Possible mechanism of late systolic mitral valve prolapse: systolic superior shift of leaflets secondary to annular dilatation that causes papillary muscle traction.

Progressive superior shift of the mitral valve (MV) during systole is associated with abnormal papillary muscle (PM) superior shift in late systolic MV prolapse (MVP). The causal relation of these superior shifts remains unclarified. We hypothesized that the MV superior shift is related to augmented MV superiorly pushing force by systolic left ventricular pressure due to MV annular dilatation, which can be corrected by surgical MV plasty, leading to postoperative disappearance of these superior shifts. In 35 controls, 28 patients with holosystolic MVP, and 28 patients with late systolic MVP, the MV coaptation depth from the MV annulus was measured at early and late systole by two-dimensional echocardiography. The PM tip superior shift was monitored by echocardiographic speckle tracking. MV superiorly pushing force was obtained as MV annular area × (systolic blood pressure - 10). Measurements were repeated after MV plasty in 14 patients with late systolic MVP. Compared with controls and patients with holosystolic MVP, MV and PM superior shifts and MV superiorly pushing force were greater in patients with late systolic MVP [1.3 (0.5) vs. 0.9 (0.6) vs. 3.9 (1.0) mm/m2, 1.3 (0.5) vs. 1.2 (1.0) vs. 3.3 (1.3) mm/m2, and 487 (90) vs. 606 (167) vs. 742 (177) mmHg·cm2·m-2, respectively, means (SD), P < 0.001]. MV superior shift was correlated with PM superior shift ( P < 0.001), which was further related to augmented MV superiorly pushing force ( P < 0.001). MV and PM superior shift disappeared after surgical MV plasty for late systolic MVP. These data suggest that MV annulus dilatation augmenting MV superiorly pushing force may promote secondary superior shift of the MV (equal to late systolic MVP) that causes subvalvular PM traction in patients with late systolic MVP. NEW & NOTEWORTHY Late systolic mitral valve prolapse (MVP) is associated with mitral valve (MV) and papillary muscle (PM) abnormal superior shifts during systole, but the causal relation remains unclarified. MV and PM superior shifts were correlated with augmented MV superiorly pushing force by annular dilatation and disappeared after surgical MV plasty with annulus size and MV superiorly pushing force reduction. This suggests that MV annulus dilatation may promote secondary superior shifts of the MV (late systolic MVP) that cause subvalvular PM traction.

Repair of bileaflet prolapse in Barlow syndrome: The 4-chord technique.

Barlow syndrome is a form of degenerative mitral valve (MV) disease found in a subset of patients with bileaflet prolapse. The hallmark of Barlow's disease includes excessive and billowing leaflet tissue caused by myxomatous tissue proliferation, elongated chordae, and pronounced annular dilatation. Surgical repair of patients with Barlow's disease is challenging due to the extent of the leaflet and annular abnormalities. Several techniques have been described to repair Barlow's MV including currently popular "non-resectional" approaches. Repair with neochordae has been associated with excellent results and includes the advantage of preserved leaflet mobility and a large surface of coaptation. We describe a simple approach to the use of neochordae to repair bileaflet prolapse in patients with Barlow syndrome and avoid systolic anterior motion.

Pattern of Rheumatic valvular involvement and its contribution towards valvular malfunction in young adults

Objective: To study the different patterns of valvular malfunction in Rheumatic heart disease (RHD) and assess the factors contributing towards it. Methods: This is an observational study among patients with chronic RHD. One hundred patients (female 81 and 19 males) within ages 12 to 40 years (Mean age 27.3) were analyzed. A relevant clinical history including that of an initial episode of acute rheumatic fever (ARF) and recurrent episodes was obtained. 2D echo assessment of the cardiac valves was performed with an estimation of Wilkins score for the mitral valve (MV). Results: Among the study population female: male ratio was 4:1. 30% had recurrent episodes of ARF. Only 60% had at least some evidence of ARF at any time in their life. The posterior mitral valve appears to be affected more than the anterior leaflet giving an average Wilkins score of 9.7 and 6.7 respectively. The total score had a positive correlation with Mitral stenosis (MS) (p <0.05). MV involvement was noted in 97%. 44% had significant mitral valve prolapse (MVP) but no statistical correlation was noted with mitral regurgitation (MR) (p>0.05). A regurgitant grade of 2 or more was found in 41%. High sensitive C reactive protein of more than 1mg/dl was noted in 55% of patients. Conclusion: Chronic rheumatic MV disease can exist as MS, MR, MVP or simply an elevated valve score. Apart from recurrent streptococcal infections and chronic sub clinical inflammation, a number of different components of valve damage contribute towards the end result.

Mitral valve prolapse and aortic root dilation in adults with hypermobile Ehlers-Danlos syndrome and related disorders.

Ehlers-Danlos syndromes (EDSs) are a group of inherited connective tissue disorders, and among them, classical EDS (cEDS) and hypermobile EDS (hEDS) are the most common. Mitral valve prolapse (MVP) and aortic root dilation (ARD) have previously been reported to occur at an increased frequency within cEDS and hEDS. More recently, a study performed in the pediatric population did not show increased prevalence (Ritter et al., American Journal of Medical Genetics Part A, 173(6), 1467-1472, 2017). The purpose of this study was to review a large population of individuals with cEDS, hEDS, and hypermobility spectrum disorders to determine the frequency of MVP and ARD. A retrospective chart review of 209 individuals with echocardiograms was performed. Overall, 6.4% (13/209) had MVP and 1.6% (3/189) were found to have ARD. Although the presence of MVP is higher than what has been reported in the general population, no patients had severe MVP or required surgical intervention. No patients in this cohort had an aortic root diameter requiring surgical repair. Based on the results of this study and previous studies, routine echocardiograms to assess for valvular diseases and ARD may not be necessary unless warranted by presence of symptoms or family history.

Severe mitral regurgitation due to mitral leaflet aneurysm diagnosed by three-dimensional transesophageal echocardiography: a case report.

BACKGROUND: A small mitral valve aneurysm (MVA) presenting as severe mitral regurgitation (MR) is uncommon. CASE PRESENTATION: A 47-year-old man with a history of hypertension complained of exertional chest discomfort. A transthoracic echocardiogram (TTE) revealed the presence of MR and prolapse of the posterior leaflet. A 6-mm in diameter MVA, not clearly visualized by TTE, was detected on the posterior leaflet on a three-dimensional (3D) transesophageal echocardiography (TEE). The patient underwent uncomplicated triangular resection of P2 and mitral valve annuloplasty, and was discharged from postoperative rehabilitation, 2 weeks after the operation. Histopathology of the excised leaflet showed myxomatous changes without infective vegetation or signs of rheumatic heart disease. CONCLUSIONS: A small, isolated MVA is a cause of severe MR, which might be overlooked and, therefore, managed belatedly. 3D TEE was helpful in imaging its morphologic details.

Hemodynamic comparison of mitral valve repair: techniques for a flail anterior leaflet.

BACKGROUND AND AIM OF THE STUDY: Anterior leaflet flail resulting from elongated or ruptured marginal chordae is frequently diagnosed among adults, and is amenable to surgical repair. The study aim was to investigate the efficacy of three surgical techniques, namely neochordoplasty, limited triangular resection and edge-to-edge repair, to correct anterior leaflet flail in an in-vitro experimental model. METHODS: Seven porcine mitral valves were evaluated in a pulsatile heart simulator before surgical manipulation, after anterior marginal chordae transection, and with each surgical repair. Marginal chordal transection induced leaflet flail with moderate mitral regurgitation (MR). Following the confirmation of MR via direct flow measurements, it was corrected by three repairs: neochordoplasty with ePTFE sutures, limited triangular resection, and edge-to-edge repair. The post-repair valve hemodynamics were quantified under pulsatile conditions of 120 mmHg peak transmitral pressure and 5 l/min cardiac output at 70 beats/min. Hemodynamic, geometric and echocardiographic indices were also measured. RESULTS: Transecting the marginal chordae induced A2 prolapse and produced the regurgitant fraction to 18.7 +/- 10.2%. Surgical repair effectively reduced the regurgitant fraction to 6.9 +/- 6.3% (p = 0.019 to prolapse, p = 0.0117 to baseline) with neochordae, to 5.8 +/- 7.0% (p = 0.03 to prolapse, p = 0.0378 to baseline) with triangular resection, and to 13.3 +/- 10.2% (p = 0.2091 to prolapse, p = 0.0045 to baseline) with edge-to-edge repair. Remnant regurgitation was largest with edge-to-edge repair compared to limited leaflet resection and neochordoplasty, though central leaflet coaptation was restored equally by the three repairs, with mild systolic leaflet restriction after repair. CONCLUSION: Anterior leaflet repair and a reduction in MR is achievable with the three techniques, although neochordoplasty and triangular resection proved superior to edge-to-edge repair in eliminating MR.

Mitral valve disease.

In industrially developed countries, moderate or severe mitral valve disease is relatively common and is usually caused by prolapse or is secondary to left ventricular disease. Mitral stenosis (MS), however, is uncommon and usually a sequela of rheumatic fever. This article discusses the natural history of mitral regurgitation and MS and their medical and surgical management.

[Connective tissue dysplasia as a reason of recurrent inguinal hernia].

The examination results of 78 patients with recurrent inguinal hernia revealed presence of systemic connective tissue abnormalities in addition to dysplasia of posterior wall of inguinal canal in 48 (61.6%) patients. Hernial disease was observed in 37 (47.4%) patients including umbilical hernia in 12 cases, femoral hernia in 8 patients, hiatal hernia in 3 patients and bilateral inguinal hernia in 14 cases. Group of other diseases included varicose veins of lower limbs in 15 (19.2%) patients, mitral valve prolapse in 3 (3.8%) patients, violation of skin elasticity (striae) in 6 (7.7%) cases, diverticulum of bladder in 2 (2.6%) patients, diverticulum of esophagus in 1 (1.3%) patient, diverticulosis of small intestine in 2 (2.6%) cases. Our data prove that inguinal hernia is local manifestation of systemic disease.

Floppy mitral valve (FMV)/mitral valve prolapse (MVP) and the FMV/MVP syndrome: pathophysiologic mechanisms and pathogenesis of symptoms.

Mitral valve prolapse (MVP) results from the systolic movement of a portion or segments of the mitral valve leaflets into the left atrium during left ventricular systole. It is well appreciated today that floppy mitral valve (FMV) is the central issue in the MVP and mitral valve regurgitation (MVR) story. The term FMV refers to the expansion of the area of the mitral valve leaflets with elongated chordae tendineae, chordae rupture and mitral annular dilation. FMV/MVP occurs in a heterogeneous group of patients with a wide spectrum of mitral valve involvement from mild to severe. Two types of symptoms can be defined in FMV/MVP patients. In one group of patients, symptoms are directly related to progressive MVR. In the other group, symptoms cannot be explained by the degree of MVR alone; activation of the autonomic nervous system has been implicated for the explanation of symptoms in this group of patients which is referred to as the FMV/MVP syndrome. In this brief review, the natural history, pathophysiologic mechanisms and management of patients with FMV/MVP/MVR and FMV/MVP syndrome are discussed.

Unique experiences with intercontinental trials in stroke - part II.

Supported by the Canadian Medical Research Council we performed a randomized trial extending from Newfoundland to British Columbia. With others a number of observations showed that aspirin will reduce stroke. With National Institute of Neurological Disorders and Stroke support we learned who would benefit and not from surgery in these stroke threatened carotid diseased patients. We evaluated the upper limits of acceptability of complications beyond which harm was done. Amassing this large data base of approximately 5000 individuals, followed for five years, previously unknown carotid phenomena were observed: 1. Ischemic stroke occurs in patients with prolapsing mitral valves; 2. There is risk of stroke in patients with residual thrombi in the occluded stump of the carotid artery; 3. We detected a lower risk than expected in patients with nearly occluded carotid arteries. We support the contention of Yusuf and Cairns' that Canada needs to give more financial support to purely clinical research. It pays off !

Valvular heart disease in patients with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) or "brittle bone disease" is a rare connective tissue hereditary disorder. The most common clinical presentation of OI is bone fractures. OI also involves extraskeletal structures; however, cardiovascular manifestations are rare. In this report, we describe the cardiovascular anomalies of patients with OI who underwent valve surgery and review the literature on this subject.

Left ventricular noncompaction complicated by mitral valve prolapse: report of a case.

A 31-year-old male was diagnosed with congestive heart failure due to left ventricular noncompaction and coarctation of the aorta by echocardiography and computed tomography. He also developed mitral valve prolapse of the posteromedial commissural leaflet due to rupture of chordae tendineae. Segmental leaflet resection was performed with ring annuloplasty. Aorto-bifemoral bypass was carried out simultaneously to attenuate the ventricular afterload. His postoperative course was uneventful.

[Mitral valve prolapse and mitral annulus disjunction: be aware of a potential arrhythmogenic substrate]. / Prolasso valvolare mitralico e disgiunzione mitro-anulare. La consapevolezza di un possibile substrato aritmico.

Mitral valve prolapse is a relatively common disease with a good overall prognosis. However, in specific clinical and instrumental contexts, patients at high risk of ventricular arrhythmias and sudden cardiac death can be identified. Female sex, history of palpitations or syncope, bi-leaflet myxomatous valve, ECG repolarization abnormalities in the inferior leads, complex ventricular arrhythmias, left ventricular fibrosis detected by cardiac magnetic resonance correlate with a higher risk clinical profile. Additionally, morpho-functional abnormalities of the mitral valve annulus, particularly mitral annulus disjunction, may cause a mechanical stretch at the inferior basal ventricular wall and posterior papillary muscles, predisposing to myocardial fibrosis and arrhythmias. A risk stratification strategy is needed to identify patients with mitral valve prolapse and/or mitral annulus disjunction at high risk of arrhythmias; however, few data are available. Further prospective multicenter studies are warranted, focusing on medical therapy, the role of implantable cardioverter-defibrillators for primary prevention, efficacy of targeted catheter ablation or mitral valve surgery.

Finite element analysis of mitral valve annuloplasty in Barlow's disease.

Barlow's Disease affects the entire mitral valve apparatus causing mitral regurgitation. Standard annuloplasty procedures lead to an average of 55% annular area reduction of the end diastolic pre-operative annular area in Barlow's diseased valves. Following annular reduction, mitral valvuloplasty may be needed, usually with special focus on the posterior leaflet. An in silico pipeline to perform annuloplasty by utilizing the pre- and -postoperative 3D echocardiographic recordings was developed. Our objective was to test the hypothesis that annuloplasty ring sizes based on a percentage (10%-25%) decrease of the pre-operative annular area at end diastole can result in sufficient coaptation area for the selected Barlow's diseased patient. The patient specific mitral valve geometry and finite element model were created from echocardiography recordings. The post-operative echocardiography was used to obtain the artificial ring geometry and displacements, and the motion of the papillary muscles after surgery. These were used as boundary conditions in our annuloplasty finite element analyses. Then, the segmented annuloplasty ring was scaled up to represent a 10%, 20% and 25% reduction of the pre-operative end diastolic annular area and implanted to the end diastolic pre-operative finite element model. The pre-operative contact area decrease was shown to be dependent on the annular dilation at late systole. Constraining the mitral valve from dilating excessively can be sufficient to achieve proper coaptation throughout systole. The finite element analyses show that the selected Barlow's diseased patient may benefit from an annuloplasty ring with moderate annular reduction alone.

[Diagnosis and classification of mitral valve prolapse in children and adolescents].

We examined 1734 children and adolescents with admittance diagnosis mitral valve prolapse (MVP) and confirmed its presence using accepted Framingham criteria in 32.3% of cases. Reason for overdiagnosis in other cases was incorrect interpretation of auscultation or echocardiography data. Most often MVP was familial with recessive or dominant inheritance according to genealogical analysis. Contrary to MVP in adults children and adolescents commonly had no myxomatous transformation of valves. Taking into account constitutional and physiological peculiarities of the body in children and adolescents we distinguished two forms of MVP characteristic for this age: MVP as a variant of asthenic constitution and physiological MVP. Both forms are widely spread and represent normal states for juvenile population.

The Mitral Annular Disjunction of Mitral Valve Prolapse: Presentation and Outcome.

OBJECTIVES: The aim of this study was to assess in patients with mitral valve prolapse (MVP) mitral annular disjunction (MAD) prevalence, phenotypic characteristics, and long-term outcomes (clinical arrhythmic events and excess mortality). BACKGROUND: Clinical knowledge regarding MAD of MVP remains limited and controversial, and its potential link with untoward outcomes is unsubstantiated. METHODS: A cohort of 595 (278 women, mean age 61 ± 16 years) consecutive patients with isolated MVP, with comprehensive clinical, rhythmic, Doppler echocardiographic, and consistent MAD assessment, were examined. MAD prevalence, associated MVP phenotypes, and outcomes (survival, clinical arrhythmic events) starting at diagnostic echocardiography were analyzed. To balance important baseline differences, propensity scoring matching was conducted among patients with and those without MAD. RESULTS: The presence of MAD was common (n = 186 [31%]) in patients with MVP, generally in younger patients, and was not random but was independently associated with severe myxomatous disease involving bileaflet MVP and marked leaflet redundancy (both P ≤ 0.0002). The presence of MAD was also independently associated with a larger left ventricle (P = 0.005). Age-matched cohort survival after MVP diagnosis was not worse with MAD (10-year survival 93% ± 2% for patients without MAD and 97% ± 1% for those with MAD; P = 0.40), even adjusted comprehensively for MVP characteristics (P = 0.80) and accounting for time-dependent mitral surgery (P = 0.60). During follow-up, 170 patients had clinical arrhythmic events (ventricular tachycardia, n = 159; arrhythmia ablation, n = 14; cardioverter-defibrillator implantation, n = 14; sudden cardiac death, n = 3). MAD was independently associated with higher risk for arrhythmic events (adjusted HR: 2.60; 95% CI: 1.87-3.62; P < 0.0001). The link between MAD and arrhythmic events persisted with time-dependent mitral surgery (adjusted HR: 2.54; 95% CI: 1.84-3.50; P < 0.0001), was strong under medical management (adjusted HR: 3.21; 95% CI: 2.03-5.06; P < 0.0001) but was weaker after mitral surgery (adjusted HR: 2.07; 95% CI: 1.24-3.43; P = 0.005). CONCLUSIONS: This large cohort with MVP comprehensively characterized shows that MAD is frequent at MVP diagnosis and is strongly linked to advanced myxomatous degeneration. The presence of MAD was independently associated with long-term excess incidence of clinical arrhythmic events. However, within the first 10 years post-diagnosis, MAD was not linked to excess mortality, and although reassurance should be provided from the survival point of view, careful monitoring for arrhythmias is in order for MAD.

Association of Mitral Annular Disjunction With Cardiovascular Outcomes Among Patients With Marfan Syndrome.

Importance: Mitral annular disjunction (MAD) has received particular interest in patients with mitral valve prolapse, ventricular tachycardia, and sudden cardiac death. The clinical significance of MAD for patients with Marfan syndrome (MFS) remains largely unexplored. Objective: To define the prevalence of MAD and examine its association with cardiovascular outcomes and arrhythmia among patients with MFS. Design, Setting, and Participants: This retrospective, single-center cohort study included 142 patients with a diagnosis of MFS based on the revised Ghent criteria and a confirmed (likely) pathogenic variant in the FBN1 gene who underwent regular follow-up between January 1, 2004, and December 31, 2019. Main Outcomes and Measures: The presence of MAD was assessed by echocardiography, and the extent of MAD was categorized in tertiles. Patients also underwent resting electrocardiography and 24-hour Holter monitoring. Outcomes included aortic events (aortic dissection or prophylactic aortic surgery), arrhythmic events (defined as sustained ventricular tachycardia or sudden cardiac death), and mitral valve surgery. Results: A total of 142 patients (72 female patients [51%]; median age at first examination, 25 years [range, 2-64 years]) were evaluated. Forty-eight patients (34%) had MAD. Patients with MAD had larger aortic root z scores than patients without MAD (4.1 [interquartile range, 2.8-5.7] vs 3.0 [interquartile range, 1.8-4.0]; P < .001) and more often had mitral valve prolapse (34 of 48 [71%] vs 14 of 94 [15%]; P < .001), ventricular ectopy (14 of 33 [42%] vs 15 of 70 [21%]; P = .03), and nonsustained ventricular tachycardia (13 of 33 [39%] vs 12 of 70 [17%]; P = .01). During follow-up, aortic events occurred at similar rates among patients with vs without MAD (15 of 43 [35%] vs 21 of 84 [25%]; P = .24), but patients in the upper MAD tertile (>10 mm) showed a higher occurrence of aortic events compared with patients with MAD of 10 mm or smaller (9 of 15 [60%] vs 6 of 28 [21%]; P = .01). Patients with arrhythmic events (n = 5) and patients requiring mitral valve surgery (n = 7) were observed exclusively in the group displaying MAD. Conclusions and Relevance: This study suggests that MAD among patients with MFS is associated with the occurrence of arrhythmic events, a higher need for mitral valve intervention, and, among patients with extensive MAD, more aortic events. Cardiac imaging for patients with MFS should consider the assessment of MAD as a potential marker for adverse outcomes.

The pathogenesis of aortopathy in Marfan syndrome and related diseases.

Marfan syndrome is a systemic connective tissue disorder that is inherited in an autosomal-dominant pattern with variable penetrance. Although there are many clinical manifestations of this disease, the most life threatening are cardiovascular complications, including mitral valve prolapse and aortic root aneurysm. When the primary defect was discovered in the fibrillin-1 gene, it was hypothesized that mutations in fibrillin-1 resulted in a weakened and disordered elastic architecture. However, recent evidence has suggested that the Marfan syndrome is caused by more than just a disordered microfibril matrix. Interest was stimulated when it was discovered that fibrillin-1 mutations enhanced the release of sequestered latent transforming growth factor-beta, a well-described mediator of vascular remodeling. This article focuses on the pathophysiology of aortopathy in the Marfan syndrome and related diseases, with special emphasis on the role of transforming growth factor-beta in mediating the pathogenesis of this disease.