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Hemodynamic Profiles and Clinical Response to Transcatheter Mitral RepairFree Access

Focus on Mitral Valve Repair

J Am Coll Cardiol Intv, 15 (17) 1697–1707
Sections

Central Illustration

Abstract

Background

Prediction of the clinical response to transcatheter edge-to-edge repair (TEER) remains a vexing challenge.

Objectives

This study sought to examine the relation between hemodynamic profiles and outcomes following mitral TEER.

Methods

Among 378 patients (median age 82 years; 43.9% women), 3 hemodynamic profiles using residual left atrial pressure (LAP) and mitral regurgitation (MR) were defined: type I (optimal), grade ≤1 MR and mean LAP (mLAP) ≤15 mm Hg; type II (mixed), MR grade >1 or mLAP >15 mm Hg; and type III (poor), MR grade >1 and mLAP >15 mm Hg. The discrimination of these profiles for predicting outcomes was examined. A positive clinical response to TEER was defined as improvement in New York Heart Association functional class ≥I grade at 1 year without heart failure rehospitalization or death.

Results

There were 148 (39.0%) patients classified as optimal (type I), 187 (49.0%) patients as mixed (type II), and 43 (11.0%) patients as poor (type III). For all-cause mortality, survival at 1 year was 91.6%, 82.6%, and 67.9% for types I, II, and III, respectively (HR: 2.13; 95% CI: 1.44-3.15; P < 0.001). For the composite endpoint of all-cause mortality and rehospitalization for heart failure, event-free survival at 1 year was 84.1%, 70.7%, and 53.2% for types I, II, and III, respectively (HR: 1.93; 95% CI: 1.41-2.65; P < 0.001). Hemodynamic profiling was strongly associated with a positive response to TEER, occurring in 73.9%, 57.0%, 35.0%, for types I, II, and III, respectively (P < 0.001).

Conclusions

In patients undergoing mitral TEER, hemodynamic profiling is prognostic, with superior survival occurring among patients with optimal reduction in MR and normal postprocedural LAP.

Introduction

Transcatheter edge-to-edge repair (TEER) with the MitraClip system (Abbott Structural) is an established therapy, with guideline indications for both primary and secondary mitral regurgitation (MR).1-4 Nevertheless, continued insight into the best responders to the therapy is needed.5 In some studies, the degree of residual MR after TEER has been associated with long-term survival, but measurement of left atrial pressure (LAP) has been proposed as a better reflection of the hemodynamic burden in these patients.6 Assessment of LAP may help to account for variations in left atrial and ventricular compliance, as well as the severity of the preprocedural and subsequent iatrogenic mitral stenosis. Nevertheless, there is a paucity of data on the prognostic significance for the measurement of LAP in the context of residual MR for patients undergoing TEER.

Accordingly, we undertook this investigation to examine the clinical utility of LAP assessment in patients undergoing mitral TEER. We compared hemodynamic profiles according to postprocedural LAP and residual MR for the prediction of survival, in an effort to gain insight into the clinical impact of these parameters that could be addressable during TEER procedures. Furthermore, an analysis was performed to examine the relation of these hemodynamic profiles to clinical response to therapy.

Methods

Study population

All patients with symptomatic, moderately severe or severe MR who underwent TEER using the MitraClip system at Abbott Northwestern Hospital (Minneapolis, Minnesota, USA) between October 1, 2013, and December 31, 2020, were considered for this study. The indication for the procedure was symptomatic primary MR and high or prohibitive surgical risk, or symptomatic secondary MR refractory to guideline-directed medical therapy, as determined by a comprehensive heart team evaluation. Patients with missing periprocedural LAP or aborted MitraClip implantation were excluded. All TEER with MitraClip procedures were performed under general anesthesia with transesophageal echocardiography and fluoroscopic guidance as described previously.1-3

In accordance with state statutory requirements, all patients provided consent for use of their medical record for the present study. All study procedures were conducted in accordance with the Declaration of Helsinki. The present investigation was approved by the Allina Institutional Review Board.

Invasive hemodynamics

LAP measurements were performed using an 8-F transseptal sheath at baseline prior to insertion of the clip delivery system. Following completion of the final MitraClip implantation, LAP measurement was repeated via the steerable guide catheter. For all LAP measurements, digital acquisitions of 10-second intervals were performed with standard tidal volumes, without intravenous fluid apart from that used for medication administration, without vasoactive medications, and under normotensive state (ie, systolic blood pressure between 100 and 130 mm Hg) under general anesthesia for offline review. Mean LAP (mLAP), the peak V-wave, and the changes in these variables were defined using standard definitions.7

Echocardiographic assessment

All patients underwent comprehensive imaging with baseline transthoracic echocardiography (TTE), intraprocedural transesophageal echocardiography, and TTE on postoperative day 1. Echocardiography was performed by experienced specialists with severity of MR assessed using a 4-grade classification (ie, grade 1, mild or none; grade 2, moderate; grade 3, moderate to severe; grade 4, severe) for all studies.8 This grading scheme was chosen based on commercial indications for MitraClip, which requires the presence of grade 3 or 4 MR.

Clinical evaluation

The electronic medical record was reviewed in its entirety with manual abstraction for patient demographics, symptoms, morbidity, and adverse events. Symptom severity was classified with New York Heart Association (NYHA) functional class. Major adverse events noted were death due to any cause, cardiac death, stroke or transient ischemic attack, myocardial infarction, bleeding, mitral valve surgery, and heart failure rehospitalization using standard definitions.9

Data analysis

Patients were placed into 3 hemodynamic profiles according to the presence of normal mLAP immediately after the procedure and optimal MR reduction evident on the TTE performed on postprocedural day 1 (ie, grade ≤1 residual MR) after MitraClip therapy10: type I (optimal), grade ≤1 residual MR and postprocedural mLAP ≤15 mm Hg; type II (mixed), residual MR grade >1 or postprocedural mLAP >15 mm Hg; and type III (poor), residual MR grade >1 and postprocedural mLAP >15 mm Hg. A cutoff of 15 mm Hg was used, as this value is the threshold for diastolic dysfunction or precapillary pulmonary hypertension as previously defined.11 The primary endpoints of interest were survival free of all-cause mortality, and the composite endpoint of survival free of all-cause mortality and rehospitalization for heart failure at 1-year follow-up. A positive clinical response to TEER was defined as survival free of all-cause mortality at 1 year, with an increase in NYHA functional class ≥I, and no heart failure hospitalization. Continuous variables were described as median (IQR) and compared using Mann-Whitney U test or Kruskal-Wallis test. The Kaplan-Meier method was used to calculate survival estimates for the endpoints, with comparisons performed using the log-rank test. Cox proportional hazards models were used to estimate the association between the risk of the endpoints and the hemodynamic profiles. A multivariable logistic regression analysis was performed to examine clinical predictors of all-cause death. A P value of <0.05 was considered a priori to be statistically significant. All statistical analyses were performed with SPSS version 27 (IBM Corporation).

Results

Study patients

The present study examined 378 patients who underwent TEER with MitraClip for symptomatic MR (Table 1). Patients were elderly (median age 82 years [IQR: 77-87 years]; 43.9% women), and frequently had significant cardiovascular morbidity, with 349 (92.3%) patients having severe symptoms (NYHA functional class III or IV). Median duration of follow-up was 365 days (IQR: 332-365 days). In accordance with the predominant clinical indication for TEER during the study period, the most common etiology of MR was primary (83.1% of patients), with a median left ventricular ejection fraction of 58.0% (IQR: 50.0%-63.0%) for the entire patient population. Among patients with a mixed hemodynamic profile (type II), the overwhelming majority (n = 163 patients, or 87.2%) had abnormal LAP (ie, mLAP >15 mm Hg) and mild or no residual MR. The remaining 24 (12.8%) type II patients had residual MR grade >1. For group comparisons, patients with a poor hemodynamic profile (type III) tended to have greater morbidity, with a higher prevalence of atrial fibrillation, renal insufficiency, diabetes mellitus, secondary MR, and moderate or severe tricuspid regurgitation (Table 1).

Table 1 Baseline Clinical and Echocardiographic Characteristics According to Hemodynamic Profile

Type I (Optimal): Residual MR ≤1 and mLAP ≤15 mm Hg (n = 148)Type II (Mixed): Residual MR >1 or mLAP >15 mm Hg (n = 187)Type III (Poor): Residual MR >1 and mLAP >15 mm Hg (n = 43)P Value
Age, y82 (78-87)82 (75-86)81 (74-86)0.37
Women63 (42.6)85 (45.5)18 (41.9)0.84
Body mass index, kg/m225.3 (22.1-28.8)26.5 (23.9-31.1)25.4 (22.5-29.8)0.007
NYHA functional class III or IV136 (91.9)171 (91.4)42 (97.7)0.37
Atrial fibrillation or flutter83 (56.1)128 (68.4)32 (74.4)0.02
Hypertension106 (71.6)143 (76.5)32 (74.4)0.60
Diabetes mellitus17 (11.5)51 (27.3)11 (25.6)0.001
Coronary artery disease65 (43.9)86 (46.0)19 (44.2)0.93
Prior myocardial infarction24 (16.2)22 (11.8)7 (16.3)0.30
Prior PCI44 (29.7)42 (22.5)10 (23.3)0.30
Prior CABG26 (17.6)50 (26.7)5 (11.6)0.032
Prior valve surgery24 (16.2)41 (21.9)10 (23.3)0.36
Pacemaker/ICD implantation27 (18.2)49 (26.2)8 (18.6)0.18
COPD28 (18.9)41 (21.9)8 (18.6)0.76
Creatinine, mg/dL1.05 (0.83-1.29)1.19 (0.95-1.47)1.26 (1.01-1.56)<0.0001
Hemoglobin, g/dL12.8 (11.9-13.7)12.4 (10.8-13.7)11.9 (10.5-13.7)0.07
Primary MR131 (88.5)149 (79.7)34 (79.1)0.08
LVEF, %60.0 (54.9-63.0)57.0 (45.0-63.0)57.0 (47.0-67.0)0.05
Left ventricular end-systolic dimension, cm5.0 (4.4-5.7)5.0 (4.5-5.7)5.6 (4.9-5.9)0.03
Mitral valve area, cm23.9 (3.6-4.5)4.0 (3.6-4.5)4.2 (3.8-4.6)0.46
Left atrial volume index, mL/m258.0 (47.0-75.0)61.5 (46.0-75.3)64.0 (51.0-98.8)0.11
Moderate or more AS7 (4.7)10 (5.3)2 (4.7)0.96
Moderate or more AR8 (5.4)7 (3.4)2 (4.7)0.77
Moderate or more TR46 (31.1)98 (52.4)28 (65.1)<0.0001
STS-PROM for mitral valve repair, %3.6 (2.2-6.0)4.6 (2.8-7.3)4.9 (2.9-7.5)0.01
Medical therapy
 ACE inhibitor or ARB70 (47.3)72 (38.5)15 (34.9)0.17
 Beta-receptor antagonist88 (59.5)120 (64.2)30 (69.8)0.42
 Diuretics88 (59.5)130 (69.5)33 (76.7)0.05

Values are median (IQR) or n (%). P values by Kruskal-Wallis analysis.

ACE = angiotensin-converting enzyme; AR = aortic regurgitation; ARB = angiotensin receptor blocker; AS = aortic stenosis; CABG = coronary artery bypass grafting; COPD = chronic obstructive pulmonary disease; ICD = implantable cardioverter-defibrillator; LVEF = left ventricular ejection fraction; mLAP = mean left atrial pressure; MR = mitral regurgitation; NYHA = New York Heart Association; PCI = percutaneous coronary intervention; STS-PROM = Society of Thoracic Surgeons Predicted Risk of Mortality; TR = tricuspid regurgitation.

For all patients with normal LAP (n = 120), the etiology of MR was primary in 99 (82.5%) patients and left ventricular ejection fraction was ≥60.0% in 60 (50.0%) patients; 34.2% of the patients with mLAP >15 mm Hg had no evidence of moderate or severe valvular heart disease besides MR. Among all patients with elevated mLAP (n = 257), the etiology of MR was primary in 214 (83.3%) patients and left ventricular ejection fraction was ≥60.0% in 107 (41.6%) patients; 41.2% of the patients with mLAP >15 mm Hg had no evidence of moderate or severe valvular heart disease besides MR.

Invasive hemodynamic data

Overall, grouping by the study definitions led to different levels of mLAP and LAP V-wave, with mixed hemodynamic profile patients (type II) having intermediate values (Table 2). Among the 3 groups, the degrees of change in mLAP and LAP V-wave due to the MitraClip procedures did not differ. Overall, the median values postprocedure of mLAP were 11.5 mm Hg (IQR: 9.0-14.0 mm Hg), 19.0 mm Hg (IQR: 16.0-22.0 mm Hg), and 22.0 mm Hg (IQR: 18.0-25.0 mm Hg) for type I, II, and III patients, respectively. Type II and III patients had higher postprocedural mean mitral gradients in comparison with type I patients (P < 0.001).

Table 2 Hemodynamic Findings for the 3 Profiles

Type I (Optimal): Residual MR ≤1 and mLAP ≤15 mm Hg (n = 148)Type II (Mixed): Residual MR >1 or mLAP >15 mm Hg (n = 187)Type III (Poor): Residual MR >1 and mLAP >15 mm Hg (n = 43)P Value
Baseline mLAP, mm Hg15.0 (12.0 to 19.0)22.0 (17.0 to 27.0)25.0 (19.0 to 29.0)<0.001
Baseline LAP V-wave, mm Hg24.0 (18.0 to 36.0)36.0 (24.0 to 45.0)46.0 (32.0 to 59.0)<0.001
Postprocedural mLAP, mm Hg11.5 (9.0 to 14.0)19.0 (16.0 to 22.0)22.0 (18.0 to 25.0)<0.001
Postprocedural LAP V-wave, mm Hg17.0 (14.0 to 20.0)28.0 (22.0 to 33.0)35.0 (27.0 to 44.0)<0.001
mLAP, mm Hg4.0 (0.0 to 7.0)3.0 (-2.0 to 7.0)2.0 (-2.0 to 7.0)0.13
LAP V-wave, mm Hg7.0 (2.0 to 19.0)8.0 (-1.0 to 15.0)7.0 (-1.0 to 23.0)0.53
Postprocedural mean mitral gradient, mm Hg3.0 (2.0 to 4.6)4.0 (3.0 to 5.0)4.0 (3.0 to 5.0)<0.001

Values are median (IQR). P values by Kruskal-Wallis analysis.

LAP = left atrial pressure; other abbreviations as in Table 1.

Clinical events and survival

All-cause mortality and cardiac death, measured at 30 days and at 1 year after MitraClip implantation, was lowest for patients with optimal hemodynamic profiles (type I). The 1-year survival free of all-cause mortality was 91.6%, 82.6%, and 67.9% for optimal (type I), mixed (type II), and poor hemodynamic profiles (type III), respectively (HR: 2.13; 95% CI: 1.44-3.15; P < 0.001) (Figure 1). Similar trends were seen with cardiac mortality (Supplemental Figure 1). For the composite endpoint of death and heart failure rehospitalization, the 1-year survival was 84.1%, 70.5%, and 53.2% for type I, II, and III patients, respectively (HR: 1.93; 95% CI: 1.41-2.65; P < 0.001) (Figure 2). Among survivors, patients with an optimal hemodynamic profile also had the highest rates of being free of severe symptoms (78.8% with NYHA functional class I or II) at 1 year and the highest rates of a positive clinical response to TEER (Figure 3). Among those with optimal (type I), mixed (type II), and poor (type III) hemodynamic profiles, a positive clinical response to TEER occurred in 73.9%, 57.0%, and 35.0%, respectively (P < 0.001). Overall, there were no differences in occurrence of other adverse events, including mitral surgery, myocardial infarction, bleeding, and stroke either at 30 days or at 1 year among the patient groups (Table 3). Of note, the differences in survival according to mLAP remained when restricting the analyses to those patients with mild or no residual MR after MitraClip implantation; among these patients, the 1-year survival was 91.6%, 85.5%, and 80.0% for type I, II, and III patients, respectively (HR: 1.60; 95% CI: 1.08-2.37; P = 0.02) (Figure 4).

Figure 1
Figure 1

Hemodynamic Profile and Survival Free of All-Cause Mortality in Patients Undergoing Transcatheter Edge-to-Edge Repair (N = 378)

Patients were classified according to residual mitral regurgitation (MR) and postprocedural mean left atrial pressure (mLAP). Survival was greatest for patients with an optimal hemodynamic profile following transcatheter edge-to-edge repair.

Figure 2
Figure 2

Hemodynamic Profile and Survival Free of All-Cause Mortality and Rehospitalization for Heart Failure in Patients Undergoing Transcatheter Edge-to-Edge Repair (N = 378)

Patients were classified according to residual MR and postprocedural mLAP. Survival was greatest for patients with an optimal hemodynamic profile following transcatheter edge-to-edge repair. Abbreviations as in Figure 1.

Figure 3
Figure 3

Hemodynamic Profiles and Clinical Response to Transcatheter Edge-to-Edge Repair

Each chart shows the frequency of positive clinical responses to transcatheter edge-to-edge repair evident at 1-year follow-up. (A) All patients; (B) patients grouped according to hemodynamic profile. NYHA = New York Heart Association.

Table 3 Major Adverse Cardiac Events in Follow-Up According to Hemodynamic Profile

Type I (Optimal): Residual MR ≤1 and mLAP ≤15 mm Hg (n = 148)Type II (Mixed): Residual MR >1 or mLAP >15 mm Hg (n = 187)Type III (Poor): Residual MR >1 and mLAP >15 mm Hg (n = 43)P Value
1-mo events
 All-cause death1 (0.7)4 (2.1)4 (9.3)0.05
 Cardiac death1 (0.7)2 (1.1)1 (2.3)0.65
 Mitral surgery3 (2.0)1 (0.5)1 (2.3)0.41
 HF rehospitalization1 (0.7)5 (2.7)1 (2.3)0.26
 Myocardial infarction1 (0.7)1 (0.5)0 (0.0)0.87
 Stroke0 (0.0)4 (2.1)0 (0.0)0.13
 Bleeding3 (2.0)6 (3.2)2 (4.7)0.63
 NYHA functional class III or IV24 (16.2)35 (18.7)21 (48.8)<0.001
 Death, HF hospitalization, or NYHA functional class III or IV24 (16.2)39 (20.9)23 (53.5)<0.001
1-y events
 All-cause death12 (8.1)30 (16.0)13 (30.2)0.001
 Cardiac death5 (3.4)15 (8.0)5 (11.6)0.09
 Mitral surgery8 (5.4)15 (8.0)7 (16.3)0.07
 HF rehospitalization12 (8.1)26 (13.9)6 (14.0)0.23
 Myocardial infarction3 (2.0)2 (1.1)1 (2.3)0.72
 Stroke2 (1.4)9 (4.8)2 (4.7)0.20
 NYHA functional class III or IV18 (12.2)40 (21.2)15 (34.9)<0.001
 Death, HF hospitalization, or NYHA functional class III or IV33 (22.3)70 (37.4)27 (62.8)<0.001

Values are n (%). P values by Kruskal-Wallis analysis.

HF = heart failure; other abbreviations as in Table 1.

Figure 4
Figure 4

Survival According to Postprocedural mLAP in Patients With Mild or No Residual MR After TEER (N = 311)

In analyses restricted to patients with mild or no residual MR, survival free of all-cause mortality was greatest among patients with lowest mLAP. Abbreviations as in Figure 1.

Predictors of survival

Table 4 shows variables associated with survival free of all-cause mortality at 1 year. Hemodynamic profiling according to the 3 classifications (ie, type I, II, and III) was a greater predictor of outcome than either residual MR or LAP alone. Hemodynamic profiles remained significantly associated with survival in multivariable analyses that accounted for age, morbidities, severity of tricuspid regurgitation, etiology of MR, left ventricular ejection fraction, and postprocedural mitral gradient.

Table 4 Predictors of All-Cause Mortality in 1 Year

Univariable ResultsMultivariable Results
OR95% CIP ValueOR95% CIP Value
Age (per 1 y)1.000.97-1.040.83
Female0.830.46-1.480.53
Moderate or severe TR2.381.31-4.300.042.021.09-3.760.03
LVEF (per 1%)0.970.95-0.990.009
Primary MR0.430.22-0.820.01
Baseline mLAP (per 1 mm Hg)1.030.97-1.070.08
Baseline LAP V-wave (per 1 mm Hg)1.021.00-1.030.11
Baseline mitral valve area (per 1 cm2)1.120.79-1.600.53
Postprocedural mLAP (per 1 mm Hg)1.061.01-1.110.01
Postprocedural LAP V-wave (per 1 mm Hg)1.041.02-1.070.003
 In mLAP (per 1 mm Hg)1.000.95-1.040.82
 In LAP V-wave (per 1 mm Hg)1.000.98-1.020.70
Postprocedural mean mitral gradient (per 1 mm Hg)1.000.96-1.060.76
Residual MR grade (per 1 grade)1.851.22-2.800.04
Hemodynamic profile (per increasing type)2.211.43-3.44<0.0011.921.21-3.050.006

Postprocedural mLAP and residual MR were not used in multivariable analysis due to significant collinearity with mLAP and the residual MR group.

Abbreviations as in Tables 1 and 2.

Discussion

The present investigation examined the clinical utility of LAP assessment in a cohort of 378 patients who underwent TEER with MitraClip. In this study, patients predominantly had primary MR and were classified according to postprocedural LAP and MR into 3 hemodynamic profiles (ie, optimal, mixed, or poor) (Central Illustration). We observed superior survival and clinical outcomes among patients with an optimal hemodynamic profile, consisting of normal postprocedural LAP (ie, mLAP <15 mm Hg) and mild or no residual MR after TEER. Hemodynamic profiling was strongly predictive of a positive clinical response to TEER at 1-year follow-up and remained predictive in multivariable analyses that adjusted for age, morbidities, and left ventricular function, and was a stronger predictor than residual MR alone. Moreover, in analyses restricted to patients with mild or no residual MR, LAP assessment was prognostic for survival free of all-cause mortality after the procedure. Taken together, these findings suggest that assessment of LAP should be performed routinely in conjunction with residual MR in patients with undergoing mitral TEER.

Central Illustration
Central Illustration

Hemodynamic Profile and Clinical Response to TEER

(Top) Patients were placed into 3 hemodynamic profiles. (Middle) Hemodynamic profile was associated with clinical response. (Bottom) Survival was greater with an optimal hemodynamic profile with transcatheter edge-to-edge repair (TEER). mLAP = mean left atrial pressure; MR = mitral regurgitation; NYHA = New York Heart Association.

TEER with the MitraClip is an established therapy for selected patients with MR, and, in some studies, has been associated with improved survival.12 A primary aim of the therapy is to reduce or eliminate MR, which occurs in the majority of patients with a low risk of adverse events.13 Nevertheless, the degree of residual MR after TEER may not completely mirror hemodynamic burden in these patients, owing to variations in atrial and ventricular compliance, as well as to potential iatrogenic mitral stenosis. Moreover, patients with poor chamber compliance theoretically might be more susceptible to LAP elevation with relatively lesser degrees of residual MR.

The assessment of LAP has been found to be prognostic in various cardiovascular disease states.6 As a measure of ventricular preload, assessment of residual MR can be subjected to relative pressure differences between the left atrium and left ventricle, while LAP is an absolute variable that reflects a common pathway for multiple etiologies of heart failure. Certainly, residual MR and LAP can correlate. In our study, 39.0% (n = 148) had normal LAP with mild or residual MR, while 11.0% (n = 43) had moderate or severe residual MR with elevated LAP.

However, it is notable that such hemodynamic concordance was observed in only 50.0% of the patients in our study. Approximately one-half of the patients (49.0%, or n = 187) had discordant LAP and residual MR, which may be considered a mixed hemodynamic profile (type II). The survival of the patients with a mixed hemodynamic profile was significantly impaired compared with those with optimal hemodynamics, with an absolute difference of 9.0% between these 2 groups for 1-year mortality. For the rates of death, heart failure rehospitalization, and severe symptoms at 1 year, the absolute difference between type I and II hemodynamic profiles was 15.1% (ie, 22.3% vs 37.4%) (Table 3). Overall, in comparison with those with an optimal hemodynamic profiles (ie, type I), patients with elevations in LAP or more than mild residual MR had a 2- to 4-fold increase in mortality at 1 year. Our findings are particularly notable in light of recent studies that have highlighted the need to identify responders to TEER therapy.5

Study limitations

By examining patients with discordant or mixed hemodynamic profile, our findings extend prior reports on mitral TEER that have focused on LAP alone. Similar to prior reports, baseline LAP elevation and type of MR was related to outcome, though we found that integration of LAP with MR may be helpful to recognize load abnormalities not related to MR reduction that could affect survival. Of note, we utilized a cutoff value of LAP ≥15 mm Hg to define abnormal, which is lower than used in prior reports. This value reflects the accepted definition of diastolic heart failure or precapillary pulmonary hypertension, and its relatively lower value would be expected to increase the sensitivity for detecting abnormalities. An important limitation of our paper is that, while LAP elevation was prognostic even when MR reduction occurred, we do not have mechanistic insights for such elevation.

Our findings may have implications for intraprocedural management. Persistent elevation of LAP may raise inquiry into the need for further optimization of MR reduction with TEER. While we used postprocedural TTE for assessment in this study, it is known that MR severity can be affected by general anesthesia that is widely used to facilitate TEER, and therefore can be underestimated in procedure settings.14 Elevations in LAP can also be related to acute iatrogenic mitral stenosis. Our patients with either mixed or poor hemodynamic profiles had relatively higher mitral gradients, which have been found to be prognostic in other TEER studies.15,16 For TEER procedures, careful intraprocedural consideration of reduction in MR vs causing mitral stenosis is essential.

When examining only patients with mild or no residual MR (n = 311), LAP was related to survival, with an absolute increase of 8.3% in 1-year mortality for patients with mLAP >15 mm Hg in comparison with those with normal LAP (log-rank test, P = 0.03). Certainly, LAP elevation may arise from chamber compliance abnormalities that may not be addressable with TEER.17 The findings do support the notion for improved medical therapy for heart failure and address concomitant lesions that can be overlooked in these patients.18 Notably, in comparisons according to LAP, there were similarities with regard to prevalence of primary MR, while left ventricular ejection fraction was 60.0% in 50.0% of patients with normal LAP, and 42.0% in those with abnormal LAP. Thus, the differences in survival according to LAP were not likely related abnormalities in left ventricular dysfunction and concomitant valvular disease. Many of our patients had evidence of chronic heart failure and preserved left ventricular ejection, and further investigation into their appropriate medical management is needed. Such improvement should be considered in order to achieve patient success with TEER.9

Conclusions

Among patients undergoing mitral TEER, an optimal hemodynamic profile with normal mLAP and mild or no residual MR is associated with superior survival with regard to all-cause mortality, heart failure rehospitalization, and severe symptoms. These findings may have implications for procedural management as well as for medical therapy for associated chronic heart failure.

Perspectives

WHAT IS KNOWN? Despite clinical benefit of mitral TEER in patients with MR, predictors of long-term survival remain a significant concern.

WHAT IS NEW? Hemodynamic profiling according to both LAP and MR after TEER predicts 1-year survival, with the best outcomes occurring among patients with normalization of LAP and optimal MR reduction after TEER. Patients with mixed hemodynamic profiles (eg, elevated LAP and mild or no residual MR; normal LAP and grade 3 or 4 MR) or those with concomitantly poor residual lesions (ie, high LAP and grade 3 or 4 MR) had a relatively poorer prognosis.

WHAT IS NEXT? Mechanistic insights into residual LAP elevation despite optimal MR reduction in patients with mitral TEER is needed.

Funding Support and Author Disclosures

Dr Cavalcante has received consulting fees from Boston Scientific and Abbott Vascular; has received research grant support from Circle Cardiovascular Imaging, Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott Vascular; and has been a speaker for Medtronic, Circle Cardiovascular Imaging, and Siemens Healthineers. Dr Bae has received consulting fees from Abbott Vascular. Dr Enriquez-Sarano has received consulting fees from Cryolife, Edwards Lifesciences, Highlife, and CHemImage. Dr Bapat has received consulting fees from Abbott Structural, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr Gössl has received consulting fees from Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Abbreviations and Acronyms

LAP

left atrial pressure

mLAP

mean left atrial pressure

MR

mitral regurgitation

NYHA

New York Heart Association

TEER

transcatheter edge-to-edge repair

TTE

transthoracic echocardiography

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Footnotes

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