response.

Functional Mitral Regurgitation: Patient Selection and Optimization.

Functional mitral regurgitation appears commonly among all heart failure phenotypes and can affect symptom burden and degree of maladaptive remodeling. Transcatheter mitral valve edge-to-edge repair therapies recently became an important part of the routine heart failure armamentarium for carefully selected and medically optimized candidates. Patient selection is considering heart failure staging, relevant comorbidities, as well as anatomic criteria. Indications and device platforms are currently expanding.

Interpapillary muscle distance independently predicts recurrent mitral regurgitation.

OBJECTIVE: Ischaemic secondary mitral regurgitation (ISMR) after surgery is due to the displacement of papillary muscles resulting from progressive enlargement of the left ventricle end-diastolic diameter (LVEDD). Our aim was to prove that if the interpapillary muscle distance (IPMD) is surgically stabilized, an increase in LVEDD will not lead to a recurrence of ischaemic mitral regurgitation (MR). METHODS: Ninety-six patients with ISMR, who underwent surgical revascularisation and annuloplasty, were randomly assigned in a 1:1 ratio to undergo papillary muscle approximation (PMA). At the 5-year follow-up, we assessed the correlation between PMA and echocardiographic improvements, the effect size of PMA on echocardiographic improvements, and a prediction model for recurrent MR using inferential tree analysis. RESULTS: There was a significant correlation between PMA and enhancements in both the α and ß angles (Spearman's rho > 0.7, p < 0.01). The α angle represents the angle between the annular plane and either the A2 annular-coaptation line or the P2 annular-coaptation line. The ß angle indicates the angle between the annular plane and either the A2 annular-leaflet tip line or the P2 annular-leaflet tip line. PMA led to substantial improvements in LVEDD, tenting area, α and ß angles, with a large effect size (Hedge's g ≥ 8, 95% CI ORs ≠ 1). The most reliable predictor of recurrent MR grade was the interpapillary distance, as only patients with an interpapillary distance greater than 40 mm developed ≥ 3 + grade MR. For patients with an IPMD of 40 mm or less, the best predictor of recurrent MR grade was LVEDD. Among the patients, only those with LVEDD greater than 62 mm showed moderate (2+) MR, while only those with LVEDD less than or equal to 62 mm had absent to mild (1+) MR. CONCLUSION: Prediction of recurrent ischaemic MR is not independent of progressive LVEDD increase. PMA-based surgical procedure stabilises IPMD.

Clinical Impact of the Volumetric Quantification of Ventricular Secondary Mitral Regurgitation by Three-Dimensional Echocardiography.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Artificial intelligence-derived risk score for mortality in secondary mitral regurgitation treated by transcatheter edge-to-edge repair: the EuroSMR risk score.

BACKGROUND AND AIMS: Risk stratification for mitral valve transcatheter edge-to-edge repair (M-TEER) is paramount in the decision-making process to appropriately select patients with severe secondary mitral regurgitation (SMR). This study sought to develop and validate an artificial intelligence-derived risk score (EuroSMR score) to predict 1-year outcomes (survival or survival + clinical improvement) in patients with SMR undergoing M-TEER. METHODS: An artificial intelligence-derived risk score was developed from the EuroSMR cohort (4172 and 428 patients treated with M-TEER in the derivation and validation cohorts, respectively). The EuroSMR score was validated and compared with established risk models. RESULTS: The EuroSMR risk score, which is based on 18 clinical, echocardiographic, laboratory, and medication parameters, allowed for an improved discrimination of surviving and non-surviving patients (hazard ratio 4.3, 95% confidence interval 3.7-5.0; P < .001), and outperformed established risk scores in the validation cohort. Prediction for 1-year mortality (area under the curve: 0.789, 95% confidence interval 0.737-0.842) ranged from <5% to >70%, including the identification of an extreme-risk population (2.6% of the entire cohort), which had a very high probability for not surviving beyond 1 year (hazard ratio 6.5, 95% confidence interval 3.0-14; P < .001). The top 5% of patients with the highest EuroSMR risk scores showed event rates of 72.7% for mortality and 83.2% for mortality or lack of clinical improvement at 1-year follow-up. CONCLUSIONS: The EuroSMR risk score may allow for improved prognostication in heart failure patients with severe SMR, who are considered for a M-TEER procedure. The score is expected to facilitate the shared decision-making process with heart team members and patients.

Impact of the MitraClip G4 System on Routine Practice and Outcomes in Patients With Secondary Mitral Regurgitation.

BACKGROUND: The MitraClip G4 system is a new iteration of the transcatheter edge-to-edge repair system. We assessed the impact of the G4 system on routine practice and outcomes in secondary mitral regurgitation (2°MR).Methods and Results: Consecutive patients with 2°MR treated with either the MitraClip G2 (n=89) or G4 (n=63) system between 2018 and 2021 were included. Baseline characteristics, procedures, and outcomes were compared. Inverse probability of treatment weighting and Cox regression were used to adjust for baseline differences. Baseline characteristics were similar, except for a lower surgical risk in the G4 group (Society of Thoracic Surgeons Predicted Risk of Mortality ≥8: 38.1% vs. 56.2%; P=0.03). In the G4 group, more patients had short (≤2 mm) coaptation length (83.7% vs. 54.0%; P<0.001) and fewer clips were used (17.5% vs. 36.0%; P=0.02). Acceptable MR reduction was observed in nearly all patients, with no difference between the G4 and G2 groups (100% vs. 97.8%, respectively; P=0.51). The G4 group had fewer patients with high transmitral gradients (>5mmHg; 3.3% vs. 13.6%; P=0.03). At 1 year, there was no significant difference between groups in the composite endpoint (death or heart failure rehospitalization) after baseline adjustment (10.5% vs. 20.2%; hazard ratio 0.39; 95% confidence interval 0.11-1.32; P=0.13). CONCLUSIONS: The G4 system achieved comparable device outcomes to the early-generation G2, despite treating more challenging 2°MR with fewer clips.

Parameters of the mitral apparatus in patients with ischemic and nonischemic dilated cardiomyopathy.

The mitral valve apparatus is a complex structure consisting of several coordinating components: the annulus, two leaflets, the chordae tendineae, and the papillary muscles. Due to the intricate interplay between the mitral valve and the left ventricle, a disease of the latter may influence the normal function of the former. As a consequence, valve insufficiency may arise despite the absence of organic valve disease. This is designated as functional or secondary mitral regurgitation, and it arises from a series of distortions to the valve components. This narrative review describes the normal anatomy and the pathophysiology behind the mitral valve changes in ischemic and non-ischemic dilated cardiomyopathies. It also explains the value of a complete multiparametric assessment of this structure. Not only must an assessment include quantitative measures of regurgitation, but also various anatomical parameters from the mitral apparatus and left ventricle, since they carry prognostic value and are predictors of mitral valve repair success and durability.

Relationship between stress hyperglycemia and worsening heart failure in patients with significant secondary mitral regurgitation.

BACKGROUND AND AIMS: Secondary mitral regurgitation (sMR), a major valvular disease, is prevalent in patients with coronary artery disease (CAD), and is associated with higher incidence of heart failure (HF) and mortality when present in combination with abnormal glucose metabolism. We aimed to evaluate the relationship between stress hyperglycemia ratio (SHR) and worsening HF in CAD patients with significant (grade ≥2) sMR. METHODS: We performed a multi-center observational study of 874 participants with significant sMR following percutaneous coronary intervention (PCI) in the Cardiorenal Improvement-II (CIN-II) cohort. Patients with glucose and glycated hemoglobin (HbA1c) data at admission were included in the analysis, and categorized according to the SHR, the ratio of mmol/L blood glucose to % HbA1c, as quartiles: Q1: <0.74; Q2: 0.74-0.91; Q3: 0.91-1.14; and Q4: ≥1.14. The primary clinical endpoint was worsening HF and the secondary endpoint was major adverse cardiac events (MACE). RESULTS: Of the 874 participants (64.1 ± 10.8 years, 80% male), 174 showed worsening HF and 226 developed MACE during a median follow-up of 3.7 years (interquartile range: 1.8-6.2 years). Compared to participants in the lowest quartile (Q1) of SHR, the highest quartile group (Q4) was at significantly higher risks of worsening HF (adjusted hazard ratio, 2.44; 95% confidence interval, 1.51-3.94; p< 0.001), while this was not associated with increased risk of MACE (p>0.05) after adjustment for potential covariates. For worsening HF, the results obtained for the normal glucose regulation subgroup may be more meaningful than those for the diabetes mellitus (DM) and pre-DM groups (p-interaction<0.001). For MACE, the acute myocardial infarction (AMI) (Q4 vs. Q1; HR: 0.65, 95%CI: 0.26-1.59) and non-AMI (Q4 vs. Q1; HR: 2.20, 95%CI: 1.36-3.54) subgroups differed significantly on MACE (p-interaction = 0.006). CONCLUSIONS: Increasing SHR is associated with a higher risk of worsening of HF in patients with significant sMR, especially in those with normoglycemia.

Perspectives on Secondary Mitral Regurgitation in Heart Failure.

PURPOSE OF THE REVIEW: This review focuses on broader perspectives of mitral regurgitation (MR) in patients with heart failure. RECENT FINDINGS: The ratio of regurgitant volume to end-diastolic volume appears to help identify patients who may benefit from valve interventions. Secondary MR is not only attributed to geometric changes of the LV but also related to the structural changes in the mitral valve that include fibrosis of the mitral leaflets and changes in the extracellular matrix. The transition from mild to severe secondary MR can occur at different rates, from a slow LV remodeling process to a more abrupt process precipitated by an inciting event such as atrial fibrillation. Septal flash and apical rocking, two new visual markers of LV mechanical dyssynchrony, appear to be predictive of MR reduction following cardiac resynchronization therapy. Optimal guideline-directed medical therapy has been shown to decrease the severity of secondary MR effectively. A theoretical framework to characterize secondary MR as it relates to the onset of MR is proposed. Type A: Early onset of MR contemporaneous with myocardial injury. The maladaptive LV remodeling occurs in parallel with MR. Type B: LV remodeling proceeds without significant MR until the LV is moderately dilated, which coincides with or without inciting factors such as atrial fibrillation. Type C: LV remodeling proceeds after myocardial injury without significant MR until the LV is severely dilated. MR is a late manifestation of LV remodeling.

Right ventricle to pulmonary artery coupling as a predictor of perioperative outcome in patients with secondary mitral valve insufficiency.

BACKGROUND: The aim of the study was to assess some parameters of right ventricle (RV) function as predictors of short-term mortality in patients with severe secondary mitral regurgitation (SMR) after mitral valve surgery. METHODS: We conducted a retrospective analysis of 112 consecutive patients with severe SMR who had undergone mitral valve repair or replacement with or without concomitant coronary artery bypass surgery. We assessed RV to pulmonary artery coupling by calculating the ratio of tricuspid annular plane systolic excursion (TAPSE) to non-invasively estimated RV systolic pressure (RVSP). The study endpoint was 30 days post-procedural mortality. RESULTS: Overall, the 30-day mortality was 6%. TAPSE/RVSP ratio < 0.42 mm/mmHg was a significant predictor of mortality and remained so after adjusting for age and sex. The Kaplan-Meier survival analysis showed that patients with RVSP > 55 mmHg and those with TAPSE/RVSP ratio < 0.42 mm/mmHg had a lower survival probability. CONCLUSIONS: TAPSE/RVSP < 0.42 mm/mmHg is a strong predictor of short-term mortality in patients with SMR when considered for valve surgery.