Biomedical subjects
Publications and source records attributed to Marco Stramba-Badiale.
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AIMS: The aim of the present study was to assess the effects of exercise training on heart rate, QT interval, and on the relation between ventricular repolarization and heart rate in men and women. METHODS AND RESULTS: A 24 h Holter recording was obtained in 80 healthy subjects (40 males) who differed for the degree of physical activity. Trained individuals showed a lower heart rate and a higher heart rate variability than sedentary subjects, independent of the gender difference in basal heart rate. Mean 24 h QTc was similar in trained and non-trained men, while a significant difference was observed between trained and non-trained women. Exercise training reduced the QT/RR slope in both genders. This effect on the QT/RR relation was more marked in women; in fact, the gender difference in the ventricular repolarization duration at low heart rate observed in sedentary subjects was no longer present among trained individuals. CONCLUSION: The results of this study suggest that the cardiovascular response to exercise training may be different in men and women. Women may benefit more from interventions aimed to increase physical activity as a tool for prevention of cardiovascular morbidity and mortality.
Cardiovascular diseases (CVD) are the leading cause of mortality both in men and women. In Europe, about 55% of all females' deaths are caused by CVD, especially coronary heart disease and stroke. Unfortunately, however, the risk of heart disease in women is underestimated because of the perception that women are 'protected' against ischaemic heart disease. What is not fully understood is that women during the fertile age have a lower risk of cardiac events, but this protection fades after menopause thus leaving women with untreated risk factors vulnerable to develop myocardial infarction, heart failure, and sudden cardiac death. Furthermore, clinical manifestations of ischaemic heart disease in women may be different from those commonly observed in males and this factor may account for under-recognition of the disease. The European Society of Cardiology has recently initiated an extensive 'Women at heart' program to coordinate research and educational initiatives on CVD in women. A Policy Conference on CVD in Women was one of the first steps in the development of this program. The objective of the conference was to collect the opinion of experts in the field coming from the European Society of Cardiology member countries to: (1) summarize the state-of-the-art from an European perspective; (2) to identify the scientific gaps on CVD in women; and (3) to delineate the strategies for changing the misperception of CVD in women, improving risk stratification, diagnosis, and therapy from a gender perspective and increasing women representation in clinical trials. The Policy Conference has provided the opportunity to review and comment on the current status of knowledge on CVD in women and to prioritize the actions needed to advance this area of knowledge in cardiology. In the preparation of this document we intend to provide the medical community and the stakeholders of this field with an overview of the more critical aspects that have emerged during the discussion. We also propose some immediate actions that should be undertaken with the hope that synergic activities will be implemented at European level with the support of national health care authorities.
OBJECTIVE: Cardiovascular disease is a major contributor to the increased mortality of acromegalic patients. Prolongation of the QT interval is considered an established risk factor for potentially fatal cardiac arrhythmias, an event frequently observed in acromegaly. Changes in ventricular repolarization have been observed with the use of octreotide, one of the somatostatin analogues (SSA) currently used for the medical treatment of this disease. Furthermore, octreotide is listed among the drugs able to prolong the QT interval. Thus, we elected to study the effects of long-term SSA administration on QT duration and left ventricular mass (LVM) in a group of acromegalic patients. DESIGN AND PATIENTS: In a retrospective study, 30 acromegalic patients (19 women and 11 men, aged 25-77 years) were studied under basal conditions; 24 of them (15 women and nine men, aged 25-77 years) were studied again after 3-63 months of treatment (median 18 months) with SSA. Twenty-four healthy volunteers served as controls. MEASUREMENTS: Patients and controls underwent electrocardiographic (ECG) analysis, and QT interval duration corrected for heart rate (QTc) was established according to the Bazett formula. In 17 of the SSA-treated patients, M- and B-mode echocardiography for the assessment of LVM index (LVMi) was performed. RESULTS: Baseline QTc was significantly longer in patients than in controls. SSA administration was followed by a significant decrease in QTc, which reached a mean value similar to that measured in the controls. In particular, treatment with SSA normalized QTc in three out of the six patients with abnormally elevated values at baseline. After treatment, a significant reduction in heart rate was recorded, while LVMi displayed a slight but not significant decrease. CONCLUSIONS: Acromegalic patients frequently display an abnormally prolonged QT interval, a known risk factor for potentially fatal arrhythmias. Treatment of these patients with SSA is able to improve and even normalize this alteration, probably contributing to the beneficial effects of these drugs on cardiac rhythm in this endocrine disorder. The inclusion of octreotide in the list of drugs that may increase QTc should be reconsidered as regards its indication in acromegaly.
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Short QT syndrome (SQTS) leads to an abbreviated QTc interval and predisposes patients to life-threatening arrhythmias. To date, two forms of the disease have been identified: SQT1, caused by a gain of function substitution in the HERG (I(Kr)) channel, and SQT2, caused by a gain of function substitution in the KvLQT1 (I(Ks)) channel. Here we identify a new variant, "SQT3", which has a unique ECG phenotype characterized by asymmetrical T waves, and a defect in the gene coding for the inwardly rectifying Kir2.1 (I(K1)) channel. The affected members of a single family had a G514A substitution in the KCNJ2 gene that resulted in a change from aspartic acid to asparagine at position 172 (D172N). Whole-cell patch-clamp studies of the heterologously expressed human D172N channel demonstrated a larger outward I(K1) than the wild-type (P<0.05) at potentials between -75 mV and -45 mV, with the peak current being shifted in the former with respect to the latter (WT, -75 mV; D172N, -65 mV). Coexpression of WT and mutant channels to mimic the heterozygous condition of the proband yielded an outward current that was intermediate between WT and D172N. In computer simulations using a human ventricular myocyte model the increased outward I(K1) greatly accelerated the final phase of repolarization, and shortened the action potential duration. Hence, unlike the known mutations in the two other SQTS forms (N588K in HERG and V307L in KvLQT1), simulations using the D172N and WT/D172N mutations fully accounted for the ECG phenotype of tall and asymmetrically shaped T waves. Although we were unable to test for inducibility of arrhythmia susceptibility due to lack of patients' consent, our computer simulations predict a steeper steady-state restitution curve for the D172N and WT/D172N mutation, compared with WT or to HERG or KvLQT1 mutations, which may predispose SQT3 patients to a greater risk of reentrant arrhythmias.
The aim of this paper is to estimate the infant mortality rate and the incidence of sudden infant death syndrome (SIDS) in Lombardy, Northern Italy, in the period 1990-2000 and to provide basic information for a subsequent comparison of the SIDS incidence before and after the risk-intervention campaign. A retrospective epidemiological study was carried out using all deaths of resident infants occurring up to 1 year of age as recorded by the health districts mortality registries of the Lombardy region, between 1990 and 2000. The infant mortality rate was 4.1 per 1000 live births, with a significant decreasing trend. This decrease is mainly due to the fall in mortality for congenital malformations and perinatal diseases. The SIDS incidence rate was 0.13 per 1000 live births; the annual incidence of SIDS during the study period decreased significantly by 60% from 0.20 to 0.08 deaths per 1000 live births (P = 0.001). When 'possible SIDS deaths', not directly labelled as SIDS, were also considered, the rate of SIDS was 0.54 per 1000 live births. The incidence of SIDS in Northern Italy appears much lower than anticipated. SIDS remains the single leading cause of death in the first year of life after the early neonatal period.
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OBJECTIVE: To analyse the duration of the QT interval and its relationship with heart rate changes in patients with uraemia, before and during haemodialysis. METHODS: QT and RR intervals were measured automatically using a dedicated algorithm with 24-h Holter recordings in 29 patients (15 women) receiving chronic haemodialysis. QT corrected for heart rate (QTc) and the slope of QT/RR linear regression were calculated. Arterial blood pressure (ABP) was measured before and during haemodialysis. Plasma concentrations of K+, Mg2+ and Ca2+ were assessed before and after haemodialysis. RESULTS: ABP decreased significantly from baseline (102.7 +/- 11.0 mmHg) during the first (100.6 +/- 8.8 mmHg, P < 0.05), second (95.6 +/- 10.6 mmHg, P < 0.05), and third (94.9 +/- 10.3 mmHg, P < 0.05) hours of haemodialysis. QTc was longer during haemodialysis than during a 4-h period of no dialysis (447 +/- 28 ms compared with 429 +/- 22 ms, P < 0.001), and increased progressively during haemodialysis, with the greatest value during the last hour of haemodialysis (454 +/- 32 ms compared with 426 +/- 22 ms, P < 0.001). QT/RR slopes and correlation coefficients were lower during haemodialysis than during the period of no dialysis (0.13 +/- 0.08 compared with 0.20 +/- 0.07, P < 0.001 and 0.48 +/- 0.30 compared with 0.81 +/- 0.20, respectively; P < 0.001), suggesting a reduced ability to adapt the QT interval in response to changes in heart rate. The effects of haemodialysis on QT interval and the QT/RR relationship were greater in women than in men. QTc variations during dialysis were not correlated with changes in ABP, but were inversely related to changes in Ca2+ concentration (r2 = 0.35; P = 0.001). CONCLUSIONS: In patients with uraemia, the haemodialysis session induces a progressive increase in QT interval and modifies its relationship with heart rate. These effects may predispose some individuals to ventricular arrhythmias at the end of and immediately after the haemodialysis session.
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Congenital heart block (CHB), defined as an atrioventricular block diagnosed in utero, at birth, or within the neonatal period (0-27 d after birth), is a rare disorder closely linked to transplacental transport of maternal antibodies anti-Ro/SSA and anti-La/SSB. These antibodies may induce a myocarditis, or interact directly with calcium channel proteins with disturbance of transmembrane signaling at the level of the conduction tissue, or interfere with apoptosis. Depending on the severity of the process, the fetus may die in utero or a few days after birth or survive to the perinatal period and have a near-normal life; in most survivors a pace-maker must be implanted. Skin lesions, haematological disorders, and hepatic cholestasis are other transient clinical features of the syndrome. Sinus bradycardia and QT interval prolongation may be observed as well in babies born from anti-Ro/SSA positive mothers. The risk of recurrence of complete block ranges from 10-17%. Most of the mothers are asymptomatic at delivery and are identified only by the birth of an affected child. Their long-term outcome generally is more reassuring than previously assumed and arthralgias and dry eyes are the most common symptoms. A standard therapy for blocks detected in utero still does not exist. The prevalence of complete CHB in newborns of anti-Ro/SSA positive women and with known connective-tissue disease was 2%. Serial echocardiograms and obstetric sonograms, performed at least every 2 wk starting from the 16 wk gestation, are recommended in anti-Ro/SSA positive pregnant women.
A case of long QT syndrome diagnosed in the early neonatal period is described. A full-term male baby was delivered by cesarean section at 38 weeks of gestation. The indication to cesarean section was sudden marked fetal bradycardia. At birth, he presented the following rhythm disorders: a) an ectopic atrial rhythm with T wave alternans, and b) atrioventricular conduction disorders. Sinus rhythm, with a prolonged QT interval and T wave alternans, was recovered soon after birth, before starting beta-blocker therapy. The family history was negative for the long QT syndrome: sudden unexpected death and/or syncopal episodes and cases of congenital deafness have not been reported. Molecular screening of the five long QT syndrome-related genes did not reveal the presence of any mutation. At 3 years of follow-up, the child is well and he did not present with symptoms or arrhythmias during this period.
OBJECTIVE: To estimate the infant mortality rate and the incidence of Sudden Infant Death Syndrome (SIDS) which is not known in Italy. DESIGN: Retrospective mortality study using all deaths of resident infants occurring up to one year of age as recorded by the Italian Institute of Statistics, between 1994 and 1996. SETTING: Lombardy, Northern Italy. MAIN OUTCOME MEASURES: Infant mortality rate (deaths occurring in the 1st year of life), early neonatal mortality rate (1st-7th days of life), late neonatal mortality rate (8th day of life-1st month of life), post-neonatal rate (1st month-one year of life), and incidence of SIDS (Sudden Infant Death Syndrome). RESULTS: The infant mortality rate was 4.76 per 1,000 live births, with no significant differences among the three years and lower than the Italian rates. The SIDS incidence rate was 0.14 per 1,000 live births, and 0.39 per 1,000 live births when deaths not directly labelled as SIDS were considered. SIDS was the single leading cause of death in the first year of life after the early-neonatal period. CONCLUSIONS: The decrease of the infant mortality rate is due to the drop in mortality for congenital malformations and perinatal diseases. The incidence of SIDS in Northern Italy turns out to be low, while SIDS remains the single leading cause of death in the first year of life after the early neonatal period.