Traditional approaches to the characterization of secondary or functional mitral regurgitation (MR) have largely ignored the critical importance of the left ventricle (LV). We propose that patients ...with secondary MR represent a heterogenous group, which can be usefully subdivided based on understanding that the effective regurgitant orifice area (EROA) is dependent on left ventricular end-diastolic volume (LVEDV). According to the Gorlin hydraulic orifice equation, patients with heart failure, an LV ejection fraction of 30%, an LVEDV of 220 to 250 ml, and a regurgitant fraction of 50% would be expected to have an EROA of ≈0.3 cm
independent of specific tethering abnormalities of the mitral valve leaflets. The MR in these patients is proportionate to the degree of LV dilatation and can respond to drugs and devices that reduce LVEDV. In contrast, patients with EROA of 0.3 to 0.4 cm
but with LVEDV of only 160 to 200 ml exhibit degrees of MR that are disproportionately higher than predicted by LVEDV. These patients appear to preferentially benefit from interventions directed at the mitral valve. Our proposed conceptual framework explains the apparently discordant results from 2 recent randomized controlled trials of mitral valve repair. The MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial enrolled patients who had MR that was proportionate to the degree of LV dilatation, and during long-term follow-up, the LVEDV and clinical outcomes of these patients did not differ from medically-treated control subjects. In comparison, the patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial had an EROA ≈30% higher but LV volumes that were ≈30% smaller, indicative of disproportionate MR. In these patients, transcatheter mitral valve repair reduced the risk of death and hospitalization for heart failure, and these benefits were paralleled by a meaningful decrease in LVEDV. Thus, characterization of MR as proportionate or disproportionate to LVEDV appears to be critical to the selection of an optimal treatment for patients with chronic heart failure and systolic dysfunction.
Two distinct pathways can lead to functional mitral regurgitation (MR) in patients with chronic heart failure and a reduced ejection fraction. When remodeling and enlargement of the left ventricle ...(LV) cause annular dilatation and tethering of the mitral valve leaflets, there is a linear relationship between LV end-diastolic volume and the effective regurgitant orifice area of the mitral valve. These patients, designated as having proportionate MR, respond favorably to treatments that lead to reversal of LV remodeling and a decrease in LV volumes (eg, neurohormonal antagonists and LV assist devices), but they may not benefit from interventions that are directed only at the mitral valve leaflets (eg, transcatheter mitral valve repair). In contrast, when ventricular dyssynchrony causes functional MR attributable to unequal contraction of the papillary muscles, the magnitude of regurgitation is greater than that predicted by LV volumes. These patients, designated as having severe but disproportionate MR, respond favorably to treatments that are directed to the mitral valve leaflets or their supporting structures (eg, cardiac resynchronization or transcatheter mitral valve repair), but they may derive little benefit from interventions that act only to reduce LV cavity size (eg, pharmacological treatments). This novel conceptual framework reflects the important interplay between LV geometry and mitral valve function in determining the clinical presentation of patients, and it allows characterization of the determinants of functional MR to guide the most appropriate therapy in the clinical setting.
Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes.
At ...78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). The primary effectiveness end point was all hospitalizations for heart failure within 24 months of follow-up. The primary safety end point was freedom from device-related complications at 12 months; the rate for this end point was compared with a prespecified objective performance goal of 88.0%.
Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval CI, 0.40 to 0.70; P<0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P<0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001).
Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079 .).
Apical strain did not change significantly after TAVR (19.5 ± 7.2% to 18.7 ± 7.7%, p = 0.20), however; mid-basal strain increased significantly (12.9 ± 4.2% to 14.2 ± 4.0%, p ≤0.00112.9 ± 4.2% to ...14.2 ± 4.0%, p ≤0.001). ...apical strain sparing, defined as apical to mid-basal strain ratio >1 was present in 88% of patients before TAVR compared with 77% after TAVR. A ratio >2 was present in 19% before TAVR compared with 5% afterward. ...apical strain sparing is common in elderly patients who underwent TAVR and improves after TAVR relieves the LV pressure overload of AS. Importantly, as the Singh study shows, an apical sparing pattern of LV longitudinal strain is often present in AS and resolves with TAVR. ...simple apical sparing, defined as apical to mid-basal longitudinal strain >1 is not pathognomonic for CA in patients with AS.
Traditionally, physicians distinguished between mitral regurgitation (MR) as a determinant of outcomes and MR as a biomarker of left-ventricular (LV) dysfunction by designating the lesions as primary ...or secondary, respectively. In primary MR, leaflet abnormalities cause the MR, resulting in modest increases in LV end-diastolic volume over time, whereas in patients with classic secondary MR, LV dysfunction and dilatation lead to MR without structural leaflet abnormalities. However, certain patients with global LV disease (eg, those with left bundle branch block or regional wall motion abnormalities) have the features of primary MR and might respond favorably to interventions that aim to restore the proper functioning of the mitral valve apparatus.
A novel conceptual framework is proposed, which classifies patients with meaningful LV disease based on whether the severity of MR is proportionate or disproportionate to the LV end-diastolic volume. Treatments that reduce LV volumes (eg, neurohormonal antagonists) are effective in proportionate MR but not disproportionate MR. Conversely, procedures that restore mitral valve function (eg, cardiac resynchronization and mitral valve repair) are effective in patients with disproportionate MR but not in those with proportionate MR. The proposed framework explains the discordant findings in the Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR) and the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trials; differences in procedural success and medical therapy in the 2 studies cannot explain the different results. In addition, the small group of patients in the COAPT trial who had the features of proportionate MR and were similar to those enrolled in the MITRA-FR trial did not respond favorably to transcatheter mitral valve repair.
The characterization of patients with functional MR into proportionate and disproportionate subtypes may explain the diverse range of responses to drug and device interventions that have been observed.
Severe aortic stenosis (AS) and mitral regurgitation (MR) frequently coexist. Although some observational studies have reported that moderate or severe MR is associated with higher mortality, the ...optimal management of such patients is still unclear. Simultaneous replacement of both aortic and mitral valves is linked to significantly higher morbidity and mortality. Recent advances in minimally invasive surgical or transcatheter therapies for MR allow for staged procedures in which surgical or transcatheter aortic valve replacement (SAVR/TAVR) is done first and MR severity re-evaluated afterwards. Current evidence suggests MR severity improves in some patients after SAVR or TAVR, depending on several factors (MR aetiology, type of valve used for TAVR, presence/absence of atrial fibrillation, residual aortic regurgitation, etc). However, as of today, the absence of randomised clinical trials does not allow for evidence-based recommendations about whether or not MR should be addressed at the time of SAVR or TAVR. A careful patient evaluation and clinical judgement are recommended to distinguish patients who might benefit from a double valve intervention from those in which MR should be left alone. The aim of this review is to report and critique the available data on this subject in order to help guide the clinical decision making in this challenging subset of patients.
Tricuspid regurgitation (TR) is the most common lesion of the tricuspid valve (TV). Mild TR is common and usually is benign. However, moderate or severe TR can lead to irreversible myocardial damage ...and adverse outcomes. Despite these findings, few patients with significant TR undergo surgery. The treatment of functional (secondary) TR in particular remains controversial because of high rates of residual or recurrent TR and poor outcomes following surgical intervention. Traditional teaching that functional TR resolves on its own if the underlying disease is successfully treated has proven to be incorrect. This review aims to clarify management of TR by describing the anatomy, pathophysiology, diagnosis, and treatment of TR, including the eventual possibility of percutaneous TV therapy.
Symptomatic mitral regurgitation (MR) is associated with high morbidity and mortality that can be ameliorated by surgical valve repair or replacement. Despite this, many patients with MR do not ...undergo surgery. Transcatheter mitral valve replacement (TMVR) may be an option for selected patients with severe MR.
This study aimed to examine the effectiveness and safety of TMVR in a cohort of patients with native valve MR who were at high risk for cardiac surgery.
Patients underwent transcatheter, transapical delivery of a self-expanding mitral valve prosthesis and were examined in a prospective registry for short-term and 30-day outcomes.
Thirty patients (age 75.6 ± 9.2 years; 25 men) with grade 3 or 4 MR underwent TMVR. The MR etiology was secondary (n = 23), primary (n = 3), or mixed pathology (n = 4). The Society of Thoracic Surgeons Predicted Risk of Mortality was 7.3 ± 5.7%. Successful device implantation was achieved in 28 patients (93.3%). There were no acute deaths, strokes, or myocardial infarctions. One patient died 13 days after TMVR from hospital-acquired pneumonia. Prosthetic leaflet thrombosis was detected in 1 patient at follow-up and resolved after increased oral anticoagulation with warfarin. At 30 days, transthoracic echocardiography showed mild (1+) central MR in 1 patient, and no residual MR in the remaining 26 patients with valves in situ. The left ventricular end-diastolic volume index decreased (90.1 ± 28.2 ml/m
at baseline vs. 72.1 ± 19.3 ml/m
at follow-up; p = 0.0012), as did the left ventricular end-systolic volume index (48.4 ± 19.7 ml/m
vs. 43.1 ± 16.2 ml/m
; p = 0.18). Seventy-five percent of the patients reported mild or no symptoms at follow-up (New York Heart Association functional class I or II). Successful device implantation free of cardiovascular mortality, stroke, and device malfunction at 30 days was 86.6%.
TMVR is an effective and safe therapy for selected patients with symptomatic native MR. Further evaluation of TMVR using prostheses specifically designed for the mitral valve is warranted. This intervention may help address an unmet need in patients at high risk for surgery. (Early Feasibility Study of the Tendyne Mitral Valve System Global Feasibility Study; NCT02321514).
PDF
