natriuretic-peptide--brain and Marfan-Syndrome

Marfan syndrome (MFS) is an inherited connective tissue disorder characterized by ectopia lentis, aortic root dilation and dissection and specific skeletal features. Obstructive sleep apnea (OSA) in MFS has been described earlier but the prevalence and its relation with the cardiovascular risk is still controversial. This study aimed to further investigate these aspects.. In this prospective longitudinal study, we performed an attended polysomnography in 40 MFS patients (60% women, 37 ± 12.8 years) and evaluated several cardiovascular parameters through echocardiography, resting electrocardiogram, 24 hr-Holter monitoring and serum NT-ProBNP measurements.. We found that OSA was present in 42.5% of the patients and that higher body mass index was the most important factor associated with the presence of OSA. We observed that overweight was present in 27.5% of the patients in the whole cohort and in 55.6% if >40 years. Furthermore, when evaluating the impact of OSA on the cardiovascular system, we observed that patients with OSA tended to have higher systolic blood pressure, larger distal aortic diameters and a higher prevalence of ventricular arrhythmia. These differences were, however, not significant after adjusting for confounders.. Our study shows a high prevalence of OSA and a high prevalence of overweight in MFS patients. We found some trends between OSA and cardiovascular features but we could not establish a solid association. Our study, however might be underpowered, and a multicenter collaborative study could be very useful to answer some important open questions.

Topics: Adult; Aortic Aneurysm; Aortic Dissection; Arrhythmias, Cardiac; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Electrocardiography; Female; Fibrillin-1; Genetic Association Studies; Humans; Male; Marfan Syndrome; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Polysomnography; Prevalence; Prospective Studies; Risk Factors; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Young Adult

Marfan syndrome (MFS) is associated with a substantial risk for ventricular arrhythmia and sudden cardiac death (SCD). We used heart rate turbulence (HRT) and deceleration capacity (DC), to evaluate the risk stratification for these patients.. We enrolled 102 patients [45 male (44.1 %), age 40.5 ± 14.6 years] with MFS. Blood samples were obtained to determine N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Transthoracic echocardiography studies were conducted to evaluate heart function parameters and a 24-h holter ECG was performed. An analysis of two HRT parameters, turbulence onset (TO) and turbulence slope (TS), and DC was performed. Therefore, optimal cut-off values were calculated. Primary endpoint was the combination of SCD, ventricular arrhythmia and arrhythmogenic syncope. Secondary endpoint was total mortality.. During a follow-up of 1145 ± 491 days, 12 (11.7 %) patients reached the primary and 8 (7.8 %) patients the secondary endpoint. Patients reaching the primary were significantly older, had a higher burden of premature ventricular complexes and NT-proBNP levels and lower values of LVEF, DC and HRT TS. Multivariate analysis identified NT-proBNP (HR 1.25, 95 % CI 1.01-1.56, p = .04) and the abnormal HRT (abnormal TS and/or TO (HR 7.04, 95 % CI 1.07-46.27, p = .04) as independent risk predictor of arrhythmogenic events.. Patients with Marfan syndrome are at risk for severe ventricular arrhythmias and SCD. Abnormal HRT parameters and NT-proBNP values are independent risk factors for arrhythmogenic events and SCD. The assessment of these tools may help predicting SCD patients with MFS.

Topics: Adult; Age Factors; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Deceleration; Echocardiography; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Heart Rate; Humans; Male; Marfan Syndrome; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Registries; Risk Factors; Ventricular Premature Complexes

Topics: Aortic Rupture; Biomarkers; Female; Humans; Marfan Syndrome; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Care; Prenatal Diagnosis

Although periodontitis is a risk factor for cardiovascular disease (CVD), the influence of periodontitis on Marfan syndrome (MFS) with CVD is unclear. The aim of this study was to assess the relationship between periodontal bacterial burden and MSF with CVD.. The subjects were patients with MFS with CVD (n = 47); age and gender matched non-MFS CVD patients (n = 48) were employed as controls. Full-mouth clinical measurements, including number of teeth, probing of pocket depth (PD), bleeding on probing (BOP) and community periodontal index (CPI) were recorded. We also evaluated the existence of three periodontal pathogens, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella intermedia using polymerase chain reaction assays. Serum antibody titers against the pathogens were also measured. We revealed that MFS with CVD patients had periodontitis more frequently than the age and gender matched non-MFS CVD control subjects. MFS with CVD patients had significantly severer periodontitis, fewer remaining teeth and deeper PD compared to the non-MFS CVD controls. Furthermore, the serum antibody titer level against Prevotella intermedia was significantly lower in MFS plus CVD patients compared to the non-MFS CVD patients.. Periodontitis may influence the pathophysiology of cardiovascular complications in MFS patients. A specific periodontal pathogen might be a crucial therapeutic target to prevent CVD development.

Topics: Adult; Antibodies, Bacterial; Bacteroidaceae Infections; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Male; Marfan Syndrome; Natriuretic Peptide, Brain; Periodontitis; Prevotella intermedia

Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation.. We performed an observational cohort study of 80 consecutive adults (30 men, 50 women aged 42±15 years) with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h), as ventricular couplets (Couplet), or as non-sustained ventricular tachycardia (nsVT), and during 31±18 months of follow-up as ventricular tachycardia (VT) events (VTE) such as sudden cardiac death (SCD), and sustained ventricular tachycardia (sVT). We identified >10 PVC/h in 28 (35%), Couplet/nsVT in 32 (40%), and VTE in 6 patients (8%), including 3 with SCD (4%). PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro-brain natriuretic peptide serum levels(P<.001). All arrhythmias related to increased NT-proBNP (P<.001), where PVC>10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020), to moderate mitral valve regurgitation (P = .018 and P = .003), and to prolonged QTc intervals (P = .001 and P = .006), respectively. Moreover, VTE related to mutations in exons 24-32 (P = .021). Kaplan-Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001) and with mutations in exons 24-32 (P<.001).. Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24-32 may be risk factors of VTE.

Topics: Adult; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Electrocardiography, Ambulatory; Exons; Female; Fibrillin-1; Fibrillins; Humans; Kaplan-Meier Estimate; Male; Marfan Syndrome; Microfilament Proteins; Middle Aged; Mutation; Natriuretic Peptide, Brain; Peptide Fragments; Tachycardia, Ventricular