The fibroblast growth factor-23 and Vitamin D emerge as nontraditional risk factors and may affect cardiovascular risk.

OBJECTIVES: Fibroblast growth factor-23 (FGF-23) and vitamin D are hormones involved in phosphate homoeostasis. They also directly influence cardiomyocyte hypertrophy. We examined whether the relationships between levels of vitamin D or FGF-23, cardiac phenotype and outcome were independent of established cardiac biomarkers in a large cohort of community-dwelling elderly subjects. DESIGN AND SETTING: Plasma levels of FGF-23 and vitamin D were measured in 1851 men and women (65-84 years) resident in the Lazio region of Italy. Participants were referred to eight cardiology centres for clinical examination, electrocardiography, comprehensive Doppler echocardiography and blood sampling. All-cause mortality or hospitalizations were available after a median follow-up of 47 months with record linkage of administrative data. RESULTS: Vitamin D deficiency (<20 ng mL(-1) ) was found in 72.3% of subjects, but FGF-23 levels were normal [74 (58-97) RU per mL]. After adjustment for cardiovascular risk factors and morbidities, low concentrations of vitamin D and high levels of FGF-23 were associated with a higher left ventricular (LV) mass index. Levels of FGF-23 [hazard ratio (HR) (95% confidence interval (CI)) 1.71 (1.28-2.28), P < 0.0001] but not vitamin D [0.76 (0.57-1.01), P = 0.08] were independently associated with mortality after adjustment for clinical risk factors and two cardiac markers together (N-terminal pro-brain natriuretic peptide and high-sensitivity cardiac troponin T), but did not predict hospital admission. People with above median values of FGF-23 and below median values of vitamin D had greater LV hypertrophy and higher mortality. CONCLUSIONS: In community-dwelling elderly individuals with highly prevalent vitamin D deficiency, FGF-23 levels were associated with LV hypertrophy and predicted mortality independently of two robust cardiac biomarkers. A causal relationship was not demonstrated, but the hormones involved in mineral metabolism emerged as nontraditional risk factors and may affect cardiovascular risk.

High-sensitivity cardiac troponin T for detection of subtle abnormalities of cardiac phenotype in a general population of elderly individuals.

OBJECTIVE: To investigate the association between circulating cardiac biomarkers and minor abnormalities in cardiac phenotype [left ventricular (LV) mass and midwall fractional shortening (MFS)] in elderly individuals in a general population sample. DESIGN AND SETTING: We examined the relationship between plasma concentrations of high-sensitivity cardiac troponin T (hs-cTnT) or N-terminal probrain natriuretic peptide (NT-proBNP) and elevated LV mass (LV mass/body surface area >95 g m(-2) for women and 115 g m(-2) for men), reduced MFS (<15%) or isolated LV diastolic dysfunction in 1973 elderly subjects (mean age 73 ± 5 years, range 65-84) resident in the Lazio region of Italy and enrolled in the PREDICTOR study. RESULTS: Overall, 24.8% of subjects had elevated LV mass, and 30.4% had reduced MFS. Median [quartile 1-3] plasma concentrations of hs-cTnT and NT-proBNP were higher in individuals with elevated than those with normal LV mass: 6.6 [3.5-11.6] and 147 [64-296] ng L(-1) vs. 4.6 [3.0-8.1] and 79 [41-151] ng L(-1) respectively (P < 0.001). There was a graded increase in median hs-cTnT concentrations across clinical categories of LV hypertrophy: 4.6 [3.0-8.1], 5.8 [3.1-10.2], 7.6 [3.8-13.7] and 8.4 [3.8-17.6] ng L(-1) for subjects with normal LV mass and mild, moderate or severe LV hypertrophy respectively (P < 0.0001); hs-cTnT also increased with increasing quartiles of MFS or grades of isolated LV diastolic dysfunction. CONCLUSIONS: Within an extremely low range of concentrations, increased hs-cTnT amongst community-dwelling elderly subjects is associated with subtle alterations in cardiac phenotype, suggesting that minor injury to cardiac myocytes and subsequent release of troponin reflect subclinical pathophysiological LV deterioration in this population.

Global cardiovascular risk management in different Italian regions: an analysis of the Evaluation of Final Feasible Effect of Control Training and Ultra Sensitisation (EFFECTUS) educational program.

BACKGROUND AND AIM: The Final Evaluation Feasible Effect of Ultra Control Training and Sensitization (EFFECTUS) is an educational program, aimed at improving global CV risk stratification and management in Italy. The present study evaluates differences on clinical approach to global CV risk among physicians involved in the EFFECTUS program and stratified in three geographical macro-areas (North, Center, South) of our Country. METHODS AND RESULTS: Physicians were asked to submit data already available in their medical records, covering the first 10 adult outpatients, consecutively seen in the month of May 2006. Overall, 1.078 physicians (27% females, aged 50 ± 7 years) collected data of 9.904 outpatients (46.5% females, aged 67 ± 9 years), among which 3.219 (32.5%) were residents in Northern, 3.652 (36.9%) in Central and 3.033 (30.6%) in Southern Italy. A significantly higher prevalence of major CV risk factors, including obesity, physical inactivity, hypertension and diabetes, was recorded in Southern than in other areas. Accordingly, Southern physicians more frequently prescribed antihypertensive, glucose and lipid lowering agents than other physicians, who paid significantly more attention to life-style changes in their clinical practice. CONCLUSIONS: This analysis of the EFFECTUS study demonstrates a high prevalence of CV risk factors in Italy, particularly in Southern areas, and indicates some important discrepancies in the clinical management of global CV risk among physcians working in different Italian regions.

Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA-in-CHF study.

BACKGROUND AND AIM: We analyzed the effect of the mineralocorticoid receptor antagonist canrenone on LV mechanics in patients with or without metabolic syndrome (MetS) and compensated (Class II NYHA) heart failure (HF) with reduced ejection fraction (EF≤45%) on optimal therapy (including ACE-i or ARB, and ß-blockers). METHODS AND RESULTS: From a randomized, double-blind placebo-controlled trial (AREA-in-CHF), patients with (73 on canrenone [Can] and 77 on placebo [Pla]), based on modified ATPIII definition (BMI≥30kg/m(2) instead of waist girth) or without MetS (146 by arm). In addition to traditional echocardiographic parameters, we also evaluated myocardial mechano-energetic efficiency (MME) based on a previously reported method. At baseline, Can and Pla did not differ in age, BMI, blood pressure (BP), metabolic profile, BNP, and PIIINP. Compared with MetS-Pla, and controlling for age, sex and diabetes, at the final control MetS-Can exhibited increased MME, preserved E/A ratio, and decreased atrial dimensions (0.04

Impact of physicians' age on the clinical management of global cardiovascular risk: analysis of the results of the Evaluation of Final Feasible Effect of Control Training and Ultra Sensitisation Educational Programme.

AIM: To evaluate the potential impact of physicians' age on global cardiovascular (CV) risk management in the population of the Evaluation of Final Feasible Effect of Ultra Control Training and Sensitisation (EFFECTUS) study. METHODS: Involved physicians were stratified into three age groups (≤ 45, 46-55 and > 55 years), and asked to provide clinical data covering the first 10 adult outpatients, consecutively seen in May 2006. RESULTS: Overall 1078 physicians, among whom 219 (20%) were aged ≤ 45, 658 (61%) between 46 and 55, and 201 (19%) > 55 years, collected data of 9904 outpatients (46.5% female patients, aged 67 ± 9 years), who were distributed into three corresponding groups: 2010 (20%), 6111 (62%) and 1783 (18%), respectively. A higher prevalence of myocardial infarction and stroke was recorded by younger physicians rather than those aged > 46 years. Older physicians frequently recommended life-style changes, whereas a higher number of antihypertensive, antiplatelet, glucose and lipid-lowering prescriptions was prescribed by physicians aged ≤ 45 years. CONCLUSIONS: This analysis of the EFFECTUS study indicates a higher prevalence of vascular diseases among outpatients who were followed by younger physicians, who prescribed a higher number of CV drugs than older physicians. These older physicians have more attitude for prescribing favourable life-style changes than younger physicians.

[Arterial hypertension and heart failure]. / L'ipertensione arteriosa nella genesi dello scompenso cardiaco.

Systemic hypertension is a condition that frequently occurs before the onset of heart failure; furthermore, left ventricular hypertrophy (LVH) is an important risk factor for the development of heart failure (HF). Many studies have demonstrated that a linear relationship exists between increasing values of LV mass and the relative risk of the development of congestive HF. Hypertrophy-hyperplasy of cardiomyocytes and endothelial cells leads to a reduction in coronary reserve and to cell death due to apoptosis or focal necrosis. This characteristic has been defined as 'load dependent myocyte dysfunction' and it is characterized both by structural dysfunctions with cell death and by functional alterations that are detectable early with the evaluation of myocardial function measuring the mid-wall shortening. The detection of extremely high myocardial growth is another factor that could help to make an early diagnosis of HF. The presence of 'load geometrical adaptation' markers, together with an early detection of systolic function anomalies that are often accompanied by diastolic modifications, could help to identify, in an early phase, patients who will develop symptomatic LV dysfunction; therefore, these patients can be intensively treated and undergo a specific follow-up.

Left ventricular filling in arterial hypertension. Influence of obesity and hemodynamic and structural confounders.

We assessed the relations of left ventricular filling to load and geometry by Doppler echocardiography in 80 normotensive subjects (40 normal-weight [36 +/- 12 years, 24 women] and 40 obese [35 +/- 13 years, 24 women]) and 61 hypertensive subjects without silent coronary heart disease (29 normal-weight [43 +/- 13 years, 15 women] and 32 obese [42 +/- 13 years, 19 women]) and comparable left ventricular midwall performance. Left ventricular mass divided by height to the 2.7 power was higher in all groups than in normotensive normal-weight subjects (all P < .0001) and in hypertensive than normotensive obese subjects (P < .001). After controlling for age, sex, blood pressure, and heart rate, isovolumic relaxation time was prolonged in hypertensive subjects and normotensive obese subjects compared with normotensive normal-weight subjects (all P < .0001). Body mass index, left ventricular dimension and mass, and circumferential end-systolic stress did not influence these differences. In pooled groups, prolonged isovolumic relaxation time was predicted by high mean blood pressure (beta = 0.52, P < .001), low end-systolic stress (beta = -0.33, P < .001), increased left ventricular mass (beta = 0.24, P < .004), and high body mass index (beta = 0.14, P < .05, multiple R = .72, SEE = 16.5 milliseconds, P < .0001). Between-group differences in peak early transmitral flow velocity, the deceleration time of early filling velocity, and the ratio of early to late left ventricular filling disappeared after controlling for left ventricular mass. Thus, (1) isovolumic relaxation time is prolonged in both arterial hypertension and obesity; (2) the presence of obesity does not significantly increase isovolumic relaxation time in hypertension; and (3) abnormalities of left ventricular filling in arterial hypertension are offset after controlling for left ventricular mass.

Interaction between body size and cardiac workload: influence on left ventricular mass during body growth and adulthood.

The development of the left ventricle parallels body growth. During infancy, the relation between body size and left ventricular (LV) mass is very close. With advancing age, variability of LV mass in relation to body size markedly increases. To test the hypothesis that the age-related increase in variability of LV mass is due to the progressive impact of hemodynamic stimuli on LV growth, quantitative M-mode echocardiograms were obtained in 766 normal-weight, normotensive individuals over a range of ages from 1 day to 85 years (330 female subjects, 373 subjects younger than 18 years). LV mass was linearly related to height2.7 (r2=.69). Prediction of values of LV mass by body size was more accurate at birth and progressively less precise with increasing age. Stroke work (stroke volume times systolic pressure) was closely related to LV mass (r2=.74). The explained variance of LV mass increased from 69% in the univariate regression with height2.7 to 82% in a multivariate model including height2.7, stroke work, and gender. In children and adolescents (younger than 18 years), height2.7 was the main determinant of LV mass, whereas during adulthood stroke work and gender were more important predictors of LV mass than height2.7. Thus (1) the influence of body growth on development of LV mass decreases after early infancy because of both the variability of hemodynamic load and the increasing effect of gender; (2) after adolescence, during adulthood, in normotensive, normal-weight individuals, the impact of hemodynamic load and male gender on LV mass is greater than the one of body size; and (3) an appreciable proportion of variability of LV mass remains unexplained with the studied models. This might be due to genotypic variations and/or measurement error.

Influence of obesity on left ventricular midwall mechanics in arterial hypertension.

The evaluation of the effect of obesity on left ventricular systolic performance may differ in relation to the method used to measure left ventricular function and to the type of study population. Whether obesity worsens left ventricular midwall mechanics in arterial hypertension has never been investigated. Accordingly, we assessed echocardiographic left ventricular midwall shortening-circumferential end-systolic stress relations in 156 normotensive and normal-weight (reference) adults, 94 normotensive and overweight (1985 National Institutes of Health partition values) to obese (body mass index > 30 kg/m2) adults, 263 hypertensive and normal-weight adults, and 224 hypertensive and overweight-to-obese adults. There was an inverse relation of midwall shortening to circumferential end-systolic stress in all groups (all P < .005). Left ventricular performance as a ratio of observed to predicted midwall shortening fell below the fifth percentile in 4 of 94 (4%) of overweight-to-obese normotensive individuals. Eighty-eight of 487 hypertensive subjects (18.1%) exhibited depressed midwall shortening as a percentage of the value predicted from wall stress, with no difference between normal-weight (50 of 263 [19%]) and overweight (38 of 224 [17%]) subjects. Sixty-one normotensive and 131 hypertensive subjects were frankly obese. After adjustment for sex and age, midwall shortening, as either absolute values or a percentage of predicted, was not statistically different among obese, overweight, and normal-weight subjects in both normotensive and hypertensive groups. For each quartile of observed-to-predicted midwall shortening ratio, obese subjects had greater left ventricular end-diastolic volume than normal-weight subjects among both normotensive and, more evidently, hypertensive subjects. A predicted midwall shortening was generated from both wall stress and left ventricular volume with the use of multiple regression analysis. High body mass index, mean blood pressure, aging, and male sex independently predicted low afterload and left ventricular volume-independent midwall left ventricular performance (multiple R = .31, P < .0001). Thus, (1) midwall left ventricular systolic performance in asymptomatic overweight or frankly obese individuals is comparable to that in normal-weight individuals in both the presence and absence of arterial hypertension; (2) however, maintenance of normal life ventricular performance in obese individuals is associated with the use of Starling reserve; and (3) this compensatory mechanism is especially evident when arterial hypertension and obesity coexist.

Relations of left ventricular geometry and function to body composition in children with high casual blood pressure.

To determine whether abnormal casual blood pressure (BP) is associated with left ventricular (LV) abnormalities in children, 190 6- to 11-year-old children (77 girls, 113 boys) were studied at a school site in Naples, Italy, by limited echocardiography and bioelectric impedance to calculate fat-free body mass (FFM). Single-visit BP measurements (defined as casual BP) were high (based on the Italian tables of BP) in 34 children (18%; 9 girls, 25 boys; 133+/-8/81+/-10 mm Hg) and obesity was present in 44 (23%; 15 girls, 29 boys). Sex- and age-independent risk of high casual BP value was 2.9-fold (odds ratio) greater in obese than in normal-weight children (95% confidence interval, 1.3 to 6.5; P<.01). LV mass (as both absolute value and normalized for height or FFM) was higher and relative wall thickness increased in children with high casual BP (all P<.01). Prevalence of LV hypertrophy was 21% among children with high casual BP (P<.004 versus 4.3% in normal group). Risk of LV hypertrophy was 5.5-fold higher in the presence of high casual BP (P<.004), whereas obesity, age, and sex did not have independent effects. Endocardial shortening was slightly higher in children with high casual BP (36.8+/-8.2%) than in children with normal BP (34.3+/-4.8%, P<.02), whereas midwall shortening was identical in the two groups (20%). Both endocardial shortening and midwall shortening were negatively related to end-systolic stress (r=-.62, SEE=3.8% and r=-.32, SEE=2.4% in normal children). Shortening as a percentage of predicted from wall stress was increased in children with high casual BP at the endocardial level (P<.001), whereas it was normal at the midwall. Therefore, (1) casual detection of high BP in school children is associated with LV geometric abnormalities similar to those found in adults with sustained hypertension (LV hypertrophy, concentric pattern); (2) similar to in adult hypertension, endocardial chamber function in children is supranormal; and (3) in contrast to findings in adults, midwall shortening is normal in children with high casual BP.

Appropriate or inappropriate left ventricular mass in the presence or absence of prognostically adverse left ventricular hypertrophy.

OBJECTIVES: To evaluate whether assessment of appropriateness of left ventricular mass (LVM) adds to the traditional definition of left ventricular hypertrophy (LVH). DESIGN: Cross-sectional, relational. METHODS: Echocardiographic LVH and appropriateness of LVM were studied in 562 subjects (231 normotensive controls, aged 35+/-11 years, 142 women; 331 hypertensive patients, aged 47+/-11 years, 135 women) classified on the basis of either the presence or the absence of both LVH (LVM index > or = 51 g/m2.7) and inappropriate LVM (LVM > 128% of the value predicted by an equation including age, sex and stroke work). RESULTS: Body mass index was comparable in hypertensive patients and controls. Hypertensive patients without LVH but with inappropriate LVM (n = 21) had higher relative wall thickness and total peripheral resistance than all other groups, whereas cardiac output was lower (all P < 0.001). Midwall mechanics was normal with appropriate LVM, independently of presence of LVH, whereas it was depressed in inappropriate LVM, either with or without LVH (both P < 0.0001). There was no substantial difference in ejection fraction among controls and hypertensive groups. Stress-corrected midwall shortening was more closely related to deviation of LVM from the value appropriate for stroke work, body size and gender (r = -0.56, P < 0.0001) than to LVM index (r = -0.26). CONCLUSIONS: Inappropriate LVM is associated with concentric geometry, high peripheral resistance and depressed wall mechanics. The deviation of LVM from the value appropriate for stroke work, body size and sex correlates with measures of myocardial function better than LVM.

Left ventricular filling pattern in uncomplicated obesity.

To determine if uncomplicated obesity is associated with systolic dysfunction or impairment of left ventricular (LV) filling, 40 normotensive, white, asymptomatic, obese subjects (16 men and 24 women, mean +/- SD age 35 +/- 13 years; body mass index 36 +/- 6 kg/m2) and 40 normotensive, normal-weight, white volunteers matched for age and sex distribution, were studied by Doppler echocardiography. Endocardial and midwall shortening did not show differences between groups (obese = 33 +/- 4% and 17 +/- 2%; normal weight = 33 +/- 3% and 18 +/- 2%, respectively). LV mass index was higher in obese than in normal-weight subjects (p <0.0001). Obese persons had prolonged isovolumic relaxation time (p <0.0001), lower transmitral peak early diastolic filling wave (E) velocity (p <0.02), higher E velocity deceleration time (p <0.002) and lower E/atrial diastolic filling wave (A) flow velocity ratio (p <0.01) than did normal-weight subjects, even after controlling for age and blood pressure. Between-group differences in E and E velocity deceleration time disappeared when controlling for LV mass index, whereas prolonged isovolumic relaxation time in obesity was independent of LV mass, chamber dimension, and end-systolic stress. LV filling variables were not statistically related to endocardial or midwall shortening, both as absolute value or as a percentage of that predicted from wall stress. We conclude that uncomplicated obesity is associated with primary impairment of LV isovolumic relaxation; abnormalities of early passive filling flow in obesity are associated with increased LV mass.

Inappropriate left ventricular mass in normotensive and hypertensive patients.

We evaluated cardiovascular features of normotensive and hypertensive adults with left ventricular (LV) mass values exceeding levels predicted for given stroke work, gender, and height, termed "inappropriate" LV mass. Inappropriate LV mass is associated with overweight, concentric LV geometry, and low myocardial systolic function not only in hypertensive subjects, but also in normotensive subjects.

Estimation of left ventricular chamber and stroke volume by limited M-mode echocardiography and validation by two-dimensional and Doppler echocardiography.

This study has been designed to improve estimation of stroke volume from linear left ventricular (LV) dimensions measured by M-mode echocardiography, in symmetrically contracting ventricles. In experimental studies, the ratio of LV epicardial long/short axes "Z" is about 1.3. We measured systolic and diastolic epicardial long and short axes by 2-dimensional echocardiography in 115 adults with widely varying LV short-axis dimensions (LV end-diastolic dimension = 3.95 to 8.3 cm). In a learning series of 23 normotensive and 27 hypertensive subjects, Z(diastole) was 1.3 +/- 0.1 and Z(systole) = 1.2 +/- 0.1, similar to findings in experimental animals. Regression equations were developed by comparing LV volumes by M-mode and 2-dimensional echocardiography. In a test series (65 subjects), LV volumes were calculated using separate regression equations for end-diastolic volume ([LV end-diastolic dimension] 4.765 - 0.288 x posterior wall thickness]) and for end-systolic volume ([LV end-systolic dimension] [4.136 - 0.288 x posterior wall thickness]). Because the term 0.288 x wall thickness was only about 8% of the first term between brackets, the average wall thickness in the learning series was substituted in the Z-volume formulas applied to the test series: end-diastolic volume = (4.5 x [LV end-diastolic dimensions]2) and end-systolic volume = (3.72 x [LV end-diastolic dimension]2). The mean relative error produced with this simplified method was 0.9%. in diastole and 1.4% in systole. Compared with Teichholz' M-mode volume method, Z-derived end-diastolic volume in the test series was equally well related to 2-dimensional volumes (both r = 0.88), with a better intercept (1.5 vs -23 ml, p <0.001) and a slope closer to the identity line (1.1 vs 1.4). Similar results were found for systolic volumes. In a second test series of 1,721 American Indian participants in the Strong Heart Study without mitral regurgitation or segmental LV wall motion abnormalities, Doppler-derived LV stroke volume (70 +/- 14 ml/beat) was similarly predicted by the Z-derived method (r = 0.65, 70 +/- 11 ml/beat) and Teichholz formulas (r = 0.64, 72 +/- 13 ml/beat), but Z-derived volumes had a regression line significantly closer to the identity line (p <0.005). Thus, LV chamber and stroke volumes can be determined from M-mode LV diameters over a wide range of LV sizes and in epidemiologic as well as clinical populations. The performance of this new method appears better than that obtained using the Teichholz formula, with a formula that is easy to handle and makes calculation of LV volumes by pocket calculator possible, even from limited echocardiographic studies.

Ambulatory blood pressure monitoring in offspring of hypertensive patients. Relation to left ventricular structure and function.

The relation between 24-h ambulatory blood pressure monitoring and echocardiographic left ventricular (LV) anatomy and function was examined in 30 young, normotensive offspring (16 men, 14 women) of hypertensive, parents and in 20 offspring (12 men, 8 women) of normotensive parents, comparable for age, clinical blood pressure, and gender. Offspring of hypertensive subjects exhibited higher body mass index (P < .01), relative wall thickness, and LV mass/height (both P < .001). No significant difference was found in LV chamber dimensions and in either systolic or diastolic function. The 24-h systolic and diastolic blood pressures were higher in offspring of hypertensive subjects than in controls (P < .001 and P < .0001, respectively), as was the coefficient of variation of 24 h systolic blood pressure (P < .01). In pooled groups, LV mass was positively related to daytime systolic blood pressure (r = 0.48), daytime diastolic blood pressure (r = 0.47) (both P < .001), and the coefficient of variation of 24 h diastolic blood pressure (r = 0.37, P < .01). In a multiple regression model, including as variables, body mass index, daytime systolic and diastolic blood pressures, male gender, and family history of hypertension were the major independent predictors of LV mass (both P < .0001), with an additional contribution of the coefficient of variation of 24 h diastolic blood pressure (P < .05). We conclude that male gender and a family history of hypertension are stronger determinants of early changes in cardiac structure than hemodynamic load in a group of young, normotensive adults.

Left ventricular hypertrophy, compliance and ventricular filling.

A total of 20 untreated hypertensive patients were divided into two equal groups matched for sex, age and blood pressure but with [mean diastolic wall thickness (MDWT) greater than 1.2 cm] or without (MDWT greater than 1.2 cm) left ventricular hypertrophy (LVH). All patients underwent pulsed doppler echocardiography and 99Tc radionuclide ventriculography at rest to assess diastolic and systolic abnormalities. In hypertensives with LVH the interventricular wall thickness, posterior wall thickness and relative diastolic wall thickness were significantly (P less than 0.01) higher and peak filling rate was significantly (P less than 0.01) lower than in hypertensives without LVH. The indices of systolic function, however, were not significantly different in the two patient groups. In hypertensives without LVH peak filling rate directly correlated with heart rate, whereas in those with LVH peak filling rate directly correlated with heart rate and the ratio of peak velocity of early left ventricular filling : peak velocity of late left ventricular filling due to atrial contraction. It is concluded that diastolic parameters may be useful tools for assessing myocardial compliance and may be effective markers of diastolic dysfunction.

Effects of nicardipine on chronic stable effort angina: a non-invasive assessment.

The effects of 60 mg/day nicardipine hydrochloride were evaluated in a 4-week single-blind study on 12 patients with chronic stable effort angina. All patients completed the treatment with few reports of adverse effects. Nicardipine hydrochloride was effective in reducing the incidence of anginal attacks and consumption of glyceryl trinitrate. Treadmill exercise time, angina onset time and the time to 1 mm ST-segment depression were increased. The extent of ST-segment depression was reduced at maximum comparable exercise, with a reduced rate-pressure product and, at maximum exercise, with an increased rate-pressure product. Myocardial stress 201Tl scintillography was carried out in eight of the patients and showed improved washout in antero-septal, infero-apical and postero-lateral segments. Echocardiographic measures of left ventricular function were enhanced because of reduction of afterload. Systemic vascular resistance and end-systolic stress were also decreased and a significant correlation was found between the increase in ejection fraction and reduction of systolic blood pressure. It is concluded that nicardipine hydrochloride is effective in the control of stable effort angina by reducing myocardial oxygen consumption and enhancing coronary blood flow thereby improving left ventricular function.

Pulmonary venous flow and mitral inflow velocity pattern in uncomplicated obesity: evidence for late diastolic dysfunction.

BACKGROUND: Active left ventricular relaxation, assessed by Doppler isovolumic relaxation time, is impaired in obesity. There is little information on left ventricular passive properties during filling. METHODS: To evaluate left ventricular late diastolic stiffness in obesity, Doppler echocardiographic interrogation of mitral inflow tract and pulmonary vein flow velocities were obtained from 47 normotensive, young obese subjects (11 males, 36 females) and 43 normotensive, young normal-weight volunteers (13 males, 30 females) of comparable age. RESULTS: After controlling the effect of blood pressure and left ventricular mass, isovolumic relaxation time was prolonged in obese subjects (p < 0.0001 vs normal-weight controls). No difference was found in transmitral peak early and late flow velocities. Obese subjects exhibited prolonged pulmonary vein reverse flow velocity during atrial contraction (p < 0.004), and a higher difference or ratio between duration of pulmonary reverse flow and duration of transmitral forward late flow (6 +/- 31 vs -20 +/- 39 ms or 1.06 +/- 0.3 vs 0.84 +/- 0.3, p < 0.002 and p < 0.001, respectively). These differences were also confirmed after controlling blood pressure and left ventricular mass. Non-invasively estimated left ventricular end-diastolic pressure was higher in obese subjects than in controls (p < 0.002). At multivariate analysis a higher body mass index was the sole predictor of prolonged difference between duration of pulmonary reverse flow and duration of transmitral forward late flow (beta = 0.38, p < 0.001). CONCLUSIONS: Obesity is associated with prolonged left ventricular active relaxation and abnormalities of filling pressure not detectable by the sole mitral inflow velocity pattern. These latter abnormalities are consistent with the presence of early increased left ventricular passive stiffness.

Cardiac abnormalities in type 1 diabetes.

BACKGROUND: Left ventricular (LV) structural and hemodynamic consequences of type 1 diabetes mellitus are not fully understood. METHODS: To evaluate LV geometry, systolic and diastolic function in type 1 diabetes, Doppler echocardiograms were performed in 40 normotensive, type 1 diabetic patients without coronary heart disease or valvular lesions (22 men, 18 women, mean age 43 +/- 6 years, body mass index 24.7 +/- 2.8 kg/m2) and in 40 age and sex-matched non-diabetic normotensive controls (22 men, 18 women, mean age 43 +/- 5 years, body mass index 23.2 +/- 2.8 kg/m2), in a case-control design. RESULTS: Patients had higher systolic blood pressure than controls (p < 0.03) and comparable diastolic blood pressure and heart rate. LV dimension and mass were higher in patients than in controls (both p < 0.0001) whereas relative wall thickness did not differ. For comparable levels of end-systolic stress, patients exhibited a higher ejection fraction than controls (p < 0.01) and normal midwall shortening. Cardiac output was also higher (p < 0.001), whereas total peripheral resistance was lower in patients than in controls (p < 0.0001). Isovolumic relaxation time and E deceleration were prolonged in patients and peak A velocity was greater than in controls (all p < 0.01), whereas the difference in duration between A and pulmonary vein peak reverse flow at atrial contraction was comparable. In subgroup analyses, all reported features were independent of a) presence of target organ damage; b) duration of disease; c) levels of glycosylated hemoglobin. CONCLUSIONS: In normotensive patients with type 1 diabetes: 1) there was a moderate increase in LV mass; 2) LV chamber function was supernormal and wall mechanics was normal; 3) LV active relaxation was impaired but chamber stiffness was normal.

Arrhythmias, hypertension and the elderly: Holter evaluation.

In order to clarify the role of age and hypertension in determining arrhythmias, we evaluated the average heart rate, and the number of supraventricular and ventricular premature beats and their severity (Lown grade) by 24-h Holter electrocardiography of 336 patients. We excluded 54 patients with prolonged runs of atrial fibrillation or supraventricular tachycardia because these arrhythmias reduce the possibility of determining the number of premature beats. Analysis of variance, carried out after dividing the patients into four different groups according to age and blood pressure (excluding patients aged 60-65 years with diastolic blood pressure of 91-94 mmHg) showed that the hypertensives had a higher average heart rate (P less than 0.01) and more supraventricular (P less than 0.05) and premature ventricular (P less than 0.01) beats than the normotensives; no difference was found among groups of different ages. The severity of premature ventricular beats was higher in hypertensives than in normotensives, and also higher in elderly than in 'young' patients (P less than 0.01). In the evaluation of all 336 patients we found correlations between age and severity of premature ventricular beats in both normotensives (P less than 0.05) and hypertensives (P less than 0.001). Multilinear regression showed that mean blood pressure was independently related to the average heart rate, and supraventricular and premature ventricular beats and their severity, while age was correlated independently only with the severity of premature ventricular beats (P less than 0.001). We conclude that hypertension induces arrhythmias, and that age increases their severity.