The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies.

Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition.

Diagnosis, management and mortality in acute aortic syndrome: results of the Spanish Registry of Acute Aortic Syndrome (RESA-II).

BACKGROUND: Recent advances in the diagnosis and treatment of acute aortic syndrome should improve the outcome of this disease. The Spanish Registry of Acute Aortic Syndrome aimed to assess current results in acute aortic syndrome management in a wide cohort of hospitals in the same geographical area. METHODS: From January 2012 to January 2014, 26 tertiary hospitals included 629 consecutive patients with acute aortic syndrome: 73% men, mean age 64.7±14 years (range 22-92), 443 type A (70.4%) and 186 type B (29.6%). RESULTS: Time elapsed between symptom onset and diagnosis was <12 hours in 70.7% of cases and <24 hours in 84.0% (median 5 hours; 25th-75th percentiles, 2.7-15.5 hours). Computed tomography was the first diagnostic technique in 78% of patients and transthoracic echocardiography in 15%. Surgical treatment was indicated in 78.3% of type A acute aortic syndrome. The interval between diagnosis and surgery was 4.8 hours (quartile 1-3, 2.5-11.4 hours). Among the patients with type B acute aortic syndrome, treatment was medical in 116 cases (62.4%), endovascular in 61 (32.8%) and surgical in nine (4.8%). Type A mortality during hospitalisation was 25.1% in patients treated surgically and 68% in those treated medically. Mortality in type B was 13.8% in those with medical treatment, 18.0% with endovascular therapy and 33.0% with surgical treatment. CONCLUSION: Improvements in the diagnosis and treatment of acute aortic syndrome have not resulted in a significant reduction in hospital mortality. The results of this study reflect more overall and less selected information on acute aortic syndrome management and the need for sustained advances in the therapeutic strategy of acute aortic syndrome.

Etiology and short-term prognosis of severe mitral regurgitation.

PURPOSE: To describe the etiology and to document the course of severe mitral regurgitation (MR). METHODS: Prospective registry of 272 patients diagnosed with chronic severe MR in an echocardiographic study. RESULTS: Mean age was 70.2 +/- 13.8 years and 143 patients were women (53%). The most frequent causes of regurgitation were rheumatic disease (72 patients; 26%), ischemic etiology (58; 21%), valve prolapse (57; 21%), and dilated cardiomyopathy (49; 18%). A total of 43 patients (16%) died during follow-up (mean 0.9 +/- 0.3 years, total 2,785 patient-months): 30 from cardiac causes, 9 from non-cardiac causes, and 4 from unknown causes. Actuarial transplant-free survival was 87% at 6 months, and 81% at 1 year. Renal disease, previous stroke, ischemic etiology, and poor left ventricular ejection fraction were independent predictors of mortality. CONCLUSIONS: Rheumatic disease is still the main cause of severe MR in Spain. Patients with severe MR have advanced age and present poor short-term prognosis.

Successful transcatheter closure of a postmyocardial infarction ventricular septal rupture in a patient rejected for cardiac surgery: usefulness of transesophageal echocardiography.

Acute ventricular septal rupture is a high-risk complication of myocardial infarction. Although early surgical treatment improves the prognosis of this condition, hospital mortality after emergency surgery ranges from 10% to 60%. Transcatheter closure is an established method of treating selected congenital septal defects; less experience exists regarding its usefulness for postmyocardial infarction ventricular septal defect. We report a case of successful transcatheter closure of a postmyocardial infarction ventricular septal defect with a septal occluder in a 71-year-old patient rejected for surgery.

Isolated noncompaction of the ventricular myocardium: infrequent because of missed diagnosis?

Isolated noncompaction of the ventricular myocardium is frequently mistaken for other cardiomyopathies. We report a case of a 49-year-old woman admitted to hospital for heart failure and initially given the diagnosis of apical hypertrophic cardiomyopathy. In this case, myocardial contrast echocardiography and magnetic resonance imaging played a pivotal role in establishing the diagnosis of isolated noncompaction of the ventricular myocardium.