Reference Ranges and Physiologic Variations of Left E/e' Ratio in Healthy Adults: Clinical and Echocardiographic Correlates.

BACKGROUND: Transthoracic Doppler echocardiographic examination is commonly performed to define the diastolic ventricular function since it is widely available, noninvasive, and inexpensive with respect to other diagnostic imaging modalities. However, data regarding age- and gender-matched reference values are scanty and sometimes conflicting. This study aims to explore the physiologic variations of left ventricular (LV) E/e' ratio as assessed in a large cohort of healthy adults and to investigate clinical and echocardiographic correlates. METHODS: From June 2007 to February 2014, 1168 healthy Caucasian adults (mean age 45.1 ± 15.6 years) performed standard echocardiographic examination (transthoracic echocardiogram). RESULTS: E/e' constantly increases across all the age classes (P < 0.0001, analyses of variance both for males and females) with a strong statistically significant linear positive correlation with age. Stepwise multiple linear regression analysis identified age (P < 0.0001), LV mass (P < 0.001), LV end-diastolic volume (P < 0.01), and left atrial volume (P < 0.001) as the only independent determinants of E/e' ratio (model R2 = 0.54, P < 0.0001). CONCLUSIONS: In healthy subjects, transmitral E velocity to e' ratio changes in relation to the age: it increased with a statistically significant correlation in individuals older than 60 years. Hence, differences related to demographic and anthropometric measurements may potentially develop a misclassification of otherwise normal individuals when established on dichotomically suggested normal reference values. Our study can demonstrate that it is indispensable to apply specific cutoff related to the age and gender to properly assess LV diastolic function.

The impact of age and gender on right ventricular diastolic function among healthy adults.

BACKGROUND: Doppler echocardiography is ideally suited for assessment of diastolic function, being widely available, non-invasive, and less expensive than other techniques. However, data regarding age- and gender-matched reference values of right ventricular diastolic function are limited. This study aims to explore the physiologic variations of right ventricle (RV) diastolic function in a large cohort of healthy adults, and to investigate clinical and echocardiographic correlates. METHODS: From June 2007 to February 2014, 1168 healthy Caucasian subjects [mean age 45.1±15.6 years, range 16-92; 555 (47.5%) men] underwent comprehensive transthoracic echocardiography (TTE) following current guidelines. The following RV main diastolic measurements were measured: peak early inflow velocity (E), annular both early (e') and atrial (a') velocities, E/e' ratio. RESULTS: RV E/e' constantly increases with age in females, but do not change substantially in males. RV E/A constantly decreases with age in both genders. Stepwise multiple linear regression analysis underlined a close significant association of RV diastolic function with both right and left heart morphologic measurements (right atrial area, RV diameters, left atrial volume) and functional indexes (TAPSE, RV tissue Doppler peak systolic velocity, left ventricular E/Ee'), as well as with indexes of increased pulmonary resistance. CONCLUSION: Our data highlight the potential usefulness of different normal reference values according to the age and gender to correctly evaluate RV diastolic function. Differences in terms of demographic and anthropometric parameters could be useful to avoid potential misclassification of RV diastolic function when based on dichotomously suggested normal cut-off values.

Comparison of arterial stiffness/compliance in the ascending aorta and common carotid artery in healthy subjects and its impact on left ventricular structure and function.

Arterial stiffness and compliance parameters from two adjacent elastic arteries [aorta and common carotid artery (CCA)] were compared and their relationship with left ventricular (LV) structure and function and clinical parameters was assessed. 584 healthy subjects were prospectively enrolled [mean age 47.8 ± 18.4 years, range 16-94; 318 (54.4%) men]. They underwent comprehensive transthoracic echocardiography; M-mode diameters were measured at the level of the ascending aorta in systole and diastole and by echo-tracking at the level of the left CCA. The ß-stiffness, pressure-strain elastic modulus, arterial compliance and one-point pulse wave velocity were derived. A significant correlation was observed between aortic and CCA stiffness and compliance parameters (p < 0.0001 for all). At multiple regression analysis, CCA stiffness parameters were constantly correlated with age and systolic blood pressure, and accounted for up to 56% of the variability (vs. only 29% in aortic stiffness and compliance). CCA stiffness parameters were found to better predict LV structure, diastolic function than aortic stiffness parameters. Aortic and CCA stiffness and compliance were found to correlate with each other and with age, with the correlation being higher for CCA stiffness. At multiple regression analysis, CCA stiffness parameters were better predictors of LV structure and function than aortic stiffness.

Left Ventricular Function Assessed by One-Point Carotid Wave Intensity in Newly Diagnosed Untreated Hypertensive Patients.

OBJECTIVES: To investigate whether newly diagnosed untreated hypertensive patients show higher left ventricular (LV) contractility, as assessed by traditional echocardiographic indices and carotid wave intensity (WI) parameters, including amplitude of the peak during early (W1 ) and late systole (W2 ). METHODS: A total of 145 untreated hypertensive patients were compared with 145 age- and sex-matched normotensive subjects. They underwent comprehensive echocardiography and WI analysis. WI analysis was performed at the level of the common carotid artery. The diameter changes were the difference between the displacement of the anterior and posterior walls, with the cursors set to track the media-adventitia boundaries 2 cm proximal to the carotid bulb and calibrated by systolic and diastolic BP. Peak acceleration was derived from blood flow velocity measured by Doppler sonography with the range-gate positioned at the center of the vessel diameter. WI was based on the calculation of (dP/dt)×(dU/dt), where dP/dt and dU/dt were the derivatives of BP (P) and velocity (U) with respect to time. One-point pulse wave velocity (PWVß) and the interval between the R wave on ECG and the first peak of WI (R-W1 ), using a high definition echo-tracking system implemented in the ultrasound machine (Aloka), were also derived. RESULTS: After adjustment for body weight, heart rate, and physical activity, the two groups had similar general characteristics and diastolic function. However, hypertensives showed significantly higher LV mass, LV ejection fraction (LVEF), circumferential and LV end-systolic stress, and one-point PWV as well as W1 (13.646 ± 7.368 vs 9.308 ± 4.675 mmHg m/s3 , P =.001) and W2 (4.289 ± 2.017 vs 2.995 ± 1.868 mmHg m/s3 , P =.001). Hypertensives were divided into tertiles according to LVEF: W1 (11.934 ± 5.836 vs 11.576 ± 5.857 vs 17.227 ± 8.889 mmHg m/s3 , P <.0001) was higher in the highest LVEF tertile along with relative wall thickness, midwall fractional shortening, endocardial fractional shortening, and R-W1 . CONCLUSIONS: Newly diagnosed hypertensives show increased LVM and LV contractility, including carotid WI parameters and R-W1 values, as compared with normotensive subjects, but no differences in LV diastolic function.

Sex-specific predictors of left ventricular diastolic dysfunction in untreated hypertension.

BACKGROUND: Little is known about the sex-specific differences in left ventricular (LV) diastolic dysfunction (DD) predictors. We hypothesized that arterial stiffness (AS) may play a different role in the etiology of LV DD in hypertensive men and postmenopausal women, acting independently from other established predictors of this condition, such as age, obesity, diabetes mellitus, LV remodeling, and systolic function. OBJECTIVES: The aim of the study was to analyze the sex-specific differences in AS and other predictors of LV DD in men and postmenopausal women with untreated hypertension (HTN). PATIENTS AND METHODS: The study included 144 patients (63 postmenopausal women and 81 men, mean age 62.7±6.7 years) with previously untreated HTN and no history of cardiovascular diseases. All patients were subjected to detailed echocardiography, vascular ultrasound, and high-resolution echotracking (eTracking) of carotid arteries. RESULTS: In the multivariate analysis, concomitant diabetes mellitus turned out to be an independent predictor of LV DD in women (P=0.02). In turn, two independent predictors of LV DD have been identified in men: S'-tissue Doppler-derived peak LV longitudinal systolic shortening velocity (P=0.001) and ß, beta stiffness index (P=0.004). CONCLUSION: There are sex differences in the predictors of LV DD in untreated HTN. In postmenopausal women, LV DD is mostly determined by diabetes, while in men, it is determined by S', reflecting LV systolic longitudinal function, and ß, a parameter of AS.

Relationship of carotid arterial functional and structural changes to left atrial volume in untreated hypertension.

ABSTRACT: The contribution of arterial functional and structural changes to left ventricular (LV) diastolic dysfunction has been the area of recent research. There are some studies on the relationship between arterial stiffness (a.s.) and left atrial (LA) remodelling as a marker of diastolic burden. Little is known about the association of arterial structural changes and LA remodelling in hypertension (H). AIM: The aim of this study was to examine the relationship between carotid a.s. and intima-media thickness (IMT) and LA volume in subjects with H. The study included 245 previously untreated hypertensives (166 women and 79 men, mean age 53.7 ± 11.8 years). Each patient was subjected to echocardiography with measurement of LA volume, evaluation of left ventricular hypertrophy (LVH) and LV systolic/diastolic function indices, integrated assessment of carotid IMT and echo-tracking of a.s. and wave reflection parameters. RESULTS: Univariate regression analysis revealed significant correlations between indexed LA volume and selected clinical characteristics, echocardiographic indices of LVH and LV diastolic/systolic function and a.s./wave reflection parameters. The following parameters were identified as independent determinants of indexed LA volume on multivariate regression analysis: diastolic blood pressure (beta = -0.229, P < 0.001), left ventricular mass index (LVMI; beta = 0.258, P < 0.001), E/e' index (ratio of early mitral flow wave velocity ­ E to early diastolic mitral annular velocity ­ e'; beta = 0.266, P = 0.001), augmentation index (AI; beta = 0.143, P = 0.008) and body mass index (BMI; beta = 0.132, P = 0.017). No correlations between indexed LA volume and IMT were found. CONCLUSION: There is a significant relationship between carotid arterial stiffness but not intima-media thickness and LA volume in patients with untreated hypertension.

Non-invasive one-point carotid wave intensity in a large group of healthy subjects: A ventricular-arterial coupling parameter.

The analysis of wave intensity (WI) evaluates the working condition of the heart interacting with the arterial system. WI in normal subjects has two peaks, the first (W 1) reflects left ventricle (LV) contractile performance, the second (W 2) is related to the ability of the LV to actively stop aortic blood flow. The aim of the study was to investigate the reference values of W 1 and W 2 in a group of apparently healthy subjects through a radiofrequency-based system. 680 subjects (388 men mean age 43.0 ± 17.4 years, range 16-92; 292 women mean age 44.8 ± 17.7 years, range 16-86) were enrolled and underwent physical examination, blood pressure (BP) and heart rate (HR) measurements and comprehensive transthoracic echocardiogram was performed. Measurement of local WI was obtained at the level of the left common carotid artery before the bifurcation, using a high definition echo-tracking system. W 1 was (12.37 ± 6.89) × 10(3) and (9.76 ± 4.8) × 10(3) mmHg m/s(3), p < 0.0001; W 2 was (3.21 ± 1.81) × 10(3) and (2.98 ± 1.69) × 10(3) mmHg m/s(3), p = ns in men and women, respectively. The cohort was divided into 5 age groups (ages 16-29; 30-39; 40-49; 50-59; >60) and stratified by gender. After adjustment for height, systolic BP and HR, W 1 decreased with age (p < 0.0001 in men and p = 0.026 in women for trend) while no relation was found for W 2. Multivariable regression analysis using age, gender, height, systolic BP, HR, ejection fraction and stroke volume indexed by body surface are predicted W 1 and age, systolic BP, HR and E/A as a measure of diastolic function, predicted W 2. Inter and intra-observer variability and feasibility of WI analysis were satisfactory. We reported the values and their clinical correlations of the two peaks (W 1 and W 2) of WI, a non-invasive hemodynamic index for assessing ventricular-arterial coupling in a large group of apparently healthy subjects.

Deleterious effects of obesity on physical fitness in pre-pubertal children.

The prevalence of obesity in children has increased dramatically during the past decades in Europe and understanding physical fitness and its components in children is critical to design and implement effective interventions. The objective of the present study was to analyse the association between physical fitness (aerobic, speed, agility, power, flexibility and balance) and body mass index (BMI) in pre-pubertal children. A total of 2411 healthy schoolchildren (7-11 years) participated in this study. Anthropometric characteristics and body composition were assessed by skinfold thickness. Physical fitness was measured by nine physical fitness tests: endurance running, 20 m running speed, agility, handgrip strength, standing long jump and squat jump, sit and reach, medicine ball forward throw and static balance. No relevant differences were observed between boys and girls regarding anthropometric characteristics, body composition and physical fitness. However, overweight and obese children showed significantly lower physical fitness levels in endurance running, speed and agility (mean: +18.8, +5.5 and +14.5% of time to complete tasks, respectively), lower limb power normalised to body mass (-23.3%) and balance tests (number of falls: +165.5%) than their normal weight counterparts. On the other hand, obesity did not affect handgrip, throwing and flexibility. In conclusion, increased BMI was associated with lower performance capabilities limiting proper motor skill development, which directly affects the ability of children to take on sports skills. Actions undertaken to promote children's wellness and fitness should be prioritised and introduced early in life with the aim of enhancing physical fitness as well as preventing overweight and obesity.

Normal values of aortic root dimensions in healthy adults.

The reported ranges of aortic root (AR) diameters are limited by small sample size, different measurement sites, and heterogeneous cohorts. The aim of this study was to explore the full spectrum of AR diameters by 2-dimensional transthoracic color Doppler echocardiography (TTE) in a large cohort of healthy adults. From June 2007 to December 2013, a total of 1,043 Caucasian healthy volunteers (mean age 44.7 ± 15.9 years, range 16 to 92 years, 503 men [48%]) underwent comprehensive TTE. TTE measurements of the AR were made at end-diastole in parasternal long-axis views at 4 levels: (1) annulus, (2) sinuses of Valsalva, (3) sinotubular junction, and (4) proximal ascending aorta. The absolute aortic diameters were significantly greater in men than in women at all levels, whereas body surface area-indexed aortic diameters were greater in women (p = 0.0001). No significant gender differences were registered for sinuses of Valsalva and sinotubular junction to annulus diameter ratios (p = 0.9), whereas ascending aorta to annulus diameter ratio was higher in women (p = 0.0001). There was a straight correlation between aortic diameters (absolute and indexed values), their ratios, and age in both genders (p = 0.0001). In conclusion, we provide the full range of AR diameters by TTE. Knowledge of upper physiological limits of aortic dimensions is mandatory to detect aorta dilatation, follow up the disease over time, and plan appropriate therapeutic interventions.

Structural and functional left ventricular impairment in subjects with chronic spinal cord injury and no overt cardiovascular disease.

CONTEXT: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in subjects with long-term spinal cord injury (SCI). More specific recommendations for CVD prevention in this population are needed. METHODS: One hundred thirty male subjects (47 subjects with SCI and 83 able-bodied persons (ABPs), mean age 43.89 ± 1.9 and 45.44 ± 12.2 years; P = 0.48) underwent transthoracic echocardiography (TTE). The effects of age, weight, mean arterial pressure (MAP) and level of physical training on cardiac adaptations were evaluated through multiple regression analysis. RESULTS: In subjects with SCI, TTE revealed increased wall thickness (P < 0.05), lower E wave, E/A ratio and early diastolic myocardial relaxation velocity on Tissue Doppler Imaging (TDI) (P < 0.05) and higher systolic myocardial contraction velocity on TDI (0.10 ± 0.02 vs. 0.09 ± 0.02 m/seconds, P = 0.002) and peak systolic pressure to end-systolic volume ratio (3.62 ± 1.39 vs. 2.82 ± 0.90, P < 0.001) compared with ABPs. Aortic diameters were larger in subjects with SCI than ABPs. Differences remained statistically significant even after adjustment for age, weight, MAP, and level of physical training. Weight and age were found to be independent variables that substantially affected left ventricular structure and function in subjects with SCI. CONCLUSIONS: Subjects with post-traumatic chronic SCI and no overt cardiovascular risk factors, exhibit initial left ventricular remodeling (as assessed by TTE) compared with ABPs. Lifestyle modifications, including regular physical exercise and weight control, should be implemented in all subjects with SCI, even at a very early stage, in order to reduce cardiovascular risk and prevent the development of CVD.

Aortic root dimensions and stiffness in healthy subjects.

The aim of the present study was to investigate the full range of aortic root diameters and stiffness in a group of subjects without known cardiovascular risk factors and/or overt cardiovascular disease. Four hundred and twenty-two healthy subjects (mean age 44.35 ± 16.91 years, range 16 to 90, 284 men [67%]) underwent comprehensive transthoracic echocardiography. The leading edge method was used for the end-diastolic aortic root diameters measured at 4 locations (1) the aortic annulus, (2) the sinuses of Valsalva, (3) the sinotubular junction, and (4) the maximum diameter of the proximal ascending aorta. Aortic wall stiffness was assessed using 2-dimensional guided M-mode evaluation of systolic and diastolic aortic diameter, 3 cm above the aortic valve. The absolute aortic root diameters increased with age in both genders. Aortic measurements were significantly greater in men than in women at all levels, whereas body surface area-indexed values were similar in men and women, except for the ascending aorta for which women tended to have greater values. Multivariable regression analysis using age and body size (weight, height, and body surface area) predicted all aortic diameters, whereas blood pressure indexes predicted only the distal part of the aorta. Aortic stiffness increased with age in men and women with no differences between genders; only age predicted aortic stiffness. The increment in aortic diameter with age was lesser when adjusted for aortic stiffness. In conclusion, we define the physiologic range of aortic root diameters and related stiffness in healthy subjects stratified by age and gender. Moreover, aortic stiffness should also be taken into account when the increase of aortic diameter is considered.

Whole-body glucose oxidation rate during prolonged exercise in type 1 diabetic patients under usual life conditions.

OBJECTIVE: Fuel oxidation during exercise was studied in type 1 insulin-dependent (T1DM) patients mainly under quite constant insulin and glycemia; these protocols, however, likely do not reflect patients' usual metabolic conditions. The glucose oxidation rate (GLUox) in T1DM patients under usual life conditions was thus investigated during prolonged exercise (3-h) and its behavior was described mathematically. MATERIALS/METHODS: Whole-body GLUox was determined in eight T1DM patients (4/8 M; aged 35-59 years) and eight well-matched healthy subjects. Venous blood was drawn prior to and every 30 min until the end of exercise; glycemia, insulin, cortisol, and growth hormone concentrations were determined. Oxygen consumption, carbon dioxide production, and ventilation were measured at rest and thereafter every 30 min of the exercise. To prevent hypoglycemia, patients were given fruit fudge (93% sucrose) prior to / during exercise. RESULTS: Insulin concentration and glycemia were significantly higher in patients across the entire exercise period (group effect, p<0.001 for both). GLUox decreased significantly with increasing exercise duration (time effect, p<0.001), but no significant difference was detected between the two groups (group effect, p=NS). GLUox, expressed as the percentage of the starting value, was described by an exponential function showing a time constant of 90 min (n=96; mean corrected R(2)=0.666). CONCLUSIONS: GLUox in T1DM patients was not significantly different from the rate observed in the control subjects. The function describing the time course of GLUox may be useful to correct an estimated GLUox for the duration of exercise and help T1DM patients avoiding exercise-induced glycemic imbalances.

Tako-tsubo cardiomyopathy: insights from a community hospital.

AIMS: To describe the actual incidence, prevalence among acute coronary syndrome patients and rate of recurrences of tako-tsubo cardiomyopathy in an emergency department of a community hospital. METHODS: We report the in-hospital and long-term clinical course (7.5 years follow-up) of 25 consecutive tako-tsubo cardiomyopathy patients (mean age 66.8 ±â€Š11.76 years; F/M: 21/4) admitted to a community hospital (referring population: 97,000 inhabitants). RESULTS: The incidence rate of tako-tsubo cardiomyopathy was 0.03 cases per 1000 person-years; the prevalence was 3.0% among those with acute coronary syndrome and 7.6% among ST elevation myocardial infarction patients. Clinical presentations included mainly chest pain (n = 16, 64%) and dyspnea (n = 3, 12%). Precipitating conditions were emotional (n = 10, 40%), physical stress (n = 5, 20%) or both (n = 1, 4%); no stressors were recorded in nine patients (36%). Two patients died during hospitalization (8%). At the end of follow-up (mean time: 960.24 ± 724.34 days), all patients (n = 23) were alive and no major cardiovascular events were observed. Five patients had recurrences (22%). The mean time of recurrence was 105.4 ± 82.92 days and the clinical presentation was less severe compared with the first event: ECG had less ST involvement, ejection fraction was higher and cardiac injury biomarkers were lower. CONCLUSIONS: In our population incidence and prevalence of tako-tsubo cardiomyopathy among acute coronary syndrome patients, as well as the recurrence rate of tako-tsubo cardiomyopathy, were higher than previously reported, suggesting that probably this syndrome often passes undiagnosed.

Comparison of sequentially measured Aloka echo-tracking one-point pulse wave velocity with SphygmoCor carotid-femoral pulse wave velocity.

OBJECTIVES: Recently, echo-tracking-derived measures of arterial stiffness have been introduced in clinical practice for the assessment of one-point pulse wave velocity. The purpose of this study was to find a relation between carotid-femoral pulse wave velocity and one-point carotid pulse wave velocity, and to find a value of one-point carotid pulse wave velocity that predicts carotid-femoral pulse wave velocity higher than 12 m/s. METHODS: A total of 160 consecutive subjects (112 male/48 female, mean age = 51.5 ± 14.1 years; 96 healthy, 44 hypertensives, 13 with aortic valve disease, and 7 with left ventricular dysfunction) were studied. Carotid-femoral pulse wave velocity was measured with the SphygmoCor system and one-point carotid pulse wave velocity with high-definition echo-tracking system (ProSound Alpha10; Aloka, Tokyo, Japan). RESULTS: Both carotid-femoral pulse wave velocity and one-point carotid pulse wave velocity correlated significantly with each other (r = 0.539, p < 0.001) and with age (one-point carotid pulse wave velocity r = 0.618, carotid-femoral pulse wave velocity r = 0.617, p < 0.0001 for both). Median value of carotid-femoral pulse wave velocity (7.2 m/s, 95% confidence interval = 6.2-8.9) was systematically higher than that of one-point carotid pulse wave velocity (5.8 m/s, 95% confidence interval = 5-6.6). The area under the receiver operating characteristic curve was 0.85, identifying the cutoff for one-point pulse wave velocity of 6.65 m/s as the best predictor of carotid-femoral pulse wave velocity more than 12 m/s (sensitivity = 0.818, specificity = 0.819). CONCLUSIONS: One-point carotid pulse wave velocity correlates with carotid-femoral pulse wave velocity, and the cutoff of 6.65 m/s was the best predictor of carotid-femoral pulse wave velocity over 12 m/s.

[Italian cold cuts evolution. New opportunities for diet in athletes]. / Evoluzione nutrizionale dei salumi italiani. Nuove opportunità nella dieta dello sportivo.

Italian cold cuts were not recommended for cardiac patients, healthy people, and athletes because of their high content in salt, fat, calories, and cholesterol. Recent studies from INRAN (National Institute of Research for Food and Nutrition) have provided new insights into Italian cold cuts, showing that they are more digestible, with less sodium, fat, cholesterol and calories, than previous products. Thanks to these new chemical-physical characteristics, Italian cold cuts can now be indicated for nutrition in the general population and athletes.

[Hypertension and sports activity]. / Ipertensione arteriosa e sport.

The importance of physical activity in primary and secondary prevention of cardiovascular disease has been demonstrated in many studies. In particular, the effect of exercise, especially aerobioc exercise, is to reduce blood pressure and heart rate by reducing sympathetic tone, and to correct many factors of the metabolic syndrome. Exercise prescription should be based on knowledge of the changes induced by training, but also on risk assessment, both cardiovascular and non-cardiovascular, of hypertensive subjects. It is generally accepted that for prevention and treatment of hypertension is useful to perform 3-4 weekly sessions of aerobic exercise for 30-45 min, at 50-70% of maximum working capacity. The recommended activities are walking, running, cycling and programs of mixed aerobic exercise. People with hypertension may follow their own personal inclinations, by choosing a sport and doing it at a competitive level. In hypertensive athletes the eligibility for competitive sports activities implies a careful medical evaluation, according to the recently published Italian COCIS cardiac guidelines.