Antinuclear antibody-negative lupus? An ominous presentation of hydralazine-induced lupus syndrome.

Up to 10% of systemic lupus erythematosus (SLE) cases are drug-induced; hence, they are called drug-induced lupus syndrome (DILS). Antinuclear antibody (ANA) should be present to diagnose SLE and DILS. ANA-negative lupus is very rare; therefore, it presents a diagnostic challenge. In the medical literature, two cases of ANA-negative hydralazine-induced lupus syndrome (HILS) have been described within the last year. Here, we present the third such case of HILS with negative ANA serology in a patient who developed considerable pericardial effusion. The association between ANA-negative HILS and pericardial effusion warrants future research.

The 212A variant of the APJ receptor gene for the endogenous inotrope apelin is associated with slower heart failure progression in idiopathic dilated cardiomyopathy.

BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) has multiple genetic and acquired causes. Apelin is an endogenous peptide that increases cardiac inotropism through his APJ receptor. No data are available concerning the APJ gene mutations responsible for IDC or on the role of APJ receptor gene variants in predicting heart failure (HF) progression. METHODS AND RESULTS: We prospectively evaluated 202 consecutive patients with IDC and 202 matched controls: 90 were screened for APJ gene mutations and all 202 were genotyped for G212A and A445C APJ receptor polymorphisms. No mutations were found within the coding or untranslated regions of the APJ receptor, and no differences in allelic or genotype frequencies were observed comparing patients with a healthy control population. The correlations between APJ receptor polymorphisms and HF progression were assessed. During a median follow-up of 37 months, 35 patients experienced HF progression. Univariate analysis showed that patients carrying at least 1 copy of 212A had a significantly lower risk for HF-related events than those who were homozygous for the G212 variant, and multivariate analysis confirmed that it was significantly related to a more favorable prognosis. CONCLUSIONS: APJ is unlikely to be a gene causing IDC, but the independent correlation between the 212A allele and a better prognosis suggests that it might act as a modifier gene.

Beta1- and beta2-adrenergic receptor polymorphisms affect susceptibility to idiopathic dilated cardiomyopathy.

OBJECTIVE: Beta1- and beta2-adrenergic receptors (ARs) play a pivotal role in myocardial function. We investigated whether functionally relevant polymorphisms within the genes encoding for these receptors indicate susceptibility to idiopathic dilated cardiomyopathy (DCM). METHODS: This case-control association study involved 189 patients with DCM and 378 gender- and age-matched control subjects. All of the subjects were characterised by polymerase chain reaction-restriction fragment length polymorphism analysis in terms of Ser49Gly and Arg389Gly polymorphisms in the beta1-AR, and the 5' leader cistron Arg19Cys, Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms in the beta2-AR. Genotype, allele and haplotype frequencies were analysed. RESULTS: Univariate analysis showed that the distribution of genotype and allele frequencies of the beta1-Ser49Gly, beta1-Arg389Gly and beta2-Arg16Gly polymorphisms was significantly different between the patients and controls, and the beta1-Gly49/beta1-Arg389 haplotype was significantly more represented in the patients. Multivariate analysis showed that only the beta1-Gly49 variant (odds ratio 1.91; 95% confidence interval 1.24-2.95; P = 0.003) and beta2-Gly16Gly genotype (odds ratio 1.58; 95% confidence interval 1.10-2.26; P = 0.013) carriers were at significantly higher risk of developing DCM. CONCLUSIONS: In our population from southern Italy, the Gly49 allele of the beta1-AR and the Gly16Gly genotype of the beta2-AR were significantly and independently associated with the DCM phenotype, thus suggesting their role in favouring susceptibility to the disease.

Ventricular repolarization dynamicity provides independent prognostic information toward major arrhythmic events in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: The purpose of this work was to evaluate whether ventricular repolarization dynamicity predicts major arrhythmic events in patients with idiopathic dilated cardiomyopathy (DCM). BACKGROUND: Arrhythmic risk stratification in patients with DCM is still an open issue. Ventricular repolarization analysis should provide relevant information, but QT interval and QT dispersion failed in predicting arrhythmic risk. METHODS: The following parameters were evaluated in 179 consecutive DCM patients without history of sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) at enrollment: QRS duration, QT interval corrected for heart rate, and QT dispersion at electrocardiogram (ECG); left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter at echocardiogram; and nonsustained ventricular tachycardia (NSVT), heart rate variability (standard deviation of RR intervals), and ventricular repolarization dynamicity as measured by means of 24-h ECG monitoring, by calculating the slope of linear regression analysis of QT end and RR intervals (QTe-slope) and the value of mean QT end corrected for heart rate. RESULTS: During a mean follow-up of 39 months, 9 patients died suddenly and 15 experienced VT and/or VF. At multivariate analysis, LVEF (p = 0.047), NSVT (p = 0.022), and QTe-slope (p = 0.034) were significantly associated with arrhythmic events. Among the patients with a low LVEF, NSVT and/or steeper QTe-slope identified a subgroup at highest arrhythmic risk. CONCLUSIONS: In patients with DCM, QT dynamicity is independently associated with the occurrence of major arrhythmic events and improves the predictive accuracy of stratifying arrhythmic risk of these patients.

SCN5A polymorphism restores trafficking of a Brugada syndrome mutation on a separate gene.

BACKGROUND: Brugada syndrome is associated with a high risk of sudden cardiac death and is caused by mutations in the cardiac voltage-gated sodium channel gene. Previously, the R282H-SCN5A mutation in the sodium channel gene was identified in patients with Brugada syndrome. In a family carrying the R282H-SCN5A mutation, an asymptomatic individual had a common H558R-SCN5A polymorphism and the mutation on separate chromosomes. Therefore, we hypothesized that the polymorphism could rescue the mutation. METHODS AND RESULTS: In heterologous cells, expression of the mutation alone did not produce sodium current. However, coexpressing the mutation with the polymorphism produced significantly greater current than coexpressing the mutant with the wild-type gene, demonstrating that the polymorphism rescues the mutation. Using immunocytochemistry, we demonstrated that the R282H-SCN5A construct can traffic to the cell membrane only in the presence of the H558R-SCN5A polymorphism. Using fluorescence resonance energy transfer and protein fragments centered on H558R-SCN5A, we demonstrated that cardiac sodium channels preferentially interact when the polymorphism is expressed on one protein but not the other. CONCLUSIONS: This study suggests a mechanism whereby the Brugada syndrome has incomplete penetrance. More importantly, this study suggests that genetic polymorphisms may be a potential target for future therapies aimed at rescuing specific dysfunctional protein channels.

[Yentl syndrome. The underestimate of cardiovascular risk in women]. / La sindrome di Yentl. La sottostima del rischio cardiovascolare nel sesso femminile.

Cardiovascular diseases are the leading cause of death for women in all countries of the world. Aging of the population and the high prevalence of risk factors among young and middle-aged women allow to hypothesize that this situation will continue in the future. Differences exist between women and men in the impact of risk factors, symptoms and therapeutic response. However, the main problem limiting prevention and control of cardiovascular diseases among women is gender inequality in health care. Myocardial infarction and stroke continue to be seen as "male" diseases and this view has deeply limited research and clinical management improvements. Furthermore, factors related to the socioeconomic environment strongly influence the development of cardiovascular diseases. For women, the ability to stop smoking, have a healthy eating and regular physical activity and live in a supportive psychosocial environment is strongly influenced by their level of income, education, role, control over their lives, culture, religion, access to health care. For the majority of women these factors represent the main barriers to cardiovascular disease prevention. The promotion of cardiovascular health among women could be accomplished only by removing all the obstacles to women's active participation in public and private life allowing them to share a full and equal role in economic, social, cultural and political decision-making processes. This strategy will not only improve women's health, but also that of children and men.

Comparative effect of lercanidipine, felodipine, and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the Lercanidipine in Adults (LEAD) Study.

This multicenter, double-blind, parallel-group study compared the effects of three dihydropyridine calcium channel blockers (lercanidipine, felodipine, and nifedipine gastrointestinal therapeutic system) on blood pressure and heart rate in 250 patients with mild to moderate hypertension (diastolic blood pressure > or =95 and 109 mm Hg). Patients were randomized to 4 weeks of treatment with once-daily doses of lercanidipine 10 mg, felodipine 10 mg, or nifedipine gastrointestinal therapeutic system 30 mg. After 4 weeks of treatment, the dose was doubled in nonresponding patients. At 8 weeks, no significant differences in blood pressure were observed among the three groups. Increases in heart rate in all three groups induced by stressful conditions before and after treatment were not exacerbated during active treatment. The incidence of adverse drug reactions was lower in the lercanidipine and nifedipine groups than in the felodipine group (p<0.05); in particular, the incidence of edema for lercanidipine was 5.5% vs. 13% for felodipine and 6.6% for nifedipine.

[Diagnosis of neurogenic syncope--current views]. / Diagnosi di sincope neurocardiogena. Recenti vedute.

Neurocardiogenic syncope is a very common clinical problem and represents the most frequent cause of syncope. Its diagnosis is difficult because there are several and heterogeneous causes of syncope, that can interact each other, and the accuracy of the available diagnostic instruments is sometimes not high enough. For these reasons, the classification of a syncope as neurocardiogenic is the result of an evaluation, whose main purpose is the exclusion of the other possible causes of syncope with worse prognosis. The head tilt-up test is recommended for the diagnosis of the most frequent type of neurocardiogenic syncope, the vasovagal syncope. The methodological improvement of tilt test could, in the future, improve its diagnostic accuracy and could optimise the time of execution.

Enhanced reflex response to baroreceptor deactivation in subjects with tilt-induced syncope.

OBJECTIVES: We sought to evaluate whether changes in resting baroreflex control of heart rate are a distinctive feature of healthy subjects with a history of syncope prone to a positive tilt-test response. BACKGROUND: The mechanisms involved in the pathogenesis of vasovagal syncope (VVS) are still poorly understood; in particular, the contribution of arterial baroreflex control of heart rate is matter of discussion. METHODS: A passive tilt-table test was performed in 312 consecutive, otherwise healthy subjects (age 36 +/- 15 years) with unexplained syncope and 100 control subjects. At baseline, spontaneous baroreflex sensitivity (BRS; ms/mm Hg) and the baroreflex effectiveness index (BEI) were assessed using the sequence method. RESULTS: The study population showed normal baroreflex function. Tilt-induced VVS in 94 subjects who were younger than both the tilt-negative and control subjects (30 +/- 14, 38 +/- 15, and 37 +/- 14 years, respectively; p = 0.00005) showed greater BRS (17.4 +/- 9.8, 13.2 +/- 7.9, and 12.8 +/- 8.2 ms/mm Hg, respectively; p = 0.0001), but had a similar BEI (0.59 +/- 0.18, 0.56 +/- 0.19, and 0.58 +/- 0.2, respectively; p = NS). On Cox multivariate analysis, the occurrence of VVS during tilt was inversely related to age (hazard ratio 0.97; p = 0.0004) and directly related to the BRS slope of sequences, implying a baroreceptor deactivation (hazard ratio 1.05; p = 0.02), but not of sequences characterized by arterial baroreceptor stimulation. CONCLUSIONS: Subjects with tilt-induced VVS showed greater resting BRS but had a normal BEI. The enhanced reflex tachycardic response to arterial baroreceptor deactivation at rest may represent a characteristic feature of subjects prone to tilt-induced VVS.

Shortened head-up tilting test guided by systolic pressure reductions in neurocardiogenic syncope.

BACKGROUND: Asymptomatic reductions in arterial pressure have been reported to occur before the onset of tilt-induced syncope. We investigated the predictive value of these reductions for a positive tilt result. METHODS AND RESULTS: In a first study, 238 consecutive healthy subjects with unexplained syncope underwent a passive tilt table test. Finger systolic arterial pressure (SAP) recordings made it possible to calculate how many of the beat-to-beat SAP values during the first 15 minutes of tilt were lower than the lowest value recorded at baseline. Neurocardiogenic syncope was diagnosed in 73 subjects; 28 fainted after 15 minutes of tilt and experienced more pressure reductions than did the subjects with a negative test (328+/-400 versus 119+/-284; P<0.01). More than 14 SAP reductions during the first 15 minutes of tilt allowed us to predict a positive test with 93% sensitivity, 58% specificity, and positive and negative predictive values of 28% and 98%, respectively. In a second prospective study (80 consecutive subjects), the online analysis of this criterion by visually inspecting a Finapres monitor showed 80% sensitivity, 85% specificity, and positive and negative predictive values of 57% and 94%. CONCLUSIONS: In healthy subjects with unexplained syncope, the evaluation of SAP reductions during the first 15 minutes of tilt is a marker of systolic pressure instability preceding syncope and constitutes a simple and good predictor of tilt outcome that could be used to guide test duration.