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Comparative study of postoperative functional mitral stenosis avoidance rate using flexible valvular band or semi-rigid valvular band in mitral annuloplasty for asymptomatic mitral regurgitation (FLEXMAP)

Comparative study of postoperative functional mitral stenosis avoidance rate using flexible valvular band or semi-rigid valvular band in mitral annuloplasty for asymptomatic mitral regurgitation (FLEXMAP)

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A total of 24 patients with severe mitral regurgitation were enrolled. All had preserved cardiac function and sinus rhythm, forming a homogeneous cohort without serious cardiovascular comorbidities. Eleven patients received a flexible band and 13 received a semirigid band. The median age was 59.5 years, and 75 percent were male. Mean left ventricular ejection fraction was 67.6 plus or minus 3.9 percent, left ventricular end diastolic diameter 51.5 plus or minus 5.5 millimeters, and left atrial diameter 42.9 plus or minus 5.4millimeters. Minimally invasive surgery was performed in 75 percent of cases, artificial chordae in 70.8 percent, leaflet resection in 16.7 percent, and a combination in 12.5 percent. Mean band size was 31.7 plus or minus 2.68 millimeters, with no relevant difference between groups

The Safety Analysis Set consisted of all participants who initiated the protocol treatment. The Full Analysis Set consisted of all participants who received the protocol treatment and were not found to be ineligible after enrollment. A total of twenty four participants were enrolled, with eleven in the flexible band group and thirteen in the semirigid band group. All twenty four participants were included in both the Safety Analysis Set and the Full Analysis Set. The Per Protocol Set consisted of twenty three participants, excluding one participant in whom the assigned band was not used. This resulted in ten participants in the flexible band group and thirteen participants in the semi rigid band group for the Per Protocol Set.

Throughout the study period, in both groups there were no serious or non serious illnesses that required reporting to the CRB, regulatory authorities or the device manufacturer, meaning there were no serious adverse events for which a causal relationship with the investigational device could not be ruled out. One serious adverse event was observed, and it was judged that the causal relationship with the investigational device could be ruled out. The event was pericarditis. According to the study protocol, non serious adverse events for which a causal relationship with the investigational device could be ruled out were not collected. The pericarditis event was unrelated to the investigational device. The onset date was April 21 2024, the seriousness was hospitalization and the clinical severity was mild. The study subject was registered as KPU 12, a male who was 60 years old at the time of registration. He had been followed at another hospital since March 2016 for asymptomatic mitral regurgitation, which had been detected due to a heart murmur. Although left ventricular wall motion was preserved and the ejection fraction at the time was fifty nine percent, a gradual decline had been observed over time. Based on mitral regurgitation guidelines recommending early surgical intervention, he was referred for an initial consultation at Kyoto Prefectural University of Medicine Hospital on February 19 2024. Informed consent for participation in this study was obtained on March 25 2024 and the subject was registered on March 26 2024 in the flexible band group. At the time of registration he was a healthy and physically active adult who routinely engaged in mountain climbing and gym training. He had no past or concurrent medical conditions other than asymptomatic mitral regurgitation. On March 28 2024 he underwent mitral valve repair using a flexible band together with pulmonary vein isolation as the investigational treatment. The perioperative course was uneventful and there were no complications. Oral diuretics consisting of furosemide forty milligrams and spironolactone fifty milligrams, which had been initiated immediately after surgery, were discontinued soon after and he was discharged on April 11 2024 which corresponded to postoperative day fourteen. The early discontinuation of diuretics was considered appropriate given his good cardiac and renal function and high physical activity level.After discharge, the subject experienced no symptoms and returned to his normal daily life, resuming mountain climbing and gym training shortly thereafter. On April 21 2024 which corresponded to postoperative day twenty four he visited the hospital with a complaint of fatigue during stair climbing. On April 22 2024 his blood pressure was one hundred twenty two over sixty six millimeters of mercury and heart rate was seventy one beats per minute, indicating stable hemodynamics. Echocardiography revealed a moderate amount of pericardial effusion and postoperative pericarditis was diagnosed. From the time of discharge until the onset of pericarditis there had been no strong chest pain or dyspnea. Only mild fatigue was present and there was no impairment in daily activities.Regarding treatment options, both conservative therapy using oral medication and invasive therapy using pericardial drainage were considered appropriate. Because hemodynamics remained stable, conservative treatment alone would have been acceptable. However, because the patient was relatively young, strongly wished to resume training early, and the puncture risk was considered low, pericardial drainage was selected in order to prevent the development of cardiac tamponade. He was admitted to Kyoto Prefectural University of Medicine Hospital on April 22 2024 and the drainage procedure was performed on the same day. Follow up echocardiography on April 25 2024 confirmed that there was no recurrence of mitral regurgitation and no device related abnormalities such as detachment or deformation of the implanted band. Blood tests showed no evidence of infectious inflammation and there were no signs of infection in the pericardial fluid or at the surgical site. The patient condition improved and he was discharged on May 3 2024 with complete recovery. The cause of the pericarditis was assessed as a transient inflammatory response that can occasionally occur after cardiac surgery, often referred to as postpericardiotomy syndrome. In this case, the early discontinuation of diuretics and the relatively intense level of physical activity soon after discharge may have contributed to delayed resolution of pericardial effusion. Because imaging, laboratory findings and the clinical course did not suggest any structural or mechanical abnormality of the device, the event was determined to be unrelated to the investigational device. As the hemodynamic status was stable throughout and daily activities remained unimpaired, the severity was assessed as mild. The serious adverse event was therefore classified as unrelated and was recorded as such in the case report form.

The primary endpoint of this study was the proportion of patients whose mean pressure gradient across the mitral valve during exercise stress testing at six months after surgery was below ten millimeters of mercury. The achievement rate was seventy two point seven percent in the flexible band group and seventy six point nine percent in the semi-rigid band group, with no statistically significant difference. The mean pressure gradient during exercise at six months was seven point eight zero plus or minus two point two six millimeters of mercury in the flexible group and seven point eight five plus or minus three point one five millimeters of mercury in the semi-rigid group, also without a significant difference. These results indicate that there was no clear difference in the avoidance of elevated pressure gradient between the two band types at six months after surgery.In the analysis of secondary endpoints, the intraoperative mean pressure gradient measured by transesophageal echocardiography was lower in the flexible group at zero point nine nine plus or minus zero point three seven millimeters of mercury compared with one point seven three plus or minus zero point eight seven millimetersof mercury in the semi rigid group. At two weeks after surgery, the resting mean pressure gradient was one point nine seven plus or minus zero point six four in the flexible group and two point one three plus or minus zero point eight nine in the semi rigid group, with no meaningful difference. During exercise stress testing at two weeks, the mean pressure gradient values were five point nine one plus or minus two point zero three and six point two nine plus or minus two point two six millimeters of mercury, and all patients in both groups achieved values below ten millimeters of mercury. At six months, moderate recurrent mitral regurgitation was observed in one patient in each group, and no major cardiovascular events occurred in either group. The change in mean pressure gradient from rest to exercise at six months was five point three two plus or minus one point seven four in the flexible group and five point five one plus or minus three point one eight in the semi-rigid group, with no significant difference. Subgroup analyses based on age, body surface area and concomitant procedures also showed no difference. These results suggest that the hemodynamic influence of band type is limited and that both devices can maintain stable postoperative hemodynamics.

Both flexible and semi-rigid bands were shown to be safe and demonstrated no significant differences in postoperative hemodynamics following mitral valve repair in asymptomatic patients with mitral regurgitation. Although the study was limited by sample size, it provides valuable data specifically focused on early surgical cases and represents an important contribution to optimizing future annuloplasty device selection and surgical strategies.

Dec. 31, 2025

Dec. 31, 2025

No

no

https://jrct.mhlw.go.jp/latest-detail/jRCTs052220097

Kobayashi Takuma

University Hospital Kyoto Prefectural University of Medicine

465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan

takuma.kobayashi.0824@gmail.com

Kobayashi Takuma

University Hospital Kyoto Prefectural University of Medicine

465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan

+81-752515752

flexmap@koto.kpu-m.ac.jp

Complete

Nov. 01, 2022

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1) Patients with a diagnosis of primary mitral regurgitation
2) Patients with a left ventricular ejection fraction (LVEF) of 50% or greater on echocardiography at the time of enrollment.
3) Patients who are able to give written consent to participate in the study of their own free will.
4) Patients who are at least 20 years old and less than 85 years old at the time of consent.

1) Patients with heart failure symptoms such as symptoms of exertional dyspnea due to primary mitral regurgitation
2) Patients with left ventricular enlargement
3) Patients with atrial fibrillation
4) Patients who are unable to perform exercise stress echocardiography due to orthopedic or other diseases
5) Patients undergoing emergency surgery for mitral regurgitation such as acute rupture of tendon cords
6) Patients with a diagnosis of moderate or severe aortic stenosis by echocardiography
7) Patients with moderate or severe aortic regurgitation diagnosed by either echocardiography, cardiac MRI or cardiac catheterization.
7) Patients diagnosed with moderate or severe aortic regurgitation by either echocardiography or cardiac MRI or cardiac catheterization
8) Patients who are participating or planning to participate in an interventional trial at the time consent is obtained
9) Other patients deemed inappropriate as research subjects by the principal investigator.

Both

primary mitral regurgitation

non blinded randamization

primary mitral regurgitation

c14

Achievement of a mean pressure gradient of less than 10 mmHg during exercise stress 6 months after surgery

1) Mean intraoperative pressure gradient (transesophageal ultrasonography)
2) Mean pressure gradient at rest 2 weeks after surgery
3) Achievement of a mean pressure gradient of less than 10 mmHg during exercise 2 weeks after surgery
4) MR recurrence at 6 months postoperatively
5) Occurrence of major cardiovascular events (MACE: cardiovascular death, myocardial infarction, or stroke) at 6 months postoperatively
6)Change from rest in mean pressure gradient during exercise at 6 months postoperatively

+81-75-251-5337

Sept. 15, 2022

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