Myxomatous Valve Research Articles

Surgery for Asymptomatic Severe Mitral Regurgitation in the Elderly

Cardiovascular disease is the major cause of death in subjects >75 years of age, a healthcare problem that will increase as the population continues to age. In the United States, the predicted population >75 years of age will exceed 50 million by the year 2038. Epidemiological studies have shown that the prevalence of mitral regurgitation (MR) also increases progressively with age; thus, MR is a common and growing problem in the elderly.1 The most frequently encountered types of MR in the elderly are degenerative mitral valve disease, which results from primary floppy, myxomatous valves with prolapsing or flail leaflets and calcified mitral annulus, and ischemic MR (IMR), now that rheumatic mitral valve disease has declined and endocarditis remains comparatively rare. Article p 265 Although there are American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the optimal management of a broad spectrum of patients with severe MR,2 attention has not focused specifically on the elderly, in whom the condition predominates. In addition, operative mortality is increased in the elderly by major comorbidities that include coronary artery disease, cerebrovascular disease, heart failure, atrial fibrillation, and renal insufficiency. Furthermore, little is known regarding the difference in life expectancy and risk of adverse events in elderly patients with severe MR undergoing successful mitral valve surgery versus those who decline or are denied surgical intervention. A delicate balance must be struck in optimally managing elderly patients with severe MR that not only favors symptomatic benefit over perioperative risk of an adverse clinical outcome, but also improves long-term outcome with regard to morbidity and mortality. Over the past 2 decades, surgical strategies in the treatment of MR have changed from routine mitral valve replacement to mitral valve repair. Because the surgeons’ understanding of normal mitral valve functional anatomy has improved, largely because of …

A fibrous membrane causing left ventricular outflow tract stenosis as the result of endocarditis

chanical properties of the chordae are affected. There are several indications of a genetic link to myxomatous mitral valve disease. Thus patients with autosomal dominant polycystic kidney disease have an increased occurrence of cardiac valve abnormalities, and in patients with Marfan syndrome caused by fibrillin gene defects, myxomatous mitral valve disease is the leading cause of mitral regurgitation. Moreover, a high frequency of the angiotensin-converting enzyme II genotype has been demonstrated in myxomatous mitral valve disease, and a gene associated with the disease has been located on Xq28. The presented patients had remarkably similar morphologic findings, with a large myxomatous valve and posterior leaflet prolapse combined with chordal rupture. Both of the patients, in addition, had an enlargement of the left ventricle. Eliminating the MR, if performed early, will reduce the volume overload, allowing the left ventricle to recover in size and function. The timing of surgical intervention in asymptomatic patients might be difficult, but when the EF decreases to 60% or less, the LVESD increases to greater than 40 mm, or both, surgical intervention is advocated. Patient 2 came to surgical intervention almost a year later than patient 1 and was found to have a more severely enlarged heart. In view of the importance of promoting ventricular reversed remodeling and ensuring a reduction of ventricular size to minimize the risk of potential residual functional MR, the CSD was positioned around the heart. Obviously this proved to be most efficient because the heart rapidly decreased in size with maintained LV function. To what extent passive containment operations should be applied more generally in patients with cardiac LV dilatation remains to be established.

Tetralogy of Fallot with Congenital Aortic Valvar Stenosis: The Tetralogy–Truncus Interrelationship

Two rare patients are reported with tetralogy of Fallot and congenital aortic valvar stenosis. The anatomic and developmental interrelationship between tetralogy of Fallot and truncus arteriosus is summarized. A study of 100 randomly selected postmortem cases of tetralogy revealed aortic valve pathology in 8%, myxomatous aortic valve leaflets without stenosis in 4%, bicuspid aortic valves without stenosis in 3%, and congenital aortic valvar stenosis in 1%. The frequency of systemic semilunar valve pathology in truncus was much higher (66%): moderate to marked myxomatous change in 44%, mild myxomatous change in 22%, truncal valvar stenosis in 11%, and truncal valvar regurgitation in 15%. Being aware of the tetralogy-truncus interrelationship and knowing that myxomatous aortic valves are prone to premature calcific aortic stenosis and/or regurgitation, physicians should follow the aortic valves of surgically repaired patients with tetralogy of Fallot and truncus arteriosus long term with great care. Timely aortic valvuloplasty or replacement may well prove life-saving in such patients.

CD117-positive cells and mast cells in adult human cardiac valves—observations and implications for the creation of bioengineered grafts

Background There is no report to date of stem cells in human cardiac valves. We examined their possible presence, number, and distribution in valves removed at cardiac surgery from patients with a variety of underlying valve pathologies. Methods Grossly normal aortic and mitral valves were obtained from live heart transplant patients. Surgically excised valves with rheumatic mitral stenosis, aortic valve age-related degeneration, aortic valve changes of aortoannular ectasia, and mitral valves with myxomatous degeneration were studied. Immunohistochemical and histochemical studies were performed on sequential valve sections, including hematoxylin and eosin, hematoxylin phloxine saffron, Movat pentachrome, toluidine blue, CD31, CD34, and CD117. Results There were small clusters of CD117-positive cells in the fibrosa and spongiosa of mitral and aortic valves from all groups of valves. Sequential sectioning and staining showed that almost all of these cells were mast cells. However, in the mitral myxomatous valves and the mitral rheumatic valves, there were rare CD117-positive cells that did not have corresponding toluidine blue staining and thus could be valve mesenchymal stem cells. Conclusions Most of the CD117-positive cells in normal and diseased adult heart valves are mast cells. These valve cells could play a role in valve pathology and injury. A very small number of possible valve stem cells were also identified. It is unlikely that these valve stem cells are sufficient in number to allow isolation and expansion for tissue engineering purposes.

Ultrastructural morphologic evaluation of the phenotype of valvular interstitial cells in dogs with myxomatous degeneration of the mitral valve

To evaluate morphologic changes in valvular interstitial cells of dogs and to find evidence for disease-associated phenotypic changes in these cells. 5 clinically normal dogs and 5 dogs with severe mitral valve endocardiosis. Mitral valve leaflets were evaluated by use of transmission electron microscopy. Differences in cell type and cell location were identified. A change in cell type toward a myofibroblast or smooth muscle cell phenotype was detected, with the smooth muscle cell type being most common. These cells had long amorphous cytoplasmic extensions, fibrillar cytoplasm, incomplete basal lamina, few mitochondria, and eccentrically placed nuclei but lacked smooth endoplasmic reticulum or Golgi complexes. Remaining valvular interstitial cells had heterochromatic nuclei and produced only minimal quantities of collagen. Compared with normal valves, myxomatous valves ha many interstitial-like cells located adjacent to the endothelium. Deeper within the abnormal valves, cells with a heterogenous phenotype formed groupings that appeared to be anchored to adjacent collagen. Myxomatous degeneration of the mitral valve in dogs is associated with phenotypic alteration, changing from an interstitial to a mixed myofibroblast or smooth muscle cell phenotype. A closer association between interstitial cells and the endothelium is evident in diseased valves. In response to the disease process, valvular interstitial cells of dogs appear to change toward a smooth muscle phenotype, possibly in an attempt to maintain valve tone and mechanical function.

Prevention of Systolic Anterior Motion After Repair of the Severely Myxomatous Mitral Valve With an Anterior Leaflet Valvuloplasty

Systolic anterior motion after mitral valve repair of severely myxomatous valves is due to excess tissue or anterior displacement, or both, of the leaflet coaptation point. Our series of anterior leaflet valvuloplasty, an alternative to the sliding leaflet technique to prevent systolic anterior motion, is presented. Between January 1, 1996 and January 6, 2003, we performed elliptical excisions of the base of the anterior leaflet in 47 patients with a mean age of 66 years (range, 29 to 86). All patients had an anterior leaflet height of 3.0 cm or more and an annular diameter of 4.0 cm or more. Repairs included posterior leaflet (37; 80%), and anterior leaflet (28; 61%) resections, with occasional transposition flaps (9; 19%). All 47 (100%) had an annuloplasty ring (9, Physio; 37, Seguin). Four (8%) included tricuspid repair, 6 (13%) aortic valve replacement, and 9 (19%) coronary artery bypass. Follow-up was between 2 months and 8 years. There was no systolic anterior motion or in-hospital (30-day) mortality. Postoperative echocardiography revealed an average anterior leaflet height of 2.2 +/- 0.3 cm, with an annular diameter of 3 +/- 0.2 cm. The anterior/posterior leaflet ratio decreased from 1.6 +/- 0.2 to 1.4 +/- 0.1 cm while the coaptation point-annular plane distance decreased from 1.2 +/- 0.2 to 0.9 +/- 0.1 cm. There were 4 late noncardiac deaths. Two patients have required mitral valve replacement owing to progressive disease and 6 patients were lost to follow-up. The 35 patients remaining have trace-mild mitral regurgitation. Our anterior mitral valve leaflet valvuloplasty, regardless of the ring, results in a decrease in surface area and excursion of the anterior leaflet without systolic anterior motion.

CD34 + fibrocytes in normal mitral valves and myxomatous mitral valve degeneration

We investigated a total of 15 mitral valves with myxomatous degeneration and compared these with normal mitral valves. In normal mitral valves, stromal cells located in the fibrosa and spongiosa showed small bipolar cytoplasmic processes and were found to be positive for CD34, suggesting a close relationship to CD34 + fibrocytes. In cases of myxomatous degeneration, stromal cells showed an altered morphology in that they exhibited multipolar cytoplasmic processes, appeared to be hyperplastic, and were increased in number. This study is the first to report on CD34 + fibrocytes making up the majority of mitral valve stromal cells. Major factors in the development of myxomatous valve degeneration are MMP-9, as well as collagen I and III, which have been reported to be secreted by CD34 + fibrocytes. Therefore, it is likely that CD34 + fibrocytes are involved in the pathogenesis of myxomatous mitral valve degeneration.

TGF-β–dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome

Mitral valve prolapse (MVP) is a common human phenotype, yet little is known about the pathogenesis of this condition. MVP can occur in the context of genetic syndromes, including Marfan syndrome (MFS), an autosomal-dominant connective tissue disorder caused by mutations in fibrillin-1. Fibrillin-1 contributes to the regulated activation of the cytokine TGF-beta, and enhanced signaling is a consequence of fibrillin-1 deficiency. We thus hypothesized that increased TGF-beta signaling may contribute to the multisystem pathogenesis of MFS, including the development of myxomatous changes of the atrioventricular valves. Mitral valves from fibrillin-1-deficient mice exhibited postnatally acquired alterations in architecture that correlated both temporally and spatially with increased cell proliferation, decreased apoptosis, and excess TGF-beta activation and signaling. In addition, TGF-beta antagonism in vivo rescued the valve phenotype, suggesting a cause and effect relationship. Expression analyses identified increased expression of numerous TGF-beta-related genes that regulate cell proliferation and survival and plausibly contribute to myxomatous valve disease. These studies validate a novel, genetically engineered murine model of myxomatous changes of the mitral valve and provide critical insight into the pathogenetic mechanism of such changes in MFS and perhaps more common nonsyndromic variants of mitral valve disease.

Glycosaminoglycan profiles of myxomatous mitral leaflets and chordae parallel the severity of mechanical alterations

ObjectivesThis biochemical study compared the extracellular matrix of normal mitral valves and myxomatous mitral valves with either unileaflet prolapse (ULP) or bileaflet prolapse (BLP). BackgroundMyxomatous mitral valves are weaker and more extensible than normal valves, and myxomatous chordae are more mechanically compromised than leaflets. Despite histological evidence that glycosaminoglycans (GAGs) accumulate in myxomatous valves, previous biochemical analyses have not adequately examined the different GAG classes. MethodsLeaflets and chordae from myxomatous valves (n = 41 ULP, 31 BLP) and normal valves (n = 27) were dried, dissolved, and assayed for deoxyribonucleic acid, collagen, and total GAGs. Specific GAG classes were analyzed with selective enzyme digestions and fluorophore-assisted carbohydrate electrophoresis. ResultsBiochemical changes were more pronounced in chordae than in leaflets. Myxomatous leaflets and chordae had 3% to 9% more water content and 30% to 150% higher GAG concentrations than normal. Collagen concentration was slightly elevated in the myxomatous valves. Chordae from ULP had 62% more GAGs than those from BLP, primarily from elevated levels of hyaluronan and chondroitin-6-sulfate. ConclusionsThe GAG classes elevated in the myxomatous chordae are associated with matrix microstructure and elastic fiber deficiencies and may influence the hydration-related “floppy” nature of these tissues. These abnormalities may be related to the reported mechanical weakness of myxomatous chordae. The biochemical differences between ULP and BLP confirm previous mechanical and echocardiographic distinctions.

Decreased plasma concentration of nitric oxide metabolites in dogs with untreated mitral regurgitation.

Endothelium-dependent (nitric oxide [NO]-mediated) vasodilation is impaired in humans with heart failure. This dysfunction is an important therapeutic target. The plasma concentration of the NO metabolites nitrate and nitrite (collectively referred to as NOx) is a measure of whole-body NO production, provided that the dietary intake of the ions is low. Fifty clinically healthy dogs older than I year (median 5.0 years; interquartile interval 2.6-8.2 years) were studied, including 9 controls of various breeds, 23 Cavalier King Charles Spaniels (CKCSs) with no or minimal mitral regurgitation (MR), 9 CKCSs with mild MR (regurgitant jet occupying 15-50% of the left atrial area), and 9 CKCS with moderate to severe MR (jet >50%) due to myxomatous valve disease. None of the dogs received medication. The dogs were given NOx-free water and a diet with a low concentration of NOx for 96 hours before blood sampling. Multiple linear regression analysis revealed that dog group, but not gender, age, serum creatinine concentration, and platelet count, was associated with NOx concentrations. Control dogs had the same NOx concentration (median 20.0 microM; interquartile interval 15.1-25.5 microM) as CKCSs without MR (median 18.7 microM; interquartile interval 15.5-25.9 microM). Compared to CKCSs without MR, the NOx concentration was lower in CKCSs with mild (median 12.9 microM; interquartile interval 11.0-13.5 microM; P = .04) and moderate to severe (median 11.2 microM; interquartile interval 6.9-17.1 microM; P = .02) MR. In conclusion, CKCSs with mild to severe, clinically silent MR have decreased plasma NOx concentrations, suggesting that endothelial dysfunction develops early in the course of developing MR in dogs.

Endothelium and valvular diseases of the heart

It has become increasingly evident that the endothelium plays a critical role in the pathogenesis of valvular heart disease. The endothelium helps regulate vascular tone, inflammation, thrombosis, and vascular remodeling. Dysfunction of the endothelial cells has been linked to many vascular disorders including atherosclerosis. Common valvular diseases such as senile degenerative valve disease, myxomatous (or floppy) valves, rheumatic valves, and infective endocarditis valves show changes in the synthetic, morphologic, and metabolic functions of the valvular endothelial cells. These diseases are active processes related to endothelial cell dysfunction. Endothelial cell dysfunction is caused by mechanical forces, bacterial infection, autoantibodies, and circulating modulators of endothelial cell function. This study reviews the role of endothelial cell dysfunction in the more common valvular diseases. Continued research on endothelial cell dysfunction is crucial to our understanding of valvular heart diseases and may elucidate novel treatment and prevention strategies.

Decreased Plasma Concentration of Nitric Oxide Metabolites in Dogs with Untreated Mitral Regurgitation

Endothelium-dependent (nitric oxide [NO]-mediated) vasodilation is impaired in humans with heart failure. This dysfunction is an important therapeutic target. The plasma concentration of the NO metabolites nitrate and nitrite (collectively referred to as NOx) is a measure of whole-body NO production, provided that the dietary intake of the ions is low. Fifty clinically healthy dogs older than 1 year (median 5.0 years; interquartile interval 2.6–8.2 years) were studied, including 9 controls of various breeds, 23 Cavalier King Charles Spaniels (CKCSs) with no or minimal mitral regurgitation (MR), 9 CKCSs with mild MR (regurgitant jet occupying 15–50% of the left atrial area), and 9 CKCS with moderate to severe MR (jet ± 50%) due to myxomatous valve disease. None of the dogs received medication. The dogs were given NOx-free water and a diet with a low concentration of NOx for 96 hours before blood sampling. Multiple linear regression analysis revealed that dog group, but not gender, age, serum creatinine concentration, and platelet count, was associated with NOx concentrations. Control dogs had the same NOx concentration (median 20.0 μM; interquartile interval 15.1–25.5 μM) as CKCSs without MR (median 18.7 μM; interquartile interval 15.5–25.9 μM). Compared to CKCSs without MR, the NOx concentration was lower in CKCSs with mild (median 12.9 μM; interquartile interval 11.0–13.5 μM; P= .04) and moderate to severe (median 11.2 μM; interquartile interval 6.9–17.1 μM; P= .02) MR. In conclusion, CKCSs with mild to severe, clinically silent MR have decreased plasma NOx concentrations, suggesting that endothelial dysfunction develops early in the course of developing MR in dogs.

Transoesophageal Echocardiography in Patients without Arterial and Major Cardiac Sources of Embolism: Difference between Stroke Subtypes

We studied the records of 175 consecutive patients referred to our neurologic ward between January 1994 and February 2000 with a diagnosis of ischaemic cerebrovascular disease (ICVD) (stroke or transient ischaemic attack – TIA) who underwent transoesophageal echocardiography (TEE). We excluded patients with large vessel disease, high-risk embolic cardiopathies and other rare causes of stroke. According to clinical and neuroimaging findings, patients were divided into two groups. The lacunar (LAC) group (69/175 (39.4%)) and the nonlacunar (N-LAC) one (106/175 (60.6%)). The control population consisted of 78 consecutive patients, referred to the echocardiography laboratory for TEE without history of ICVD and known heart disorders. Patent foramen ovale (PFO) frequency was significantly higher in case patients than in control subjects (55/175 (31.4%) vs. 13/78 (16.6%); p = 0.02). Among case patients, PFO was more prevalent in the N-LAC group than in the LAC one (43/106 (40.6%) vs. 12/69 (17.4%); p = 0.0005). A large degree of shunt occurred in 53.5% of N-LAC patients and in 16.7% of LAC ones (p = 0.04). Atrial septal aneurysm (ASA) was detected in 12% of case patients and 1.3% of control subjects (p = 0.003) and was more frequent in the N-LAC group than in the LAC one (16 vs. 5.8%; p = 0.05). Mitral prolapse (MP) was present in 6/175 (3.4%) ICVD patients (vs. 1/78 among controls) in most cases associated with myxomatous valve redundancy. Aortic arch atheromas (AA) were detected in 12% of ICVD patients and in 10.2% of controls. The frequency was 9.4% in N-LAC and 15.9 in LAC. No complicated AA (plaque thickness >4 mm, ulcerated atheroma, superimposed thrombus) were detected. After multivariate analysis, PFO (OR = 3.8; 95% CI = 2.7–7.9) and ASA (OR = 8.01; 95% CI = 3.0–16.1) appeared to be independent predictors of ICVD. PFO (OR = 2.24; 95% CI = 1.24–4.92) was also independently associated with N-LAC stroke subtype and its importance was even higher in younger patients. Our study provides further evidence that TEE is a helpful diagnostic tool in stroke patients without arterial and major cardiac sources of embolism. However, its utility differs according to type and localization of the ischaemic lesion being more relevant in patient with N-LAC infarctions.

Efficacy of Enalapril for Prevention of Congestive Heart Failure in Dogs with Myxomatous Valve Disease and Asymptomatic Mitral Regurgitation

We evaluated the long-term effect of early angiotensin-converting enzyme (ACE) inhibition (enalapril maleate) as monotherapy to postpone or prevent congestive heart failure (CHF) in asymptomatic dogs with mitral regurgitation (MR) attributable to myxomatous valvular disease (MVD) in a prospective, randomized, double-blinded, placebo-controlled multicenter trial involving 14 centers in Scandinavia. Two hundred twenty-nine Cavalier King Charles (CKC) Spaniels with MR attributable to MVD but no signs of CHF were randomly allocated to treatment with enalapril 0.25-0.5 mg daily (n = 116) or to placebo groups (n = 113). Each dog was evaluated by physical examination, electrocardiography, and thoracic radiography at entry and every 12 months (+/-30 days). The number of dogs developing heart failure was similar in the treatment and placebo groups (n = 50 [43%] and n = 48 [42%], respectively; P = .99). The estimated means, adjusted for censored observations, for the period from initiation of therapy to heart failure were 1,150 +/- 50 days for dogs in the treatment group and 1,130 +/- 50 days for dogs in the placebo group (P = .85). When absence or presence of cardiomegaly at the entrance of the trial was considered, there were still no differences between the treatment and placebo groups (P = .98 and .51, respectively). Multivariate analysis showed that enalapril had no significant effect on the time from initiation of therapy to heart failure (P = .86). Long-term treatment with enalapril in asymptomatic dogs with MVD and MR did not delay the onset of heart failure regardless of whether or not cardiomegaly was present at initiation of the study.

Efficacy of Enalapril for Prevention of Congestive Heart Failure in Dogs with Myxomatous Valve Disease and Asymptomatic Mitral Regurgitation

We evaluated the long-term effect of early angiotensin-converting enzyme (ACE) inhibition (enalapril maleate) as monotherapy to postpone or prevent congestive heart failure (CHF) in asymptomatic dogs with mitral regurgitation (MR) attributable to myxomatous valvular disease (MVD) in a prospective, randomized, double-blinded, placebo-controlled multicenter trial involving 14 centers in Scandinavia. Two hundred twenty-nine Cavalier King Charles (CKC) Spaniels with MR attributable to MVD but no signs of CHF were randomly allocated to treatment with enalapril 0.25–0.5 mg daily (n = 116) or to placebo groups (n = 113). Each dog was evaluated by physical examination, electrocardiography, and thoracic radiography at entry and every 12 months (±30 days). The number of dogs developing heart failure was similar in the treatment and placebo groups (n = 50 [43%] and n = 48 [42%], respectively; P= .99). The estimated means, adjusted for censored observations, for the period from initiation of therapy to heart failure were 1,150 ± 50 days for dogs in the treatment group and 1,130 ± 50 days for dogs in the placebo group (P= .85). When absence or presence of cardiomegaly at the entrance of the trial was considered, there were still no differences between the treatment and placebo groups (P= .98 and .51, respectively). Multivariate analysis showed that enalapril had no significant effect on the time from initiation of therapy to heart failure (P= .86). Long-term treatment with enalapril in asymptomatic dogs with MVD and MR did not delay the onset of heart failure regardless of whether or not cardiomegaly was present at initiation of the study.

Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves.

The mechanisms of extracellular matrix changes accompanying myxomatous valvular degeneration are uncertain. To test the hypothesis that valvular interstitial cells mediate extracellular matrix degradation in myxomatous degeneration by excessive secretion of catabolic enzymes, we examined the functional characteristics of valvular interstitial cells in 14 mitral valves removed for myxomatous degeneration from patients with mitral regurgitation and in 11 normal mitral valves obtained at autopsy. Immunohistochemical staining assessed (1) cell phenotype using antibodies to alpha-actin (microfilaments), vimentin and desmin (intermediate filaments), smooth muscle myosin (SM1), and SMemb (a nonmuscle myosin produced by activated mesenchymal cells) and (2) the expression of proteolytic activity using antibodies to collagenases (matrix metalloproteinase [MMP]-1, MMP-13), gelatinases (MMP-2, MMP-9), cysteine endoproteases (cathepsin S and K), and interleukin-1beta, a cytokine that can induce secretion of proteolytic enzymes. Although interstitial cells in normal valves stained positively for vimentin, but not alpha-actin or desmin, cells in myxomatous valves contained both vimentin and alpha-actin or desmin (characteristics of myofibroblasts). Moreover, cells in myxomatous valves strongly expressed SMemb, MMPs, cathepsins, and interleukin-1beta, which were weakly stained in controls. Nevertheless, interstitial cells in both groups strongly expressed procollagen-I mRNA (in situ hybridization), suggesting preserved ability to synthesize collagen in myxomatous valves. Interstitial cells in myxomatous valves have features of activated myofibroblasts and express excessive levels of catabolic enzymes, without altered levels of interstitial collagen mRNA. We conclude that valvular interstitial cells regulate matrix degradation and remodeling in myxomatous mitral valve degeneration.

Invited commentary

Mitral valve repair for valvular insufficiency secondary to myxomatous valve disease has been demonstrated to be superior to mitral valve replacement in most circumstances. The functional characterization of the cause of the mitral valve insufficiency by Carpentier and the techniques he developed for its correction have proved durable. Techniques of repair such as quadrangular resection, annular plication, sliding plasty and annular remodeling using annuloplasty rings are easily learned and are in wide use. Degenerative mitral valve disease in the majority of cases involves primarily the posterior leaflet and annular dilatation. In the majority of cases where the posterior leaflet is prolapsed and the annulus is dilated, quadrangular resection alone with placement of a ring is all that is needed and can be accomplished easily in most cardiac centers. Anterior leaflet involvement is uncommon. Mild cases of anterior leaflet prolapse, associated with more pronounced posterior leaflet prolapse, generally do not need to be addressed if the primary pathology of the posterior leaflet and the dilated annulus is corrected.

Artificial mitral valve chordae replacement made simple

Mitral valve repair techniques are now widely applied in patients with myxomatous valve disease. The use of artificial chords to achieve correct height adjustment of the prolapsing anterior leaflet segment can often be challenging. We describe a simple method of artificial chord reconstruction performed after annuloplasty, which allows for easy identification of functional prolapse and accurate chordal height adjustment.

Clinical characteristics of a familial inherited myxomatous valvular dystrophy mapped to Xq28

OBJECTIVESThe purpose of this study was to describe the phenotypic characteristics of an inherited myxomatous valvular dystrophy mapped to Xq28.BACKGROUNDMyxomatous valve dystrophies are a frequent cause of valvular diseases, the most common being idiopathic mitral valve prolapse. They form a group of heterogeneous diseases difficult to subclassify. The first mapping of the gene for a myxoid valvular dystrophy to Xq28 allowed investigation of the phenotype of affected members in a large family and characterization of the disease.METHODSAmong the 318 members in the pedigree, 89 agreed to participate in this study. Phenotypic characteristics were investigated using clinical examination, transthoracic echocardiography and biological analysis (F.VIII activity). Genetic status was based on haplotype analysis.RESULTSAmong 46 males, 9 were hemizygous to the mutant allele and had an obvious mitral and/or aortic myxomatous valve defect, and 4 had undergone valvular surgery. All had typical mitral valve prolapse associated in six cases with moderate to severe aortic regurgitation. The valve defect cosegregated with mild hemophilia A (F.VIII activity = 0.32 ± 0.05). The 37 remaining males had normal valves and normal F.VIII activity. Heterozygous women were identified on the basis of their haplotypes. Among the 17 women heterozygous to the mutant allele, moderate mitral regurgitation was present in 8, associated with mild mitral valve prolapse in 1 and aortic regurgitation in 3, whereas 2 women had isolated mild aortic regurgitant murmur. In heterozygotes, the penetrance value was 0.60 but increased with age.CONCLUSIONX-linked myxomatous valvular disease is characterized by mitral valve dystrophy frequently associated with degeneration of the aortic valves affecting males and, to a lower severity, females. The first localization of a gene for myxomatous valvular diseases is the first step for the subclassification of these diseases.

Relationship between different natriuretic peptides and severity of naturally acquired mitral regurgitation in dogs with chronic myxomatous valve disease

To study the responses of atrial natriuretic peptide (ANP), N-terminal fragment of pro-atrial natriuretic peptide (NT-proANP) and brain natriuretic peptide (BNP) to varying severity of mitral regurgitation (MR) in dogs with myxomatous valve disease (MVD). Case-control. DOGS: 103 Cavalier King Charles Spaniels, 27 normal individuals and 76 with varying degree of MR. Dogs were evaluated by physical examination, collection of venous blood, thoracic radiography and echocardiography. NT-proANP, ANP and BNP were measured in plasma using radio immunoassay (RIA). The mean concentrations of NT-proANP were 37.4 and 83.5 times higher than ANP and BNP, respectively. The mean ANP to BNP molar ratio was 2.6. Plasma concentrations of NT-proANP and ANP were slightly increased in asymptomatic dogs with increased cardiac dimensions; those with signs of decompensated heart failure (HF) had mean concentrations of NT-proANP and ANP 3 to 7 times higher than normal dogs. The BNP concentrations were increased only in dogs with decompensated HF and the levels were approximately twice as high in these dogs as in normal individuals. Univariate and multiple regression analysis showed that primarily left atrial and ventricular size influenced the plasma concentrations of all 3 peptides (increased with increasing measurement). Analyses of response operating characteristic (ROC) curves indicated that NT-proANP and ANP were more discriminating than BNP for either cardiomegaly of HF. Natriuretic peptides, particularly NT-proANP and ANP, may be of benefit in the overall assessment of dogs with naturally occurring MR. Analysis of NT-proANP may be more useful than ANP owing to easier handling of the samples and less laborious assay.