Changes in Left Ventricular Global Longitudinal Strain in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.

Background Left ventricular (LV) global longitudinal strain (GLS) provides incremental prognostic information over LV ejection fraction in patients with heart failure (HF) and secondary mitral regurgitation. We examined the prognostic impact of LV GLS improvement in this population. Methods and Results The COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial randomized symptomatic patients with HF with severe (3+/4+) mitral regurgitation to transcatheter edge-to-edge repair with the MitraClip device plus maximally tolerated guideline-directed medical therapy (GDMT) versus GDMT alone. LV GLS was measured at baseline and 6-month follow-up. The relationship between the improvement in LV GLS from baseline to 6 months and the composite of all-cause death or HF hospitalization between 6- and 24-month follow-up were assessed. Among 383 patients, 174 (45.4%) had improved LV GLS at 6-month follow-up (83/195 [42.6%] with transcatheter edge-to-edge repair+GDMT and 91/188 [48.4%] with GDMT alone; P=0.25). Improvement in LV GLS was strongly associated with reduced death or HF hospitalization between 6 and 24 months (P<0.009), with similar risk reduction in both treatment arms (Pinteraction=0.40). By multivariable analysis, LV GLS improvement at 6 months was independently associated with a lower risk of death or HF hospitalization (hazard ratio [HR], 0.55 [95% CI, 0.36-0.83]; P=0.009), death (HR, 0.48 [95% CI, 0.29-0.81]; P=0.006), and HF hospitalization (HR, 0.50 [95% CI, 0.31-0.81]; P=0.005) between 6 and 24 months. Conclusions Among patients with HF and severe mitral regurgitation in the COAPT trial, improvement in LV GLS at 6-month follow-up was associated with improved outcomes after both transcatheter edge-to-edge repair and GDMT alone between 6 and 24 months. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Prognostic implications of mitral valve geometry in patients with secondary mitral regurgitation: the COAPT trial.

AIMS: The impact of mitral valve geometry on outcomes after MitraClip treatment in secondary mitral regurgitation (MR) has not been examined. We therefore sought to evaluate the association between mitral valve geometry and outcomes of patients with heart failure (HF) and secondary MR treated with guideline-directed medical therapy (GDMT) and MitraClip. METHODS AND RESULTS: Mitral valve geometry was assessed from the baseline echocardiograms in 614 patients from the COAPT trial. The primary endpoint for the present study was the composite of all-cause mortality or HF hospitalization (HFH) within 2 years. Effect of treatment arm (MitraClip plus maximally tolerated GDMT vs. GDMT alone) on outcomes according to baseline variables was assessed. Among 29 baseline mitral valve echocardiographic parameters, increasing anteroposterior mitral annular diameter was the only independent predictor of the composite endpoint of all-cause mortality or HFH [adjusted hazard ratio (aHR) per cm 1.49; P = 0.04]. The effective regurgitant orifice area (EROA) was independently associated with all-cause mortality alone (aHR per cm2 2.97; P = 0.04) but not with HFH, whereas increasing anteroposterior mitral annular diameter was independently associated with HFH alone (aHR per cm 1.85; P = 0.005) but not all-cause mortality. Other mitral valve morphologic parameters were unrelated to outcomes. MitraClip reduced HFH and mortality independent of anteroposterior mitral annular diameter and EROA (Pinteraction = 0.77 and 0.27, respectively). CONCLUSION: In patients with HF and severe secondary MR, a large anteroposterior mitral annular diameter and greater EROA were the strongest echocardiographic predictors of HFH and death in patients treated with GDMT alone and with the MitraClip.

Relation of Myocardial Work Indexes and Forward Flow Reserve in Patients With Significant Secondary Mitral Regurgitation Undergoing Transcatheter Mitral Valve Repair.

Left ventricular (LV) myocardial work (LVMW) indexes have shown incremental value over LV ejection fraction and were found to have prognostic significance in patients with secondary mitral regurgitation. We therefore aimed to investigate the association between LVMW indexes and forward flow reserve in patients with secondary mitral regurgitation, treated with transcatheter edge-to-edge repair (TEER). LVMW indexes were evaluated at baseline and forward stroke volume index (FSVI) was evaluated at baseline and 6-month follow-up after TEER. Patients were divided in 2 groups: improvers (improvement in FSVI ≥20%) and nonimprovers (improvement in FSVI <20%). A total of 70 patients (median age 76 years, 59% men) were included. FSVI was the only echocardiographic parameter that improved after TEER. There was a significant decrease in LV global longitudinal strain in the nonimprovers (p = 0.002) but not in the improvers (p = 0.177). Global work index and global constructive work worsened in nonimprovers (p = 0.005 and p = 0.004, respectively), whereas no difference was seen in these indexes in improvers (p = 0.093 and p = 0.112, respectively). Global work efficiency remained independently associated with forward flow reserve after adjusting for a variety of potential confounders. In conclusion, FSVI nonimprovers demonstrated worsening of LV systolic function after TEER compared with improvers, in whom LV systolic function remained stable. Global work efficiency was associated with FSVI improvement after TEER, independent of LV systolic function.

Left Atrial Reservoir Function and Outcomes in Secondary Mitral Regurgitation.

BACKGROUND: Left atrial (LA) size is a marker of disease severity and is related to worse outcomes in secondary mitral regurgitation (MR). The prognostic value of LA function assessed by LA reservoir strain (LARS), however, remains unknown. The aim of this study was to investigate the prognostic implications of LARS in patients with significant secondary MR. METHODS: LARS was evaluated using speckle-tracking echocardiography in patients with more than mild (grade ≥ 2) secondary MR. The population was divided into two groups according to the median LARS value (9.8%). The primary end point was all-cause mortality. RESULTS: A total of 666 patients (mean age, 66 ± 11 years; 68% men) were included. On multivariable analysis, more severe MR was independently associated with more impaired LARS (LARS < 9.8%; odds ratio, 0.419; 95% CI, 0.249-0.704; P = .001). During a median follow-up period of 5 years (interquartile range, 2-10), 383 patients (58%) died. Patients with LARS < 9.8% had significantly lower survival rates at 1-, 2-, and 5-year follow-up (85%, 70%, and 45%, respectively) compared with patients with LARS ≥ 9.8% (96%, 93%, and 78%, respectively; P < .001). After multivariable adjustment (including LA volume and left ventricular global longitudinal strain), more preserved LARS (≥9.8%; hazard ratio, 0.499; 95% CI, 0.386-0.645; P < .001) was independently associated with lower all-cause mortality. LARS provided incremental prognostic value over LA volume and left ventricular global longitudinal strain. CONCLUSIONS: LARS is independently associated with all-cause mortality in patients with significant secondary MR and has incremental prognostic value over LA volume and left ventricular global longitudinal strain. LARS may improve risk stratification of patients with secondary MR.

Extramitral Valvular Cardiac Involvement in Patients With Significant Secondary Mitral Regurgitation.

Patients with secondary mitral regurgitation (SMR) often have extramitral valve cardiac involvement, which can influence the prognosis. SMR can be defined according to groups of extramitral valve cardiac involvement. The prognostic implications of such groups in patients with moderate and severe SMR (significant SMR) are unknown. A total of 325 patients with significant SMR were classified according to the extent of cardiac involvement on echocardiography: left ventricular involvement (group 1), left atrial involvement (group 2), tricuspid valve and pulmonary artery vasculature involvement (group 3), or right ventricular involvement (group 4). The primary end point was all-cause mortality. The prevalence of each cardiac involvement group was 17% in group 1, 12% in group 2, 23% in group 3%, and 48% in group 4. Group 3 and group 4 were independently associated with all-cause mortality (hazard ratio 1.794, 95% confidence interval 1.067 to 3.015, p = 0.027 and hazard ratio 1.857, 95% confidence interval 1.145 to 3.012, p = 0.012, respectively). In conclusion, progressive extramitral valve cardiac involvement (group 3 and group 4) was independently associated with all-cause mortality in patients with significant SMR.

Left Atrial Deformation Imaging and Atrial Fibrillation in Patients with Rheumatic Mitral Stenosis.

BACKGROUND: Atrial fibrillation (AF) is a frequent complication of rheumatic mitral stenosis (MS) and is associated with worse outcomes. Prediction of new-onset AF by assessing left atrial (LA) mechanics with speckle-tracking echocardiography might be useful for risk stratification and guiding therapeutic strategies. Therefore, the aim of this study was to assess the association of LA reservoir strain (LASr) and strain rate (LASRr) with AF at follow-up in patients with rheumatic MS. METHODS: Left atrial reservoir strain and LASRr measured by speckle-tracking echocardiography were assessed in 125 patients (mean age, 50 ± 15 years; 80.8% female) with rheumatic MS and without a history of AF. Patients were followed up for the occurrence of a first episode of AF after the index echocardiogram. RESULTS: During a median follow-up of 32 (9.5-70) months, 41 patients (32.8%) developed new-onset AF. Patients who developed AF had significantly more impaired LASr (13.4% ± 5.2% vs 18.9% ± 8.2%; P < .001) and LASRr (0.72 ± 0.26 s-1 vs 0.98 ± 0.36 s-1;P < .001) compared with patients who remained in sinus rhythm. On multivariable Cox regression analysis, LASr < 21% and LASRr < 0.8 s-1 were independently associated with the development of AF at follow-up (hazard ratio = 7.03, 95% CI, 2.08-23.77, P = .002; and hazard ratio = 3.42, 95% CI, 1.59-7.34, P = .002, respectively). CONCLUSIONS: LASr and LASRr are impaired in patients with rheumatic MS, and the degree of impairment is associated with new-onset AF at follow-up.

Prognostic Implications of Left Ventricular Myocardial Work Indices in Patients With Secondary Mitral Regurgitation.

BACKGROUND: Assessment of left ventricular (LV) function in patients with secondary mitral regurgitation (SMR) remains challenging but is an important parameter for risk stratification. The association of LV myocardial work components (work index [GWI], constructive [GCW] and wasted [GWW] work, and work efficiency) derived from pressure-strain loops obtained with speckle tracking echocardiography, and all-cause mortality in patients with SMR was investigated. METHODS: LV myocardial GWI, GCW, GWW, and global work efficiency were measured with speckle tracking strain echocardiography in 373 patients (72% men, median age 68 years) with various grades of SMR. All-cause mortality was the primary end point. RESULTS: Mild SMR was observed in 143 patients, 128 had moderate SMR, and 102 had severe SMR. Patients with severe SMR had the largest LV volumes and the worst LV ejection fraction and LV global longitudinal strain. In patients with severe SMR, LV GWI and GCW were more impaired (500 mm Hg% versus 680 mm Hg% P=0.024 and 678 mm Hg% versus 851 mm Hg% P=0.006, respectively), while GWW was lower (130 mm Hg% versus 260 mm Hg% P<0.001, respectively) and global work efficiency was significantly higher (82% versus 76%, P=0.001) compared with patients with mild SMR. After a median follow-up of 56 months, 161 patients died. LV GWI≤500 mm Hg%, LV GCW≤750 mm Hg%, and LV GWW<300 mm Hg% were independently associated with excess mortality. CONCLUSIONS: Patients with severe SMR had the worst LV GWI and LV GCW but better LV GWW and global work efficiency reflecting the unloading of the LV in the low-pressure left atrial chamber. These parameters were independently associated with worse long-term survival in patients with SMR.

Sex differences in prognosis of significant secondary mitral regurgitation.

AIMS: Secondary mitral regurgitation (MR) is more frequent in men than in women. However, little is known about differences in prognosis between men and women with secondary MR. The objective of this study is to investigate the sex distribution of secondary MR and the prognostic differences between sexes. METHODS: Patients with significant secondary MR, of both ischaemic and non-ischaemic aetiologies, were identified through the departmental electronic patient files and retrospectively analysed. The primary endpoint was all-cause mortality. RESULTS: A total of 698 patients (mean age 66 ± 11 years) with significant secondary MR were included: 471 (67%) men and 227 (33%) women. Ischaemic heart failure was significantly more common in men (61%), whereas non-ischaemic heart failure was more prevalent in women (63%). Women had significantly smaller left ventricular (LV) volumes when compared with men and more preserved LV systolic function when assessed with LV global longitudinal strain (GLS; 8.5 ± 4.1% vs. 7.5 ± 3.6%; P = 0.004). Women more often underwent surgical mitral valve repair (34%) when compared with men (26%), although no differences were observed for transcatheter mitral valve repair. During a median follow-up of 57 [interquartile range 29-110] months, 373 (53%) patients died. Women showed significantly lower mortality rates at 1-, 2- and 5-year follow-up (9%, 16% and 33% vs. 10%, 20% and 42%) when compared with men (P = 0.001). CONCLUSIONS: Significant secondary MR is more frequently observed in men as compared with women and is associated with worse prognosis.

Left Ventricular Global Longitudinal Strain as a Predictor of Outcomes in Patients with Heart Failure with Secondary Mitral Regurgitation: The COAPT Trial.

BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) is a sensitive marker of LV function and may help identify patients with heart failure (HF) and secondary mitral regurgitation who would have a better prognosis and are more likely to benefit from edge-to-edge transcatheter mitral valve repair with the MitraClip. The aim of this study was to assess the prognostic utility of baseline LV GLS during 2-year follow-up of patients with HF with secondary mitral regurgitation enrolled in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation trial. METHODS: Patients with symptomatic HF with moderate to severe or severe secondary mitral regurgitation who remained symptomatic despite maximally tolerated guideline-directed medical therapy (GDMT) were randomized to transcatheter mitral valve repair plus GDMT or GDMT alone. Speckle-tracking-derived LV GLS from baseline echocardiograms was obtained in 565 patients and categorized in tertiles. Death and HF hospitalization at 2-year follow-up were the principal outcomes of interest. RESULTS: Patients with better baseline LV GLS had higher blood pressure, greater LV ejection fraction and stroke volume, lower levels of B-type natriuretic peptide, and smaller LV size. No significant difference in outcomes at 2-year follow-up were noted according to LV GLS. However, the rate of death or HF hospitalization between 10 and 24 months was lower in patients with better LV GLS (P = .03), with no differences before 10 months. There was no interaction between GLS tertile and treatment group with respect to 2-year clinical outcomes. CONCLUSIONS: Baseline LV GLS did not predict death or HF hospitalization throughout 2-year follow-up, but it did predict outcomes after 10 months. The benefit of transcatheter mitral valve repair over GDMT alone was consistent in all subgroups irrespective of baseline LV GLS.

Regurgitant Volume/Left Ventricular End-Diastolic Volume Ratio: Prognostic Value in Patients With Secondary Mitral Regurgitation.

OBJECTIVES: The purpose of this study was to investigate the prognostic implications of the ratio of mitral regurgitant volume (RVol) to left ventricular (LV) end-diastolic volume (EDV) in patients with significant secondary mitral regurgitation (MR). BACKGROUND: Quantification of secondary MR remains challenging, and its severity can be over- or underestimated when using the proximal isovelocity surface area method, which does not take LV volume into account. This limitation can be addressed by normalizing mitral RVol to LVEDV. METHODS: A total of 379 patients (mean age 67 ± 11 years; 63% male) with significant (moderate and severe) secondary MR were divided into 2 groups according to the RVol/EDV ratio: RVol/EDV ≥20% (greater MR/smaller EDV) and <20% (smaller MR/larger EDV). The primary endpoint was all-cause mortality. RESULTS: During median (interquartile range) follow-up of 50 (26 to 94) months, 199 (52.5%) patients died. When considering patients receiving medical therapy only, patients with RVol/EDV ratio ≥20% tended to have higher mortality rates than those with RVol/EDV ratio <20% (5-year estimated rates 24.1% vs. 18.4%, respectively; p = 0.077). Conversely, when considering the entire follow-up period including mitral valve interventions, patients with a higher RVol/EDV ratio (≥20%) had lower rates of all-cause mortality compared with patients with RVol/EDV ratio <20% (5-year estimated rates 39.0% vs. 44.8%, respectively; p = 0.018). On multivariable analysis, higher RVol/EDV ratio (per 5% increment as a continuous variable) was independently associated with lower all-cause mortality (0.93; p = 0.023). CONCLUSIONS: In patients with significant secondary MR treated medically, survival tended to be lower in those with a higher RVol/EDV ratio. Conversely, a higher RVol/EDV ratio was independently associated with reduced all-cause mortality. when mitral valve interventions were taken into consideration.

Insufficient Mitral Leaflet Remodeling in Relation to Annular Dilation and Risk of Residual Mitral Regurgitation After MitraClip Implantation.

OBJECTIVES: The purpose of this study was to determine whether the mitral valve (MV) total leaflet area (TLA)-to-mitral annular area (MAA) (TLA/MAA) ratio measured using 3-dimensional (3D) transesophageal echocardiography (TEE) was associated with residual mitral regurgitation (MR) after MitraClip implantation in patients with secondary MR. BACKGROUND: The factors influencing the results of MitraClip implantation for secondary MR are controversial. This study hypothesized that insufficient remodeling of the mitral leaflets relative to the annular dilation may be associated with significant MR after MitraClip implantation. METHODS: This study included patients with secondary MR treated with MitraClips. Using 3D TEE dataset, the TLA in diastole and MAA in systole were measured with dedicated software. RESULTS: In a total cohort of 119 patients (mean age 74 ± 9 years; 61% male), significant residual MR (≥2+) was present in 43 patients (36%). In patients with significant residual MR, MAA was greater than in patients without residual MR (10.7 ± 2.4 cm2 vs. 9.0 ± 2.1 cm2; p < 0.001) whereas no significant difference was observed in TLA (12.2 ± 2.6 cm2 vs. 12.0 ± 2.9 cm2; p = 0.836). TLA/MAA ratio was lower in patients with significant residual MR as compared to their counterparts (1.14 ± 0.15 vs. 1.34 ± 0.16; p < 0.001), suggesting insufficient leaflet remodeling relative to annular dilation. On receiver-operating characteristic curve analysis, the TLA/MAA ratio had better discriminative power to identify patients who will have significant residual MR compared to MAA alone (area under the curve [AUC]: 0.830 vs. 0.723; p = 0.049). CONCLUSIONS: In patients with secondary MR, insufficient mitral leaflet remodeling relative to the annulus dilation, as reflected by a lower TLA/MAA ratio, is associated with significant residual MR after MitraClip implantation.

Imaging of the mitral valve: role of echocardiography, cardiac magnetic resonance, and cardiac computed tomography.

PURPOSE OF REVIEW: This article reviews the role of multimodality imaging in the in evaluation of patients with mitral regurgitation referred for transcatheter interventions. RECENT FINDINGS: Transcatheter therapies for mitral regurgitation in patients with high surgical risk or contraindications for surgery are evolving rapidly. Three-dimensional imaging techniques (transesophageal echocardiography, computed tomography, and cardiovascular magnetic resonance) are key to determine the anatomical suitability for each transcatheter therapy, to accurately quantify mitral regurgitation, and to plan and guide the procedure. Fusion imaging is being implemented in catheterization laboratories to precisely guide the procedure and to maximize safety and optimal results. Transcatheter edge-to-edge mitral valve repair with the MitraClip device (Abbott Vascular, Santa Clara, CA) provides the largest evidence on the safety and efficacy of this minimally invasive therapy and the importance of accurate patient selection to improve outcomes has been recently shown in two randomized trials. SUMMARY: Multimodality imaging is key in the work-up of patient with mitral regurgitation undergoing transcatheter therapies. Preprocedural imaging with three-dimensional echocardiography, computed tomography, and cardiac magnetic resonance is important to evaluate the eligibility of patients for transcatheter interventions, whilst three-dimensional transesophageal echocardiography provides soft-tissue information that can be overlaid onto fluoroscopy allowing more accurate guidance of transcatheter interventions.

Prognostic Value of Left Ventricular Global Longitudinal Strain in Patients With Secondary Mitral Regurgitation.

BACKGROUND: Left ventricular (LV) systolic function may be overestimated in patients with secondary mitral regurgitation (MR) when using LV ejection fraction (EF). LV global longitudinal strain (GLS) is a less load-dependent measure of LV function. However, the prognostic value of LV GLS in secondary MR has not been evaluated. OBJECTIVES: This study sought to demonstrate the prognostic value of LV GLS over LVEF in patients with secondary MR. METHODS: A total of 650 patients (mean 66 ± 11 years of age, 68% men) with significant secondary MR were included. The study population was subdivided based on the LV GLS value at which the hazard ratio (HR) for all-cause mortality was >1 using a spline curve analysis (LV GLS <7.0%, impaired LV systolic function vs. LV GLS ≥7.0%, preserved LV systolic function). The primary endpoint was all-cause mortality. RESULTS: During a median follow-up of 56 (interquartile range: 28 to 106 months) months, 334 (51%) patients died. Patients with a more impaired LV GLS showed significantly higher mortality rates at 1-, 2-, and 5-year follow-up (13%, 23%, and 44%, respectively) when compared with patients with more preserved LV systolic function (5%, 14%, and 31%, respectively). On multivariable analysis, LV GLS <7.0% was associated with increased mortality (HR: 1.337; 95% confidence interval: 1.038 to 1.722; p = 0.024), whereas LVEF ≤30% was not (HR: 1.055; 95% confidence interval: 0.794 to 1.403; p = 0.711). CONCLUSIONS: In patients with secondary MR, impaired LV GLS was independently associated with an increased risk for all-cause mortality, whereas LVEF was not. LV GLS may therefore be useful in the risk stratification of patients with secondary MR.