Dietary atherogenicity and thrombogenicity indexes predicting cardiovascular mortality: 50-year follow-up of the Seven Countries Study.

BACKGROUND AND AIM: To study the relationships of an Atherogenicity Index (ATI) and a Thrombogenicity Index (THI), with 50-year mortality from coronary heart disease (CHD), other heart diseases of uncertain etiology (HDUE) and cerebrovascular disease or stroke (STR), in 16 international cohorts of middle-aged men. METHODS AND RESULTS: Foods from a dietary survey in subsamples of men in each cohort of the Seven Countries Study (SCS) were chemically analyzed for several types of fatty acids that were converted into ATI and THI identifying each of 16 cohorts. Ecological correlations of the ATI and THI were calculated with the three fatal CVD conditions and with all-cause mortality at 25 and 50 years. Correlation coefficients (Rs) were positive and highly significant between ATI and THI versus CHD mortality, with levels ranging from 0.79 to 0.97, depending on the duration of follow-up and the choice of 10 or of 16 cohorts. This was not the case for HDUE and STR mortality for which Rs were variable and not significant. A strong direct association was also found with all-causes deaths at 25 and 50-years. ATI and THI were also directly related with dietary saturated fat and cholesterol levels and inversely with the Mediterranean Adequacy Index (a score identifying the Mediterranean diet). CONCLUSION: These findings indicate that CHD has a different relationship with dietary lipids intake than HDUE and STR. This suggests that HDUE and STR have different underlying pathways or are different diseases.

Focus on age at death in field epidemiology.

Age at death (AD) is an old metric recently re-evaluated for the study of longevity and mainly used in demography. Developed experience using AD in field epidemiology is summarized with cohorts followed-up for variable periods of time, frequently until extinction or close to extinction, a must to correctly adopt this metric. For practical purposes, a small number of examples is reported condensing previously published results to highlight various aspects of the problem. AD became the alternative of overall death rates when comparing cohorts reaching extinction or near extinction. AD was useful to characterize different causes of death in order to describe their natural history and possible etiology. With the use of multiple linear regression, a large number of possible determinants of AD were identified and some combinations of them resulted in large estimated differences in AD of 10 years or more across individuals. AD is a powerful tool to study population samples followed-up until extinction or near extinction. It allows to compare the life-long experience of different populations, to compare the role of different causes of death and to study the determinants of AD that are conditioning longevity.

Cardiovascular risk factors predict age at death in 60-year follow-up of the Seven Countries Study.

OBJECTIVES: To study age at death (AD) and its determinants in cohorts of middle-aged men followed-up until extinction. MATERIAL AND METHODS: A total of 9063 middle-aged men enrolled in 10 cohorts of 6 countries (USA, Finland, the Netherlands, Italy, Greece and Japan) within the Seven Countries Study were examined and then followed up for 60 years until extinction. AD was computed and a small number of risk factors were tested through multiple linear regression as possibly related to attained AD. RESULTS: AD ranged across cohorts from 71.8 years in East Finland and 80.5 years in Crete with levels roughly lower in the USA and Northern Europe and higher elsewhere. Across cohorts, the correlation coefficients of systolic blood pressure (R = -0.58) and of CVD prevalence (R = -0.65) versus average AD were the only significant ones. At the individual level in the pool of all cohorts, a multiple linear regression model showed that age, vigorous physical activity, never and ex-smokers were favorably related to AD, while the reverse was true for systolic blood pressure, heart rate, serum cholesterol, CVD prevalence and silent ECG abnormalities. BMI had a parabolic relationship with AD. The predicting power of single risk factors, expressed in years gained or lost, was relatively small, but arbitrary combinations of several of them produced large differences in AD. CONCLUSIONS: A small number of CVD risk factors were strongly associated with AD in a life-long follow-up.

Determinants of longevity and age at death in a practically extinct cohort of middle-aged men followed-up for 61 years.

OBJECTIVES: To explore possible determinants of longevity as a function of many personal characteristics in a cohort of middle-aged men followed-up until practical extinction. MATERIALS AND METHODS: In the Italian Rural Area of the Seven Countries Study, 1712 men aged 40-59 were examined in 1960 and 35 personal characteristics were measured. The subsequent follow-up for life status was of 61 years when only 3 men survived. A Kaplan-Meier curve was computed. A Cox model was solved with all-cause mortality as end-point and 35 potential determinants as covariates. A Multiple Linear Regression (MLR) model was also solved with the same covariates and age at death (AD) as end-point. RESULTS: After 61 years, 99.8% of men had died and median age at death was 75. Beneficial risk factors for both models (p < 0.05) were: never smoker, vigorous physical activity, prudent and Mediterranean diets, arm circumference, subscapular skinfold, and vital capacity. Adverse risk factors (p < 0.05) were: mother early death, laterality/linearity index, systolic blood pressure, serum cholesterol, corneal arcus, xanthelasma, cardiovascular diseases, cancer, diabetes, and chronic bronchitis. Some arbitrary combinations of selected risk factors were used to estimate AD as a function of coefficients of the MLR, showing large differences up to 10 years or more. CONCLUSIONS: Several personal characteristics of anthropometric, behavioral, biophysical, biochemical, and clinical nature are strongly associated with longevity when measured in middle-aged men and then followed up until extinction.

High R wave as a risk factor for cardivoascular and all-cause mortality. A 45-year follow-up of 13 cohorts of the Seven Countries Study.

OBJECTIVES: To study the role of high R waves predicting cardiovascular (CVD) and all-cause mortality in a male middle-aged population followed-up 45 years. MATERIAL AND METHODS: A total of 7985 CVD-free men aged 40-59 years were enrolled in 13 cohorts in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece, Japan) and high R waves were classified by Minnesota Code 3.1 (as a dichotomous variable) from baseline resting otherwise normal ECG at entry examination together with other personal characteristics. Cox models were solved to detect the possible predictive role of high R waves for CVD and all-cause mortality. RESULTS: In Cox models high R waves were predictive of 45-year major CVD deaths with a hazard ratio of 1.17 (95% confidence intervals of 1.03-1.33) after adjustment for 6 major CVD risk factors (age, systolic blood pressure, serum cholesterol, cigarette smoking, physical activity and body mass index). The predictive role of high R wave was less evident for 45-year all-cause mortality and after adjustment for the 6 covariates the HR of high R wave lost its significance. A multiple logistic model indicated that body mass index, serum cholesterol, systolic blood pressure and mainly vigorous physical activity were directly related to high R wave prevalence while heart rate, subscapular skinfold, laterality index and shoulder pelvis shape did so in an inverse way. CONCLUSION: High R waves seem associated with an excess CVD mortality in a 45-year follow-up of middle-aged men, while their role is diluted when the end-point is all-cause mortality.

Age at death in elderly cohorts of four European countries of the Seven Countries Study: the role of comorbidities.

PURPOSE: To study age at death (AD) in elderly men as a function of risk factors and morbid conditions in a 25-year follow-up. MATERIALS AND METHODS: Men enrolled in the Seven Countries Study belonging to 8 cohorts in 4 European countries (Finland, The Netherlands, Italy and Serbia) were examined between 1984 and 1989 (aged 65-84 years) with measurement of some cardiovascular risk factors and recording of a few major morbid conditions. AD was measured after 25-year follow-up and used in multiple linear regression (MLR) models as dependent variable; while, risk factors and morbid conditions had the role of independent variables. RESULTS: Out of 2457 men, 2290 died during 25-year follow-up. Overall mean AD was of 82.0 years and slightly different across cohorts, the lowest being recorded in Finland. Age at entry examination and HDL cholesterol were directly associated with AD; while, blood pressure, heart rate, smoking habits and morbid conditions (major cardiovascular diseases, either independently or combined together with diabetes, chronic bronchitis, cancer and silent ECG abnormalities) were inversely related to AD. Body mass index had a parabolic relation with AD with longer survival for levels around 24 units; while, total serum cholesterol was not related to AD. However, only three independent variables were statistically significant when tested in each individual country (age, heart rate and stroke). In a MLR model, where a comorbidity score was entered as independent variable (everything else being equal), the presence of 1 morbid condition was associated with a reduced AD by 1.87 years that increased up to 6.39 years when 4 morbid conditions were present. CONCLUSION: AD seems a valuable indicator of all-cause mortality when the study population has reached or approached the extinction.

Lifestyle as determinant of all-cause mortality and age at death. A middle-aged male population followed-up 60 years until the survivors were aged 100 years.

OBJECTIVES: To relate major lifestyle habits with all-cause mortality in an almost extinct male middle-aged population. MATERIAL AND METHODS: A 40-59 aged male population of 1712 subjects was enrolled and examined in 1960 and then followed-up for 60 years. Baseline smoking habits, working physical activity and dietary habits, each subdivided into 3 classes, were related to 60-year mortality, by Kaplan-Meier survival curves, Cox proportional hazards model and to age at death during 60 years by multiple linear regression. RESULTS: Death rate in 60 years was of 99.7% with only 5 survivors and 2 lost to follow-up after 50 years. Two out of three classes of each behavior were significantly protective versus the third class in all the statistical approaches. Cox hazard ratios (and their 95% confidence limits) of never smokers versus smokers was 0.71 (0.63-0.79); that of vigorous physical activity versus sedentary activity was 0.75 (0.64-0.89); that of Mediterranean diet versus Not Mediterranean diet was 0.74 (0.66-0.84). The gain of age at death for never smokers versus smokers was 3.32 years (2.05-4.54); of vigorous physical activity versus sedentary activity was 3.53 years (1.68-5.37); that of Mediterranean diet versus Not Mediterranean diet was 3.67 years (2.32-5.02). Age at death was more than 10 years longer for men with the 3 best behaviors than for those with the 3 worst behaviors. CONCLUSIONS: Some lifestyle habits are strongly related to lifetime mortality and longevity.

Non-invasive prediction of genotype positive-phenotype negative in hypertrophic cardiomyopathy by 3D modern shape analysis.

NEW FINDINGS: What is the central question of this study? Can impaired deformational indicators for genotype positive for hypertrophic cardiomyopathy in subjects that do not exhibit a left-ventricular wall hypertrophy condition (G+LVH-) be determined using non-invasive 3D echocardiography? What is the main finding and its importance? Using 3D-STE and modern shape analysis, peculiar deformational impairments can be detected in G+LVH- subjects that can be classified with good accuracy. Moreover, the patterns of impairment are located mainly on the apical region in agreement with other evidence coming from previous biomechanical investigations. ABSTRACT: We propose a non-invasive procedure for predicting genotype positive for hypertrophic cardiomyopathy (HCM) in subjects that do not exhibit a left-ventricular wall hypertrophy condition (G+LVH-); the procedure is based on the enhanced analysis of medical imaging from 3D speckle tracking echocardiography (3D-STE). 3D-STE, due to its low quality images, has not been used so far to detect effectively the G+LVH- condition. Here, we post-processed echocardiographic images exploiting the tools of modern shape analysis, and we studied the motion of the left ventricle (LV) during an entire cycle. We enrolled 82 controls, 21 HCM patients and 11 G+LVH- subjects. We followed two steps: (i) we selected the most impaired regions of the LV by analysing its strains; and (ii) we used shape analysis on these regions to classify the subjects. The G+LVH- subjects showed different trajectories and deformational attributes. We found high classification performance in terms of area under the receiver operating characteristic curve (∼90), sensitivity (∼78) and specificity (∼79). Our results showed that (i) G+LVH- subjects present important deformational impairments relative to healthy controls and (ii) modern shape analysis can efficiently predict genotype by means of a non-invasive and inexpensive technique such as 3D-STE.

Age at death of major cardiovascular diseases in 13 cohorts. The seven countries study of cardiovascular diseases 45-year follow-up.

OBJECTIVES: To explore age at death (AD) for major cardiovascular diseases (CVD) and their risk factors in originally middle-aged men followed nearly to extinction in the Seven Countries Study. MATERIALS AND METHODS: Thirteen cohorts of men aged 40-59 years (N = 10,628) in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece, Japan) were enrolled in late 1950s and early 1960s and were followed 45 years for mortality. AD was computed for coronary heart disease (CHD), stroke (STR), heart disease of uncertain aetiology (HDUE) and for all-causes. AD was compared across CHD-HDUE-STR. Cox models were computed for each end-point using baseline age, cigarettes smoking, systolic blood pressure and serum cholesterol. RESULTS: After 45 years 92.9% of men had died. The most common CVD death was CHD in most cohorts except some Mediterranean and Japanese cohorts where STR or HDUE were most prevalent. In 13 cohorts mean AD was 74.5, 73.5, 75.7 and 79.1 years, respectively, for all-cause, CHD, STR and HDUE mortality (all possible differences were significant). The difference, across cohorts, between the highest and the lowest mean AD was 12.9, 9.0 and 4.7 years for CHD, HDUE and STR mortality, respectively. Risk factors explored were significant predictors of all three CVD end-points, except serum cholesterol, specific to CHD mortality. CONCLUSIONS: AD is a useful indicator of previous health and aging populations. STR and HDUE are diseases appearing later in life, thus being associated with a higher AD compared with CHD mortality.

Epidemiology of Heart Disease of Uncertain Etiology: A Population Study and Review of the Problem.

Background and objectives: Previous epidemiological studies have identified a group of heart diseases (here called heart diseases of uncertain etiology-HDUE) whose characteristics were rather different from cases classified as coronary heart disease (CHD), but frequently confused with them. This analysis had the purpose of adding further evidence on this issue based on a large population study. Materials and Methods: Forty-five Italian population samples for a total of 25,272 men and 21,895 women, free from cardiovascular diseases, were examined with measurement of some risk factors. During follow-up, CHD deaths were those manifested as myocardial infarction, other acute ischemic attacks, and sudden death of probable coronary origin, after reasonable exclusion of other causes. Cases of HDUE were those manifested only as heart failure, chronic arrhythmia, and blocks in the absence of typical coronary syndromes. Cox proportional hazards models were computed separately for CHD and HDUE, with 11 risk factors as possible predictors. Results: During an average of 7.4 years (extremes 1-16) there were 223 CHD and 150 HDUE fatal events. Male sex, age, smoking habits, systolic blood pressure, serum cholesterol, and plasma glucose were significantly and directly related to CHD events, while high density lipoprotein (HDL) cholesterol was so in an inverse way. The same risk factors were predictive of HDUE events except serum cholesterol and HDL cholesterol. Multivariable hazards ratio of serum cholesterol (delta = 1 mmol/L) was higher in the CHD model (1.24, 95% CI 1.11-1.39) than in the HDUE model (1.03, 0.5% C.I. 0.89-1.19) and the difference between the respective coefficients was statistically significant (p = 0.0444). Age at death was not different between the two end-points. Conclusions: CHD and HDUE are probably two different morbid conditions, only the first one is likely bound to gross atherosclerotic lesions of coronary arteries and linked to blood lipid levels. We reviewed the problem in epidemiological investigations and addressed inflammation as a potential cofactor to differentiate between CHD and HDUE.

Can we still learn from the Seven Countries Study?

PURPOSE OF REVIEW: The Seven Countries Study (SCS) of Cardiovascular Diseases started midway last century and was the pioneer investigation of coronary heart disease (CHD) at international level. The 16 cohorts of middle-aged men enrolled in eight nations of seven countries allowed to show large differences of CHD incidence and mortality across different cultures, partly explained by average levels of serum cholesterol and dietary habits, that is, Western type patterns in the high-risk populations, and Mediterranean or Oriental type in Southern Europe and Japan. Later, critics to the validity of the study were largely based on fake news, wrong or distorted information uncritically transmitted in a cascade of media. RECENT FINDINGS: Recent analyses based on 45-50 years of follow-up showed and confirmed that diet patterns were associated with all-cause mortality and age at death; that multivariate coefficients of major risk factors of CHD were not heterogeneous across different populations and cultures; that analysis of competing risks of CHD versus other conditions identified serum cholesterol as the critical determinant; that true CHD manifestations had different determinants compared with Heart Diseases of Uncertain Etiology frequently confused with CHD. SUMMARY: The SCS can still teach investigators and scholars of cardiovascular epidemiology, if old contributions are carefully read and interpreted; it is still recognized as the seminal study in this area at international level although it had limits as any other study but represented the first step into the identification of the relationship of diet with CHD and mortality across populations, and of the Mediterranean diet.

A Personal Decision Support System for Heart Failure Management (HeartMan): study protocol of the HeartMan randomized controlled trial.

BACKGROUND: Heart failure (HF) is a highly prevalent chronic disease, for which there is no cure available. Therefore, improving disease management is crucial, with mobile health (mHealth) being a promising technology. The aim of the HeartMan study is to evaluate the effect of a personal mHealth system on top of standard care on disease management and health-related quality of life (HRQoL) in HF. METHODS: HeartMan is a randomized controlled 1:2 (control:intervention) proof-of-concept trial, which will enrol 120 stable ambulatory HF patients with reduced ejection fraction across two European countries. Participants in the intervention group are equipped with a multi-monitoring health platform with the HeartMan wristband sensor as the main component. HeartMan provides guidance through a decision support system on four domains of disease management (exercise, nutrition, medication adherence and mental support), adapted to the patient's medical and psychological profile. The primary endpoint of the study is improvement in self-care and HRQoL after a six-months intervention. Secondary endpoints are the effects of HeartMan on: behavioural outcomes, illness perception, clinical outcomes and mental state. DISCUSSION: HeartMan is technologically the most innovative HF self-management support system to date. This trial will provide evidence whether modern mHealth technology, when used to its full extent, can improve HRQoL in HF. TRIAL REGISTRATION: This trial has been registered on https://clinicaltrials.gov/ct2/show/NCT03497871 , on April 13 2018 with registration number NCT03497871.

Age at death as a useful indicator of healthy aging at population level: a 50-year follow-up of the Italian Rural Areas of the Seven Countries Study.

OBJECTIVES: To explore age at death (AD), overall and for different causes of death, in a cohort followed up to quasi-extinction. MATERIALS AND METHODS: In 1960, in the Italian Rural Areas of the Seven Countries Study, 1712 men aged 40-59 years were enrolled, examined and then followed up for 50 years. AD was computed for all fatal events and compared across 12 groups of causes of death. Multiple linear regression model was used to estimate AD and Cox model to predict each of the 12 causes of death, as a function of 28 selected baseline risk factors. RESULTS: After 50 years, 97.5% of men had died. Mean AD was 75.0 years (median 76), while large variation was found across the 12 causes of death, with the highest levels for Heart Disease of Uncertain Etiology (HDUE) and Senility plus Causes Unknown (SNUNK), having means of 79.2 and 84.5 (median of 80 and 86) years, respectively. Many risk factors were directly associated with overall AD, the most significant being subscapular skinfold, arm circumference, Mediterranean diet, age at baseline examination, never smokers and vigorous physical activity. Systolic blood pressure (SBP) was inversely related. The relevant modifiable risk factors predicting single causes of death were SBP and the lifestyle behaviors of dietary, motion and smoking habits. CONCLUSIONS: AD proved to be a useful indicator of previous health and aging of populations. HDUE and SNUNK seem the most "physiological" causes of death. SBP and lifestyle risk factors are the most relevant characteristics associated with AD.

The strength of the multivariable associations of major risk factors predicting coronary heart disease mortality is homogeneous across different areas of the Seven Countries Study during 50-year follow-up.

OBJECTIVES: To compare the magnitude of multivariable coefficients and hazard ratios of four cardiovascular risk factors across five worldwide regions of the Seven Countries Study in predicting 50-year coronary deaths. MATERIAL AND METHODS: A total of 13 cohorts of middle-aged men at entry (40-59 years old) were enrolled in the mid-1900s from five relatively homogeneous groups of cohorts (areas): USA, Finland and Zutphen - the Netherlands, Italy and Greece, Serbia, Japan for a total of 10,368 middle-aged men. The major risk factors measured at baseline were age, number of cigarettes smoked, systolic blood pressure and serum cholesterol. Cox proportional hazards models were solved for 50-year (45 years for Serbia) deaths from coronary heart disease (CHD), and the multivariable coefficients were compared for heterogeneity. RESULTS: The highest levels of risk factors and CHD death rates were found in Finland and Zutphen - the Netherlands and the lowest in Japan. All four risk factors were predictive for long-term CHD mortality in all regions, except serum cholesterol in Japan where the mean levels and CHD events were lowest. Tests of heterogeneity of coefficients for single risk factors in predicting CHD mortality were non-significant across the five areas. The same analyses for the first 25 years of follow-up produced similar findings. CONCLUSIONS: The strength of the multivariable associations of four major traditional CHD risk factors with long-term CHD mortality appears to be relatively homogeneous across areas, pending needed further evidence.

Professor André Jouve (1909-2001): A French cardiologist who was a pioneer of clinical vector-electrocardiography and cardiovascular epidemiology.

André, Julien, Auguste Jouve was born in Marseilles on June 10, 1909 son of Xavier Marie Francois Louis Jouve MD and Marie Louise Charlotte Vigliengo his wife. He had a brilliant medical career in Marseilles: Resident at Marseilles Hospitals in 1931, major of his promotion, then an Assistant in 1943 and a Chief in 1951, to become Associate Professor of Medicine in 1946 and finally Full Professor of Clinical and Experimental Cardiology in 1954. Fellow of several Cardiological Societies, he became President of the French Society of Cardiology in 1968, Vice-President of the European Society of Cardiology in 1972 and finally President of the French College of Vascular Pathology in 1973. He had been a WHO Expert for degenerative and cardiovascular diseases from 1958 to 1981 and a National correspondent of the Academy of Medicine in 1977. He was decorated by the Légion d'Honneur (Officer in 1975). He retired in 1981 and died in 2001. Clinical vector-electrocardiology and cardiovascular epidemiology were the main areas of his interest where he made essential contributions such as the famous treatise on ECG. The Heart Cantini Center was considered his leading creation and action, where the first French heart transplantation was performed in 1968, the first French epidemiological investigation on coronary risk factors took place, the idea of starting prevention at pediatric age was clearly outlined and the need of concentrating on psychological and dysmetabolic factors was precisely advocated for indexing later development of ischemic heart diseases. These achievements are reviewed and put into perspective.

Frank vectorcardiographic system from standard 12 lead ECG: An effort to enhance cardiovascular diagnosis.

BACKGROUND: Vectorcardiogram (VCG) has been repeatedly found useful for clinical investigations. It may not substitute but complement Standard 12-Lead (S12) ECG. There was tremendous research between 1950s to mid-1980s on VCG in general and Frank's System in particular, however, in last three decades it has been dropped as a routine cardiac test, the major reasons being unconventional electrode placements which required training of the physicians, greater number of electrodes involved when used to supplement S12 system and additional hardware complexity involved, at least in the early days. Although it lost the interest of cardiologists, the engineering community has adopted the VCG as a tool for interdisciplinary research. We envisage that, if accurate Frank's VCG system is made available avoiding the aforementioned limitations, VCG will complement S12 system in diagnosis of cardiovascular diseases (CVDs). METHODS AND RESULTS: In this paper, we propose a methodology to construct Frank VCG from S12 system using Principal Component Analysis (PCA). We have compared our work with state-of-the-art Inverse Dower Transform (IDT) and Kors Transform (KT). Mean R(2) statistics and correlation coefficient values, obtained upon comparison of reconstructed and originally measured Frank's leads, for CSE multilead (CSEDB) and PhysioNet's PTBDB databases using our proposed method, IDT and KT were found to be (73.7%,0.869), (57.6%,0.788) and (56.2%,0.781) respectively. From remote healthcare perspective, a reduced 2-3 lead system is desired and Frank lead system seems to be promising as shown by previous works. However, cardiologists are accustomed to S12 system due to its widespread usage and derived Frank lead system might not be sufficient. Hence, to bridge the gap, we have presented the results of personalized reconstruction of S12 system from derived VCG, obtained using proposed PCA-based method and compared it with results obtained when originally measured Frank leads were used. CONCLUSIONS: The proposed methodology, without any modification in the current acquisition system, can be used to obtain Frank VCG from S12 system to complement it in CVD diagnosis. Omnipresent computerized machines can readily apply the proposed methodology and thus, can find widespread clinical application.

Dronedarone versus amiodarone in preventing premature ventricular contractions in an in vitro model of "border zone".

OBJECTIVE: To compare the acute ability of amiodarone and dronedarone (a noniodinated benzofuran derivative with a pharmacologic profile similar to amiodarone) to prevent premature ventricular contractions (PVCs) occurrence. METHODS: We used an in vitro model of rabbit right ventricle mimicking the "border zone" existing between normal and ischemic/reperfused regions to test acute electrophysiological effects of dronedarone and amiodarone both at 1 and 10 µmol/L. RESULTS: Similar to amiodarone, dronedarone affected action potential parameters with multichannel blocking properties. Dronedarone at both concentrations was equivalent to amiodarone regarding PVCs occurrence, except regarding extrasystoles occurrence during the reperfusion period (dronedarone, 10 µmol/L, was superior to amiodarone with extrasystoles incidence at 33% and 50%, respectively vs. 92% in controls, P < 0.05). Both dronedarone and amiodarone systematically induced conduction blocks during simulated ischemia (in 100% of preparations vs. 42% in controls, P < 0.05) and a marked decrease of Vmax (to 24 and 23 V/s at 10 minutes of ischemia with 1 and 10 µmol/L dronedarone versus 65 V/s in controls, P < 0.05), thus indicating class 1 antiarrhythmic effects. Both dronedarone and amiodarone at 10 µmol/L induced an increase of APD90 dispersion between normal and ischemic regions, without pro-arrhythmic effects. CONCLUSIONS: Dronedarone and amiodarone have very similar electrophysiological effects in this in vitro model of border zone and were both efficient in preventing PVCs occurrence particularly through a class 1 antiarrhythmic effect.

Proarrhythmic effects of aldosterone during myocardial ischemia-reperfusion: implication of the sarcolemmal-KATP channels.

OBJECTIVE: To assess the electrophysiological impact of aldosterone during myocardial ischemia-reperfusion. METHODS: We used an in vitro model of "border zone" using rabbit right ventricle and standard microelectrodes. RESULTS: Aldosterone (10 and 100 nmol/L) shortened ischemic action potential [action potential duration at 90% of repolarization (APD90), from 55 ± 3 to 39 ± 1 ms and 36 ± 3 ms, respectively, P < 0.05] and induced resting membrane potential (RMP) hyperpolarization in the nonischemic zone (from -83 ± 1 to -93 ± 7 mV and -94 ± 3 mV, respectively, P < 0.05) and in the ischemic zone during reperfusion (from -81 ± 2 to -88 ± 2 mV and -91 ± 2 mV, respectively, P < 0.05). Bimakalim, an ATP-sensitive potassium (K(ATP)) channel opener, also induced RMP hyperpolarization and APD90 shortening. Aldosterone (10 and 100 nmol/L) increased APD90 dispersion between ischemic and nonischemic zones (from 96 ± 3 to 117 ± 5 ms and 131 ± 6 ms, respectively, P < 0.05) and reperfusion-induced severe premature ventricular contraction occurrence (from 18% to 67% and 75%, respectively, P < 0.05). Adding glibenclamide, a nonspecific K(ATP) antagonist, to aldosterone superfusion abolished these effects different to sodium 5-hydroxydecanoate, a mitochondrial-K(ATP) antagonist. CONCLUSIONS: In this in vitro rabbit model of border zone, aldosterone induced RMP hyperpolarization and decreased ischemic APD90 evoking the modulation of K currents. Glibenclamide prevented these effects different to 5-hydroxydecanoate, suggesting that sarcolemmal-K(ATP) channels may be involved in this context.

Patterns of late gadolinium enhancement in Duchenne muscular dystrophy carriers.

BACKGROUND: This study was designed to assess whether cardiovascular magnetic resonance imaging (CMR) in Duchenne muscular dystrophy carriers (DMDc) may index any cell milieu elements of LV dysfunction and whether this cardiac phenotype may be related to genotype. The null hypothesis was that myocardial fibrosis, assessed by late gadolinium enhancement (LGE), might be similarly accounted for in DMDc and gender and age-matched controls. METHODS: Thirty DMDc patients had CMR and genotyping with 37 gender and age-matched controls. Systolic and diastolic LV function was assessed by 2D-echocardiography. RESULTS: Absolute and percent LGE were higher in muscular symptomatic (sym) than asymptomatic (asy) DMDc (1.77 ± 0.27 vs 0.76 ± 0.17 ml; F = 19.6, p < 0.0001 and 1.86 ± 0.26% vs 0.68 ± 0.17%, F = 22.1, p < 0.0001, respectively). There was no correlation between LGE and age. LGE was seen most frequently in segments 5 and 6; segment 5 was involved in all asy-DMDc. Subepicardial LGE predominated, compared to the mid-myocardial one (11 out of 14 DMDc). LGE was absent in the subendocardium. No correlations were seen between genotyping (type of mutation, gene region and protein domain), confined to the exon's study, and cardiac phenotype. CONCLUSIONS: A typical myocardial LGE-pattern location (LV segments 5 and 6) was a common finding in DMDc. LGE was more frequently subepicardial plus midmyocardial in sym-DMDc, with normal LV systolic and diastolic function. No genotype-phenothype correlation was found.