Elisabete Martins

Iron deficiency status irrespective of anemia: a predictor of unfavorable outcome in chronic heart failure patients.

Objective: To assess the prognostic significance of iron deficiency (ID) in a chronic heart failure (CHF) outpatient population. Methods and Results: We prospectively evaluated 127 patients with stable CHF and left ventricular ejection fraction ≤45%. Clinical and analytical data as well as information regarding the occurrence of the composite endpoint of overall mortality and nonfatal cardiovascular events were assessed. Among the 127 patients enrolled [81% men, median age: 62 years (25th-75th percentile: 53-68)], 46 (36%) patients had ID. Women, patients with higher plasma brain natriuretic peptide levels (>400 pg/ml) and with right ventricular systolic dysfunction presented ID more frequently (p < 0.05 for all). At 225 ± 139 days of follow-up, the composite endpoint occurred in 15 (12%) patients. It was more frequent in ID (24 vs. 5%, p = 0.001) and anemic patients (25 vs. 8%, p = 0.014). In a Cox regression analysis, ID was associated with a higher likelihood of composite endpoint occurrence (HR 5.00, 95% CI 1.59-15.78, p = 0.006). In a multivariable analysis adjusted for clinical variables, including the presence of anemia, ID remained a significant predictor of the composite endpoint (HR 5.38, 95% CI 1.54-18.87, p = 0.009). Conclusion: In a CHF outpatient population, ID carried a higher risk of unfavorable outcome, irrespectively of the presence of anemia.

Variations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma

Recent data have shown that lyso-Gb3, the deacylated derivative of globotriaosylceramide (Gb3), is possibly involved in the pathogenesis of Fabry disease (FD) and might be a clinically useful biomarker of its metabolic load. To test this hypothesis, we assayed Gb3 and lyso-Gb3 and related analogs in plasma and/or urine samples of 12 clinically well-characterized subjects carrying several different GLA variant alleles associated with a wide range of residual α-galactosidase A activities. Urinary Gb3 was measured by HPLC-MS/MS; plasma and urinary lyso-Gb3 and related analogs were measured by UPLC-MS/MS. Individual profiles of Gb3 and lyso-Gb3 and related analogs closely correlated with the phenotypic data for each subject, discerning the classical FD patient from the two patients carrying cardiac variants as well as those from all the others without FD. The lyso-Gb3 analog at m/z 836 was found at increased levels only in patients manifesting clinically severe heart disease, irrespective of the pathogenicity of the GLA variant they carried. This finding suggests that this lyso-Gb3 analog might be an earlier biomarker of progressive heart disease, non-specific of the FD cardiomyopathy. The possibility that urinary Gb3 is a specific marker of kidney involvement in FD deserves further study.

Prevalence, predictors and prognosis of ventricular reverse remodeling in idiopathic dilated cardiomyopathy

INTRODUCTION Cardiac remodeling is manifested as changes in size, shape and function of the heart. We studied the prevalence, prognosis and predictors of left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (IDCM) after optimized medical therapy. METHODS A total of 113 IDCM patients were followed for 7.1±5.6 years. LVRR was defined as an increase of 10 units in ejection fraction (EF) and decrease in left ventricular diastolic diameter (LVDD), in the absence of resynchronization therapy. RESULTS Baseline EF was 27±8% and LVDD index was 37.1±6.3 mm/m(2). LVRR occurred in 34.5% within 22.6 months. Final EF was 47.5±10.1%, LVDD index was 30.2±3.9 mm/m(2). LVRR was associated with better NYHA class (I-II) and lower BNP (p<0.01) and all patients were alive. Univariate predictive factors of LVRR (p<0.05) were mild hypertension, atrial fibrillation, ventricular hypertrophy on ECG, absence of left bundle branch block, shorter QRS duration, higher hematocrit, lower LVDD index, higher peak oxygen uptake efficiency (VO2/log 10[VE]) and lower dVE/VCO2/VO2, treatment with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) and use of maximal doses of ACEI/ARB and beta-blockers. Multivariate regression analysis showed that higher doses of ACEI/ARB (OR: 0.32, 95% CI 0.11-0.92) were independently associated with LVRR. Non-transmural late enhancement on cardiac MRI was not a predictor of LVRR. CONCLUSIONS LVRR occurred in one third of IDCM patients, especially in those with mild hypertension and with less advanced disease, who may have benefited from maximal drug titration.

Utilidad del diagnóstico molecular en una familia con síndrome de Marfan y un fenotipo vascular atípico

Marfan syndrome is mainly caused by mutations in the FBN1 gene. Diagnosis is usually based on clinical criteria, but the phenotypic presentation varies widely among affected individuals. Aortic dissection or rupture is the cause of death in over 90% of untreated patients. Early identification of individuals at risk is important given the availability of medical and surgical treatment that can significantly improve life-expectancy. Molecular testing could provide an etiologic diagnosis in patients who present with milder or atypical clinical forms of the disease. Moreover, it could contribute to preventive treatment in carriers, inform genetic counseling and offer reassurance to unaffected individuals. By describing a family with Marfan syndrome in whom the disease presented in an atypical aggressive form, this article highlights the value of tests for detecting FBN1 mutations in selected cases.

Myocardial Perfusion in Rheumatoid Arthritis Patients: Associations with Traditional Risk Factors and Novel Biomarkers

Introduction. Cardiovascular (CV) diseases are a major cause of death in rheumatoid arthritis (RA) patients. Novel biomarkers [B-type natriuretic peptide (BNP); osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL) ratio; and dickkopf-1 (DKK-1)] have been used in CV risk assessment. We analysed, in established RA patients, the presence of silent myocardial ischemia and its association with clinical variables, BNP, and bone and atheroma biomarkers. Methods. From a single-center tertiary referral hospital, RA patients asymptomatic for CV disease were submitted to myocardial perfusion scintigraphy (MPS) under adenosine stress and biomarkers measurements. Logistic regression was used to estimate crude odds ratios (OR) and 95% confidence intervals (CI). Results. In 189 patients, perfusion defects were frequent (25%) and associated with BNP ≥ 100 pg/mL (OR = 5.68; 95% CI: 2.038–15.830), fourth log OPG/RANKL ratio quartile (OR = 2.88; 95% CI: 1.091–7.622), and DKK-1 ≥ 133 pmol/L (OR = 2.69; 95% CI: 1.058–6.840). Similar associations were confirmed in those with C-reactive protein > or ≤ 3 mg/L. No relationship was found with the majority of traditional CV factors nor with disease variables. Conclusions. Our results corroborated the hypothesis that MPS could reveal subclinical CV dysfunction, supported the utility of BNP measurements as a screening tool, and put in perspective the potential usefulness of complementary approaches in CV risk assessment in RA patients.

Cardiac 123I-MIBG scintigraphy and arrhythmic risk in left ventricular noncompaction

Left ventricular noncompaction is an unusual but increasingly recognized cardiomyopathy, the etiology of which is still not definitely established. Clinical presentation includes a wide spectrum of scenarios, including heart failure, thromboembolism and malignant arrhythmias, with half of deaths occurring suddenly. Early detection of LVNC is therefore essential to prevent sudden cardiac death. To our knowledge, this is the first report of the presence of cardiac sympathetic nervous dysfunction, assessed by 123iodine-metaiodobenzylguanidine myocardial scintigraphy, in a patient with LVNC, preserved left ventricular systolic function and exercise-induced nonsustained ventricular tachycardia. This finding may be related to the increased arrhythmic risk observed in this cardiomyopathy, giving a new insight into the pathophysiology of LVNC.

Diagnostic challenges of Marfan syndrome in an XYY young man.

Tall stature is a common feature of both Marfan syndrome and XYY syndrome. Differential diagnosis between these entities has important prognostic implications. We report the case of a 21-year-old young man with a previously known diagnosis of XYY syndrome, in whom the identification of a fibrilin-1 mutation was determinant to establish an appropriate diagnosis, medical follow-up, and genetic counselling.

Post-cardiac injury syndrome following transvenous pacing: Case report

Post-cardiac injury syndrome (PCIS) is an inflammatory process involving the pericardium secondary to cardiac injury. It can develop after cardiac trauma, cardiac surgery, myocardial infarction, and, rarely, after certain intravascular procedures. We report a rare case of an iatrogenic cardiac rupture followed by PCIS with delayed inflammatory pericardial effusion after pacemaker implantation. A comprehensive literature review on this topic is provided.

Meta-iodobenzylguanidine iodine-123 and cardiac adrenergic activity in familial dilated cardiomyopathy.

Familial dilated cardiomyopathy (FDCM) is characterized by genetic heterogeneity, incomplete age-dependent penetrance, and a multifactorial pathogenesis ([1][1]). Diagnosis is still dependent on clinical criteria and familial investigation ([2][2]). On the other hand, several abnormalities have been

NAFLD and cardiovascular disease

Abstract Nonalcoholic fatty liver disease (NAFLD) is an important cause of chronic hepatic disease and liver transplant in Western societies. The increasing prevalence is related to dietary changes and sedentarism and follows the increasing frequency of obesity and type 2 diabetes mellitus. Growing evidence of association of NAFLD with cardiovascular diseases (CVD), independent of cardiovascular risk factors, has prompted the clarification of whether the liver is mainly a key-effector or a target-organ of the metabolic disarrangements in the metabolic syndrome. The therapeutic strategies able to alter liver disease progression and, through this, reduce the cardiovascular risk have also been tested in the last 2 decades. This review focus on the possible interactions between hepatic disease, metabolic syndrome, and CVD, and on their implications for clinical practice.