This article covers the initial experience of transcatheter edge-to-edge mitral valve repair with the PASCAL system in the Iberian Peninsula (Spain and Portugal). This was a multicenter study collecting individual data from an unselected all-comer population from 10 hospitals with initial access to the PASCAL and PASCAL Ace systems for the treatment of severe symptomatic MR from October 2019 to September 2021.

Demographics, baseline and procedural characteristic and clinical/echocardiographic outcomes at follow-up were prospectively collected in a dedicated, shared database at each participating center. All procedures were performed under general anesthesia and guided by transesophageal echocardiogram (TEE) and fluoroscopy. Periprocedural complications were noted during the index hospitalization. The study was conducted in accordance with the institutional ethics committee of each participating center, and all patients provided signed informed consent for the procedure.

Standardized definitions of all patient-related variables, clinical diagnoses, and in-hospital complications and outcomes were based on the Mitral Valve Academic Research Consortium criteria unless indicated otherwise.13 MR was assessed using standard 2-dimensional color Doppler methods and were graded using a 4-class grading scheme: mild, moderate, moderate-severe, and severe.

The primary efficacy endpoints were technical success (device successfully deployed as intended, delivery system successfully retrieved without procedural mortality or need for surgery or reintervention) and severity of MR at discharge in the treated population.

The main safety endpoint was freedom from major adverse events (MAE) at 30 days, including all-cause mortality, cardiac tamponade, emergent surgery, vascular complications, severe bleeding (major, extensive, life-threatening, or fatal bleeding), stroke, and myocardial infarction.

Secondary endpoints included the severity of MR at discharge on an on-treatment basis (at least 1 PASCAL device implanted, alive and without reintervention), device success (at 30 days, defined as successful device implantation, MR≤2+, mean gradient <5mmHg and freedom from mortality, stroke, unplanned surgical or interventional procedures, and device failure), clinical success (as defined in the CLASP14 approval trial as successful device implantation, MR≤2+, and freedom from mortality, stroke, unplanned surgical or interventional procedures, and device failure at 30 days), reintervention, and change in clinical evaluation of New York Heart Association (NYHA) functional class during follow-up.

Results are presented as mean±standard deviation for continuous normally distributed variables, median [interquartile range] for continuous nonnormally distributed data, and as number (percentages) for categorical data. Analysis of normality was performed with the Kolmogorov-Smirnov and Shapiro-Wilks test. Categorical data and proportions were compared using the chi-square or Fisher exact test. Comparisons of continuous variables were analyzed using the unpaired t-test and the Mann-Whitney U-test as appropriate. The McNemar paired-test and Wilcoxon matched-pairs signed-rank test were used to compare differences resulting from treatment as appropriate. An alpha error level of .05 was established and Stata 12.1 software (College Station, United States) was used for all analyses.

A total of 68 patients (median age 75 years, 62% men) with symptomatic MR underwent transcatheter mitral valve repair between October 2019 and November 2021. Baseline characteristics and center distribution are summarized in table 1 and figure 1. Patients were considered at high surgical risk, expressed by a mean EuroSCORE II of 4.5% and a relevant burden of comorbidities: 44% of patients had concomitant coronary artery disease, 13% had undergone surgical revascularization, and 7% had previous valve intervention. The prevalence of atrial fibrillation (59%) and chronic renal failure (32%) was high, most patients (71%) were in NYHA functional class III or IV and 38 patients (56%) had had a previous heart failure hospitalization in the last year.

Figure 1.

Distribution of cases performed by centers.

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Baseline echocardiographic parameters are shown in table 2. Most patients (96%) had moderate to severe (3+) or severe (4+) MR at baseline. MR etiology was classified as functional in 44 patients (65%), degenerative in 17 patients (25%), and mixed in the remaining 7 patients (10%). Median left ventricular ejection fraction was 43% and effective regurgitant orifice area 0.38 [0.30-0.49] cm2. Optimal guideline-directed medical therapy in secondary MR was achieved in a high number of patients: 84% of patients were treated with beta-blockers, 98% with angiotensin inhibition (angiotensin converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor-neprilysin inhibitors, [ACE-I/ARB/ARNI:]), and 18% were treated with cardiac resynchronization therapy (CRT).

Procedural outcomes are summarized in table 3. One PASCAL device was implanted in 52 patients (76%) and 2 devices in 16 patients (24%). Overall, technical success was achieved in 65 patients (96%). The procedure was aborted without PASCAL implantation in 3 patients (4%). One patient with a short posterior leaflet had a tear with severe MR and underwent surgical repair. The second patient had leaflet tip calcification precluding appropriate PASCAL closure; the device was removed and a MitraClip was subsequently implanted. The third patient had worsening MR after leaflet clasping due to mitral valve distortion and the device was ultimately not released. Independent clasp optimization was applied in 47 patients (73%). Median procedural time was 121 [IQR: 83-168] minutes. There were no cases of intraprocedural single leaflet device attachment. Median length of stay after the procedure was 2 IQR: 1-3] days. There were no in-hospital deaths. In the treated population, residual MR at discharge was≤2+ in 100% of the patients and≤1+ in 77%. The mean transmitral gradient increased from 1.7mmHg at baseline to 2.7mmHg at discharge (P = .0001). Transmitral gradient was significantly lower in patients treated with a single device than in those requiring 2 devices (2.4 vs 3.5mmHg, P=.0037). A mean gradient≥5mmHg was observed in 10% of patients (n=6) and was not related to the number of devices (3 patients treated with 1 device, P=.27) nor to the type of device (4 patients treated with PASCAL, 1 treated with ACE, and 1 treated with both devices, P=.10).

Thirty-day survival status was available in all patients (median follow-up time 223 [IQR: 105-439] days). Clinical success was achieved in 86.7% (59 of 68 patients). The primary safety endpoint, defined as a freedom from composite MAE rate at 30 days, occurred in 64 of 68 patients (94%). One patient died from cardiovascular causes due to sudden death at 30 days and another patient died from cardiovascular causes at 12 months of follow-up. The Kaplan-Meier survival curve of freedom from mortality is shown in figure 2. In-hospital stroke occurred in 2 patients and 1 patient had surgical conversion due to leaflet tear. At 30 days, 96% of patients were in NYHA class I or II and 95% of patients had MR≤2+, with significant clinical and echocardiographic improvement from baseline (P=.001, figure 3).

Figure 2.

Kaplan-Meier curve for survival and cardiovascular hospitalization. CV, cardiovascular.

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Figure 3.

Central Illustration. Iberian experience with PASCAL for transcatheter mitral regurgitation repair. Baseline characteristics, procedural results, and follow-up. ACE-I/ARB/ARNI, angiotensin converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor-neprilysin inhibitors; CRT, cardiac resynchronization therapy; MAE, major adverse events; MR, mitral regurgitation; NYHA, New York Heart Association; SLDA, single leaflet device attachment.

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At 12 months, 5 patients were hospitalized for cardiovascular causes with a Kaplan-Meier curve for survival and cardiovascular hospitalization of 13.85% (figure 2).

Since our first publication, the learning curve achieved with MitraClip in terms of patient selection and increased procedural experience may have strongly impacted on the positive results obtained with PASCAL in the present study. Indeed, patient selection has changed after the COAPT and Mitra-FR trials, which showed that patients with severe secondary MR with EROA> 0.3cm2 and LVESD <70mm under optimal medical treatment were more likely to benefit from TEER. Our data confirm these findings, with a median EROA value of 0.39cm2 [IQR: 0.32-0.50cm2], a mean LVESD of 50mm and optimal guideline-directed medical therapy: 84% patients with beta-blockers, 98% with ACE-I/ARB/ARNI, and 18% with cardiac resynchronization therapy.

In addition, increased procedural skills over time have led to a significant reduction in transseptal puncture-related complications (0% vs 3% in our initial experience with MitraClip), as well as a lower ratio of devices required per patient (≥ 2 devices required in 39% in MitraClip early-generation vs 24% in the present study).

The present study was observational in nature. Because the study was designed as a registry, all echocardiographic and clinical data were site reported and lacked independent adjudication by a core laboratory or an event committee. The absence of a randomized control group limits conclusions and the results for efficacy and safety should be regarded in the context of the early phase of the learning curve with a new device.