CD45 Expression in Mitral Valve Endothelial Cells After Myocardial Infarction.

RATIONALE: Ischemic mitral regurgitation, a complication after myocardial infarction (MI), induces adaptive mitral valve (MV) responses that may be initially beneficial but eventually lead to leaflet fibrosis and MV dysfunction. We sought to examine the MV endothelial response and its potential contribution to ischemic mitral regurgitation. OBJECTIVE: Endothelial, interstitial, and hematopoietic cells in MVs from post-MI sheep were quantified. MV endothelial CD45, found post MI, was analyzed in vitro. METHODS AND RESULTS: Ovine MVs, harvested 6 months after inferior MI, showed CD45, a protein tyrosine phosphatase, colocalized with von Willebrand factor, an endothelial marker. Flow cytometry of MV cells revealed significant increases in CD45+ endothelial cells (VE-cadherin+/CD45+/α-smooth muscle actin [SMA]+ and VE-cadherin+/CD45+/αSMA- cells) and possible fibrocytes (VE-cadherin-/CD45+/αSMA+) in inferior MI compared with sham-operated and normal sheep. CD45+ cells correlated with MV fibrosis and mitral regurgitation severity. VE-cadherin+/CD45+/αSMA+ cells suggested that CD45 may be linked to endothelial-to-mesenchymal transition (EndMT). MV endothelial cells treated with transforming growth factor-ß1 to induce EndMT expressed CD45 and fibrosis markers collagen 1 and 3 and transforming growth factor-ß1 to 3, not observed in transforming growth factor-ß1-treated arterial endothelial cells. A CD45 protein tyrosine phosphatase inhibitor blocked induction of EndMT and fibrosis markers and inhibited EndMT-associated migration of MV endothelial cells. CONCLUSIONS: MV endothelial cells express CD45, both in vivo post MI and in vitro in response to transforming growth factor-ß1. A CD45 phosphatase inhibitor blocked hallmarks of EndMT in MV endothelial cells. These results point to a novel, functional requirement for CD45 phosphatase activity in EndMT. The contribution of CD45+ endothelial cells to MV adaptation and fibrosis post MI warrants investigation.

Echocardiographic Outcomes With Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients.

BACKGROUND: The CLASP IID randomized trial (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial) demonstrated the safety and effectiveness of the PASCAL system for mitral transcatheter edge-to-edge repair (M-TEER) in patients at prohibitive surgical risk with significant symptomatic degenerative mitral regurgitation (DMR). OBJECTIVES: This study describes the echocardiographic methods and outcomes from the CLASP IID trial and analyzes baseline variables associated with residual mitral regurgitation (MR) ≤1+. METHODS: An independent echocardiographic core laboratory assessed echocardiographic parameters based on American Society of Echocardiography guidelines focusing on MR mechanism, severity, and feasibility of M-TEER. Factors associated with residual MR ≤1+ were identified using logistic regression. RESULTS: In 180 randomized patients, baseline echocardiographic parameters were well matched between the PASCAL (n = 117) and MitraClip (n = 63) groups, with flail leaflets present in 79.2% of patients. Baseline MR was 4+ in 76.4% and 3+ in 23.6% of patients. All patients achieved MR ≤2+ at discharge. The proportion of patients with MR ≤1+ was similar in both groups at discharge but diverged at 6 months, favoring PASCAL (83.7% vs 71.2%). Overall, patients with a smaller flail gap were significantly more likely to achieve MR ≤1+ at discharge (adjusted OR: 0.70; 95% CI: 0.50-0.99). Patients treated with PASCAL and those with a smaller flail gap were significantly more likely to sustain MR ≤1+ to 6 months (adjusted OR: 2.72 and 0.76; 95% CI: 1.08-6.89 and 0.60-0.98, respectively). CONCLUSIONS: The study used DMR-specific echocardiographic methodology for M-TEER reflecting current guidelines and advances in 3-dimensional echocardiography. Treatment with PASCAL and a smaller flail gap were significant factors in sustaining MR ≤1+ to 6 months. Results demonstrate that MR ≤1+ is an achievable benchmark for successful M-TEER. (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial [CLASP IID]; NCT03706833).

Secondary Mitral Regurgitation: Cardiac Remodeling, Diagnosis, and Management.

Secondary mitral regurgitation (MR) refers to MR resulting from left ventricular or left atrial remodeling. In ischemic or nonischemic cardiomyopathy, left ventricular dilation (regional or global) leads to papillary muscle displacement, tethering, and leaflet malcoaptation. In atrial functional MR, MR occurs in patients with left atrial dilation and altered mitral annular geometry due to atrial fibrillation. In addition to cardiac remodeling, leaflet remodeling is increasingly recognized. Mitral leaflet tissue actively adapts through leaflet growth to ensure adequate coaptation. Leaflets, however, can also undergo maladaptive thickening and fibrosis, leading to increased stiffness. The balance of cardiac and leaflet remodeling is a key determinant in the development of secondary MR. Clinical management starts with detection, severity grading, and identification of the underlying mechanism, which relies heavily on echocardiography. Treatment of secondary MR consists of guideline-directed medical therapy, surgical repair or replacement, and transcatheter edge-to-edge repair. Based on a better understanding of pathophysiology, novel percutaneous mitral repair and replacement devices have been developed and clinical trials are underway.

Left atrial function and not volume predicts mid-to-late atrial fibrillation after mitral valve repair.

OBJECTIVES: Patients undergoing surgical mitral valve repair (MVr) for degenerative mitral regurgitation are at risk of even late postoperative atrial fibrillation (AF). Left atrial (LA) function has been shown superior to LA volume in evaluating the risk of AF in diverse cardiac conditions. We therefore investigated the prognostic value of LA function and volume in predicting mid-to-late postoperative AF after MVr (>30 days postoperatively). METHODS: We retrospectively identified all patients who underwent MVr for degenerative mitral regurgitation between 2012 and 2019 at our institution. Exclusion criteria were preoperative AF, concomitant procedures, re-operations, missing or insufficiently processable preoperative echocardiograms and missing follow-up. LA function and volume measurements were conducted using speckle-tracking strain echocardiographic analysis. Postoperative LA function was measured in a subgroup with sufficient postoperative echocardiograms. RESULTS: We included 251 patients, of whom 39 (15.5%) experienced AF in the mid-to-late postoperative period. Reduced LA strain parameters and more than mild preoperative tricuspid regurgitation were independently associated with mid-to-late postoperative AF. LA volume index had no association with mid-to-late postoperative AF in univariable analysis and did not improve the performance of multivariable models. Patients with mid-to-late AF exhibited diminished improvement in LA function after surgery. CONCLUSIONS: In MVr patients, LA function (but not volume) showed independent predictive value for mid-to-late postoperative AF. Including LA function into surgical decision-making and approach may identify patients who will benefit from earlier intervention with the aim to prevent irreversible LA damage with consequent risk of postoperative AF.

Abnormal Mechanics Relate to Myocardial Fibrosis and Ventricular Arrhythmias in Patients With Mitral Valve Prolapse.

BACKGROUND: The relation between ventricular arrhythmia and fibrosis in mitral valve prolapse (MVP) is reported, but underlying valve-induced mechanisms remain unknown. We evaluated the association between abnormal MVP-related mechanics and myocardial fibrosis, and their association with arrhythmia. METHODS: We studied 113 patients with MVP with both echocardiogram and gadolinium cardiac magnetic resonance imaging for myocardial fibrosis. Two-dimensional and speckle-tracking echocardiography evaluated mitral regurgitation, superior leaflet and papillary muscle displacement with associated exaggerated basal myocardial systolic curling, and myocardial longitudinal strain. Follow-up assessed arrhythmic events (nonsustained or sustained ventricular tachycardia or ventricular fibrillation). RESULTS: Myocardial fibrosis was observed in 43 patients with MVP, predominantly in the basal-midventricular inferior-lateral wall and papillary muscles. Patients with MVP with fibrosis had greater mitral regurgitation, prolapse, and superior papillary muscle displacement with basal curling and more impaired inferior-posterior basal strain than those without fibrosis (P<0.001). An abnormal strain pattern with distinct peaks pre-end-systole and post-end-systole in inferior-lateral wall was frequent in patients with fibrosis (81 versus 26%, P<0.001) but absent in patients without MVP with basal inferior-lateral wall fibrosis (n=20). During median follow-up of 1008 days, 36 of 87 patients with MVP with >6-month follow-up developed ventricular arrhythmias associated (univariable) with fibrosis, greater prolapse, mitral annular disjunction, and double-peak strain. In multivariable analysis, double-peak strain showed incremental risk of arrhythmia over fibrosis. CONCLUSIONS: Basal inferior-posterior myocardial fibrosis in MVP is associated with abnormal MVP-related myocardial mechanics, which are potentially associated with ventricular arrhythmia. These associations suggest pathophysiological links between MVP-related mechanical abnormalities and myocardial fibrosis, which also may relate to ventricular arrhythmia and offer potential imaging markers of increased arrhythmic risk.

Impact of Pulmonary Hypertension on Outcomes in Patients With Mitral Annular Calcium and Associated Mitral Valve Dysfunction.

The prevalence of mitral annular calcium (MAC) is increasing in our aging population. However, data regarding prognostication in MAC-related mitral valve (MV) disease remain limited. This retrospective observational study aims to explore the prognostic impact of systolic pulmonary artery pressure (SPAP) in MAC-related MV dysfunction and define its determinants. We identified 4,384 patients (mean age 78 ± 11 years and 69% female) with MAC-related MV dysfunction (documented transmitral gradient ≥3 mm Hg) from a large institutional echocardiographic database between 2001 and 2019. In Cox regression analysis, higher SPAP strongly associated with all-cause mortality, independent of cardiovascular risk factors and indices of MV dysfunction (adjusted hazard ratio 1.22 per 10 mm Hg SPAP increase, 95% confidence interval 1.17 to 1.27). Patients with SPAP ≥50 mm Hg had significantly higher mortality compared with SPAP <50 mm Hg (log-rank p <0.001), a finding that was consistent across different transmitral gradient subgroups (≤5, 5 to 10, and ≥10 mm Hg). Independent determinants of SPAP included the mean transmitral gradient, mitral regurgitation severity, left ventricular ejection fraction, and ≥moderate aortic stenosis (adjusted p <0.05), and atrial fibrillation and left atrial dimension. The impact of concomitant mitral regurgitation on SPAP decreased at higher transmitral gradients and was no longer significant at gradients ≥10 mm Hg (p = 0.100). In conclusion, SPAP strongly associates with mortality in MAC, independent of cardiovascular risk factors and indices of MAC-related MV dysfunction. These findings suggest an incremental role for SPAP in the risk stratification and prognostication in this increasingly prevalent condition with expanding the scope of possible interventions.

Patient- and Process-Related Contributors to the Underuse of Aortic Valve Replacement and Subsequent Mortality in Ambulatory Patients With Severe Aortic Stenosis.

Background Many patients with severe aortic stenosis (AS) and an indication for aortic valve replacement (AVR) do not undergo treatment. The reasons for this have not been well studied in the transcatheter AVR era. We sought to determine how patient- and process-specific factors affected AVR use in patients with severe AS. Methods and Results We identified ambulatory patients from 2016 to 2018 demonstrating severe AS, defined by aortic valve area [Formula: see text]1.0 cm2. Propensity scoring analysis with inverse probability of treatment weighting was used to evaluate associations between predictors and the odds of undergoing AVR at 365 days and subsequent mortality at 730 days. Of 324 patients with an indication for AVR (79.3±9.7 years, 57.4% men), 140 patients (43.2%) did not undergo AVR. The odds of AVR were reduced in patients aged >90 years (odds ratio [OR], 0.24 [95% CI, 0.08-0.69]; P=0.01), greater comorbid conditions (OR, 0.88 per 1-point increase in Combined Comorbidity Index [95% CI, 0.79-0.97]; P=0.01), low-flow, low-gradient AS with preserved left ventricular ejection fraction (OR, 0.11 [95% CI, 0.06-0.21]), and low-gradient AS with reduced left ventricular ejection fraction (OR, 0.18 [95% CI, 0.08-0.40]) and were increased if the transthoracic echocardiogram ordering provider was a cardiologist (OR, 2.46 [95% CI, 1.38-4.38]). Patients who underwent AVR gained an average of 85.8 days of life (95% CI, 40.9-130.6) at 730 days. Conclusions The proportion of ambulatory patients with severe AS and an indication for AVR who do not receive AVR remains significant. Efforts are needed to maximize the recognition of severe AS, especially low-gradient subtypes, and to encourage patient referral to multidisciplinary heart valve teams.

Progression of Mitral Regurgitation in Rheumatic Valve Disease: Role of Left Atrial Remodeling.

Introduction: Mitral regurgitation (MR) is the most common valve abnormality in rheumatic heart disease (RHD) often associated with stenosis. Although the mechanism by which MR develops in RHD is primary, longstanding volume overload with left atrial (LA) remodeling may trigger the development of secondary MR, which can impact on the overall progression of MR. This study is aimed to assess the incidence and predictors of MR progression in patients with RHD. Methods: Consecutive RHD patients with non-severe MR associated with any degree of mitral stenosis were selected. The primary endpoint was a progression of MR, which was defined as an increase of one grade in MR severity from baseline to the last follow-up echocardiogram. The risk of MR progression was estimated accounting for competing risks. Results: The study included 539 patients, age of 46.2 ± 12 years and 83% were women. At a mean follow-up time of 4.2 years (interquartile range [IQR]: 1.2-6.9 years), 54 patients (10%) displayed MR progression with an overall incidence of 2.4 per 100 patient-years. Predictors of MR progression by the Cox model were age (adjusted hazard ratio [HR] 1.541, 95% CI 1.222-1.944), and LA volume (HR 1.137, 95% CI 1.054-1.226). By considering competing risk analysis, the direction of the association was similar for the rate (Cox model) and incidence (Fine-Gray model) of MR progression. In the model with LA volume, atrial fibrillation (AF) was no longer a predictor of MR progression. In the subgroup of patients in sinus rhythm, 59 had an onset of AF during follow-up, which was associated with progression of MR (HR 2.682; 95% CI 1.133-6.350). Conclusions: In RHD patients with a full spectrum of MR severity, progression of MR occurs over time is predicted by age and LA volume. LA enlargement may play a role in the link between primary MR and secondary MR in patients with RHD.

Proinflammatory Matrix Metalloproteinase-1 Associates With Mitral Valve Leaflet Disruption Following Percutaneous Mitral Valvuloplasty.

Mitral regurgitation (MR) is a major complication of the percutaneous mitral valvuloplasty (PMV). Despite high technical expertise and cumulative experience with the procedure, the incidence rate of severe MR has not decreased. Although some of MR can be anticipated by echocardiographic analysis; leaflet tearing, which leads to the most dreaded type of MR, remains unpredictable. Irregular valvular collagen remodeling is likely to compromise tissue architecture and increase the tearing risk during PMV balloon inflation. In this study, we evaluated histological and molecular characteristics of excised mitral valves from patients with rheumatic mitral stenosis (MS) who underwent emergency surgery after PMV due to severe MR caused by leaflet tear. Those findings were compared with patients who underwent elective mitral valve replacement surgery owing to severe MS, in whom PMV was not indicated. In vitro assay using peripheral blood mononuclear cells was performed to better understand the impact of the cellular and molecular alterations identified in leaflet tear mitral valve specimens. Our analysis showed that focal infiltration of inflammatory cells contributes to accumulation of MMP-1 and IFN-γ in valve leaflets. Moreover, we showed that IFN-γ increase the expression of MMP-1 in CD14+ cells (monocytes) in vitro. Thus, inflammatory cells contribute to unevenly remodel collagen resulting in variable thickening causing abnormalities in leaflet architecture making them more susceptible to laceration.

Active adaptation of the tethered mitral valve: insights into a compensatory mechanism for functional mitral regurgitation.

BACKGROUND: In patients with left ventricular infarction or dilatation, leaflet tethering by displaced papillary muscles frequently induces mitral regurgitation, which doubles mortality. Little is known about the biological potential of the mitral valve (MV) to compensate for ventricular remodeling. We tested the hypothesis that MV leaflet surface area increases over time with mechanical stretch created by papillary muscle displacement through cell activation, not passive stretching. METHODS AND RESULTS: Under cardiopulmonary bypass, the papillary muscle tips in 6 adult sheep were retracted apically short of producing mitral regurgitation to replicate tethering without confounding myocardial infarction or turbulence. Diastolic leaflet area was quantified by 3-dimensional echocardiography over 61+/-6 days compared with 6 unstretched sheep MVs. Total diastolic leaflet area increased by 2.4+/-1.3 cm(2) (17+/-10%) from 14.3+/-1.9 to 16.7+/-1.9 cm(2) (P=0.006) with stretch with no change in the unstretched valves despite sham open heart surgery. Stretched MVs were 2.8 times thicker than normal (1.18+/-0.14 versus 0.42+/-0.14 mm; P<0.0001) at 60 days with an increased spongiosa layer. Endothelial cells (CD31(+)) coexpressing alpha-smooth muscle actin were significantly more common by fluorescent cell sorting in tethered versus normal leaflets (41+/-19% versus 9+/-5%; P=0.02), indicating endothelial-mesenchymal transdifferentiation. alpha-Smooth muscle actin-positive cells appeared in the atrial endothelium, penetrating into the interstitium, with increased collagen deposition. Thickened chordae showed endothelial and subendothelial alpha-smooth muscle actin. Endothelial-mesenchymal transdifferentiation capacity also was demonstrated in cultured MV endothelial cells. CONCLUSIONS: Mechanical stresses imposed by papillary muscle tethering increase MV leaflet area and thickness, with cellular changes suggesting reactivated embryonic developmental pathways. Understanding such actively adaptive mechanisms can potentially provide therapeutic opportunities to augment MV area and reduce ischemic mitral regurgitation.

Mitral leaflet adaptation to ventricular remodeling: prospective changes in a model of ischemic mitral regurgitation.

BACKGROUND: Ischemic mitral regurgitation is caused by systolic traction on the mitral leaflets related to ventricular distortion. Little is known about how chronic tethering affects leaflet area, in part because it cannot be measured repeatedly in situ. Recently, a new method for 3D echocardiographic measurement of mitral leaflet area was developed and validated in vivo against sheep valves, later excised. Clinical studies (n=80) showed that mitral leaflet area increased by >30% in patients with inferior myocardial infarction and dilated cardiomyopathy versus normal; greater adaptation independently predicted less mitral regurgitation. This study explored whether mitral valve area changes over time within the same heart with ischemic mitral regurgitation. METHODS AND RESULTS: Twelve sheep were studied at baseline and 3 months after inferior myocardial infarction by 3D echocardiography; 6 were untreated and 6 were treated initially with an epicardial patch to limit left ventricular dilation and mitral regurgitation. Untreated sheep developed left ventricular dilation at 3 months, with global dysfunction (mean+/-SD ejection fraction, 24+/-10% versus 44+/-10% with patching, P=0.02) and moderate mitral regurgitation (vena contracta, 5.0+/-1.0 versus 0.8+/-1.0 mm, P<0.0002). In untreated sheep, total diastolic leaflet area increased from 13.1+/-1.3 to 18.1+/-2.5 cm(2) (P=0.0001). In patched sheep, leaflet area at 3 months was not significantly different from baseline sheep values (13.0+/-1.1 versus baseline, 12.1+/-1.8 cm(2), P=0.31). CONCLUSIONS: Mitral valve area, independent of systolic stretch, increases over time as the left ventricular remodels after inferior myocardial infarction. This increase, however, fails to compensate adequately for tethering to prevent mitral regurgitation. Understanding the mechanism of valve adaptation can potentially suggest new biological and surgical therapeutic targets.

Minimally Invasive Nonresectional Mitral Valve Repair Can Be Performed With Excellent Outcomes.

BACKGROUND: To review the efficacy of a minimally invasive surgical technique for mitral valve (MV) repair, we analyzed a nonresectional technique for degenerative mitral regurgitation. METHODS: A retrospective analysis was performed on 101 consecutive patients who underwent a minimally invasive MV repair for severe degenerative mitral regurgitation between 2014 and 2017. All patients underwent a right lateral minithoracotomy and femoral cannulation and were repaired by a nonresectional technique using neochord loop implantation and ring annuloplasty. Patients were followed with longitudinal echocardiograms. RESULTS: The median age was 58 years (interquartile range [IQR], 49-64), and 31% were women. The procedure was successfully performed using a right minithoracotomy in all patients except for 1 who required an extended thoracotomy. A median of 4 neochords were placed. The median length was 16 mm (IQR, 14-18), and ring size was 34 mm (IQR, 32-36). Concomitant procedures included left atrial appendage exclusion in 10 patients (10%) and patent foramen ovale closure in 13 (13%). Median cardiopulmonary bypass time was 152 minutes (IQR, 142-164), and aortic cross-clamp time was 90 minutes (IQR, 81-98). Operative mortality was 0% and 1-year survival 100%. At 3 years freedom from recurrent at least moderate mitral regurgitation was 100%, and no patient required a valve-related reoperation. At 1 year the median left atrial diameter decreased by 15% (44 vs 37 mm, P < .001), the left ventricular end-diastolic diameter decreased by 14% (53 vs 46 mm, P < .001), and MV gradients remained low (3.1 vs 2.9 mmHg, P = .54). CONCLUSIONS: Minimally invasive MV repair using a nonresectional technique can be performed for severe degenerative mitral regurgitation with a low complication rate, excellent durability, and promising left ventricular reverse remodeling.

Direct Planimetry of Left Ventricular Outflow Tract Area by Simultaneous Biplane Imaging: Challenging the Need for a Circular Assumption of the Left Ventricular Outflow Tract in the Assessment of Aortic Stenosis.

BACKGROUND: Evaluation of aortic stenosis (AS) requires calculation of aortic valve area (AVA), which relies on the assumption of a circular-shaped left ventricular outflow tract (LVOT). However, the LVOT is often elliptical, and the circular assumption underestimates the true LVOT area (LVOTA). Biplane imaging using transthoracic echocardiography allows direct planimetry of LVOTA. The aim of this study was to assess the feasibility of obtaining LVOTA using this technique and its impact on the discordance between AVA and gradient criteria in AS grading. METHODS: We prospectively studied 134 patients (median age, 80 years; interquartile range, 73-87 years; 39% women) with AS, including 82 (61%) with severe AS and 52 (39%) with mild or moderate AS. LVOTA was traced using direct planimetry (LVOTAbiplane) and compared with LVOTA calculated using the circular assumption (LVOTAcirc). In a subset of patients who underwent cardiac computed tomography, direct planimetry of LVOTA was used as a reference standard. RESULTS: LVOTAbiplane was significantly larger than LVOTAcirc (4.20 cm2 [interquartile range, 3.66-4.90 cm2] vs 3.73 cm2 [interquartile range, 3.14-4.15 cm2], P < .001). Among 30 patients who underwent cardiac computed tomography, LVOTAbiplane had better agreement with LVOTA by direct planimetry than LVOTAcirc (mean bias, -0.45 ± 0.63 vs -1.02 ± 0.63 cm2; P < .0001). Of 82 patients with severe AS (AVA ≤ 1 cm2 using LVOTAcirc), 40 (49%) had discordant mean gradient (<40 mm Hg). By using LVOTAbiplane, patients with discordant AVA and mean gradient decreased from 49% to 27% (P = .004), and 29% of patients with severe AS were reclassified with moderate AS, with the highest percentage of reclassification in the group with low-gradient AS with preserved left ventricular ejection fraction. CONCLUSIONS: Direct planimetry using biplane imaging avoids the inherent underestimation of LVOTA using the circular assumption. LVOTA obtained by biplane planimetry can lead to better concordance between AVA and mean gradient and classification of AS severity.

Association of Pulmonary Hypertension With Clinical Outcomes of Transcatheter Mitral Valve Repair.

Importance: Pulmonary hypertension (pHTN) is associated with increased risk of mortality after mitral valve surgery for mitral regurgitation. However, its association with clinical outcomes in patients undergoing transcatheter mitral valve repair (TMVr) with a commercially available system (MitraClip) is unknown. Objective: To assess the association of pHTN with readmissions for heart failure and 1-year all-cause mortality after TMVr. Design, Setting, and Participants: This retrospective cohort study analyzed 4071 patients who underwent TMVr with the MitraClip system from November 4, 2013, through March 31, 2017, across 232 US sites in the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy registry. Patients were stratified into the following 4 groups based on invasive mean pulmonary arterial pressure (mPAP): 1103 with no pHTN (mPAP, <25 mm Hg [group 1]); 1399 with mild pHTN (mPAP, 25-34 mm Hg [group 2]); 1011 with moderate pHTN (mPAP, 35-44 mm Hg [group 3]); and 558 with severe pHTN (mPAP, ≥45 mm Hg [group 4]). Data were analyzed from November 4, 2013, through March 31, 2017. Interventions: Patients were stratified into groups before TMVr, and clinical outcomes were assessed at 1 year after intervention. Main Outcomes and Measures: Primary end point was a composite of 1-year mortality and readmissions for heart failure. Secondary end points were 30-day and 1-year mortality and readmissions for heart failure. Linkage to Centers for Medicare & Medicaid Services administrative claims was performed to assess 1-year outcomes in 2381 patients. Results: Among the 4071 patients included in the analysis, the median age was 81 years (interquartile range, 73-86 years); 1885 (46.3%) were women and 2186 (53.7%) were men. The composite rate of 1-year mortality and readmissions for heart failure was 33.6% (95% CI, 31.6%-35.7%), which was higher in those with pHTN (27.8% [95% CI, 24.2%-31.5%] in group 1, 32.4% [95% CI, 29.0%-35.8%] in group 2, 36.0% [95% CI, 31.8%-40.2%] in group 3, and 45.2% [95% CI, 39.1%-51.0%] in group 4; P < .001). Similarly, 1-year mortality (16.3% [95% CI, 13.4%-19.5%] in group 1, 19.8% [95% CI, 17.0%-22.8%] in group 2, 22.4% [95% CI, 18.8%-26.1%] in group 3, and 27.8% [95% CI, 22.6%-33.3%] in group 4; P < .001) increased across pHTN groups. The association of pHTN with mortality persisted despite multivariable adjustment (hazard ratio per 5-mm Hg mPAP increase, 1.05; 95% CI, 1.01-1.09; P = .02). Conclusions and Relevance: These findings suggest that pHTN is associated with increased mortality and readmission for heart failure in patients undergoing TMVr using the MitraClip system for severe mitral regurgitation. Further efforts are needed to determine whether earlier intervention before pHTN develops will improve clinical outcomes.

Mitral Regurgitation After Percutaneous Mitral Valvuloplasty: Insights Into Mechanisms and Impact on Clinical Outcomes.

OBJECTIVES: The aim of this study was to assess the incidence, mechanisms, and outcomes of mitral regurgitation (MR) after percutaneous mitral valvuloplasty (PMV). BACKGROUND: Significant MR continues to be a major complication of PMV, with a wide range in clinical presentation and prognosis. METHODS: Consecutive patients with mitral stenosis undergoing PMV were prospectively enrolled. MR severity was evaluated by using quantitative echocardiographic criteria, and its mechanism was characterized by 3-dimensional transesophageal echocardiography, divided broadly into 4 categories based on the features contributing to the valve damage. B-type natriuretic peptide levels were obtained before and 24 h after the procedure. Endpoints estimated cardiovascular death or mitral valve (MV) replacement due to predominant MR. RESULTS: A total of 344 patients, ages 45.1 ± 12.1 years, of whom 293 (85%) were women, were enrolled. Significant MR after PMV was found in 64 patients (18.6%). The most frequent mechanism of MR was commissural, which occurred in 22 (34.4%) patients, followed by commissural with posterior leaflet in 16 (25.0%), leaflets at central scallop or subvalvular damage in 15 (23.4%), and central MR in 11 (17.2%). During the mean follow-up period of 3 years (range 1 day to 10.6 years), 60 patients reached the endpoint. The event-free survival rates were similar among patients with mild or commissural MR, whereas patients with damaged central leaflet scallop or subvalvular apparatus had the worst outcome, with an event-free survival rate at 1 year of only 7%. Long-term outcome was predicted by net atrioventricular compliance (Cn) at baseline and post-procedural variables, including valve area, mean gradient, and magnitude of decrease in B-type natriuretic peptide levels, adjusted for the mechanism of MR. CONCLUSIONS: Significant MR following PMV is a frequent event, mainly related to commissural splitting, with favorable clinical outcome. Parameters that express the relief of valve obstruction and the mechanism by which MR develops were predictors of long-term outcomes.

Cardiac function and brain-type natriuretic peptide in first-time flash pulmonary edema.

OBJECTIVE: To assess left ventricular (LV) function and brain-type natriuretic peptide (BNP) in patients with first-time flash pulmonary edema (FPE). PATIENTS AND METHODS: We retrospectively studied all patients presenting to Mayo Clinic's site in Rochester, MN, from January 5, 2000, to December 30, 2004, with FPE. Only patients with first-time FPE who had undergone BNP assessment and echocardiography within 24 hours of presentation were included. Patients were divided into 2 groups: those with reduced LV ejection fraction (LVEF) (less than 50%) and those with preserved LVEF (equals 50%). RESULTS: Thirty-seven patients met the inclusion criteria (22 female, 15 male). Mean plus or minus SD LVEF was 41% plus or minus 13%. The LVEF was reduced in 73% (group 1, n equals 27; mean plus or minus SD age, 75 plus or minus 8 years) and preserved in 27% (group 2, n equals 10; mean plus or minus SD age, 75 plus or minus 13 years). Most frequent underlying causes for first-time FPE were coronary artery disease and hypertension. Patients with preserved LVEF had significantly lower BNP levels at presentation (535 pg/mL [interquartile range, 352-1210 pg/mL]) vs 1320 pg/mL (interquartile range, 768-2000 pg/mL; P equals .01), despite similar elevated LV filling pressures as measured by echocardiography. The mean plus or minus SD ratio of early diastolic mitral valve inflow velocity to early diastolic mitral annulus velocity was 23 plus or minus 8 vs 22 plus or minus 10; P equals .78. Early diastolic mitral annulus velocity, a surrogate measurement for myocardial relaxation, was reduced in all patients with preserved LVEF and in 95% of patients with reduced LVEF. CONCLUSION: Coronary artery disease and hypertension are the most common precipitating factors for first-time FPE. Reduced myocardial relaxation in almost all patients regardless of LVEF supports the notion that diastolic dysfunction is a prerequisite for FPE. Levels of BNP were elevated in every patient regardless of LVEF but were significantly lower in patients with preserved LVEF despite similarly elevated LV filling pressures.

Percutaneous Balloon Mitral Valvuloplasty: Echocardiographic Eligibility and Procedural Guidance.

Rheumatic mitral stenosis remains a common disease in the developing world. Percutaneous mitral balloon valvuloplasty is an important therapy for rheumatic mitral stenosis. Echocardiography plays a critical role in the diagnosis of rheumatic mitral stenosis and the assessment of suitability for and guidance of percutaneous mitral valvuloplasty.

Evolution of secondary mitral regurgitation.

Aims: Secondary mitral regurgitation (MR) drives adverse remodelling towards late heart failure stages. Little is known about the evolution of MR under guideline-directed therapy (GDT) and its relation to cardiac remodelling and outcome. We therefore aimed to assess incidence, impact, and predictors of progressive secondary MR in patients under GDT. Methods and results: We prospectively enrolled 249 patients with chronic heart failure and reduced ejection fraction receiving GDT in this long-term observational study. Of patients with non-severe MR at baseline 81% remained stable whereas 19% had progressive MR. Those patients were more symptomatic (P < 0.001), had higher neurohumoral activation (encompassing various neurohumoral pathways in heart failure, all P < 0.05), larger left atrial size (P = 0.004) and more tricuspid regurgitation (TR, P = 0.02). During a median follow-up of 61 months (IQR 50-72), 61 patients died. Progression of MR conveyed an increased risk of mortality-univariately (HR 2.33; 95% CI 1.34-4.08; P = 0.003), that persisted after multivariate adjustment using a bootstrap-selected confounder model (adjusted HR 2.48; 95% CI 1.40-4.39; P = 0.002). In contrast, regression of MR was not associated with a beneficiary effect on outcome (crude HR 0.84; 95% CI 0.30-2.30; P = 0.73). Conclusions: Every fifth patient with chronic heart failure suffers from MR progression. This entity is associated with a more than two-fold increased risk of death even after careful multivariable adjustment. Symptomatic status, left atrial size, TR, and neurohumoral pathways help to identify patients at risk for progressive secondary MR in an early disease process and open the possibility for closer follow-up and timely intervention.