Myxomatous degeneration of the mitral valve complicated by nonbacterial thrombotic endocarditis with systemic embolization.

Myxomatous degeneration of the mitral valve is a disease of unknown etiology that is associated with many ominous complications. A case in which non-bacterial thrombotic endocarditis, superimposed on a myxomatous mitral valve, resulted in systemic embolization to the brain, heart, and kidney is presented. The purpose of this report is to describe a serious and previously unreported complication of myxomatous degeneration of the mitral valve.     

Increased NADPH-diaphorase activity in canine myxomatous mitral valve leaflets

Comparable pathological changes in the mitral valve have been described in dogs, pigs and human patients with myxomatous mitral valve disease (MMVD), i.e., primary mitral valve prolapse. The progressive myxomatous changes are probably a response to repeated impact on the leaflets, and endothelial stress or damage probably plays a central role in the pathogenesis. Little, however, is known about the vasoactive substances that mediate the subendothelial changes. The aim of this study was to investigate the expression of nitric oxide synthase (NOS) in canine mitral valve leaflets and to relate the findings to MMVD changes. The mitral valve was taken post mortem from 12 dogs (six males and six females) and a whole valve NADPH (the reduced form of nicotinamide-adenine dinucleotide phosphate) diaphorase (NADPH-d) reaction was performed. Macroscopical (semiquantitative) and microscopical (computer image analysis) evaluations of the staining due to NADPH-d activity were performed at four specific areas of the valve and related to microscopical signs of MMVD and gross signs of thickening or prolapse, or both. Macroscopically, the NADPH-d colour grade was correlated with the degree of MMVD (P=0.01). In addition, endothelial NADPH-d staining intensity was correlated with macroscopical signs of disease (P=0.004) as well as with collagen degeneration (P=0.008) and deposition of mucopolysaccharides (P=0.02). Age, gender and specific area of the valve did not seem to influence the NADPH-d activity. In conclusion, increased NADPH-d activity, suggesting increased NOS expression, was found in areas of the mitral valve with myxomatous changes. This indicates that nitric oxide (NO) may play a role in the pathogenesis of MMVD in dogs.     

Abundance and location of proteoglycans and hyaluronan within normal and myxomatous mitral valves

IntroductionExtracellular matrix changes occur in many heart valve pathologies. For example, myxomatous mitral valves are reported to contain excess proteoglycans and hyaluronan. However, it is unknown which specific proteoglycans are altered in myxomatous valves. Because proteoglycans perform varied functions in connective tissues, this study was designed to identify and localize three matrix-associated proteoglycans, as well as hyaluronan and the hyaluronan receptor for endocytosis, within myxomatous and normal mitral valves.MethodsHuman mitral posterior leaflets (control, n=6–9; myxomatous, n=14–21; mean age, 61 years for all groups) were histochemically stained for proteoglycan core proteins, hyaluronan, and the hyaluronan receptor for endocytosis. Stain intensity was semiquantitatively graded to determine differences in marker abundance between normal and myxomatous valves. The proteoglycans were localized to different regions of the leaflet by correspondence to parallel Movat-stained sections.ResultsThe proteoglycans decorin, biglycan, and versican were more abundant in myxomatous valves than in normal controls (P<.03). There was a gender effect on proteoglycan presence, but no age-related trends were observed. Hyaluronan and the hyaluronan receptor for endocytosis were distributed throughout all valves. There was no significant difference in hyaluronan between groups, but expression of the hyaluronan receptor for endocytosis was reduced in myxomatous valves compared to normal controls (P<.002).ConclusionExcess decorin, biglycan, and versican may be associated with the remodeling of other matrix components in myxomatous mitral valves. Decreased expression of the hyaluronan receptor for endocytosis in myxomatous valves suggests that hyaluronan metabolism could be altered in myxomatous mitral valve disease. These findings contribute towards elucidating the pathogenesis of myxomatous mitral valve disease and developing potential new therapies.     

Myxoid heart disease: an assessment of extravalvular cardiac pathology in severe mitral valve prolapse.

Because of the microscopic features of the affected leaflets in mitral valve prolapse (MVP), myxoid degeneration of the valve is a common pathologic designation applied to this condition. We undertook this study as a means of gaining an insight into the occurrence and prevalence of extravalvular cardiac alterations in hearts with severe MVP. Tissues of 24 hearts with severe myxomatous transformation of the mitral valve as the sole cardiac abnormality were examined. Eighteen of the 24 subjects with severe MVP died suddenly. Only two of these had pathologic evidence of severe mitral insufficiency. Twenty-four normal hearts served as controls. The two groups of hearts came from victims of homicide, suicide, accident, or natural death. Sections of the mitral valve, working myocardium, conduction system, and cardiac nerves and ganglia were studied by routine and special connective tissue and proteoglycan stains. Similar to the findings in severely affected mitral valves, prominent deposits of proteoglycans in neural and conduction tissue readily distinguished hearts with myxomatous valve changes from the control hearts. We conclude that the commonly recognized local derangement of valvular tissue in MVP is but one specific reflection of a more general myxomatous alteration in cardiac connective tissue.     

Myxomatous mitral valve disease and related entities: The role of matrix in valvular heart disease

Myxomatous mitral valve disease is a cause of prolapse of mitral valve leaflet(s) into the left atrium. In this condition there is a loss of collagen from the leaflet and an accumulation of glycosaminoglycan. Complications of myxomatous mitral valve disease include infective endocarditis, mitral regurgitation, sudden death, and stroke. Mitral valve prolapse has been reported to occur in association with many syndromes. In some of these, such as Marfan syndrome, the pathology of the mitral valve has been well described and is that of a myxomatous valve. However, in some of the other disorders associated with mitral valve prolapse, there is no information yet available on the valve pathology, and this would be useful in order to better understand the pathogenesis of myxomatous mitral valve disease.     

Coenzyme Q in cardiovascular disease

Coenzyme Q10 or ubiquinone normally present in many plant and animal cells is an antioxidant. Coenzyme Q10 deficiency has been observed in patients with congestive heart failure, angina pectoris, coronary artery disease, cardiomyopathy, hypertension, mitral valve prolapse and after coronary revascularization. Coenzyme Q10 is involved in the synthesis of ATP and hence is useful in preventing cellular damage during ischaemia-reperfusion injury. The clinical benefits are mainly due to its ability to improve energy production, antioxidant activity, and membrane stabilizing properties. Several studies showed that coenzyme Q could be useful in patients with congestive heart failure, angina pectoris, cardiomyopathy, coronary artery disease and in the preservation of myocardium. Coenzyme Q10 is normally present in the low density lipoprotein cholesterol fraction and inhibits its oxidation. It can also regenerate vitamin E. Coenzyme Q10 is known for producing minor gastrointestinal discomfort and elevation in SGOT and LDH when used.     

An autopsy case of pseudoxanthoma elasticum: histochemical characteristics

An autopsy case of pseudoxanthoma elasticum is reported. A Japanese female patient complained of yellow papules on the neck, precordium, and axilla, beginning at 54 years of age. When the patient was 58 years old, in response to her visual disturbance a funduscopic examination was performed, revealing angioid streaks, and skin biopsy identified a characteristic pseudoxanthoma elasticum (PXE) lesion. The patient developed congestive heart failure, and following mitral valve prolapse and regurgitation flow into the left atrium, mitral valve replacement with a prosthetic valve was performed when the patient was 65 years old. Soon afterward, the patient complained of gait disturbance, and she died of congestive heart failure at 68 years of age. Autopsy specimen revealed fragmented, granular, and calcified elastic fibers in the middle to deep dermis and in the thickened subendocardium, and small to medium-sized muscular arteries revealed fragmented, laminated, and calcified elastic lamina; vascular changes were seen in the heart, lung, kidney, gastrointestinal tract, and iliac artery. Disrupted elastic fibers were visualized using the Weigert resorcin fuchsin method and were stained positive by antielastin and antifibronectin antibodies. Calcification was confirmed by von Kossa staining. Affected areas were PAS-positive after diastase digestion, indicating the presence of glycoprotein. Affected areas were colloidal iron-positive, indicating the presence of proteoglycan matrix.     

Late prosthetic valve endocarditis due to Cardiobacterium hominis, an unusual complication

We report a case of prosthetic valve endocarditis caused by Cardiobacterium hominis in a patient who had undergone atrial septal defect closure and mitral valve replacement of the heart in 1978. He presented with pyrexia of unknown origin and congestive cardiac failure. Investigations revealed infective endocarditis of prosthetic valve in mitral portion. Blood culture samples grew C. hominis. The patient was empirically started on vancomycin and gentamicin intravenously and ceftriaxone was added after isolation of the organism. Though subsequent blood cultures were negative, patient remained in congestive cardiac failure and died due to complications.     

Cerebral infarction due to systemic necrotizing vasculitis in a patient with rheumatic heart disease, subacute bacterial endocarditis and status epilepticus

Systemic necrotizing vasculitis involving cerebral blood vessels is described in a 30-year-old man with rheumatic heart disease and subacute bacterial endocarditis. Fever, anaemia, splenomegaly and positive blood cultures for Gram-negative bacteria were found on admission. The fever resolved with antibiotic therapy on the third hospital day but he then developed hemiplegia and multifocal seizures. The seizures progressed to uncontrollable status epilepticus accompanied by congestive heart failure and the patient died 20 d after admission. At autopsy, exudative and necrotizing vasculitis involving medium- to small-sized arteries was seen in the brain, the heart and the skeletal muscles. Rheumatic myocarditis and endocarditis and old rheumatic mitral valve deformities were also present. In addition, verrucous endocarditis in the mitral valve and Löhlein's focal glomerulonephritis were noted. We discuss the possible mechanism of the systemic necrotizing vasculitis in relation to rheumatic fever.     

Pattern and clinical aspects of congenital heart diseases and their management in Cameroon

The aim of the study was to investigate the occurrence, pattern and clinical aspects of congenital heart diseases and their management in Cameroon. In this multicentred retrospective study from January 2006 till November 2009, out of 51,636 consulting in three referral centres, 505 were recruited. All the patients presented with the following symptoms: cyanosis, clubbing, frequent respiratory tract infections, failure to thrive, growth retardation, precordial murmur and dyspnoea. Patients were sent for the screening of congenital heart disease. After the comprehensive Doppler echocardiography, the recruited patients were diagnosed with congenital (67.2%) and in few, acquired heart disease. Heart murmur, dyspnoea and growth retardation was the triad mostly encountered. The occurrence of congenital heart diseases in Cameroon is 9.87%. In Douala, isolated ventricular septal defect, interatrial septal defect and isolated pulmonary valve stenosis were more diagnosed than in Shisong (P <0.05) and Yaoundé (P <0.05). In Yaoundé, there were more cases of common arterial trunk, transposition of great arteries with ventricular septal defect and Ebstein disease than in Shisong (P <0.05) and Douala (P < 0.05). At Shisong, tetralogy of Fallot, arterial duct, coarctation of the aorta, congenital mitral valve regurgitation, atresia of the tricuspid valve, double outlet right ventricle, anomalous pulmonary venous return and left isomerism were more diagnosed than in Yaoundé (P <0.05) and in Douala (P <0.05). Thirty percent of the patients were operated abroad; 9% in the cardiac centre. Conclusion: Our data show that congenital heart diseases are represented in Cameroon as in the literature; isolated ventricular septal defect is the predominant pathology.     

Replacing the enzyme alpha-L-iduronidase at birth ameliorates symptoms in the brain and periphery of dogs with mucopolysaccharidosis type I

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by loss of activity of α-l-iduronidase and attendant accumulation of the glycosaminoglycans dermatan sulfate and heparan sulfate. Current treatments are suboptimal and do not address residual disease including corneal clouding, skeletal deformities, valvular heart disease, and cognitive impairment. We treated neonatal dogs with MPS I with intravenous recombinant α-l-iduronidase replacement therapy at the conventional 0.58 mg/kg or a higher 1.57 mg/kg weekly dose for 56 to 81 weeks. In contrast to previous results in animals and patients treated at a later age, the dogs failed to mount an antibody response to enzyme therapy, consistent with the induction of immune tolerance in neonates. The higher dose of enzyme led to complete normalization of lysosomal storage in the liver, spleen, lung, kidney, synovium, and myocardium, as well as in the hard-to-treat mitral valve. Cardiac biochemistry and function were restored, and there were improvements in skeletal disease as shown by clinical and radiographic assessments. Glycosaminoglycan levels in the brain were normalized after intravenous enzyme therapy, in the presence or absence of intrathecal administration of recombinant α-l-iduronidase. Histopathological evidence of glycosaminoglycan storage in the brain was ameliorated with the higher-dose intravenous therapy and was further improved by combining intravenous and intrathecal therapy. These findings argue that neonatal testing and early treatment of patients with MPS I may more effectively treat this disease.     

Transcatheter Mitral Valve Repair Therapies: Evolution,Status and Challenges

Mitral regurgitation is a common cardiac valve lesion, developing from primary lesions of the mitral valve or secondary to cardiomyopathies. Moderate or higher severity of mitral regurgitation imposes significant volume overload on the left ventricle, causing permanent structural and functional deterioration of the myocardium and heart failure. Timely correction of regurgitation is essential to preserve cardiac function, but surgical mitral valve repair is often delayed due to the risks of open heart surgery. Since correction of mitral regurgitation can provide symptomatic relief and halt progressive cardiac dysfunction, transcatheter mitral valve repair technologies are emerging as alternative therapies. In this approach, the mitral valve is repaired either with sutures or implants that are delivered to the native valve on catheters introduced into the cardiovascular system under image guidance, through small vascular or ventricular ports. Several transcatheter mitral valve technologies are in development, but limited clinical success has been achieved. In this review, we present a historical perspective of mitral valve repair, review the transcatheter technologies emerging from surgical concepts, the challenges they face in achieving successful clinical application, and the increasing rigor of safety and durability standards for new transcatheter valve technologies.     

A single nucleotide deletion resulting in a frameshift in exon 4 of TAB2 is associated with a polyvalular syndrome

ObjectivePolyvalvularmyxomatous degeneration is a rare clinical condition. A 51-year-old male patient presented at our centre with all four heart valves with myxomatous degeneration and severe mitral and aortic regurgitation due to leaflet prolapse. The patient referred five further family members with valvular heart disease at different stages of presentation. The aim of this study was to investigate the genetic basis of this familial polyvalvularmyxomatous degeneration which was associated with mild dysmorphic facial anomalies and short stature.DesignA detailed family history was recorded. Nine members of the family, affected or not by valvular heart disease, were studied clinically, echocardiographically and by detailed genetic analyses.ResultsSix of the nine family members had echocardiographic features of different degrees of degenerative heart valve disease. In addition, the affected subjects shared similar mild dysmorphic facial anomalies and short stature. Exome sequencing identified a rare heterozygous single nucleotide deletion in the TAB2 gene in all affected family members, which was absent in the unaffected members.ConclusionsA variant in the TAB2 gene is proposed as the cause of syndromic congenital heart disease, displaying congenital myxomatous degenerative heart valve disease, mild dysmorphic fascial anomalies and short stature in this family.     

An Autopsy Case of Chronic Rheumatic Carditis with Myocardial Aschoff Bodies

An autopsy case of chronic rheumatic carditis is described. The patient was a woman aged 32 years and the duration of the disease was more than eight years.
At autopsy, the heart showed typical mitral stenosis with verrucous scarring, calcification and contraction of the valve. Areas of degenerating muscle cells and proliferation of the interstitial connective tissue, partly with perivascular infiltration, were seen throughout the myocardium, and heart muscles showed narrowing and fragmentation. There was fibrinoid degeneration of the wall in small coronary vessels. Numerous Aschoff bodies of various structures were found mostly in the proliferated interstitial connective tissue, between damaged muscle bundles and adjacent to the small coronary vessels of the myocardium. A small number of Aschoff bodies were situated in the subendocardial tissue in which there was no muscle.     

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.     

Floppy mitral valve chordae tendineae: histopathologic alterations

Pathologic studies of floppy or myxomatous mitral valves have focused primarily on changes in the valve cusps, with little attention given to the chordae tendineae. In a systematic study of the histopathology of floppy mitral valve chordae tendineae, 128 nonruptured chordae from 8 severely regurgitant floppy mitral valves were compared to 152 chordae from 10 normal control mitral valves and to 152 chordae from 8 control mitral valves with severe regurgitation due to ischemic heart disease. Collagen alterations were observed in 2% of normal mitral valve chordae and 3% of control regurgitant mitral valve chordae compared to 38% of floppy mitral valve chordae. Moderate or severe acid mucopolysaccharide accumulation was observed in 2% of normal mitral valve chordae and 3% of control regurgitant mitral valve chordae compared to 39% of floppy mitral valve chordae. Nonuniform histopathologic alterations, rare in normal and control regurgitant mitral valve chordae tendineae, were frequent in floppy mitral valve chordae tendineae (p less than 0.001). Histopathologic alterations provide the basis for abnormal physical properties previously demonstrated in floppy mitral valve chordae tendineae and may predispose to chordal elongation and rupture.     

Congestive heart failure due to coronary artery disease without myocardial infarction: clinicopathologic description of an unusual cardiomyopathy

Cardiomyopathies (CMs) can be classified as idiopathic dilated, hypertrophic, restrictive/obliterative, and so-called "ischemic cardiomyopathy." We have observed a subgroup of patients with congestive heart failure, dilated hearts, and severe coronary artery disease in the absence of myocardial infarction and therefore not fulfilling the criteria for ischemic CM. To better elucidate this group, which we called "coronary" CM, 54 consecutive necropsy patients who had congestive heart failure were retrospectively studied. Nineteen patients had idiopathic dilated CM, 26 had ischemic CM, and nine had coronary CM. The mean age of the patients with coronary CM and ischemic CM was significantly greater than that of the patients with idiopathic dilated CM (62 +/- 10 and 64 +/- 10 years versus 47 +/- 19 years, respectively). The duration of congestive heart failure was longest in the coronary CM group (4.1 +/- 3.4 years); half of these patients died suddenly or from arrhythmias. Hearts from patients with coronary CM had marked biventricular dilatation and severe coronary artery disease (mean number of coronary arteries with more than 75% narrowing, 2.2). No acute or healed infarcts were grossly visible, but interstitial and focal perivascular fibrosis were present in the myocardium of all coronary CM hearts. Although coronary CM may comprise a subset of so-called "ischemic cardiomyopathy," these cases may also represent idiopathic dilated CM with coincidental coronary artery disease.     

Mitral annular calcification and the risk of stroke in an elderly cohort.

BACKGROUND. Previous clinical studies have suggested that there is an association between mitral annular calcification and the risk of stroke, but it is unclear whether this association is independent of the traditional risk factors for stroke. We examined the relation between mitral annular calcification and the incidence of stroke in a population-based study. METHODS. Subjects in the Framingham Study receiving a routine examination underwent M-mode echocardiography to determine the presence and severity (thickness in millimeters) of mitral annular calcification. The incidence of stroke during eight years of follow-up was analyzed with a proportional-hazards model adjusting for the calcification, age, sex, systolic blood pressure, diabetes mellitus, cigarette smoking, atrial fibrillation, and coronary heart disease or congestive heart failure. RESULTS. Among 1159 subjects whose echocardiograms could be assessed for mitral annular calcification and who had no history or current evidence of stroke at the index examination (51 percent of all subjects), the prevalence of mitral annular calcification was 10.3 percent in the men and 15.8 percent in the women. Multivariate analysis demonstrated that the presence of mitral annular calcification was associated with a relative risk of stroke of 2.10 (95 percent confidence interval, 1.24 to 3.57; P = 0.006). There was a continuous relation between the incidence of stroke and the severity of mitral annular calcification; each millimeter of thickening as shown on the echocardiogram represented a relative risk of stroke of 1.24 (95 percent confidence interval, 1.12 to 1.37; P less than 0.001). Furthermore, even when subjects with coronary heart disease or congestive heart failure were excluded from the analysis, subjects with mitral annular calcification still had twice the risk of stroke. CONCLUSIONS. In an elderly, longitudinally followed population-based cohort, mitral annular calcification was associated with a doubled risk of stroke, independently of traditional risk factors for stroke. Whether such calcification contributes causally to the risk of stroke or is merely a marker of increased risk because of its association with other precursors of stroke remains unknown.