Passive mechanical properties of the left ventricular myocardium and extracellular matrix in hearts with chronic volume overload from mitral regurgitation.

Cardiac volume overload from mitral regurgitation (MR) is a trigger for left ventricular dilatation, remodeling, and ultimate failure. While the functional and structural adaptations to this overload are known, the adaptation of myocardial mechanical properties remains unknown. Using a rodent model of MR, in this study, we discern changes in the passive material properties of the intact and decellularized myocardium. Eighty Sprague-Dawley rats (350-400 g) were assigned to two groups: (1) MR (n = 40) and (2) control (n = 40). MR was induced in the beating heart by perforating the mitral leaflet with a 23G needle, and rats were terminated at 2, 10, 20, or 40 weeks (n = 10/time-point). Echocardiography was performed at baseline and termination, and explanted hearts were used for equibiaxial mechanical testing of the intact myocardium and after decellularization. Two weeks after inducing severe MR, the myocardium was more extensible compared to control, however, stiffness and extensibility of the extracellular matrix did not differ from control at this timepoint. By 20 weeks, the myocardium was stiffer with a higher elastic modulus of 1920 ± 246 kPa, and a parallel rise in extracellular matrix stiffness. Despite some matrix stiffening, it only contributed to 31% and 36% of the elastic modulus of the intact tissue in the circumferential and longitudinal directions. At 40 weeks, similar trends of increasing stiffness were observed, but the contribution of extracellular matrix remained relatively low. Chronic MR induces ventricular myocardial stiffening, which seems to be driven by the myocyte compartment of the muscle, and not the extracellular matrix.

A Score to Assess Mortality After Percutaneous Mitral Valve Repair.

BACKGROUND: Risk stratification for transcatheter edge-to-edge mitral valve repair (TEER) is paramount in the decision-making process for treating severe mitral regurgitation (MR). OBJECTIVES: This study sought to create and validate a user-friendly score (MitraScore) to predict the risk of mortality in patients undergoing TEER. METHODS: The derivation cohort was based on a multicentric international registry that included 1,119 patients referred for TEER between 2012 and 2020. Score discrimination was assessed using Harrell's c-statistic, and the calibration was evaluated with the Gronnesby and Borgan goodness-of-fit test. An external validation was carried out in 725 patients from the GIOTTO registry. RESULTS: After multivariate analysis, we identified 8 independent predictors of mortality during the follow-up (2.1 ± 1.8 years): age ≥75 years, anemia, glomerular filtrate rate <60 mL/min/1.73 m2, left ventricular ejection fraction <40%, peripheral artery disease, chronic obstructive pulmonary disease, high diuretic dose, and no therapy with renin-angiotensin system inhibitors. The MitraScore was derived by assigning 1 point to each independent predictor. The c-statistic was 0.70. Per each point of the MitraScore, the relative risk of mortality increased by 55% (HR: 1.55; 95% CI: 1.44-1.67; P < 0.001). The discrimination and calibration for mortality prediction was better than those of EuroSCORE II (c-statistic 0.61) or Society of Thoracic Surgeons score (c-statistic 0.57). The MitraScore maintained adequate performance in the validation cohort (c-statistic 0.66). The score was also predictive for heart failure rehospitalization and was correlated with the probability of clinical improvement. CONCLUSIONS: The MitraScore is a simple prediction algorithm for the prediction of follow-up mortality in patients treated with TEER.

Transcatheter Mitral Valve Edge-to-Edge Repair with a Novel System.

The ValveClamp system is a novel edge-to-edge mitral valve repair system that is designed for ease of operation. We aimed to report the 1-year outcomes of the early feasibility study of this system.Patients with severe degenerative mitral regurgitation (MR) at higher surgical risk and who received transapical ValveClamp implantation were followed for 1 year for clinical and echocardiographic outcomes.Twelve patients (mean age, 76.5 ± 6.3 years; mean Society of Thoracic Surgery score, 6.9 ± 1.9%) were enrolled at three sites in China. At 1 year, no patient died, received reoperation, or had long-term complications. Of the 12 patients with MR of 3+ or 4+ at baseline, 11 patients (91.67%) remained with MR ≤ 2+ at 1 year, and no patient had mitral stenosis. Significant reductions in maximum MR area (from 15.1 ± 6.51 cm2 to 4.45 ± 1.85 cm2, P < 0.001), effective orifice area (from 4.34 ± 0.34 cm2 to 2.38 ± 0.45 cm2, P < 0.001), and vena contracta width (from 8.03 ± 1.11 to 3.38 ± 2.11 mm, P < 0.001) were observed. The left cardiac dimensions were decreased, especially the mitral valve annulus diameter (from 34.79 ± 4.27 mm to 31.42 ± 2.81 mm, P < 0.05). Of the 12 patients with baseline New York Heart Association functional class III/IV, all patients experienced an improvement of at least one class (P < 0.05).Our study provides evidence that transapical ValveClamp implantation in high-risk patients with severe degenerative MR is safe and feasible, with good efficacy in the mid-long term.

Rheumatic mitral valve repair or replacement in the valve-in-valve era.

OBJECTIVE: For degenerative mitral disease, repair is superior to replacement; however, the best operative strategy for rheumatic mitral disease remains unclear. We evaluated the association between decision-making in choosing repair versus replacement and outcomes across 2 decades of rheumatic mitral surgery. METHODS: Patients undergoing isolated, first-time rheumatic mitral surgery were identified. Era 1 (1997-2008) and Era 2 (2009-2018) were distinguished by intraoperative assessment of anterior leaflet mobility/calcification (Era 2) in deciding between mitral repair versus replacement. Primary outcome was a composite of death, reoperation, and severe valve dysfunction. RESULTS: Among 180 patients, age was 59 ± 14 years, and ejection fraction was 58% ± 10%. A higher proportion in Era 1 (n = 56) compared with Era 2 (n = 124) had preoperative atrial fibrillation (68% vs 46%; P = .006); the groups were otherwise similar. Primary indication was mitral stenosis in 69% (124 out of 180; pure = 35, mixed = 89) and did not differ by era (P = .67). During Era 1, 70% (39 out of 56) underwent repair, compared with 33% (41 out of 124) during Era 2 (P < .001). Freedom from death, reoperation, or severe valve dysfunction at 5 years was higher in Era 2 (72% ± 9%) than Era 1 (54% ± 13%; P = .04). Five-year survival was higher in Era 2 than Era 1, but did not differ between repair versus replacement. Five-year cumulative incidence of reoperation with death as a competing risk did not differ by era, but was higher after repair than replacement. CONCLUSIONS: Careful assessment of anterior leaflet mobility/calcification to determine mitral repair or replacement was associated with improved outcomes. This decision-making strategy may alter the threshold for rheumatic mitral replacement in the current valve-in-valve era.

Influences of mitral annuloplasty on left ventricular flow dynamics assessed with 3-dimensional cine phase-contrast flow magnetic resonance imaging.

OBJECTIVES: We assessed the influence of annuloplasty procedures in mitral repair on left ventricular (LV) vortex flow patterns and aortic outflow patterns, and flow energy loss (EL). METHODS: Twenty healthy volunteers and 14 patients who had undergone mitral valve repair were examined using 3-dimensional cine phase-contrast magnetic resonance imaging. A band group included 7 patients with semi-rigid and 2 with flexible partial bands. The ring group included 5 patients with semi-rigid complete rings. LV vortex flow patterns, aortic outflow patterns, EL, and aortic annulus changes during one cardiac cycle were evaluated. RESULTS: Mitral repair induced different vortex flow patterns compared with that of healthy volunteers. The vortex beneath the anterior mitral leaflet with semi-rigid devices was double-stranded in early diastole, and it was single-stranded with flexible bands with a large shift toward the apex during diastole. LVEL in patients who underwent mitral repair (0.84 ± 0.42 mW) was greater than that in healthy volunteers (0.47 ± 0.10 mW). Complete rings disturbed aortic outflow patterns, with EL distribution changes. Smaller devices relative to patient body size disturbed LV flow patterns and caused high EL. No significant relationship was found between indexed ring orifice area and transmitral mean pressure gradient (r = -0.25, P = .414), but a negative relationship exists between indexed ring orifice area and LVEL (r = -0.84, P < .001). CONCLUSIONS: Mitral repair, especially with relatively small annuloplasty rings, induced abnormal LV flow patterns and EL elevation, which have the potential to be a novel hemodynamic evaluation method after mitral repair.

Multiple MitraClips: The balancing act between pressure gradient and regurgitation.

OBJECTIVE: Transcatheter mitral valve repair with the MitraClip is used for the symptomatic management of mitral regurgitation (MR). The challenge is reducing MR while avoiding an elevated mitral valve gradient (MVG). This study assesses how multiple MitraClips used to treat MR can affect valve performance. METHODS: Six porcine mitral valves were assessed using an in vitro left heart simulator in the native, moderate-to-severe MR, and severe MR cases. MR cases were tested in the no-MitraClip, 1-MitraClip, and 2-MitraClip configurations. Mitral regurgitant fraction (MRF), MVG, and effective orifice area (EOA) were quantified. RESULTS: Native MRF, MVG, and EOA were 14.22%, 2.59 mm Hg, and 1.64 cm2, respectively. For moderate-to-severe MR, MRF, MVG, and EOA were 34.07%, 3.31 mm Hg, and 2.22 cm2, respectively. Compared with the no-MitraClip case, 1 MitraClip decreased MRF to 18.57% (P < .0001) and EOA to 1.50 cm2 (P = .0002). MVG remained statistically unchanged (3.44 mm Hg). Two MitraClips decreased MRF to 14.26% (P < .0001) and EOA to 1.36 cm2 (P = .0001). MVG remained unchanged (3.29 mm Hg). For severe MR, MRF, MVG, and EOA were 59.79%, 4.98 mm Hg, and 2.73 cm2, respectively. Compared with the no-MitraClip case, 1 MitraClip decreased MRF to 30.72% (P < .0001) and EOA to 1.82 cm2 (P < .0001); MVG remained unchanged (4.03 mm Hg). MVG remained statistically unchanged. Two MitraClips decreased MRF to 23.10% (P < .0001) and EOA to 1.58 cm2 (P < .0001); MVG remained statistically unchanged (3.82 mm Hg). Both MR models yielded no statistical difference between 1 and 2 MitraClips. CONCLUSIONS: There is limited concern regarding elevation of MVG when reducing MR using 1 or 2 MitraClips, although 2 MitraClips did not significantly continue to reduce MRF.

Treatment options for ischemic mitral regurgitation: A meta-analysis.

BACKGROUND: Treatment of ischemic mitral regurgitation (IMR) is in evolution, as percutaneous procedures and complex surgical repair have been recently investigated in randomized clinical trials and matched studies. This study aims to review and compare the current treatment options for IMR. METHODS: A comprehensive literature search was conducted using electronic databases. The primary outcome was all-cause long-term mortality. The secondary outcomes were perioperative mortality, unplanned rehospitalization, reoperation, and composite end points as defined in the original articles. RESULTS: A total of 12 articles met the inclusion criteria and were included in the final meta-analysis. The MitraClip procedure did not confer a significant benefit in mortality and repeated hospitalization compared with medical therapy alone. In patients with moderate IMR, the adjunct of mitral procedure over coronary artery bypass graft is not associated with clinical improvements. When evaluating mitral valve (MV) replacement versus repair, hospital mortality was greater among patients undergoing replacement (odds ratio [OR], 1.91; P = .009), but both reoperation and readmission rates were lower (OR, 0.60, P = .05; and OR, 0.45, P < .02, respectively). Comparing restrictive annuloplasty alone with adjunctive subvalvular repair, subvalvular procedures resulted in fewer readmissions (OR, 0.50; P = .06) and adverse composite end points (P = .009). CONCLUSIONS: MitraClip procedure is not associated with improved outcomes compared with medical therapy. MV replacement is associated with increased early mortality but reduced reoperation rate and readmission rate compared with MV repair using annuloplasty in moderate-to-severe IMR. Despite no significant benefit in isolated outcomes comparing annular and adjunct subvalvular procedures, the adjunct of subvalvular procedures reduces the risk of major postoperative adverse events.

Left ventricular remodeling after mitral valve repair and papillary muscle approximation.

BACKGROUND: Mitral valve repair with papillary muscle approximation (MVr-PMA) for severe secondary mitral regurgitation (MR) decreases MR recurrence compared with MVr alone. This study assessed the effects of MVr-PMA on left ventricular (LV) remodeling and shape, systolic function and strain mechanics. METHODS: Forty-eight patients who underwent MVr-PMA for severe secondary MR and had follow-up echocardiograms available for review were identified. Student's t-test, linear regression modeling, and receiver-operating characteristic curves were used in the statistical analyses. RESULTS: Median follow-up time was 14.9 months. MVr-PMA was associated with significant LV reverse remodeling with a smaller LV end-diastolic diameter, Systolic Sphericity Index, and interpapillary muscle distance at follow-up. Nine patients (18.8%) experienced moderate recurrent MR. When compared to recurrent MR patients at follow-up, those with durable MVr-PMA had a greater LV ejection fraction (32.8 vs. 22.0%, P=0.03), a smaller end-diastolic diameter (59.6 vs. 67.3 mm, P=0.03), Systolic Sphericity Index (0.35 vs. 0.47, P=0.03), and end-systolic interpapillary muscle distance (16.3 vs. 21.1 mm, P=0.03). A durable MVr-PMA also resulted in stable global longitudinal strain when compared with pre-operative values, while the recurrent MR group experienced a further decline (no recurrent MR: -8.4 vs. -7.5%; recurrent MR: -8.2 vs. -5.4%; P<0.05). A pre-operative LV end-diastolic diameter ≥ 64 mm was a discriminative predictor of MR recurrence (sensitivity=100%, specificity=51%, AUC=0.756, P=0.02). CONCLUSIONS: A durable MVr-PMA confers improved LV geometry and function, and stable LV mechanics. The extent of baseline LV remodeling identifies patients at risk for recurrent MR.

Novel Transcatheter Mitral Prosthesis Designed to Preserve Physiological Ventricular Flow Dynamics.

BACKGROUND: Current mitral bioprostheses are akin to the aortic valve and therefore abolish the left ventricular (LV) physiological vortex. We evaluated the hemodynamic performance and the effects on intraventricular flow dynamics (IFD) of a novel mitral bioprosthesis that presents an innovative design mimicking the native valve. METHODS: A D-shaped self-expandable stent-bovine pericardium monoleaflet valve was designed to provide physiological asymmetric intraventricular flow. Transapical implantation was consecutively performed in 12 juvenile sheep. Postimplant studies using Doppler echocardiography and IFD using echo particle imaging velocimetry were obtained immediately after the implantation and at 3 months to assess the hemodynamic performance of the prostheses. RESULTS: There were 3 deaths during follow-up, 1 due to valve misplacement because of poor imaging visualization and 2 not valve related. The mean transvalvular gradient and effective orifice area were 2.2 ± 1.2 mm Hg and 4.0 ± 1.1 cm2 after implantation and 3.3 ± 1.5 mm Hg and 3.5 ± 0.5 cm2 at 3 months, respectively. LV vortex dimension, orientation, and physiological anticlockwise rotation were preserved compared with preoperative normal LV flow pattern. One animal showed a moderate paravalvular leak, others mild or none. LV outflow tract obstruction, valve thrombosis, and hemolysis were not observed. CONCLUSIONS: Our preclinical in vivo results confirm the good hemodynamic performance of this new transcatheter bioprosthesis with preservation of the physiological IFD. Clinical studies are needed to document whether these characteristics will foster LV recovery and improve the clinical outcome of patients with mitral regurgitation.

Complete atrioventricular septal defect with absent or diminutive primum component: Incidence, anatomic characteristics, and outcomes.

BACKGROUND: Repair of complete atrioventricular septal defect with absent or diminutive primum defect is challenging because of atrial septal malposition and abnormal anatomy of the left atrioventricular valve. We sought to define the incidence, anatomy, and surgical outcomes of this entity. METHODS: We identified all patients in our institutional database presenting for complete atrioventricular septal defect repair from 2006 to 2018. Operative reports and echocardiograms were reviewed to determine the presence and size of the primum defect, atrioventricular valve anatomy, degree of atrioventricular valve regurgitation, repair method, and complications, including reoperation for atrioventricular valve regurgitation. Functionally univentricular patients and those receiving repair at an outside institution were excluded. RESULTS: Of 183 patients with complete atrioventricular septal defect, absent/diminutive primum defect occurred in 16 patients (8.7%; 10 absent, 6 diminutive). Six patients (38%) had leftward malposition of the atrium septum on the common atrioventricular valve. The rate of reoperation for left atrioventricular valve regurgitation was 31% (3 early, 2 late), for which preoperative predictors included leftward malposition of the atrial septum onto the common atrioventricular valve (4/6 patients with malposition required reoperation, P = .036, Fisher exact test). One patient exhibiting this risk factor died. The overall rate of moderate or greater left atrioventricular valve regurgitation on the most recent postoperative echocardiogram was 13% (2/16 patients; median follow-up, 141 days; range, 3-2236 days). CONCLUSIONS: Complete atrioventricular septal defect with absent or diminutive primum defect is a unique variant of complete atrioventricular septal defect for which the risk of reoperation for left atrioventricular valve regurgitation after complete repair is high and risk factors include leftward malposition of the atrial septum on the common atrioventricular valve.

Validation of mitral regurgitation reversibility in patients with HeartMate 3 LVAD implantation.

The resolution of functional mitral valve regurgitation (MR) in patients awaiting left ventricular assist device (LVAD) implantation is discussed controversially. The present study analyzed MR and echocardiographic parameters of the third-generation LVAD HeartMate 3 (HM3) over 3 years. Of 135 LVAD patients (with severe MR, n = 33; with none, mild, or moderate MR, n = 102), data of transthoracic echocardiography were included preoperatively to LVAD implantation, up to 1 month postoperatively, and at 1, 2, and 3 years after LVAD implantation. Demographic data and clinical characteristics were collected. Severe MR was reduced immediately after LVAD implantation in all patients. The echocardiographic parameters left ventricular end-diastolic diameter (P < .001), right ventricular end-diastolic diameter (P < .001), tricuspid annular plane systolic excursion (P < .001), and estimated pulmonary artery pressure (P < .001) decreased after HM3 implantation independently from the grade of MR prior to implantation and remained low during the 2 years follow-up period. Following LVAD implantation, right heart failure, ventricular arrhythmias, ischemic stroke as well as pump thrombosis and bleeding events were comparable between the groups. The incidences of death and cardiac death did not differ between the patient groups. Furthermore, the Kaplan-Meier analysis showed that survival was comparable between the groups (P = .073). HM3 implantation decreases preoperative severe MR immediately after LVAD implantation. This effect is long-lasting in most patients and reinforces the LVAD implantation without MR surgery. The complication rates and survival were comparable between patients with and without severe MR.

Left atrial function analysis in patients with functional mitral regurgitation associated with dilated cardiomyopathy / Análise da função atrial esquerda em pacientes com insuficiência mitral funcional associada à miocardiopatia dilatada

BACKGROUND: Functional mitral regurgitation (FMR) is associated with dilated cardiomyopathy (DC), heart failure (HF), and worsening left atrial function (LAF). Patients with DC and FMR may present left atrial dysfunction resulting from both ventricular dysfunction and valve disease, but it is unknown whether the presence of valve disease will lead to greater LAF impairment. OBJECTIVE: This study aimed to evaluate the relationship between LAF parameters and FMR degree in patients with DC. METHODS: This cross-sectional observational study included 214 patients with DC, 46 without FMR (control group) and 168 with mild, moderate or severe FMR. An LAF analysis was performed by speckle tracking echocardiography (STE) and atrial volumetric variation. RESULTS: LAF analyzed by STE by means of reservoir strain, conduit strain and active contraction strain was reduced in the sample, with values of 14.3%, 8.49% and 5.92%, respectively. FMR degree was significantly associated with reservoir strain (0.27 ± 0.16 versus 0.15 ± 0.09; p < 0.001) and contraction strain (19.2 ± 7.3 versus 11.2 ± 2.7; p < 0.001). FMR was also associated with a reduced LAF assessed by volumetric analysis: total atrial emptying fraction of 0.51 ± 0.13 versus 0.34 ± 0.11 and active atrial emptying fraction of 0 .27 ± 0.16 versus 0.15 ± 0.09 (p < 0.001). CONCLUSION: In a population with DC, FMR was associated with reduced LAF assessed by STE and atrial volume variation.

FUNDAMENTO: A insuficiência mitral funcional (IMF) está associada à miocardiopatia dilatada (MD), à insuficiência cardíaca (IC) e à piora da função atrial esquerda (FAE). A FAE pode decair tanto pela disfunção ventricular quanto pela valvopatia, mas não se sabe se esta leva a um prejuízo maior da FAE. OBJETIVO: Avaliar a relação entre a piora de parâmetros de FAE com o grau de IMF, em pacientes com MD. MÉTODOS: Trata-se de estudo observacional transversal, que incluiu 214 pacientes com MD, sendo 46 sem IMF (controle) e 168 com IMF discreta, moderada ou grave. A análise da FAE foi realizada por ecocardiografia por speckle tracking (STE) e por variação volumétrica atrial. RESULTADOS: A FAE, analisada por STE­ por meio do strain de reservatório, conduto e contração ativa ­ encontrou-se reduzida na amostra, com valores respectivos de 14,3%, 8,49% e 5,92%. O grau de IMF associou-se significativamente com os valores do strain de reservatório (0,27±0,16 versus 0,15±0,09; p <0,001. CONCLUSÃO: Em uma população com MD, a presença de IMF associa-se à redução da FAE de reservatório e de contração, avaliada por STE e pela variação volumétrica atrial.