Recent infective endocarditis research findings suggest dentists prescribe prophylactic antibiotics for patients having a bicuspid aortic valve or mitral valve prolapse.

BACKGROUND: The scientific validity of the European Society of Cardiology's (ESC) infective endocarditis (IE) guidelines limiting provision of prophylactic antibiotics (AP) only to patients having cardiac anomalies (e.g., prosthetic valves) believed to place them at "high risk" of adverse events when undergoing high risk dental procedures (HRDP) is unclear. MATERIAL AND METHODS: A systematic review of studies conducted between 2017 and 2022 and catalogued in the PubMed database was undertaken to ascertain if this edict was associated with changes in IE incidence, development of infection in unprotected cardiac anomalies, developing infection and resultant adverse clinical outcomes. RESULTS: Retrieved were 19 published manuscripts, however of these, 16 were excluded because they did not bare upon the issues of concern. Among the three studies eligible for review were those in the Netherlands, Spain, and England. The results of the Dutch study denoted a significant increase in the incidence of IE cases over the projected historical trend (rate ratio: 1327, 95% CI 1.205-1.462; p<0.001) after the introduction of the ESC guidelines. The findings from the Spanish study evidenced the uniquely high in-hospital IE associated fatality rates suffered by patients having bicuspid aortic valves (BAV); 5.6% or mitral valve prolapse (MVP); 10%. The British study provided evidence that the incidence of fatal IE infection was significantly greater among an "intermediate risk" cohort of patients, (a group likely including those with BAC and MVP for which the ESC guidelines don't recommend AP), than among "high risk" patients (P = 0.002). CONCLUSIONS: Patients having either a BAV or MVP are at significant risk of developing IE and suffering serious sequelae including death. The ESC guidelines must reclassify these specific cardiac anomalies into the "high risk" category so that AP are recognized as being needed prior to provision of HRDP.

Beneficial Effects of Mineralocorticoid Receptor Antagonism on Myocardial Fibrosis in an Experimental Model of the Myxomatous Degeneration of the Mitral Valve.

Mitral valve prolapse (MVP) patients develop myocardial fibrosis that is not solely explained by volume overload, but the pathophysiology has not been defined. Mineralocorticoid receptor antagonists (MRAs) improve cardiac function by decreasing cardiac fibrosis in other heart diseases. We examined the role of MRA in myocardial fibrosis associated with myxomatous degeneration of the mitral valve. Myocardial fibrosis has been analyzed in a mouse model of mitral valve myxomatous degeneration generated by pharmacological treatment with Nordexfenfluramine (NDF) in the presence of the MRA spironolactone. In vitro, adult human cardiac fibroblasts were treated with NDF and spironolactone. In an experimental mouse, MRA treatment reduced interstitial/perivascular fibrosis and collagen type I deposition. MRA administration blunted NDF-induced cardiac expression of vimentin and the profibrotic molecules galectin-3/cardiotrophin-1. In parallel, MRA blocked the increase in cardiac non-fibrillar proteins such as fibronectin, aggrecan, decorin, lumican and syndecan-4. The following effects are blocked by MRA: in vitro, in adult human cardiac fibroblasts, NDF-treatment-induced myofibroblast activation, collagen type I and proteoglycans secretion. Our findings demonstrate, for the first time, the contribution of the mineralocorticoid receptor (MR) to the development of myocardial fibrosis associated with mitral valve myxomatous degeneration. MRA could be a therapeutic approach to reduce myocardial fibrosis associated with MVP.

Effect of atorvastatin on oxidative stress and inflammation markers in myxomatous mitral valve disease in dogs: A comparison of subclinical and clinical stages.

Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disorder found in dogs. The disease process can lead to heart failure (HF) and has been found to be associated with oxidative stress and inflammation. Statins exert antioxidant and anti-inflammatory effects in human HF patients. However, the beneficial effects of statins in MMVD dogs are still unclear. Thirty MMVD dogs were enrolled in the study and were divided into two groups: MMVD without HF dogs (n = 15) and MMVD with HF dogs (n = 15). Atorvastatin (8 mg kg-1  day-1 ) was administered orally to all dogs for 4 weeks. All dogs underwent physical examination and cardiac examination at the beginning and end of the experiment, including baseline values for hematology, blood chemistry profile, lipid profile, N-terminal pro B-type natriuretic peptide, oxidative stress marker (8-isoprostane), and inflammatory marker (tumor necrosis factor alpha). The results showed that atorvastatin reduced plasma cholesterol levels in both groups. In addition, plasma concentrations of 8-isoprostane, tumor necrosis factor alpha, and N-terminal pro B-type natriuretic peptide were significantly lower after atorvastatin administration, but only in MMVD dogs in the HF group. Atorvastatin found to be associated with possible antioxidant and inflammatory effects in dogs with HF secondary to MMVD. The potential benefits of statins in dogs with HF merits further investigation in larger, placebo-controlled studies.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Effects of pimobendan on myocardial perfusion and pulmonary transit time in dogs with myxomatous mitral valve disease: a pilot study.

OBJECTIVES: To describe pulmonary transit time (nPTT) and myocardial perfusion (nMP) normalised to heart rate in dogs with stable ACVIM stage C myxomatous mitral valve disease (MMVD) and to assess short-term effects of pimobendan on these variables. We hypothesised that nPTT and nMP would increase in dogs with MMVD compared with normal dogs. Additionally, we hypothesised that treatment with pimobendan would decrease nMP and nPTT in dogs with MMVD. DESIGN: Prospective, single-blind study involving 6 normal dogs and 12 dogs with MMVD. METHODS: Dogs with MMVD were treated with enalapril and furosemide for at least 1 month prior to examination. All dogs underwent standard and contrast echocardiographic examinations at the beginning of the study (T0). At this time, MMVD dogs were randomly assigned to receive either pimobendan (0.4-0.6 mg/kg) or not. All dogs with MMVD were re-evaluated by standard and contrast echocardiography after 1 week (T1) and nPTT and nMP were measured. RESULTS: nPTT was significantly increased in dogs with MMVD (P = 0.0063), compared with normal dogs. It was significantly decreased at T1 in dogs receiving pimobendan (P = 0.0250). The nMP was not significantly different in dogs with MMVD, compared with healthy dogs (P = 0.2552), and it was not significantly different at T1 in the treatment group (P = 0.8798). CONCLUSIONS: Contrast echocardiography was a valid, complementary tool for echocardiographic analysis of dogs with MMVD. Pimobendan decreased nPTT in dogs affected by MMVD. Myocardial perfusion was not different in dogs with severe MMVD.

Mitral Valve Prolapse in Pregnancy.

Mitral valve prolapse is a benign condition. Mitral regurgitation is only complicated in patients with severe mitral valve prolapse. Women with mitral valve prolapse in the absence of other cardiovascular disorders tolerate pregnancy well and do not develop remarkable cardiac complications. Nevertheless, serious complications of mitral valve prolapse, including arrhythmia, infective endocarditis and cerebral ischemic events, can be present in pregnancy. Debates remain with regard to the use of prophylactic antibiotics and ß-blockers in the pregnant women with mitral valve prolapse. The prognosis of the pregnant patients might be closely related to the pathological and (or) functional changes of the mitral valve. Non-myxomatous mitral valve prolapse poses no or little obstetric risks in terms of pregnancy, labor and neonatal complications; whereas myxomatous mitral valve prolapse is a major etiology of valvular heart disease in women of childbearing age. In the pregnant patients with mitral valve prolapse progressing into major complications, surgical interventions are considered. Medicinal treatment of such patients with ß-blockers should be a concern for the fetal safety.

[THE ROLE OF TRANSFORMING GROWTH FACTOR-B IN IMMUNOPATHOGENESIS OF DISEASES OF CONNECTIVE TISSUE].

The recent studies of molecular physiology of fibrillin and pathophysiology of inherent disorders of structure and function of connective tissue such as dissection and aneurysm of aorta, myxomatously altered cusps and prolapses of mitral valve, syndrome of hyper-mobility of joints, demonstrated that important role in development of these malformations play alterations of transfer of signals by growth factors and matrix cellular interaction. These conditions under manifesting Marfan's syndrome can be a consequence of anomalies of fibrillin-1 which deficiency unbrakes process of activation of transforming growth factor-ß (TGFß). The involvement of TGFß in pathogenesis of Marfan's syndrome permits consider antagonists of angiotensin-transforming enzymes as potential pharmaceuticals in therapy of this disease. The article presents analysis of publications' data related to this problem.

Mitral valve prolapse in pregnancy

Abstract Mitral valve prolapse is a benign condition. Mitral regurgitation is only complicated in patients with severe mitral valve prolapse. Women with mitral valve prolapse in the absence of other cardiovascular disorders tolerate pregnancy well and do not develop remarkable cardiac complications. Nevertheless, serious complications of mitral valve prolapse, including arrhythmia, infective endocarditis and cerebral ischemic events, can be present in pregnancy. Debates remain with regard to the use of prophylactic antibiotics and β-blockers in the pregnant women with mitral valve prolapse. The prognosis of the pregnant patients might be closely related to the pathological and (or) functional changes of the mitral valve. Non-myxomatous mitral valve prolapse poses no or little obstetric risks in terms of pregnancy, labor and neonatal complications; whereas myxomatous mitral valve prolapse is a major etiology of valvular heart disease in women of childbearing age. In the pregnant patients with mitral valve prolapse progressing into major complications, surgical interventions are considered. Medicinal treatment of such patients with β-blockers should be a concern for the fetal safety.

Marfan Syndrome and Related Disorders: 25 Years of Gene Discovery.

Marfan syndrome (MFS) is a rare, autosomal-dominant, multisystem disorder, presenting with skeletal, ocular, skin, and cardiovascular symptoms. Significant clinical overlap with other systemic connective tissue diseases, including Loeys-Dietz syndrome (LDS), Shprintzen-Goldberg syndrome (SGS), and the MASS phenotype, has been documented. In MFS and LDS, the cardiovascular manifestations account for the major cause of patient morbidity and mortality, rendering them the main target for therapeutic intervention. Over the past decades, gene identification studies confidently linked the aforementioned syndromes, as well as nonsyndromic aneurysmal disease, to genetic defects in proteins related to the transforming growth factor (TGF)-ß pathway, greatly expanding our knowledge on the disease mechanisms and providing us with novel therapeutic targets. As a result, the focus of the developing pharmacological treatment strategies is shifting from hemodynamic stress management to TGF-ß antagonism. In this review, we discuss the insights that have been gained in the molecular biology of MFS and related disorders over the past 25 years.

Effect of pimobendan on the incidence of arrhythmias in small breed dogs with myxomatous mitral valve degeneration.

OBJECTIVE: To determine if pimobendan, a phosphodiesterase III inhibitor and calcium sensitizer with positive survival benefits, has an effect on incidence of arrhythmias compared to placebo in small breed dogs with congestive heart failure (CHF) due to myxomatous mitral valve degeneration (MMVD). ANIMALS: Eight client-owned small breed dogs (<15 kg) with CHF due to MMVD. METHODS: A prospective double-blind randomized placebo-controlled crossover study design was used. Data were recorded at baseline and 2 weeks post-administration of placebo or pimobendan. Average heart rate and incidence of arrhythmia were determined from 24 h Holter analysis. Owners completed a quality of life (QOL) questionnaire at each time point and recorded sleeping respiratory rates (SRR). Mixed effects analysis of variance, with dog as the random variable was used to compare values obtained between baseline, placebo, and pimobendan. RESULTS: Compared to baseline, QOL scores were significantly improved following administration of either placebo or pimobendan (p = 0.021 and p < 0.001, respectively). No significant differences in type or incidence of supraventricular or ventricular arrhythmia were identified. Average heart rate with pimobendan was significantly lower than baseline (p < 0.001). Compared to baseline, SRR was significantly lower with pimobendan (p = 0.004), and significantly different from placebo (p = 0.045). CONCLUSIONS: No significant difference between pimobendan and placebo was found on incidence of supraventricular or ventricular arrhythmia. The decrease in average heart rate and SRR may be reflective of superior heart failure control achieved with pimobendan therapy.

Short-term effect of granulocyte colony-stimulating factor in dogs with severe myxomatous mitral valve disease.

BACKGROUND: Use of granulocyte colony-stimulating factor (G-CSF) to treat damaged myocardium is a relatively new concept. Clinical beneficial and safety outcomes are still controversial. OBJECTIVE: The aim of this study was to evaluate recruitment of hematopoietic stem cells and therapeutic efficacy of G-CSF in the treatment of myxomatous mitral valve disease (MMVD) of dogs. ANIMALS AND METHODS: Thirty client-owned MMVD dogs with clinical signs of heart failure were enrolled in a prospective double-blind, randomized, placebo-controlled study to compare the short-term effect of G-CSF (n = 17) with control group (n = 13) for identical periods. Clinical, hematological, and cardiovascular assessments were performed on days 0, 1, 3, and 7. Follow-up examination was conducted four weeks after the study. RESULTS: Dogs treated with G-CSF had a significantly elevated white blood cell (WBC) (×10(3)/µL) count at day 3 compared with baseline (from 10.23 ± 4.42 to 42.84 ± 11.84; P = .000). The WBC population was also changed (elevated neutrophils and decreased lymphocytes) and the numbers of CD34+ cells in the peripheral blood were also increased at day 3. However, the results of clinical, laboratory, and echocardiographic assessments did not differ significantly between the G-CSF treatment and control groups after four weeks. CONCLUSIONS: G-CSF administration elevated the peripheral WBC count, especially neutrophils, and recruited hematopoietic stem cells. However, positive effects of G-CSF on cardiac function were not detected during short-term monitoring.

A national survey of pediatric dentists on antibiotic use in children.

PURPOSE: The purposes of this study were to: (1) examine the antibiotic prescribing practices of pediatric dentists and adherence to professional guidelines; and (2) assess their knowledge of and attitudes toward antibiotic resistance. METHODS: A cross-sectional survey regarding antibiotic use, resistance, and knowledge of antibiotic stewardship programs was emailed to 4,636 members of the American Academy of Pediatric Dentistry (AAPD). RESULTS: 987 surveys (21 percent) were completed; 984 were analyzed. Lack of adherence to AAPD antibiotic guidelines was noted. There was a trend toward overuse of antibiotics for the following conditions: irreversible pulpitis with (32 percent) and without vital pulp (42 percent); localized dentoalveolar abscess with (68 percent) and without draining fistula (39 percent); mitral valve relapse with regurgitation (43 percent); intrusion (15 percent); extrusion (13 percent); and rheumatoid arthritis (12 percent). Determinants of antibiotic use were: facial swelling (88 percent); pain relief (15 percent); unavailable appointment for several weeks (six percent); and parental satisfaction (four percent). Although 98 percent of respondents believed that antibiotic resistance is of growing concern, only 15 percent were aware of antibiotic stewardship programs. CONCLUSION: AAPD members overprescribe antibiotics. Educational programs to increase knowledge of antibiotic resistance and stewardship programs should be implemented to increase adherence to professional guidelines.

[Fifteen years experience of the use of magnesium preparations in patients with mitral valve prolapse].

We followed for 15 years 31 patients with mitral valve prolapse (MVP) who during follow-up regularly took orotic acid (1500 mg/day) for 3 months twice a year. We revealed peculiarities of dynamics of clinical picture, their interrelation with phenotypic manifestations of connective tissue dysplasia, changes of electrocardiogram, structure of valvular apparatus of the heart, state of vegetative homeostasis, changes of levels and 24-hour profile of arterial pressure, tone of sympathetic and parasympathetic parts of vegetative nervous system. We noted significant reduction of mean and maximal heart rate, number of episodes of tachycardia, duration of QTc intervals, incidence of paroxysmal supraventricular and ventricular extrasystoles. We fixed statistically significant lowering of maximal systolic and diastolic arterial pressure, hypertensive burden and elevated variability of systolic and diastolic arterial pressure. Data of retrospective analysis showed absolute normalization of these parameters in all studied patients. Decrease of the tone of sympathetic part of vegetative nervous system was also established. There was 2 to fold decrease of number of persons with sympathicotonia, 3 to fold increase of those with vagotonia, and 5 times increase of number of patients with equal tone of sympathetic and parasympathetic parts. Regular use of magnesium salt of orotic acid was associated with significant elevation of quality of life of patients with MVP. Clinically valuable improvement of work and social life scores was noted in 54.8%, of personal life score - in 45.2% of individuals. In half of patients with MVP index of efficacy of therapy with orotic acid was significant.

Spontaneous resolution of severe mitral regurgitation in a patient with a flail mitral valve.

Flail mitral valve usually causes severe mitral regurgitation, which may lead to left ventricular dysfunction if left uncorrected. The authors present a case of flail posterior mitral valve leaflet and severe mitral regurgitation in which mitral valve adaptation led to enlargement of the anterior mitral valve leaflet, decrease in mitral regurgitation, and reverse left ventricular remodeling without any need for surgery.

Prophylaxis to prevent infective endocarditis: to use or not to use?

The American Heart Association (AHA) published their revised guidelines in 2007 in which they markedly limited the recommendations for the use of antimicrobial prophylaxis for the prevention of infective endocarditis (IE), except for patients who are at highest risk of adverse outcomes. A recent focused update on valvular heart diseases changed the recommendation for antibiotic use for patients with many underlying heart conditions including mitral valve prolapse (MVP) which were considered as "low risk" heart defects. In this article, we argue that antibiotic prophylaxis should be considered until concrete clinical evidence is provided to dispute against the use of this strategy, especially for patients with MVP. This approach is cost efficient, and provides a chance to prevent a dreadful disease. We have also enlisted 2 clinical cases to support our argument. These are not uncommon clinical scenarios, and emphasize that IE can be fatal in spite of optimum treatment. Patients have the right to make the final decision, and they should be allowed to participate in choosing for or against this approach until adequate clinical evidence is available.

[The use of Magne B6 in order to increase compensatory-adaptive possibilities in youths with primary mitral valve prolapse].

The aim of the study--to estimate the effect of therapy with Magne 6 on the indices of cardiac hemodynamics, tolerance to physical load, activity of antioxidant protection enzymes and grade of hypoxia in youths with 1 grade mitral valve prolapse (MVP) without regurgitation. In 73 cases with impaired compensatory adaptive possibilities the extent of main syndromes of autonomic dystonia and state of cardiac hemodynamic indices were evaluated. The activity of catalase (C), glutathione reductase (GR), superoxide dismutase (SOD), lactate (L) and pyruvate (P) level were detected in red blood cells, the coefficient lactate/pyruvate (L/P) was been calculated according to the standard method. In the study the high-grade of autonomic dystonia (36.6 +/- 2.1 scores) was been revealed. The number of scores in the control group is 10.8 +/- 1.8. There was found the confident increase of stroke by 37.18%, cardiac output by 24%, stroke index--by 38.45% and cardiac index--by 43.06% in comparison with healthy persons (a < 0.05). The time of cycle ergometer load was significantly lower than in reference group 20.22% (a < 0.05). The red blood cells levels of PVK and L were correspondingly 95.4% and 51.4% higher than in control (p < 0.05). The L/P ratio was 22.5% in excess of the value in reference group (p < 0.05). C activity was 4.59 times less, SOD and GR activity were correspondingly 6.23 and 1.85 times (p < 0.05) as mush, than in healthy persons. Associated with Magne 6 therapy for a month the improvement in indices of cardiac hemodynamics, rising of tolerance to physical load, the fall in GR activity and decrease of hypoxia were been noted. Magne 6 may be used for magnifying of compensatory--adaptive possibilities in youths with 6 MVP.