Orthostatic hypotension,catecholamines, and alpha-adrenergic receptors in mitral valve prolapse.

The reported association of mitral valve prolapse with autonomic dysfunction and neuroendocrine abnormalities is derived from studies of patients selected because of symptoms or specifically referred for investigation. To determine whether such associations occur in nonreferred and unselected women with mitral valve prolapse, we measured blood pressure, heart rate, and norepinephrine response to standing in 13 volunteers with mitral valve prolapse and in 11 control subjects. Platelet alpha-adrenergic receptor quantity and affinity on standing also were determined in all persons. No significant differences were found between the groups in any of these measurements. Although small subsets of women with mitral valve prolapse may indeed have associated neuroendocrine epiphenomena and autonomic dysfunction, it is probably incorrect to generalize these findings to the vast spectrum of those with mitral valve prolapse.     

Visual complications of mitral leaflet prolapse.

Four young women and six older men with mitral leaflet prolapse presented with visual disturbances consistent with embolism in the ophthalmic or posterior cerebral circulation. Cardiac arrhythmias were common, but these are rarely associated with focal ischaemia. The evidence that mitral leaflet prolapse caused the embolism in these patients is suggestive but not conclusive. Further studies are needed. All patients with acute cerebral or ocular ischaemia should undergo through cardiovascular assessment, which should include routine echocardiography.     

Randomized trial of therapy with platelet antiaggregants for threatened stroke. 2: Observations on the pathogenesis and natural history of threatened stroke.

Transient cerebral ischemia and stroke may occur despite previous occlusion of the artery supplying the appropriate part of the brain. After occlusion of the internal carotid artery, emboli may pass from the "stump" of the occluded artery to later produce transient cerebral ischemia or a stroke. Transient cerebral ischemia and stroke are due to a variety of conditions, some of which are strongly correlated with platelet thromboembolism, while others have little primary relation to thrombosis. The impact of this on therapeutic considerations is obvious. Thromboembolism related to myxomatous degeneration of the mitral valve (mitral valve prolapse) is a factor to consider in determining the cause of a stroke in a younger person. The prognosis for the different varieties of threatened stroke is incompletely known. When due to arteriosclerosis of the large cerebral arteries, transient cerebral ischemia and minor strokes pose a cumulative threat for a major stroke or death of 13% in the first year, 22% in the second year and 30% in the third year.     

MITRAL VALVE PROLAPSE AND CONGENITAL PYLORIC STENOSIS IN IDENTICAL TWINS

Both congenital pyloric stenosis and the mitral valve prolapse syndrome are reported to have a familial incidence. Although mitral valve prolapse has been documented in twins, only one case has received echocardiographic confirmation. The present account describes typical symptomatic mitral valve prolapse in identical twins, both of whom had undergone surgery during infancy to correct congenital pyloric stenosis.     

Robotic artificial chordal replacement for repair of mitral valve prolapse

Artificial chordal replacement (ACR) has emerged as a superior method of mitral valve repair with excellent early and late efficacy. It is also ideal to combine with robotic techniques for correction of mitral prolapse, and this article presents a current method of robotic Gore-Tex ACR. Patients with isolated posterior leaflet prolapse are approached with the fourth-generation DaVinci robotic system and endoaortic balloon occlusion. A pledgetted anchor stitch is placed in a papillary muscle, and a 2-o Gore-Tex suture is passed through the anchor pledget. After full annuloplasty ring placement, the Gore-Tex suture is woven into the prolapsing segment and positioned temporarily with robotic forceps. Chordal length is then "adjusted" by lengthening or shortening the temporary knot over 1-cm increments as the valve is tested by injection of cold saline into the ventricle. After achieving good leaflet position and valve competence, the chord is tied permanently. The "adjustable" ACR procedure preserves leaflet surface area and produces a competent valve in the majority of patients. Postoperative transesophageal echo shows a large surface area of coaptation. Patient recovery is facilitated by the minimally invasive approach, while long-term stability of similar open ACR techniques have been excellent with a 2% to 3% failure rate over 10 years of follow-up. Robotic Gore-Tex ACR without leaflet resection is a reproducible procedure that simplifies mitral repair for prolapse. The outcomes observed in early robotic applications have been excellent. It is suggested that most patients with simple prolapse might validly be approached in this manner.     

Mitral valve prolapse detected during hemodynamic studies

To estimate frequency of the posterior mitral valve leaflet prolapse in routinely performed left ventriculography, 1000 consecutive ventriculograms of the right anterior oblique projection were analyzed. A group of patients consisted of 511 women and 489 men at mean age 46,5 years. Clinical diagnosis of heart lesions, myocardial disease, pulmonary hypertension or arrhythmias were indications for hemodynamic studies. In the investigated group of patients, there were no patients with clinical diagnosis of the coronary artery disease. Prolapse of the posterior mitral valve leaflet was diagnosed in 59 patients. Idiopathic mitral valve prolapse was diagnosed in 10 patients. Prolapse of the posterior mitral valve leaflet was most frequent in atrial septal defect (16.6%), myocardial lesion (12.5%), and after mitral commissurotomy (8.9%). Posterior mitral valve leaflet prolapse is not a frequent anomaly in routinely performed left ventriculography. Relatively often occurrence of the mitral valve prolapse in atrial septal defect and only occasional in the aortic lesions and dilated cardiomyopathy seems to point out at a role of the left ventricle size in pathogenesis of this syndrome.     

Programmed atrial and ventricular stimulation in patients with mitral valve prolapse--a personal experience]

Electrophysiological tests were performed in 60 patients aged between 18 and 63 years (mean age 38 years), and divided into two groups: with mitral valve leaves prolapse syndrome, and without this abnormality, in whom no other heart disease was diagnosed. Refraction of the right atrium, atrio-ventricular node, and right ventricle was evaluated together with cardiac response to different types of electrostimulation. A supraventricular dysrhythmia (most frequently atrial fibrillation) has been produced in 17 patients (42.5%) with mitral valve leaves prolapse syndrome whereas in the control group the same was produced in 2 patients (10%). Programmed stimulation of the ventricles did not produce ventricular tachycardia in none patient of both groups. Multiple ventricular beats have been produced in 3 patients with mitral valve prolapse syndrome and pairs of ventricular beats in other 3 patients of this group. Results suggest that "arrhythmogenic tendency", especially supraventricular dysrhythmia is more frequent in patients with mitral valve prolapse syndrome than in the general population.     

Arrhythmia in patients with mitral valve prolapse]

An incidence of cardiac arrhythmias was evaluated in 119 patients with mitral valve prolapse. The disease was made basing on the results of clinical symptoms, echo-, angio- and phonocardiography. Electrocardiograms were recorded from the standard 12 lead and Holter technique for 24 hours in each patient to assess present arrhythmias. It was found that the most frequent cardiac arrhythmias accompanying mitral valve prolapse are ventricular extrasystolic contractions of Lown's class 1a and 1b. Only examination of strictly selected groups of patients (age groups with or without co-existing mitral valve insufficiency for adequate period of time) will facilitate precise evaluation of an incidence of different cardiac arrhythmias accompanying the underlying disease.     

Surgery Issue: Solving the Puzzle of Chronic Ischemic Mitral Regurgitation

Chronic ischemic mitral regurgitation is a prevalent problem among patients following a myocardial infarction. Until recently, the pathophysiology was poorly understood, resulting in surgical strategies with suboptimal results and limited durability. The surgical approach has evolved from revascularization alone to an additional mitral valve procedure, replacement, or repair. When the valve was repaired, isolated annuloplasty was performed. The dilemma that surgeons had when repairing a mitral valve was which type of ring to use and what size. In all series with annuloplasty alone, the results were poor with very high recurrence rates. The primary feature of ischemic mitral regurgitation is a prolapse of the anterior leaflet at A3 ± A2. This prolapse can be caused by fibrotic elongation of the papillary muscle supporting A3 ± A2 or tethering of P3 by a ballooning posterior left ventricular wall. Using a technique that corrects this prolapse with Gore-Tex neochords, we have achieved excellent results with effective and durable correction of the ischemic mitral regurgitation.     

Novel techniques in mitral repair: extended and rotational chordal transfer

Mitral valve repair is preferable to mitral valve replacement because of low rate of thromboembolism, resistance to endocarditis, excellent late durability, and no need for anticoagulation in the majority of patients. This article describes 2 novel techniques for repairing the anterior mitral leaflet prolapse. The extended chordal transfer is achieved by transferring an extended segment of posterior mitral leaflet and, rotational chordal transfer, by rotating the transferred segment either vertical or horizontal. Both techniques are simple and reproducible. It uses patient's own natural chorda and eliminates the problem of knotting and determination of appropriate chordal length faced with other techniques.     

ARRHYTHMIA WITH MITRAL VALVE PROLAPSE: RESULTS OF ANNULOPLASTY IN TWO PATIENTS

The effectiveness of posterior annuloplasty in two patients who failed to respond to medical treatment for atrial and ventricular arrhythmias related to mitral valve prolapse (MVP) is reported. Although the etiology of arrhythmia in MVP remains mostly speculative, anatomic correction of prolapse or billowing of the mitral leaflets appears to reverse the anatomic and pathologic conditions that cause the arrhythmia.     

Human myxomatous mitral valve prolapse: role of bone morphogenetic protein 4 in valvular interstitial cell activation

Myxomatous mitral valve prolapse (MVP) is the most common cardiac valvular abnormality in industrialized countries and a leading cause of mitral valve surgery for isolated mitral regurgitation. The key role of valvular interstitial cells (VICs) during mitral valve development and homeostasis has been recently suggested, however little is known about the molecular pathways leading to MVP. We aim to characterize bone morphogenetic protein 4 (BMP4) as a cellular regulator of mitral VIC activation towards a pathologic synthetic phenotype and to analyze the cellular phenotypic changes and extracellular matrix (ECM) reorganization associated with the development of myxomatous MVP. Microarray analysis showed significant up regulation of BMP4-mediated signaling molecules in myxomatous MVP when compared to controls. Histological analysis and cellular characterization suggest that during myxomatous MVP development, healthy quiescent mitral VICs undergo a phenotypic activation via up regulation of BMP4-mediated pathway. In vitro hBMP4 treatment of isolated human mitral VICs mimics the cellular activation and ECM remodeling as seen in MVP tissues. The present study characterizes the cell biology of mitral VICs in physiological and pathological conditions and provides insights into the molecular and cellular mechanisms mediated by BMP4 during MVP. The ability to test and control the plasticity of VICs using different molecules may help in developing new diagnostic and therapeutic strategies for myxomatous MVP.     

Arrhythmia in patients with mitral valve prolapse syndrome and the status of the sympathetic nervous system]

The study aimed at evaluating a possible relationship between the adrenergic system tone determined with the excretion of catecholamines with the urine and an incidence of the ventricular arrhythmias in patients with the mitral valve prolapse. The study included 20 patients (13 women and 7 men aged between 20 and 50 years; mean = 31.6 years) with the mitral valve prolapse syndrome diagnosed with the aid of the patients' history, physical examinations and echocardiography. Echocardiograms have shown anterior mitral leaflet prolapse in 7 patients, posterior mitral leaflet prolapse in 8 patients, and both mitral leaflets prolapse in the remaining 5 patients. Daily excretion of adrenaline and noradrenaline was measured with Van Euler and Lishajko's fluorimetric technique. Cardiac arrhythmias were determined with a 24-hour ECG monitoring and classified according to Lown. Premature ventricular contractions of class I were seen in 1 patient, of class II in 5, class III in 1, class IV in 2, and class V in 3 patients. Holter monitoring technique did not show the arrhythmias in 8 patients. Daily adrenaline and noradrenaline excretion with the urine was within the normal values (3.2-30.8 ug and 0.2-16.2 ug, respectively) in all examined patients. Daily urine noradrenaline was higher in patients with serious ventricular arrhythmias (Lown's class V) than mean values in the whole examined group.     

QT/QS2 index in patients with arterial hypertension, mitral valve prolapse and hyperthyroidism]

QT/QS2 ratio has been assessed in 26 patients with both borderline and mild hypertension and mitral valve prolapse syndrome (19 patients), and hyperthyroidism (16 patients) in comparison with method control groups. The following polycardiographic parameters have been analyzed: QT, QTp, QS2, QT/QS2, and QTp/QS2. Higher values of QT/QS2 ratio have been noted in patients with mitral valve prolapse syndrome and hyperthyroidism than that in the control group. There has been no difference in patients with mild hypertension while the values of the analyzed parameter have been significantly lower in patients with borderline hypertension. QT has been longer than QS2 (QT)QS2 1/in 9 (56%) patients with hyperthyroidism. A positive correlation between QT/QS2 ratio and ++thyroxine levels have been noted in these patients. QT values have been higher than QS2 values only in 1 patient with mild hypertension. It seems that QT/QS2 value has limited value as an indirect index of the adrenergic activity in the dysfunction of the autonomic nervous system.     

Mapping of X-linked myxomatous valvular dystrophy to chromosome Xq28.

Myxoid heart disease is frequently encountered in the general population. It corresponds to an etiologically heterogeneous group of diseases, idiopathic mitral valve prolapse (IMVP) being the most common form. A rarely observed form of myxoid heart disease, X-linked myxomatous valvular dystrophy (XMVD), is inherited in an X-linked fashion and is characterized by multivalvular myxomatous degeneration; however, the histopathological features of the mitral valve do not differ significantly from the severe form of IMVP. In this article, we describe the genetic analysis of a large family in which XMVD is associated with a mild hemophilia A. The coagulation factor VIII gene position in Xq28 provided a starting point for the genetic study, which was conducted by use of polymorphic markers. Two-point linkage analysis confirmed this localization, and a maximum LOD score of 6.57 was found at straight theta=0 for two polymorphic microsatellite markers, INT-3 and DXS1008, the first one being intronic to the factor VIII gene. Haplotype analysis of this chromosomal region allowed the definition of an 8-cM minimal interval containing the gene for XMVD, between DXS8011 and Xqter.     

The serpentine mitral valve and cerebral embolism

Valvular strands, well-delineated filiform masses, attached to cardiac valve edges are associated with cerebral embolism and stroke. Strokes, caused by emboli from valvular strands, tend to occur among younger persons. In this case report a valvular strand, giving a peculiar serpentine appearance to the mitral valve is described. This mitral valvular strand was the only explanation for an episode of cerebral embolism, presenting with a transient right sided hemiparesis. It is proposed that a randomized study involving combined treatment with aspirin and clopidogrel is warranted in young patients with valvular strands, presenting with a first episode of cerebral embolism.     

Identification of 2 loci associated with development of myxomatous mitral valve disease in Cavalier King Charles Spaniels

Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. It is characterized by chronic progressive degenerative lesions of the mitral valve. The valve leaflets become thickened and prolapse into the left atrium resulting in mitral regurgitation (MR). MMVD is most prevalent in small to medium sized dog breeds, Cavalier King Charles Spaniels (CKCS) in particular. The onset of MMVD is highly age dependent, and at the age of 10 years, nearly all CKCS are affected. The incidence of a similar disease in humans-mitral valve prolapse-is 1-5%. By defining CKCSs with an early onset of MMVD as cases and old dogs with no or mild signs of MMVD as controls, we conducted a genome-wide association study (GWAS) to identify loci associated with development of MMVD. We have identified a 1.58 Mb region on CFA13 (P(genome) = 4.0 × 10(-5)) and a 1.68 Mb region on CFA14 (P(genome) = 7.9 × 10(-4)) associated with development of MMVD. This confirms the power of using the dog as a model to uncover potential candidate regions involved in the molecular mechanisms behind complex traits.     

Surgical Treatment of Mitral Insufficiency

Sixty-four patients with pure mitral insufficiency were operated upon. Thirty of them had torn chordae tendineae. It was possible to repair the mitral valve in 57 patients and there were five operative deaths. One patient had a femoral artery embolus and another had a cerebral embolus. The incidence of peripheral embolization was 4 per cent compared with 40 per cent reported for ball valve replacement.Forty-eight of the 57 patients with repair (84 per cent) were living and well with at most a grade II/VI apical systolic murmur up to seven and a half years after operation. There has been no evidence of recurrence in these patients.In approximately 90 per cent of patients with pure mitral insufficiency, repair should be performed. When feasible, repair is more satisfactory than valvular replacement, with not only excellent long-term results, but far less morbidity than is reported with ball valve replacement.     

Percutaneous valve procedures: present and future

Percutaneous mitral commissurotomy and aortic valvuloplasty have been being performed since the mid-1980s. Balloon commissurotomy has been used in thousands of cases worldwide and it provides good short- and long-term results in a wide range of patients. It has virtually replaced surgical commissurotomy in the treatment of mitral stenosis. In contrast, percutaneous aortic valvuloplasty is almost abandoned worldwide due to its lack of efficacy and the risks involved. The new techniques of percutaneous valve intervention: aortic valve replacement and mitral valve repair are at an early stage: the first in-man applications of these fledgling techniques started in 2002. Preliminary series show that they are feasible; however, they need to be further evaluated in comparison with contemporary treatment to assess accurately how efficient they are and the risks involved. Currently potential applications concern high-risk patients, however, in the future, after thorough evaluation, this may be extended to others. Thus, percutaneous interventions already play an important role in treatment of valvular heart disease, a role that seems set for future expansion.     

Mechanics of the mitral valve

Alterations in mitral valve mechanics are classical indicators of valvular heart disease, such as mitral valve prolapse, mitral regurgitation, and mitral stenosis. Computational modeling is a powerful technique to quantify these alterations, to explore mitral valve physiology and pathology, and to classify the impact of novel treatment strategies. The selection of the appropriate constitutive model and the choice of its material parameters are paramount to the success of these models. However, the in vivo parameters values for these models are unknown. Here, we identify the in vivo material parameters for three common hyperelastic models for mitral valve tissue, an isotropic one and two anisotropic ones, using an inverse finite element approach. We demonstrate that the two anisotropic models provide an excellent fit to the in vivo data, with local displacement errors in the sub-millimeter range. In a complementary sensitivity analysis, we show that the identified parameter values are highly sensitive to prestrain, with some parameters varying up to four orders of magnitude. For the coupled anisotropic model, the stiffness varied from 119,021 kPa at 0 % prestrain via 36 kPa at 30 % prestrain to 9 kPa at 60 % prestrain. These results may, at least in part, explain the discrepancy between previously reported ex vivo and in vivo measurements of mitral leaflet stiffness. We believe that our study provides valuable guidelines for modeling mitral valve mechanics, selecting appropriate constitutive models, and choosing physiologically meaningful parameter values. Future studies will be necessary to experimentally and computationally investigate prestrain, to verify its existence, to quantify its magnitude, and to clarify its role in mitral valve mechanics.