Severe Functional Mitral Regurgitation Research Articles

Unusual origins of cardiac insufficiency: a case of iliac arteriovenous fistula post-spinal disc surgery

In this case report, we present the unique and intriguing case of a 57-year-old man who experienced exertional palpitations and shortness of breath for 5 years. He was diagnosed with idiopathic heart failure three years ago, leading to diuretic treatment. Physical examination revealed notable left lower extremity swelling, severe varicose veins, and cardiac murmurs. Echocardiography showed significant cardiac enlargement and severe functional mitral and tricuspid valve regurgitation. Computed tomography (CT) imaging uncovered a 10 mm left common iliac arteriovenous fistula, causing abnormal early filling of the inferior vena cava (IVC) and marked IVC dilation. Open surgical repair of the arteriovenous fistula resulted in symptom relief and improved cardiac function. This case underscores the importance of considering unusual causes in heart failure patients and highlights the value of early diagnosis and intervention in complex cardiac-vascular interactions.

The Characteristics and Outcomes of Nonhospitalized Patients With Heart Failure in Saudi Arabia: A Contemporary Single-Center Study.

Background Contemporary data on patients with heart failure (HF) in Saudi Arabia is limited. Methods This was a retrospective study of patients who were followed in the HF Clinic at our center after January 1, 2022. The study end date was August 31, 2023. Patients who were alive and followed for <6 months were excluded. We reported the clinical characteristics, utilization of established therapies for HF, proportion of potential candidates for ancillary HF treatments, and rates of HF events and mortality. Results A total of 202 patients met the study criteria. The mean age was 56.0 ± 15.2 years. The median follow-up from the initial visit to the study end date was 47 months (interquartile range {IQR}: 29-58 months). Coronary artery disease (CAD) was the cause of HF in 85 (42%) patients. At their latest visit, 103 (51%) patients had diabetes, 82 (41%) were obese, and 134 (66%) received quadruple therapy. Iron deficiency was present in 143 (71%) patients during follow-up. At their latest visit, moderate-to-severe or severe functional mitral regurgitation (MR) and hyperkalemia were present in 15 (7%) and 20 (10%) patients, respectively. The combined annual rate of HF hospitalization and emergency visits for HF was 20%. At least one hospitalization for HF within a year before the study end date occurred in 19 (9%) patients. The annual all-cause mortality was 1.8%. Conclusion This contemporary cohort of outpatients with HF was relatively young and had a high prevalence of diabetes, obesity, and iron deficiency. An estimate of potential candidates for iron replacement, transcatheter repair of the mitral valve, novel potassium binders, and the implantation of the pulmonary artery pressure monitorwas among the first reported regionally. All-cause mortality was low, yet the burden of HF-related events was significant.

Impact of Cardiac Magnetic Resonance Left Atrial Ejection Fraction in Advanced Ischemic Cardiomyopathy

BackgroundThe prognostic significance of cardiac magnetic resonance (CMR)-based left atrial ejection fraction (LAEF) is not well defined in the ischemic cardiomyopathy (ICM) cohort. ObjectivesThe authors sought to assess the prognostic impact of LAEF, when adjusted for left ventricular remodeling, myocardial infarct size (MIS), left atrial volume index, and functional mitral regurgitation (FMR), on outcomes in patients with advanced ICM. MethodsICM patients who underwent CMR were retrospectively evaluated (April 2001-December 2019). LAEF, left atrial volume index, MIS, left ventricular remodeling, and FMR were derived from CMR. The primary clinical endpoint was a composite of all-cause mortality and cardiac transplant. A baseline multivariable Cox proportional hazards regression model was constructed to assess prognostic power of LAEF. ResultsThere were 718 patients (416 primary events) evaluated, with a median duration of follow-up of 1,763 days (4.8 years) and a mean LAEF of 36% ± 15%. On multivariable analysis, higher LAEF was independently associated with reduced risk (HR: 0.24, 95% CI: 0.12-0.48, P < 0.001), even after adjusting for FMR and MIS. The highest adjusted risk was observed in patients with an LAEF <20% and an MIS of >30% (HR: 3.20, 95% CI: 1.73-5.93). The lowest risk was in patients within the comparator group with an LAEF of >50% and a MIS of <15% (HR: 1.07, 95% CI: 0.81-1.42). ConclusionsReduced LAEF is independently associated with increased mortality in ICM. Risk associated with declining LAEF is continuous and incremental to other risk factors for adverse outcomes in patients with ICM even after adjusting for MIS and FMR severity.

First-in-human experience with a novel transcatheter direct annuloplasty system for severe atrial functional mitral regurgitation.

First-in-human experience with a novel transcatheter direct annuloplasty system for severe atrial functional mitral regurgitation.

Impact of sacubitril valsartan initiation in patients with HFrEF and severe mitral regurgitation referred for percutaneous mitral repair

Abstract Background In patients with heart failure with reduced ejection fraction (HFrEF), the severity of functional mitral regurgitation (MR) is a major predictor of worsened symptoms and poor outcomes. Percutaneous MR repair has been shown to improve outcomes in HFrEF with MR. However, because MR is related to abnormal myocardial function and adverse remodeling, the optimization of guideline-directed medical therapy (GDMT) could improve loading conditions, reversal remodelling and left ventricle function and also may reduce MR severity. We sought to evaluated whether the left ventricle reverse remodeling induced by the addition of sacubitril/valsartan may reduce MR severity sufficiently to avoid need for percutaneous MR repair approach. Methods We performed a single-center, prospective assessor-blinded study to determine the reverse remodeling response of sacubitril/valsartan therapy in HFrEF patients (NYHA class II-IV) with MR evaluated for percutaneous MR repair. Echocardiographic images were assessed offline by 2 investigators blinded to both the clinical data and timing of echocardiograms. Doses of sacubitril/valsartan were optimized to individual tolerance. A clinical and echocardiographic 1 year follow-up was performed. Results Thirty-nine HFrEF patients with MR grade 3-4 were included (mean age 63 years old, 69,2% male). Optimal dose of sacubitril/valsartan was reached in 63,2% of patients. After 1-year follow-up, only 1 patient died and, as we show in Table 1, a significant improvement on NYHA functional class and NT-ProBNP values were present. Left ventricle ejection fraction improved (29.7 ± 6.7% vs 41.3 ± 13.2%; P &amp;lt; 0.001) and left ventricular end-diastolic and end-systolic volume indexed to body surface area decreased (123.4 ± 35.7 mL/m2 vs 98.4 ± 39.7 mL/m2; P &amp;lt; 0.001 and 87.7 ± 30.0 mL/m2 vs 61.9 ± 35.3 mL/m2; P &amp;lt; 0.001, respectively). Volumetric remodeling was associated with a reduction in the degree of mitral regurgitation (64.1% grade 3 and 35.9% grade 4 at the beginning to 28.9% grade 1, 36.8% grade 2, 21.5% grade 3 and 13.2% grade 4 after one year of follow-up; [scale from 0-4]). Conclusion The optimization of GDMT with sacubitril/valsartan induced an improvement on functional class and a beneficial reverse cardiac remodelling, with enhancement of left ventricle function and reducing MR severity, enough in 24 patients to avoid need for percutaneous MR repair. In HFrEF patients with grade 3-4 mitral regurgitation, our results reinforce importance of ensuring optimal GDMT before a percutaneous mitral valve repair approach.Table 1.Changes during follow-up.

Moderate functional mitral regurgitation: difference between atrial and ventricular mechanism of the regurgitation

Abstract Background/Introduction In severe functional mitral regurgitation (MR), further distinction of the mechanism of MR in atrial functional MR (aFMR) and ventricular functional MR (vFMR) has shown prognostic importance. However, no data are available on moderate functional MR, whose characteristics and prognosis are largely unknown. Purpose To assess clinical and echocardiographic characteristics of patients with moderate aFMR and vFMR and their potential difference in outcome. Methods Patients with moderate functional MR were retrospectively included. aFMR was defined as isolated mitral annulus dilatation in combination with preserved left ventricular ejection fraction (LVEF≥50%) without ischemic heart disease or LV dilatation. Patients were classified as vFMR when LVEF was reduced, LV was dilated and/or wall motion abnormalities were present. Mitral valve intervention and all-cause mortality were used as combined endpoint. Results In total 474 patients with moderate functional MR (mean age 67 ±12, 57% male) were evaluated, of which 136 (29%) had aFMR and 338 (71%) had vFMR as underlying mechanism. Among the clinical variables, patients with aFMR had more atrial fibrillation (77% vs. 35%; p&amp;lt;0.001), were less symptomatic (NYHA class ≥ III: 6% vs. 18%; p&amp;lt;0.001) and had better renal function (eGFR 73 ±23 ml/min/1,73m2 vs. 65 ±23 ml/min/1,73m2; p=0.005) as compared to vFMR. In the vFMR group, 49% of patients had ischemic heart disease. Among the echocardiographic variables, as expected in aFMR, LVEF was higher (42 ±14% vs. 55 ±13%; p&amp;lt;0.001), while LV volumes (LV end-diastolic volume index 55 ±13 mL/m2 vs. 82 ±38 mL/m2; p&amp;lt;0.001) and E/E’ ratio were smaller (10 ±4 vs. 15 ±4; p&amp;lt;0.001) as compared to vFMR. However left atrial (LA) volume index was similar between both groups (43 ±14 mL/m2 vs. 41 ±18 mL/m2; p=0.271). For the echocardiographic measures of the right heart, significant difference was observed only for TAPSE which was higher for the aFMR group (22 ±4mm vs. 20 ±5mm; p&amp;lt;0.001). During a median follow-up of 74 months [IQR: 46.8-107.0], 132 (30%) patients died and 30 (6%) underwent mitral valve intervention. Event-free survival analysis for the combined endpoint was significantly better for aFMR patients (Figure 1). Based on significant variables from the univariable Cox regression analysis, multivariable Cox regression analysis showed that the mechanism of functional MR (with aFMR being protective as compared to vFMR), age, male gender, impaired renal function, NYHA class, severe LA dilatation and TAPSE were independently associated with the combined endpoint (Table 1). Conclusion In patients with moderate functional MR, aFMR is independently associated with better event-free survival as compared to vFMR. Therefore, clear identification of the mechanism of MR implies a better risk stratification and may be helpful for the management of patients with moderate MR.

Transcatheter-edge-to-edge-repair of functional mitral regurgitation in advanced HFrEF: the impact of intrinsic left ventricular performance on the degree of MR reduction and clinical outcome

Abstract Background Transcatheter-edge-to-edge-repair (TEER) of functional mitral regurgitation (FMR) reduces rehospitalisation and all-cause mortality in patients with HFrEF/HFmrEF. Not conclusively clarified is the interaction of pre-interventional intrinsic left ventricular (LV) function with TEER success and clinical outcome. By using the gold standard of LV contractility analysis, the invasive pressure-volume loop technique, we examined the interaction of pre-and post-interventional intrinsic LV performance with the degree of MR reduction and all-cause mortality after TEER in patients with advanced HFrEF. Methods In a prospective study of 71 patients with advanced HFrEF (median EF 26%, 22-31%) and severe FMR, we quantified different intrinsic parameters of LV performance by PV-loop analysis (single beat analysis) pre-and post-interventionally. Results In 83% of the patients a MR reduction to grad &amp;lt; 2 could be achieved (hospital discharge). In the ROC analysis, the best cut-off to separate medium-term survival from all-cause mortality (median FU 2.9 years) was a post-interventional regurgitation fraction (RF) &amp;lt; 20% (AUC 0.72, p&amp;lt;0.001, sensitivity 83%, specificity 60%) and a R-volume (RV) &amp;lt; 18ml (AUC 0,7, p=0.002, sensitivity 67%, specificity 72%). The PV-loop-derived intrinsic LV contractility (LV-endsystolic elastance, Ees), LV afterload (arterial elastance, Ea), LV-Ao-coupling (Ees/Ea), LV-mechanical efficacy (ME), PV-loop area (PVA), stroke work, Tau; end-diastolic elastance (Eed), LVEF, LVEDV, and LVESV, pre- and post-TEER, were not predictive for the extent of MR reduction acutely, after 6 months FU, and for all-cause mortality. In multivariate cox-regression analysis, only a post-interventional RF&amp;lt;20% (HR 0.36, p=0.017) or RV&amp;lt;18ml (HR 0.32, p=0.005) and the pre-interventional LV-contractile reserve (LV-CR: post-extra-systolic augmentation of LV-Ees) remained independent predictors of all-cause mortality. In a second model, we included the degree of LV-remodeling (LV-R: LVESV reduction from hospital discharge to 6 months) in the model. In addition to pre-interventional LV-CR, and RF&amp;lt;20%, the LV-R remains independent predictive for all-cause mortality. Conclusion In our peri-mitral-TEER LV-PV-loop study, only the extent of MR reduction and the pre-interventional LV-CR, but not the intrinsic LV performance at rest, determine the medium-term survival of patients with advanced HFrEF and FMR. TEER-mediated MR reduction itself seems not be determined by the LV performance.

Transcatheter edge to edge repair of functional mitral regurgitation as bridge to heart transplantation: 2-years follow up results from MitraBridge international registry

Abstract Background Chronic severe functional mitral regurgitation (FMR) is a common finding in patients with advanced heart failure (AHF) who undergo evaluation for heart transplantation (HTx). Nevertheless, access to surgical strategies for AHF could be limited by scarce availability of donors and by temporary or definitive contraindications. MitraBridge registry already proved that transcatheter edge to edge repair (TEER) of FMR performed as a bridge to HTx is an effective and safe treatment strategy at 1-year follow up with 64% of patients free from composite primary endpoint of all-cause death, new admission for HF, urgent HTx or LVAD implantation. Purpose The aim of this study is to determine whether 1-year results of MitraBridge registry were maintained at 2-years follow up. Methods Mitrabridge is a retrospective, multicenter observational study that enrolled 153 adult patients with AHF and moderate-to-severe or severe FMR and considered candidates for HTx who underwent TEER between 2018 and 2021. Depending on the strategy TEER was performed for, patients were classified in bridge to transplant, candidacy or decision. Primary endpoint of the current analysis was the 2-year composite rate of all-cause death, new admission for HF, urgent HTx or LVAD implantation. Results Median age was 59 years old [53-63], most patients were in INTERMACS class 5-6 (47.5%) and mean left ventricle ejection fraction (LVEF) was 26.9±7.7%. Baseline right heart catheterization was available for 112 (73%) patients, of them 87.5% had pulmonary hypertension with mean pulmonary artery pressure (mPAP) of 33±10 mmHg. Procedural success was achieved in 89.5% of cases and no deaths at 30 days were reported. At 2-years follow up, freedom from primary endpoint was maintained in 47% of patients. A significant reduction of echocardiographic systolic pulmonary artery pressure (sPAP) was observed (from 50 [40-61] mmHg to 43 [33-53] mmHg, p-value&amp;lt;0.001). At the end of follow-up (median time of 26 months, IQR 9-52), elective HTx was successfully performed in 30 cases (21%), 19 patients (13.5%) maintained or obtained the eligibility for transplant, and 32 patients (22.5%) had no longer indication for HTx, due to clinical improvement. Nine patients underwent LVAD implantation for clinical worsening and nine (8%) urgent HTx (15% of already listed population). Conclusions MitraBridge 2-years follow up confirms that TEER is a safe option in AHF population with FMR and shows that haemodynamic and clinical benefits following the procedure are maintained at long term. In particular, it allowed 21% of patients to receive elective HTx reducing need for urgent organ transplantation and helped to expand the candidacy for HTx.

Functional mitral regurgitation and ventricular arrhythmias in patients with cardiac resynchronization therapy

Abstract Introduction In patients with heart failure (HF), the occurrence of ventricular arrhythmias (VAs) is associated with prognosis, and advanced HF can cause VAs. In HF patients developed moderate to severe functional mitral regurgitation (FMR), a transcatheter mitral valve repair therapy has significantly reduced the hospitalization and mortality rates compared to guideline-directed medical therapy. Although the mechanisms of arrhythmias are multiple, it is unclear whether FMR is involved in the development of VAs advanced HF patients. Methods and results We retrospectively examined 176 cardiac resynchronization therapy (CRT) patients (78% men, median age 67 years) without FMR before CRT implanted between 2010 and 2018. Worsening FMR was defined as developing moderate to severe FMR after CRT. During median follow-up of 40 (quartile range, 23-60) months, worsening FMR was detected in 26 (15%) patients at a median of 30 (quartile range, 12–75) months after CRT implantation. There was no difference in age, New York Heart Association functional class, QRS width before CRT and the rate of responders between patients with and without worsening FMR. Patients with worsening FMR had a tendency of larger left ventricular end-systolic dimension (58 [53-68] vs. 53 [47-60] mm, p&amp;lt;0.10), a significantly higher rate of female (38% vs. 19%, p&amp;lt;0.05) and a significantly larger left atrial volume index (LAVI) (63 [43-81] vs. 48 [35-62] ml/m2, p&amp;lt;0.05). By multivariate logistic regression analysis, female gender (odds ratio 4.3) and baseline LAVI (odds ratio 1.04 per a ml/m2 increase) were independent factors associated with worsening FMR. There was a significantly higher incidence of HF hospitalization (50% vs 15%, log-rank P&amp;lt;0.05) (Figure 1) and a higher incidence of VAs, defined as sustained ventricular tachyarrhythmias requiring implantable-cardioverter defibrillator therapy or external defibrillation, in patients with worsening FMR than patients without worsening FMR (65% vs 38%, log-rank P&amp;lt;0.05) (Figure 2). Multivariate analysis showed that worsening FMR was independently associated with the development of VAs (hazard ratio 2.77, 95% confidence interval 1.13-6.83). Conclusions In patients with HF and CRT, female gender and baseline LAVI were associated with worsening FMR after CRT. We need to pay attention to changes in the FMR that can be associated with developing VAs after CRT implantation.

Abstract 17540: Functional Mitral Regurgitation is Associated With Decreased Papillary Muscle Viability Patients With Non-Ischemic Dilated Cardiomyopathy

Background: The underlying mechanisms of functional mitral regurgitation (FMR) in non-ischemic cardiomyopathy (NICM) are incompletely understood. Aims: We investigated the correlation between papillary muscle viability and FMR in NICM. Methods: We enrolled 66 patients with NICM (LVEF&lt;40%, NHYA III) undergoing CD34 + cell transplantation. At baseline, patients underwent electroanatomical mapping; papillary muscle viability was quantified by local unipolar voltage (UV) measurement, and decreased viability was defined as UV&lt;8.3 mV. All patients received granulocyte-colony stimulating factor; CD34 + cells were collected by apheresis and delivered by transendocardial injections. Echocardiography was performed at baseline and 6 months after cell therapy; severity of FMR was graded by multi-parametric approach. FMR improvement was defined as a reduction in FMR by ≥1 grade when compared to baseline. Results: At baseline, papillary muscle viability was decreased in 24 (36%) and preserved in 42 (64%) of patients. Moderate to severe (2-3+) FMR was more common in patients with decreased papillary muscle viability (6/24; 25%) than in patients with preserved viability (2/42; 5%, P=0.015). Transendocardial cell injections were performed in the papillary muscle area in 26 patients (Group A) and in other areas of the left ventricle in 40 patients (Group B). The groups did not differ in age (56±11 years in Group A vs. 54±10 years in Group B, P=0.32), sex (male: 96% vs. 85%, P=0.21), creatinine (0.98±0.27 mg/dL vs. 0.96±0.28 mg/dL, P=0.92), bilirubin (0.89±0.37 mg/dL vs. 0.92±0.35 mg/dL, P=0.45), LVEF (34±9% vs. 31±7%, P=0.12), NT-proBNP levels (1196±994 pg/mL vs. 1077±1176 pg/mL, P=0.68), the degree of FMR (1.28±0.78 vs. 1.02±0.38, P=0.20), or papillary muscle viability (9.9±3.0 mV vs. 10.3±3.2 mV, P=0.62). At 6 months after cell injection, FMR improved in 77% of patients in Group A vs. 13% in Group B (P=0.001). On multivariate analysis, cell injection in the papillary muscle area was an independent correlate of FMR improvement (P=0.01). Conclusions: FMR in patients with NICM is associated with decreased papillary muscle viability. Transendocardial injection of CD34 + cells in the papillary muscle area may improve FMR in this patient population.

Does Sustained Reduction of Functional Mitral Regurgitation Impact Survival?

Functional mitral regurgitation (FMR) is associated with increased mortality and has been considered a marker for advanced heart disease, yet the value of mitral valve repair (MVr) in this population remains unclear. This study aims to evaluate the impact of reducing FMR burden through surgical MVr on survival. Patients with severe FMR who underwent MVr with an undersized, complete, rigid, annuloplasty between 2004 and 2017 were assessed (n = 201). Patients were categorized based on grade of recurrent FMR (0-4). Time-to-event Kaplan-Meier estimations of freedom from death or reoperation were performed using the log-rank test. Cox proportional hazards models evaluated all-cause mortality and reported in hazards ratios (HR) and 95% confidence intervals (CI). Patients were categorized by postoperative recurrent FMR: 45% (91/201) of patients had grade 0, 29% (58/201) grade 1, 20% (40/201) grade 2, 2% (4/201) grade 3%, and 4% (8/201) grade 4. The cumulative incidence of reoperation with death as a competing risk was higher in patients with grades ≥3 recurrent FMR compared to grades ≤2 (44.6% vs 14.6%, subhazard ratio 3.69 [95% CI, 1.17-11.6]; P = 0.026). Overall freedom from death or reoperation was superior for recurrent FMR grades ≤2 compared to grades ≥3 (log-rank P < 0.001). Increasing recurrent FMR grade was independently associated with mortality (HR 1.30 [95% CI, 1.07-1.59] P = 0.009). Reduced postoperative FMR grade resulted in an incrementally lower risk of death or reoperation after MVr. These results suggest that achieving a durable reduction in FMR burden improves long-term survival.

Successful transcatheter mitral valve repair for functional mitral regurgitation in a patient with mitochondrial cardiomyopathy: a case report

Abstract Background Mitochondrial diseases are a group of genetic disorders caused by nuclear or mitochondrial DNA gene mutations and characterized by multiorgan disorders, including cardiomyopathy. Mitochondrial cardiomyopathy is occasionally complicated by hypertrophic cardiomyopathy with/without left ventricular systolic dysfunction, dilated cardiomyopathy, and left ventricular non-compaction. In such cases, the dilated left ventricle impairs coaptation of the mitral leaflets and leads to functional mitral regurgitation. To date, valvular interventions in patients with mitochondrial cardiopathy have not been investigated. Case summary A 64-year-old woman with mitochondrial cardiopathy was referred to our hospital owing to dyspnoea. She experienced her first admission with heart failure at age 60 years. At 62 years old, she was diagnosed with maternally inherited diabetes and deafness with mitochondrial cardiomyopathy based on mitochondrial DNA sequencing. Despite administration of guideline-directed medical therapy and high-dose taurine supplementation, she was repeatedly hospitalized for heart failure. At admission, transthoracic echocardiography revealed severe functional mitral regurgitation due to left ventricular dilatation. Surgical risk was considered high (Society of Thoracic Surgeons score of 12.6%); therefore, transcatheter edge-to-edge repair with the MitraClip system was performed. Two devices deployed at the middle segment of the anterior and posterior leaflet successfully reduced mitral regurgitation. The patient was free from cardiovascular events during the 2-year follow-up period. Discussion Transcatheter edge-to-edge repair is a less invasive and effective treatment for severe drug-refractory mitral regurgitation in patients with mitochondrial disease. Given the limited therapeutic options for mitochondrial cardiopathy, further studies are required to uncover the mechanism underlying mitochondrial diseases and establish disease-specific treatments.

Heart failure medical therapy prior to mitral transcatheter edge-to-edge repair: the STS/ACC Transcatheter Valve Therapy Registry.

Guideline-directed medical therapy (GDMT) is recommended before mitral valve transcatheter edge-to-edge repair (MTEER) in patients with heart failure (HF) and severe functional mitral regurgitation (FMR). Whether MTEER is being performed on the background of optimal GDMT in clinical practice is unknown. Patients with left ventricular ejection fraction (LVEF) < 50% who underwent MTEER for FMR from 23 July 2019 to 31 March 2022 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were identified. Pre-procedure GDMT utilization was assessed. Cox proportional hazards models were constructed to evaluate associations between pre-MTEER therapy (no/single, double, or triple therapy) and risk of 1-year mortality or HF hospitalization (HFH). Among 4199 patients across 449 sites, beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors were used in 85.1%, 44.4%, 28.6%, and 19.9% before MTEER, respectively. Triple therapy was prescribed for 19.2%, double therapy for 38.2%, single therapy for 36.0%, and 6.5% were on no GDMT. Significant centre-level variation in the proportion of patients on pre-intervention triple therapy was observed (0%-61%; adjusted median odds ratio 1.48 [95% confidence interval (CI) 1.25-3.88]; P < .001). In patients eligible for 1-year follow-up (n = 2014; 341 sites), the composite rate of 1-year mortality or HFH was lowest in patients prescribed triple therapy (23.0%) compared with double (24.8%), single (35.7%), and no (41.1%) therapy (P < .01 comparing across groups). Associations persisted after accounting for relevant clinical characteristics, with lower risk in patients prescribed triple therapy [adjusted hazard ratio (aHR) 0.73, 95% CI .55-.97] and double therapy (aHR 0.69, 95% CI .56-.86) before MTEER compared with no/single therapy. Under one-fifth of patients with LVEF <50% who underwent MTEER for FMR in this US nationwide registry were prescribed comprehensive GDMT, with substantial variation across sites. Compared with no/single therapy, triple and double therapy before MTEER were independently associated with reduced risk of mortality or HFH 1 year after intervention.

External validation of the unifying concept for the quantitative assessment of functional mitral regurgitation.

A novel conceptual framework was introduced to enhance the quantitative assessment of functional mitral regurgitation (FMR) and improve risk stratification. However, the data was derived from a single-center cohort and lack external validation. We aimed to validate the proposed algorithm using a different patient population. Patients with at least mild FMR and reduced left ventricular ejection fraction (< 50%) were retrospectively identified at a single-center. The cohort was stratified in low, intermediate and high-risk according to the proposed framework, on the basis of effective regurgitant orifice area (EROA) and regurgitant volume (RegVol). Patients within the intermediate-risk group were subsequently reclassified into either the low-risk category (Regurgitant Fraction, RegFrac < 50%) or the high-risk category (RegFrac ≥ 50%) based on their regurgitant fraction. The primary endpoint was all-cause mortality. A total of 572 patients were included. During a median follow-up of 3.8 years there were 254 deaths (44%). On multivariable analysis, the proposed thresholds for FMR severity remained independently associated with all-cause mortality (adjusted hazard ratio: 1.488; 95% confidence interval [CI]: 1.110-2.013; p-value = 0.010). This algorithm demonstrated superior discriminative ability (C-statistic: 0.664) compared to contemporary guidelines (C-statistic: 0.522; p-value for comparison < 0.001). Additionally, it resulted in a significant improvement in the net reclassification index (0.162; p-value < 0.001). Within our cohort, the application of the proposed concept demonstrated a significant association with a higher risk of all-cause mortality. Moreover, this conceptual framework showcased the potential to improve the accuracy of risk prediction beyond current guidelines.

Prognostic Power of Quantitative Assessment of Functional Mitral Regurgitation and Myocardial Scar Quantification by Cardiac Magnetic Resonance.

The severity classification of functional mitral regurgitation (FMR) remains controversial despite adverse prognosis and rapidly evolving interventions. Furthermore, it is unclear if quantitative assessment with cardiac magnetic resonance can provide incremental risk stratification for patients with ischemic cardiomyopathy (ICM) or non-ICM (NICM) in terms of FMR and late gadolinium enhancement (LGE). We evaluated the impact of quantitative cardiac magnetic resonance parameters on event-free survival separately for ICM and NICM, to assess prognostic FMR thresholds and interactions with LGE quantification. Patients (n=1414) undergoing cardiac magnetic resonance for cardiomyopathy (ejection fraction<50%) assessment from April 1, 2001 to December 31, 2017 were evaluated. The primary end point was all-cause death, heart transplant, or left ventricular assist device implantation during follow-up. Multivariable Cox analyses were conducted to determine the impact of FMR, LGE, and their interactions with event-free survival. There were 510 primary end points, 395/782 (50.5%) in ICM and 114/632 (18.0%) in NICM. Mitral regurgitation-fraction per 5% increase was independently associated with the primary end point, hazards ratios (95% CIs) of 1.04 (1.01-1.07; P=0.034) in ICM and 1.09 (1.02-1.16; P=0.011) in NICM. Optimal mitral regurgitation-fraction threshold for moderate and severe FMR were ≥20% and ≥35%, respectively, in both ICM and NICM, based on the prediction of the primary outcome. Similarly, optimal LGE thresholds were ≥5% in ICM and ≥2% in NICM. Mitral regurgitation-fraction×LGE emerged as a significant interaction for the primary end point in ICM (P=0.006), but not in NICM (P=0.971). Mitral regurgitation-fraction and LGE are key quantitative cardiac magnetic resonance biomarkers with differential associations with adverse outcomes in ICM and NICM. Optimal prognostic thresholds may provide important clinical risk prognostication and may further facilitate the ability to derive selection criteria to guide therapeutic decision-making.

Transcatheter edge-to-edge-repair of functional mitral regurgitation induces significant remodeling of mitral annular geometry.

Mitral annular alterations in the context of heart failure often lead to severe functional mitral regurgitation (FMR), which should be treated with transcatheter edge-to-edge repair (M-TEER) according to current guidelines. M-TEER's effects on mitral valve (MV) annular remodeling have not been well elucidated. 141 consecutive patients undergoing M-TEER for treatment of FMR were included in this investigation. Comprehensive intraprocedural transesophageal echocardiography was used to assess the acute effects of M-TEER on annular geometry. Average patient age was 76.2 ± 9.6 years and 46.1% were female patients. LV ejection fraction was reduced (37.0% ± 13.7%) and all patients had mitral regurgitation (MR) grade ≥III. M-TEER achieved optimal MR reduction (MR ≤ I) in 78.6% of patients. Mitral annular anterior-posterior diameters (A-Pd) were reduced by -6.2% ± 9.5% on average, whereas anterolateral-posteromedial diameters increased (3.7% ± 8.9%). Overall, a reduction in MV annular areas was observed (2D: -1.8% ± 13.1%; 3D: -2.7% ± 13.7%), which strongly correlated with A-Pd reduction (2D: r = 0.6, p < 0.01; 3D: r = 0.65, p < 0.01). Patients that achieved A-Pd reduction above the median (≥6.3%) showed significantly lower rates of the composite endpoint rehospitalization for heart failure or all-cause mortality than those with less A-Pd reduction (9.9% vs. 28.6%, p = 0.037, log-rank p = 0.039). Furthermore, patients reaching the composite endpoint had an increase in annular area (2D: 3.0% ± 15.4%; 3D: 1.9% ± 15.3%), whereas those not reaching the endpoint showed a decrease (2D: -2.7% ± 12.4%; 3D: -3.6% ± 13.3%), although residual MR after M-TEER was similar between these groups (p = 0.57). In multivariate Cox regression adjusted for baseline MR, A-Pd reduction ≥6.3% remained a significant predictor of the combined endpoint (OR: 0.35, 95% CI: 0.14-0.85, p = 0.02). Our findings indicate that effects of M-TEER in FMR are not limited to MR reduction, but also have significant impact on annular geometry. Moreover, A-Pd reduction, which mediates annular remodeling, has a significant impact on clinical outcome independent of residual MR.

Left atrial function assessed by speckle tracking echocardiography as a marker of atrial reverse remodeling in patients with mitral regurgitation treated with transcatheter edge-to-edge repair

Abstract Funding Acknowledgements Type of funding sources: None. Background Left atrial reverse remodeling has been defined relying on changes in left atrial volume following specific procedures. Little is known about functional assessment of the left atrium by left atrial strain and left atrial emptying fraction (LAEF) following edge-to-edge mitral repair. Purpose The aim of this study is to assess left atrial function by speckle tracking echocardiography and changes in LAEF, as markers of atrial reverse remodeling, in patient with mitral regurgitation treated with edge-to-edge repair technique. Methods A total of 35 patients diagnosed with severe functional or organic mitral regurgitation who underwent trans-catheter edge-to-edge mitral valve repair were selected. Demographic, clinical and echocardiographic data were collected at the time of enrollment and after a minimum follow-up of six months. The primary endpoint was to assess if left atrial speckle tracking echocardiographic parameters (LASr, LAScd, LASct) and changes in LAEF were reliable indicators of left atrial reverse remodeling, defined as a reduction in indexed left atrial volume ≥ 15% with respect to basal assessment. Collaterally, we tried to identify clinical and standard echocardiographic parameters significantly related to atrial reverse remodeling. Changes between baseline and follow-up parameters were assessed using paired t-test. Results LASr, LASct and LAEF improved significantly in patients with left atrial remodeling during follow-up (LASr: 15,8%±8,43 vs 19,7%±12,22 - P 0,047; LASct: −6,4%±6,21 vs − 9,9%±8,52 - P 0,036; LAEF: 35,5%±14,17 vs 44,1%±15,17 - P 0,003). Collaterally, among all demographics, clinical and echocardiographic data, the absence of coronary artery disease, a systolic dominant pulmonary vein flow, as assessed with pulse-wave-Doppler after the repair, therapy with ACEi/ARB, lower increases in mitral valve pressure gradient after the procedure and lower pulmonary artery systolic pressure at discharge significantly correlated with reverse atrial remodeling. Conclusions In patients with mitral regurgitation treated with edge-to-edge repair, the assessment of left atrial function by speckle tracking echocardiography and left atrial emptying fraction correlates with atrial reverse remodeling, after a minimum follow-up of six months from the procedure. Further studies are needed to better clarify the impact of left atrial remodeling on strong clinical outcomes in patient with mitral regurgitation treated with edge-to-edge repair technique and the role of functional parameters in the definition of the optimal candidate and timing for the repair.

Determinants of disproportionate functional mitral regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background Recent studies have suggested that "disproportionate" functional mitral regurgitation (FMR) defined by greater MR than expected from the degree of left ventricular (LV) dilatation may be a good candidate for transcatheter edge-to-edge repair (TEER). Determinants of disproportionate FMR (d-FMR) is unknown. We hypothesized that additional factors such as asymmetric tethering, extreme mitral annular dilatation, and deep indentation, might worsen the severity of FMR regardless of LV volumes and lead to d-FMR. Purpose To investigate the impact of the additional factors on the proportionality of FMR. Methods We reviewed consecutive FMR patients who underwent TEER and 3D transesophageal echocardiography (3DTEE) in our institute between 2018 and 2022. d-FMR and proportionate FMR (p-FMR) were defined by the effective regurgitant orifice area (EROA)/LV end-diastolic volume (LVEDV) &amp;gt;0.2 and ≤0.2 mm2/mL, respectively. Results A total of 110 FMR patients (63 d-FMR and 47 p-FMR, 75±12 years old, 46.3% female) were included. Patients with d-FMR had significantly larger EROA than p-FMR (41 ± 12 vs 33 ± 11 mm2, P&amp;lt;0.001) despite smaller LVEDV index (100 ± 28 vs 138 ± 49 mL/m2, P&amp;lt;0.001), better LV ejection fraction (37 ± 10% vs 27 ± 8%, P&amp;lt;0.001), and lower tenting height (7.6 ±2.9 vs 9.4 ± 2.7 mm, P=0.009). The 3DTEE analysis revealed that patients with d-FMR were more likely to have asymmetric tethering (29% vs 21%), extreme mitral annular dilatation (&amp;gt;700 mm2/m2; 54% vs 30%), and deep indentation (22% vs 4.3%) The presence of such additional factors was independently associated with d-FMR (odds ratio 3.83, P=0.0081) after adjustment by body surface area and LVEDV index. Furthermore, EROA/LVEDV increased as the number of additional factors increased. (Jonckheere-Terpstra test, P&amp;lt;0.001). TEER successfully reduced FMR regardless of the presence of such additional factor (success rate 95% vs. 96%, P&amp;gt;0.99). Conclusions The presence of additional factors exacerbates MR independently of LV size and is an important mechanism of d-FMR. TEER is an effective therapy to reduce FMR regardless of these factors.

Outcomes and predictors of patients with moderate or severe functional mitral regurgitation and nonischemic dilated cardiomyopathy.

Patients with functional mitral regurgitation (FMR) and nonischemic dilated cardiomyopathy (DCM) are associated with high mortality. Our study aimed to compare the clinical outcomes between different treatment strategies and identify predictors associated with the adverse outcomes. A total of 112 patients with moderate or severe FMR and nonischaemic DCM were included in our study. The primary composite outcome was all-cause death or unplanned hospitalization for heart failure. The secondary outcomes were individual components of the primary outcome and the cardiovascular death. In this study, the primary composite outcome occurred in 26 patients (44.8%) in mitral valve repair (MVr) group and 37 patients (68.5%) in medical group (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.14-0.55; p < .001). The 1-, 3-, and 5-year survival rates for patients with MVr were 96.6%, 91.8%, and 77.4%, respectively, which were significantly higher than that of medical group: 81.2%, 71.9%, and 65.1%, respectively (HR, 0.32; 95% CI, 0.12-0.87; p = .03). Left ventricular ejection fraction (LVEF) < 41.5% (p < .001) and atrial fibrillation (p = .02) were independently associated with the primary outcome. LVEF < 41.5% (p = .007), renal insufficiency (p = .003), and left ventricular end-diastolic diameter > 66.5 mm (p < .001) were independently associated with heightened risk for all-cause death. Compared with medical therapy, MVr was associated with a better prognosis in patients with moderate or severe FMR and nonischemic DCM. We observed that LVEF < 41.5% was the only independent predictor of the primary outcome and all individual components of secondary outcomes.

Successful management of the leaflet perforation after the transcatheter edge-to-edge repair procedure using transcatheter occlusion.

A 57-year-old female was diagnosed with chronic heart failure and severe functional mitral regurgitation (FMR) despite guideline-directed medical therapy. An echocardiogram revealed severe mitral regurgitation (MR) (4+) vena contracta width 8 mm with ejection fraction (21%), and no calcification on the annulus and leaflets was noted. Mitral transcatheter edge-to-edge repair (TEER) was attempted for this patient. Transcatheter edge-to-edge repair was done under general anaesthesia with transoesophageal echocardiography (TEE) guidance using a novel designed SQ-Krin TEER system (Shenqi Medical). After transseptal puncture was achieved, a 24F guiding sheath was placed in the left atrium (LA). Then, one LW-size clip (6 mm width with 12 mm arm length) was placed in the A2/P2 region (Panel A). Mitral regurgitation severity was reduced to none (Panel A). However, 20 min after release, TEE revealed a large regurgitant gap (7–8 mm) between the anterior mitral leaflet (AML) and the clip arm with torrential MR (Panels B–D), and clip-induced leaflet perforation was confirmed. Considering the high risk of open-heart surgery, transcatheter occlusion was attempted. A 14F steerable catheter was placed in the LA through the previous puncture site, and the guide wire was placed into the left ventricle (LV) through the tear hole, and then a 14 mm Amplatzer Vascular Plug II (St Jude Medical, Abbott) was implanted through the delivery system to occlude the hole (Panels E and F). Mitral regurgitation was reduced to a mild degree after the procedure (Panels G and H). Post-operative recovery was uneventful and no sign of haemolysis. In the 1-year follow-up, the patient presented good condition with mild MR, and both the clip and the plug were in a stable position (Panel I). Leaflet perforation after the TEER procedure is a rare complication with a poor prognosis, especially for an FMR patient. Other than open-heart surgery, transcatheter occlusion may provide a reliable salvage management option.