E. Malshi

Impact of prolonged cardiac unloading on left ventricular mass and longitudinal myocardial performance: an experimental bed rest study in humans

Objective This study evaluated the impact of prolonged circulatory unloading and subsequent left ventricular (LV) mass decrease on LV myocardial performance. Five-week head-down tilt (−6°) bed rest (HDTBR) was used as a model of prolonged circulatory unloading. Methods Ten young healthy male volunteers (age 23 ± 2 years) were studied a day before and within the first 24 h after the end of HDTBR by two-dimensional Doppler echocardiography and carotid applanation tonometry. LV preload and afterload, cardiac workload, LV mass and wall stress, LV chamber function and diastolic filling were assessed. Longitudinal, radial and circumferential myocardial strain rate were evaluated by tissue tracking algorithm. Results After HDTBR, stroke volume (P < 0.01), stroke work (P = 0.01) and LV mass (P < 0.001) decreased, whereas relative wall thickness, peak and end-systolic wall stress and ejection fraction remained unchanged. HDTBR was also followed by a decrease in longitudinal systolic strain rate (−1.11 ± 0.05 vs. −1.00 ± 0.05 s−1, P = 0.02) and a prolongation of isovolumic relaxation time (IVRT) (74 ± 2 vs. 82 ± 3 ms, P < 0.01). Bed rest-induced changes in LV mass index were directly related to changes in stroke work index (r = 0.65, P < 0.05), and changes in longitudinal systolic strain rate and IVRT correlated with changes in stroke volume index, directly and inversely, respectively (r = 0.69 and −0.64, P < 0.05 for both). Conclusion A decrease in LV mass following HDTBR parallels the reduction in cardiac workload and is associated with an attenuation of longitudinal systolic myocardial deformation rate and prolongation of IVRT that seem to reflect a functional adaptation of cardiac muscle to lower LV volume load.

Arterial wave reflection during antihypertensive therapy with barnidipine: a 6-month, open-label study using an integrated cardiovascular ultrasound approach in patients with newly diagnosed hypertension

BACKGROUND Increased central aortic pressure resulting from large artery stiffening and increased wave reflection is associated with higher hypertension-related morbidity. OBJECTIVE The goal of this study was to evaluate the effects of a vasodilator-based therapy with the calcium channel blocker barnidipine on arterial stiffness, wave reflection, and left ventricular (LV) performance using an integrated cardiovascular ultrasound approach (including wave intensity analysis). METHODS Newly diagnosed, previously untreated patients with grade 1 or 2 essential hypertension (systolic blood pressure [BP] > or =140 and <180 mm Hg, and/or diastolic BP > or =90 and <110 mm Hg), and with no signs of clinical cardiovascular disease, were eligible for study. Carotid artery mechanics were investigated at baseline and after 3 and 6 months of barnidipine therapy (10-20 mg once daily, according to an open-label design) using a double-beam carotid ultrasound technique. This provided a simultaneous recording of diameter-derived pressure and flow velocity signals and allowed analysis of wave intensity. Indices of local arterial stiffness and wave reflection, as well as separated forward and backward pressure waves, were estimated. LV geometry, mass, and systolic and diastolic performance were also assessed using Doppler echocardiography. All ultrasound examinations and readings were performed by investigators blinded to patient demographics and treatment phase. Normotensive control subjects (office BP <140/90 mm Hg) were included as a reference group. RESULTS Twenty-one white, treatment-naive patients with hypertension (mean [SD] age, 58 [8] years; 14 males; mean body mass index, 27 [5] kg/m(2); mean BP, 159 [14]/96 [5] mm Hg) were enrolled. Twenty normotensive subjects comprised the control group. Compared with the control subjects, patients with hypertension had a higher mean augmentation index ([AIx] 22.0% [7.0%] vs 13.1% [5.2%]; P < 0.01), Petersons pressure-strain elastic modulus (175 [49] vs 126 [41] kPa; P < 0.01), and forward and backward pressure waves (137 [17] vs 108 [7] mm Hg [P < 0.001] and 21 [6] vs 17 [5] mm Hg [P < 0.05], respectively) at baseline. After 6 months of barnidipine treatment, mean office BP in the patients with hypertension decreased from 159 (14)/96 (5) mm Hg at baseline to 138 (16)/81 (9) mm Hg (P < 0.001) due to a significant reduction in forward and backward pressure waves, and AIx decreased to 17.0% (8.0%) (P < 0.01); there were no significant changes in indices of intrinsic arterial stiffness. A significant direct relationship between AIx and pulse pressure (r = 0.45 [P < 0.05]) was observed at baseline in hypertensive patients but not after therapy (r = 0.26 [P = NS]). Mean stress-adjusted LV midwall shortening increased from 110% (17%) at baseline to 118% (13%) at 6 months (P < 0.05), which was comparable to baseline values in the control subjects (119% [10%]). CONCLUSION In these middle-aged patients with newly diagnosed mild to moderate hypertension, vasodilator therapy with barnidipine reduced central BP by a parallel reduction of forward and backward pressure waves, together with a later arrival of the reflected waves, with no significant changes in intrinsic arterial stiffness.

LARGE ARTERY FUNCTION AND VENTRICULAR ARTERIAL COUPLING FOLLOWING CARDIOVASCULAR UNLOADING RELATED TO PROLONGED BED REST IN YOUNG HEALTHY SUBJECTS: PP.31.218

Background: prolonged head-down tilt bed rest (HDTBR) is followed by a decrease in circulating volume possibly affecting large artery structure and function. Aim of the study was to investigate common carotid artery (CCA) remodelling and ventricular-arterial (VA) coupling after HDTBR. Methods: ten healthy male volunteers (age 23 ± 2) were studied before and after a 35-day HDTBR. Ultrasound (Esaote MyLab30) was used to estimate LV volumes, transmitral and aortic flow velocity (FV), CCA diameter and FV, high resolution IMT (Q-IMT). Applanation tonometry (PulsePen, DiaTecne), was used to explore large artery dynamics and wave reflection (WR). Carotid-femoral pulse wave velocity (PWV) was also estimated (Complior, Alam). Results: no changes were observed for central BP vs baseline, while LV volumes and stroke volume significantly decreased and HR increased (from 58 ± 2 to 73 ± 6, p < 0.05). Myocardial performance index (MPI), a Doppler derived index of global LV function [isovolumic contraction time+isovolumic relaxation time)/LV ejection time], increased after HDTBR (0.71 ± 0.12 vs 0.52 ± 0.06, p < 0.005), as well as arterial elastance (Ea = end systolic pressure/stroke volume) and LV elastance [Elv = end systolic pressure (ESP)/end systolic volume (ESV)] (for Ea: 1.08 ± 0.198 vs 1.31 ± 0.21, p = 0.01; for Elv 1.478 ± 0.32 vs 1.765 ± 0.42, p = 0.04), with unchanged Ea/Elv (0.74 ± 0.09 vs 0.76 ± 0.1). PWV, CCA diameter, systolic FV and QIMT did not change, while diastolic and mean FV significantly increased (p < 0.05: FVd from 25 ± 4 to 29 ± 4 cm/s, FVm from 42 ± 8 to 52 ± 11 cm/s). Pulsatility index [PI = (peak systolic velocity-diastolic velocity)/Mean velocity] decreased from 2.3 ± 0.3 to 1.9 ± 0.2, p < 0.02). Applanation tonometry showed no significant changes for Augmentation Index (AIx) and time to WR, while PPI (Pulse Pressure Index: PP/MBP) decreased from 0.55 ± 0.14 to 0.45 ± 0.09, p < 0.05). Conclusions: after prolonged HDTBR, a reduction in LV pump function is observed with unchanged VA coupling. No significant changes are found in intrinsic arterial stiffness, CCA remodelling and WR, while changes in arterial dynamics indicate a reduction in the pulsatile component and an increase in the steady component of BP, possibly associated with reduced circulating volume and increased peripheral vasodilation.

Preclinical Structural and Functional Vascular Involvement in Young Subjects With Type 1 Diabetes Without Overt Complications.

Background: Increased carotid intima-media thickness (IMT), endothelial dysfunction and arterial stiffness (AS) have been reported in young subjects with type 1 diabetes (DM1). However, the relations between these vascular abnormalities remain unknown. Aim of the Study: To assess by a multiparametric approach the preclinical vascular involvement in young patients with early onset DM1 and adequate glycaemic control. Methods: 31 DM1 patients, free of macro- and microvascular complications (20 males, age 19.3 ± 3.1, BMI 22.1 ± 2.7 kg/m2, disease duration: 11 ± 5 years, average HbA1c: 7.7 ± 1.0%), and 31 controls (NL: 16 males, age 20.1 ± 1.6; BMI 21.6 ± 2.1 kg/m2) were studied. IMT was measured by radiofrequency-based ultrasound (Q-IMT, Esaote MyLab70). AS was estimated by carotid-femoral pulse wave velocity (PWV, Complior), and endothelial function by forearm reactive hyperemia index (RHI, EndoPAT). Carotid augmentation index (AIx) was measured by applanation tonometry (Pulsepen, Diatecne). Results: Compared to controls, DM1 patients, although normotensive, had significantly higher (p < 0.05) SBP (119 ± 15 vs 110 ± 9 mmHg), Q-IMT (440 ± 64 vs 401 ± 55 μm), PWV (7.4 ± 1.3 vs 6.5 ± 1.1 m/s) and AIx (12 ± 7 vs 1.8 ± 7%). RHI was lower (p < 0.05) in patients with HbA1c >7.5 % than in those with HbA1c < 7,5 % and NL (1.5 ± 0.35; 2.1 ± 0.69 and 2.1 ± 0.53). Lipid profile was comparable in DM1 vs NL. Within vascular parameters, in the entire population, Q-IMT was directly related with AIx (r = 0.53, p < 0.005) and inversely with RHI (r = -0.33, p < 0.05). In multivariate models, DM1 was independent predictor (p < 0.001) of SBP (together with sex and BMI, R2 = 0.62), Q-IMT (together with sex and RHI, R2 = 0.39), PWV (together with age and SBP, R2 = 0.28) and AIx (together with Q-IMT, R2 = 0.45). Conclusions: In young subjects with adequately controlled DM1 free of overt complications, a mildly increased IMT is associated with augmented wave reflection and reduced RHI. Higher HbA1c levels are associated with endothelial dysfunction, suggesting that an aggressive glycaemic control may be a critical factor for preventing preclinical vascular involvement.