Impact of arterial elastance as a measure of vascular load on left ventricular geometry in hypertension.

OBJECTIVE: Effective arterial elastance (Ea), integrating the pulsatile component of left ventricular (LV) afterload, is an estimate of aortic input impedance. We evaluated relationships of Ea with left ventricular anatomy and function in essential hypertension. DESIGN: A cross-sectional analysis in 81 normotensive and 174 untreated hypertensive individuals enrolled in a referral hypertension centre. METHODS: Using echocardiography we determined left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume (SV), endocardial (FSe) and midwall (FSm) fractional shortening and total peripheral resistance (TPR). Carotid pressure waveforms were obtained by arterial tonometry, and end-systolic pressure (Pes) was measured at the dicrotic notch. Ea index (EaI) was calculated as Pes/(SV index); LV elastance (Ees) was estimated as Pes/LV end-systolic volume, and ventriculo-arterial coupling was evaluated by the Ea/Ees ratio. RESULTS: EaI was higher in hypertensives than in normotensives (3.02 +/- 0.63 versus 2.40 +/- 0.52 mmHg/l per m2; P< 0.0001). Using the 95% upper confidence limit in normotensives, hypertensives were divided in two groups with normal or elevated EaI. The 38 hypertensives with elevated EaI had higher RWT (0.41 +/- 0.06 versus 0.37 +/- 0.05), lower LVMI (87.5 +/- 18.5 versus 96.8 +/- 19.3 g/m2), higher TPR (2247 +/- 408 versus 1658 +/- 371 dynes/cm s(-5)) and lower FSe and FSm (35 +/- 5 versus 39 +/- 5 and 16 +/- 2 versus 18 +/- 2%; all P< 0.05) than patients with normal EaI. Ea/Ees ratio was increased and cardiac output was reduced in hypertensives with elevated EaI. CONCLUSIONS: High values of EaI identify a minority of hypertensive patients characterized by elevated TPR, left ventricular concentric remodelling, depressed left ventricular systolic function and impaired ventriculo-arterial coupling.     

Value of cardiovascular interaction by exercise echocardiography according to gender

Background The cardiovascular interaction is important for the heart to achieve maximal cardiac work.The cardiovascular stiffness contributes to exercise intolerance. However, the difference in cardiovascular stiff-ness between genders is seldom reported when the objects do exercise. This study was to evaluate the ventricu-lar and arterial stiffness at rest and exercise according to gender. Methods Forty healthy volunteers were studied. The left ventricular function, structure and blood flow were measured by echocardiograph at rest and exercise. The derived variables including left ventricular end-systolic and diastolic elastance（Ees and Ed）, arterial elastance（Ea）, ventricular-vascular coupling index（VVI） and total stiffness index（TSI） were calculated.Results During exercise, all of the Ed, Ees, Ea and TSI showed significant increase, but VVI was no difference compared with them at rest. Both at rest and exercise, Ed, VVI and TSI had significantly higher in women than in men. The area under the receiver operating characteristic curves showed the area of Ed, Ees, Ea and TSI was greater than that of VVI. There were significant differences in Ed, Ees, Ea and TSI（P 〈 0.05）, but no significant difference in VVI（P 〉 0.05） between rest and exercise. Only in women, the Ed, Ees and Ea were correlated with the TSI, rate pressure product, E/e and EF. Conclusions Exercise leads to synchronous increase in ventricular and arterial stiffness, and ventriculoarterial coupling is maintained for healthy objects. The exercise intolerance is lower in women than in men.     

Dynamic effects of carotid sinus baroreflex on ventriculoarterial coupling studied in anesthetized dogs.

We evaluated dynamic effects of the carotid sinus baroreflex on ventriculoarterial coupling. In seven anesthetized, vagotomized dogs, we bilaterally isolated carotid sinuses and randomly changed carotid sinus pressure while measuring aortic pressure, aortic flow, and left ventricular pressure. Estimating left ventricular end-systolic elastance (Ees) and effective arterial elastance (Ea) on a beat-to-beat basis, we determined transfer functions from the carotid sinus pressure to Ees (HEes) and from the carotid sinus pressure to Ea (HEa) over the frequency range spanning 0.002-0.25 Hz. Both HEes and HEa exhibited characteristics of a second-order low-pass filter. The gains of HEes and HEa were 0.085 +/- 0.065 (mean +/- SD) and 0.081 +/- 0.049 mm Hg/ml/mm Hg, respectively. There were no significant differences in natural frequencies (0.039 +/- 0.013 versus 0.039 +/- 0.007 Hz) or damping ratios (0.65 +/- 0.11 versus 0.64 +/- 0.24). The results indicated that the carotid sinus baroreflex dynamically altered Ees and Ea to the same extent in the process of stabilizing arterial pressure. Because the arterial system extracts maximal external work from a given heart when Ea equals Ees, the carotid sinus baroreflex appeared to be designed to regulate the ventricular and arterial properties to optimize the energy transmission from the left ventricle to the arterial system in anesthetized, vagotomized dogs.     

Ventricular load optimization by unloading therapy in patients with heart failure

The effects of unloading a depressed heart were assessed in terms of optimal coupling between the ventricle and arterial system. To assess the effects of preload on ventricular load coupling, preload was reduced with a lower body negative pressure of -20 mm Hg. Nitroprusside was used to evaluate the effects of afterload on the coupling under the condition that preload reduction was comparable to that with lower body negative pressure. In 13 patients with heart failure (ejection fraction 32 +/- 3%, mean +/- SE), direct arterial pressure was simultaneously recorded with the left ventricular echocardiogram as the pressure was elevated by phenylephrine. Left ventricular contractile properties were defined by the slope (Ees) of the end-systolic pressure-volume relation. The effective arterial elastance (Ea) was expressed by the slope of the end-systolic pressure-stroke volume relation. Left ventricular external work, end-systolic potential energy and work efficiency, defined as external work per pressure volume area (external work + potential energy), were determined. Baseline ventricular load coupling in these patients was characterized by an increase in the ratio of arterial elastance to ventricular elastance (Ea/Ees) (1.96 +/- 0.31). This ratio decreased significantly, to 1.45 +/- 0.22, with nitroprusside, and increased to 2.37 +/- 0.34 with lower body negative pressure. Therefore, end-systolic potential energy was decreased by nitroprusside but was unaltered by lower body negative pressure while external work was comparably decreased by both manipulations, indicating that work efficiency was significantly augmented with nitroprusside but declined with lower body negative pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventricular-load optimization in patients with heart failure.

The effects of unloading or inotropic agent in 22 patients with dilated cardiomyopathy were assessed in terms of optimal coupling between the ventricle and arterial system. In 13 patients (group A), lower body negative pressure (LBNP) was applied to reduce preload and nitroprusside was used to decrease afterload. In 9 patients (group B), dobutamine was used to enhance inotropic state. In all patients, the direct arterial pressure was simultaneously recorded with left ventricular echocardiogram as the pressure was elevated by phenylephrine. The left ventricular contractile properties were defined by the slope (Ees) of the end-systolic pressure-volume relation. The arterial system properties were expressed by the slope (Ea) of the end-systolic pressure-stroke volume relation. When the Ea/Ees ratio ranged from 0.5 to 1.0, both external work and mechanical efficiency are nearly maximized. In group A, baseline ventricular-load coupling was characterized by an increase in the Ea/Ees ratio (1.96 +/- 1.08) where the heart could maximize neither external work nor mechanical efficiency. Ea/Ees significantly fell to 1.45 +/- 0.77 with nitroprusside, while increasing to 2.37 +/- 1.17 during LBNP. In group B, Ea/Ees was decreased from 1.43 +/- to 0.82 +/- 0.47 with dobutamine. It is concluded that reduction in afterload rather than preload, or augmentation of contractility could restore optimal ventricular-load coupling in patients with severe cardiac dysfunction.     

Pressure-volume analysis as a method for quantifying simultaneous drug (amrinone) effects on arterial load and contractile state in vivo

Pressure-volume relation analysis was used to independently quantify changes in ventricular contractile performance and vascular loading in intact anesthetized dogs before and after a single bolus of intravenous amrinone. Ventricular systolic property changes were characterized by the end-systolic elastance (Ees = slope of the end-systolic pressure-volume relation) and arterial properties by the effective arterial elastance (Ea = end-systolic pressure/stroke volume ratio). Pressure-volume data were obtained by the conductance catheter technique with loading varied by transient inferior vena cava occlusion. Amrinone induced a 27% increase in ejection fraction at 10 min (from 44% to 56%) as a result of both a significant rise in contractility (mean Ees 4 +/- 2 to 6 +/- 3 mm Hg/ml, p less than 0.001) and simultaneous reduction in arterial loading (Ea reduction from 6 +/- 2 mm Hg/ml to 5 mm Hg/ml, p less than 0.001). Over the subsequent 30 min, Ea revealed a significant recovery toward baseline, whereas Ees was less altered. Mean percent changes (% delta) in both variables were linearly correlated: % delta Ea = -1.6 x % delta Ees + 3.1, r = 0.96, p less than 0.001. In addition to separating ventricular from vascular property changes, the pressure-volume coupling framework was used to predict net pump performance (ejection fraction). Model predictions showed good agreement with experimental data. Thus, pressure-volume relations can be used to separately quantitate simultaneous changes in ventricular and vascular loading properties in vivo produced by pharmacologic agents with complex actions. Use of this approach in drug testing in humans should simplify data interpretation regarding mechanisms of action in specific clinical settings.     

Facilitated recovery of cardiac performance by triiodothyronine following a transient ischemic insult.

Reperfusion following a transient ischemic insult has been shown to result in a delayed recovery of myocardial function. A reduction in plasma triiodothyronine (T3) has been reported in these acute cardiovascular challenges. To test whether the replacement of T3 can facilitate the recovery of myocardial function following a transient regional ischemia, we investigated cardiac performance for 3 h after a 15-min, left anterior descending coronary artery occlusion in a canine model. Three groups of dogs were studied: I--control (n = 10); II--receiving T3 (0.25 micrograms/kg i.v. and 0.25 micrograms/kg/h for 3 h, n = 9), and III--receiving T3 (0.25 micrograms/kg i.v. and 0.5 micrograms/kg/h for 3 h, n = 9). Three hours following reperfusion, the T3 level in blood was significantly decreased in group I. Concomitantly, local segmental shortening was reduced from preocclusion control levels in group I (15.2 to 5.1%, p < 0.05), but recovered in both treated groups. The endsystolic elastance (Ees) and the external work (EW) efficiency (EW/PVA) in group I were depressed from preocclusion control (Ees = 95.5 +/- 0.8%; EW/PVA = 90.2 +/- 1.8%, both p < 0.05), the effective arterial elastance (Ea) and ventriculoarterial coupling (Ea/Ees) in group I were still elevated from preocclusion control (Ea = 122.5 +/- 5.1%; Ea/Ees = 128.3 +/- 5.3%, both p < 0.05). But these measures of global cardiac performance in the treated groups recovered following reperfusion, and the extent of recovery was dose dependent. These data suggest that T3 facilitates recovery of the stunned myocardium by improvement in local and global contractile function, in ventriculoarterial coupling, and in the energy efficiency.     

Effects of endotoxic shock on right ventricular systolic function and mechanical efficiency

OBJECTIVE: To investigate the effects of endotoxin infusion on right ventricular (RV) systolic function and mechanical efficiency. METHODS: Six anesthetized pigs (Endo group) received a 0.5 mg/kg endotoxin infusion over 30 min and were compared with six other anesthetized pigs (Control group) receiving placebo for 5 h. RV pressure-volume (PV) loops were obtained by the conductance catheter technique and pulmonary artery flow and pressure were measured with high-fidelity transducers. RESULTS: RV adaptation to increased afterload during the early phase of endotoxin-induced pulmonary hypertension (T30) was obtained by both homeometric and hetereometric regulations: the slope of the end-systolic PV relationship of the right ventricle increased from 1.4+/-0.2 mmHg/ml to 2.9+/-0.4 mmHg/ml (P<0.05) and RV end-diastolic volume increased from 56+/-6 ml to 64+/-11 ml (P<0.05). Consequently, right ventricular-vascular coupling was maintained at a maximum efficiency. Ninety minutes later (T120), facing the same increased afterload, the right ventricle failed to maintain its contractility to such an elevated level and, as a consequence, right ventricular-vascular uncoupling occurred. PV loop area, which is known to be highly correlated with oxygen myocardial consumption, increased from 1154+/-127 mmHg/ml (T0) to 1798+/-122 mmHg/ml (T180) (P<0.05) while RV mechanical efficiency decreased from 63+/-2% (T0) to 45+/-5% (T270) (P<0.05). CONCLUSIONS: In the very early phase of endotoxinic shock, right ventricular-vascular coupling is preserved by an increase in RV contractility. Later, myocardial oxygen consumption and energetic cost of RV contractility are increased, as evidenced by the decrease in RV efficiency, and right ventricular-vascular uncoupling occurs. Therefore, therapies aiming at restoring right ventricular-vascular coupling in endotoxic shock should attempt to increase RV contractility and to decrease RV afterload but also to preserve RV mechanical efficiency.     

Efficiency of energy transfer from pressure-volume area to external mechanical work increases with contractile state and decreases with afterload in the left ventricle of the anesthetized closed-chest dog

We studied the effects of ventricular end-systolic elastance (Ees) and effective arterial elastance (Ea) on the efficiency of energy transfer from pressure-volume area (PVA) to external mechanical work (EW) in the left ventricle of anesthetized closed-chest dogs. PVA represents the total mechanical energy generated by ventricular contraction, which is an intermediate form of energy between oxygen consumption, the total energy input, and EW, the effective energy output. PVA and EW were determined from ventricular pressure and volume, which were continuously measured with a volumetric conductance catheter. Measurements of Ees were obtained by transiently increasing afterload by an inflation of a Fogarty catheter in the thoracic descending aorta. Ea was determined as the ratio of end-systolic pressure to stroke volume. The EW/PVA efficiency of a steady-state contraction increased from 55% to 64%, with a 58% increase in Ees after dobutamine. Ees, which was smaller than Ea before dobutamine, became nearly equal to Ea after dobutamine, maximizing EW for a given end-diastolic volume. EW/PVA efficiency decreased with an abrupt increase in afterload before and after dobutamine. The sensitivity of the decrease in the EW/PVA efficiency to an increase in end-systolic pressure was significantly less after than before dobutamine. We could account for all these changes in EW/PVA efficiency by the relative changes in Ees and Ea in the pressure-volume diagram.     

Left ventricular performance, ventriculo-arterial coupling and mechanical output in hypertensive patients with and without left ventricular hypertrophy]

Left ventricular hypertrophy (LVH) is a physiological process of adaptation of the heart to mechanical load increase. Despite depression of left ventricular (LV) contractile performance, work efficiency is preserved and ventriculoarterial coupling is almost normal in hypertensive patients with LVH. To assess the differences between patients with and without LVH, LV contractile performance, the ventriculoarterial coupling and mechanical efficiency were compared in 2 groups of hypertensive patients with similar body surface area and arterial pressures, 23 without LVH (group 1) and 30 with LVH (group 2) and compared to data of 20 normotensive subjects. Left ventricular angiography coupled with simultaneous recording of pressures with micromanometer were used to determine end-systolic stress-to-volume ratio (ESSVR), end-systolic elastance (Ees), effective arterial elastance (Ea), external work (EW) and pressure-volume area (PVA). Left ventricular contractile performance assessed by Ees/100 g myocardial mass and EESVR were lower in group 2 than in group 1 (1.23 +/- 0.28 vs 1.89 +/- 0.48 mmHg/mL/100 g and 6.22 +/- 1.07 vs 9.56 +/- 0.97 g/cm2/mL/m2, respectively, both p < 0.0001, control subjects: 1.47 +/- 0.41 and 6.97 +/- 1.22, respectively). Ventriculoarterial coupling evaluated through Ea/Ees ratio (0.51 +/- 0.05 in group 1 vs 0.53 +/- 0.08 in group 2, 0.49 +/- 0.09 in control subjects), and work efficiency evaluated through EW/PVA ratio (0.80 +/- 0.02 in group 1 vs 0.78 +/- 0.03 in group 2, 0.80 +/- 0.03 in control subjects), were similar in the 2 groups and were comparable to control subject values. In conclusion, this study shows that ventriculoarterial coupling and work efficiency are comparable in hypertensive patients with and without LVH. These results suggest that in patients without LVH the matching between left ventricle and arterial receptor is preserved through an enhancement of myocardial contractility which is energetically costly. Conversely, LVH seems to be a useful adaptation which minimizes the energetical cost of high pressure generation.     

The effect of prostaglandin E1 on acute pulmonary artery hypertension during oleic acid-induced respiratory dysfunction

This study examined the general effect of intravenous PGE1 on RV Ees and effective PA elastance (EA) during acute pulmonary hypertension associated with oleic acid infusion. In eight pigs, RV end-systolic elastance was quantified with the Ees and Ea was defined with reference to the Windkessel model. Oleic acid infusion increased mean PAP and Ea. Prostaglandin E1 reduced PAP and decreased Ea. Ees did not change throughout the study. Mean arterial pressure was reduced and the pulmonary shunt was increased after PGE1 infusion. The PaO2 was reduced. Data from this study suggest that although PGE1 is effective in reducing PAP, it is not as effective in reducing RV afterload. Furthermore, PGE1 does have significant side effects such as reduction of systemic arterial pressure and an increase in pulmonary shunt.     

Comparison of cardiac and peripheral arterial stiffening and ventriculovascular uncoupling in patients with uncomplicated hypertension versus patients with hypertension after heart transplantation

Despite normal ejection fractions, patients who undergo heart transplantation (HT) have low peak aerobic capacity and reduced arterial compliance, suggesting "ventriculovascular uncoupling." To what extent this is related to post-transplantation hypertension versus the unique characteristics of the donor-recipient relation remains poorly understood. Echocardiograms were retrospectively reviewed from 126 normal subjects, 309 patients with uncomplicated hypertension (UH), and 58 consecutive patients with HT >1 year after the procedure who were stable without evidence of rejection. Left ventricular (LV) end-systolic elastance (Ees), a measure of LV systolic performance; effective arterial elastance (Ea), a measure of vascular stiffness; and Ea/Ees, a parameter describing ventriculovascular coupling, were obtained. Compared with normal subjects, tandem increases in Ea (+24% and +85%, all p values <0.0001) and Ees (+23% and +33%, all p values <0.0001) were observed in patients with UH and HT, respectively, with patients with HT having significantly higher values than those with UH (both p values <0.05). Although the Ea/Ees ratio remained similar between normal subjects and patients with UH, patients with HT exhibited increases in the Ea/Ees ratio (all p values <0.01) and reduced stroke volume indexes (-20% and -22%, respectively, all p values <0.05). These changes were associated with a doubling of LV concentric remodeling in patients with HT compared with those with UH (67% vs 34%, p <0.0001). In conclusion, HT is associated with increases in Ees, Ea, and the Ea/Ees ratio, suggesting ventriculovascular uncoupling and maximal LV stroke work. These aberrations, which determine cardiovascular performance in the setting of HT, are not simply explained by vascular age or post-transplantation hypertension but may adversely affect functional capacity.     

Ventricular energetics in aortic root replacement for annuloaortic ectasia with aortic regurgitation

Aortic root replacement (Bentall operation) is the standard operation for patients who have lesions of the ascending aorta associated with aortic valve disease. We analyzed the mid-term results for left ventricular energetics after the Bentall operation for annuloaortic ectasia with aortic regurgitation. We measured left ventricular contractility (end-systolic elastance; Ees), afterload (effective arterial elastance; Ea), and efficiency (ventriculoarterial coupling; Ea/Ees, and the ratio of stroke work and pressure-volume area; SW/PVA) based on transthoracic echocardiography data before, after, and approximately 1 year after the Bentall operation in 15 patients with annuloaortic ectasia with aortic regurgitation. Left ventricular volume was calculated by the Teichholz M-mode method. Ees and Ea were approximated as follows: Ees = mean blood pressure/minimal left ventricular volume, and Ea = systolic blood pressure/(maximal left ventricular volume — minimal left ventricular volume). Ea/Ees and SW/PVA were then calculated. Left ventricular volume was normalized with body surface area. Ees increased after the Bentall operation and around 1 year later (from 2.17 ± 1.09 to 3.92 ± 2.26 and 5.33 ± 1.90 mmHg·m²/ml, P < 0.001), thus resulting in an improvement in SW/PVA (from 68.8 ± 8.2 to 70.9 ± 9.5 and 74.7 ± 5.2%, P = 0.045). Ea also increased after the Bentall operation and 1 year later (from 1.77 ± 0.61 to 2.88 ± 1.28 and 3.54 ± 1.43 mmHg·m²/ml, P < 0.001). The mid-term results for ventricular contractility and efficiency after the Bentall operation for annuloaortic ectasia with aortic regurgitation are excellent and satisfactory.     

Pulmonary arterial elastance for estimating right ventricular afterload in systolic heart failure

Assessment of right ventricular afterload in systolic heart failure seems mandatory as it plays an important role in predicting outcome. The purpose of this study is to estimate pulmonary vascular elastance as a reliable surrogate for right ventricular afterload in systolic heart failure. Forty-two patients with systolic heart failure (ejection fraction <35%) were studied by right heart catheterization. Pulmonary arterial elastance was calculated with three methods: Ea(PV) = (end-systolic pulmonary arterial pressure)/stroke volume; Ea*(PV) = (mean pulmonary arterial pressure - pulmonary capillary wedge pressure)/stroke volume; and PPSV = pulmonary arterial pulse pressure (systolic - diastolic)/stroke volume. These measures were compared with pulmonary vascular resistance ([mean pulmonary arterial pressure - pulmonary capillary wedge pressure]/CO). All estimates of pulmonary vascular elastance were significantly correlated with pulmonary vascular resistance (r=0.772, 0.569, and 0.935 for Ea(PV), Ea*(PV), and PPSV, respectively; P <.001). Pulmonary vascular elastance can easily be estimated by routine right heart catheterization in systolic heart failure and seems promising in assessment of right ventricular afterload.     

Vascular ventricular coupling in patients with malignant phase hypertension: the West Birmingham malignant hypertension project

Patients with malignant hypertension (MHT) have persistent vascular dysfunction and a much worse clinical prognosis than non-MHT hypertensive patients, despite good long-term blood pressure (BP) control. We hypothesized that abnormal arterial (arterial elastance (Ea); arterial elastance index (EaI)) and ventricular (End-systolic elastance (Ees) and End-diastolic elastance (Eed)) elastances are present in treated MHT patients, compared with non-MHT hypertensive controls. Echocardiographic parameters of cardiac and vascular stiffness (EaI, Ees and Eed) were quantified in patients with stable MHT and treated 'high-risk' hypertension patients (HHT, but non-MHT). All patients had well-controlled BP, with a median follow-up time for MHT of 144 months. Ea was calculated from stroke volume and systolic BP and adjusted by body area (EaI). Ees was calculated using systolic and diastolic BP, stroke volume, ejection fraction, time intervals and estimated normalized ventricular elastance at arterial end diastole. Eed was calculated from Doppler parameters and the diastolic filling volume. Both study groups had preserved left ventricular contractility, with no significant differences on 3D-echocardiography (P=0.10) There were no significant differences in EaI (P=0.83), Ees (P=0.32), Eed (P=0.23) and arterial-ventricular interaction (Ees/Ea, P=0.69). In the MHT group, Eed positively correlated with age (r=0.56, P=0.38) and systolic BP (r=0.68, P=0.008). On multivariable regression analysis, MHT status was not predictive of the ventricular and Ea. Despite documented vascular dysfunction in patients with previously diagnosed stable MHT, the arterial and systolic elastances were similar to HHT patients, suggesting that adequate BP control in MHT patients allows preservation or restoration of normal arterial-ventricular coupling.     

Effects of carvedilol on ventriculo-arterial coupling in patients with heart failure.

BACKGROUND: Ventriculo-arterial coupling, defined as the ratio of the effective afterload (Ea) to contractility (Ees), reflects the mechano-energetic performance of the heart and is increased in chronic heart failure (CHF); the aim of treatment is to reduce its value. We studied the effect of carvedilol on the Ea/Ees ratio in patients with CHF treated with ACE-inhibitors, diuretics, and digoxin. METHODS: Between November 1999 and October 2001, 36 consecutive ambulatory patients (aged 31 to 76 years) with stable CHF and idiopathic or hypertensive cardiomyopathy, in sinus rhythm and with a left ventricular ejection fraction < or = 40%, were started on carvedilol and the dose was increased to the maximum tolerated. Ees was calculated as the left ventricular systolic pressure--taken as the systolic arterial pressure measured using the cuff manometer simultaneously with two-dimensional echocardiographic recordings--divided by the left ventricular end-systolic volume. Ea was measured as the ratio of the left ventricular systolic pressure to the stroke volume. All patients were investigated prospectively after 6 and 12 months of treatment. RESULTS: Out of 36 patients, 4 did not tolerate the drug and were dropped out. At 6.35 +/- 1 months, the daily dosage of carvedilol was 49.7 +/- 21 mg. The NYHA functional class improved from 1.52 +/- 0.67 to 1.29 +/- 0.53 (p = 0.017), the heart rate markedly diminished from 73.6 +/- 13.3 to 60.8 +/- 10.8 b/min (p < 0.001) and so did Ea (3.35 +/- 0.91 to 2.84 +/- 0.93, p = 0.001). Peripheral resistances and Ees did not change. Therefore, the decrease in the Ea/Ees ratio (2.61 +/- 0.78 vs 2.19 +/- 0.89, p = 0.004) and the related increase in left ventricular ejection fraction (28.8 +/- 5.68 vs 33.3 +/- 7.5%, p < 0.001) were due to the decrease in Ea, while Ees did not vary significantly. Moreover, the Ea reduction was related linearly to the decrease in heart rate (r = 0.46, p = 0.001). There was no change in diuretic or ACE-inhibitor dosing during carvedilol titration. At 14.7 +/- 2 months of follow-up, no further variation occurred, short of a trend toward a slight increase in Ees (1.38 +/- 0.49 to 1.58 +/- 0.65, p = 0.07). CONCLUSIONS: Carvedilol, added to the conventional therapy of CHF, improves left ventricular performance and reduces the Ea/Ees ratio by decreasing Ea, mainly through a reduction in heart rate. This effect is already evident at 6 months and persists later on, while only after 12 months does Ees tend to increase slightly.     

Urocortin 2 infusion in human heart failure.

AIMS: To document the haemodynamic, neurohormonal, and renal responses to Urocortin 2 (UCN2) infused in human heart failure (HF). METHODS AND RESULTS: Eight male patients with HF [left ventricular ejection fraction (LVEF) < 40%, NYHA class II-III] received placebo and 25 [low dose (LD)] and 100 microg [high dose (HD)] of UCN2 intravenously over 1 h in a single-blind, placebo-controlled, dose-escalation design. UCN2 increased cardiac output (CO) (mean peak increments +/- SEM; placebo 0.3 +/- 0.1; LD 1.0 +/- 0.3; HD 2.0 +/- 0.2 L/min; P < 0.001) and LVEF (0.0 +/- 1.5; LD 5.9 +/- 2.1; HD 14.1 +/- 2.7%; P = 0.001) and decreased mean arterial pressure (placebo 6.7 +/- 1.3; LD 11.4 +/- 1.7; HD 19.4 +/- 3.3 mmHg; P = 0.001), systemic vascular resistance (SVR) (placebo 104 +/- 37; LD 281 +/- 64; HD 476 +/- 79 dynes s/cm(5); P < 0.003), and cardiac work (CW) (placebo 48 +/- 12; LD 66 +/- 22; HD 94 +/- 13 mmHg/L/min; P < 0.001). No significant effect on vasoconstrictor/volume-retaining neurohormones was noted. UCN2 decreased urinary volume (P = 0.035) but not creatinine excretion (P = 0.962). CONCLUSION: Intravenous UCN2 in HF induced increases in CO and LVEF with falls in SVR and CW. No hormone response occurred. The role of UCN2 in circulatory regulation and its potential therapeutic application in heart disease warrant further investigation.     

Comparison of metoprolol with low, middle and high doses of carvedilol in prevention of postinfarction left ventricular remodeling in rats

The dose-related beneficial effects of carvedilol on survival in heart failure have been verified, however, the effects on left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) have not been defined. This experiment was designed to compare the effects of low, middle, and high doses of carvedilol (LD-car, MD-car, and HD-car) with metoprolol (Meto) in preventing postinfarction LVRM in rats. After the left coronary artery was ligated, 177 surviving female SD rats were randomized to: (1) AMI (n = 35), (2) LD-car (0.1 mg x kg(-1) x d(-1), n = 35), (3) MD-car (1 mg x kg(-1) x d(-1), n = 35), (4) HD-car (10 mg x kg(-1) x d(-1), n = 37) and (5) Meto (2 mg x kg(-1) x d(-1), n = 35) groups. A sham-operated group (n = 16) was also randomly selected. Gastric gavage therapy lasted for 4 weeks. After hemodynamic studies, the rat hearts were fixed and pathologically analyzed. After exclusion of rats which died or had an infarct size < 35% or > 55%, complete data were obtained in 69 rats, comprising AMI (n = 11), LD-car (n = 11), MD-car (n = 12), HD-car (n = 12), Meto (n = 11) and sham (n = 12) groups. There were no significant differences in MI size among the five AMI groups (44.5-46.3%, all P > 0.05). Compared with the sham group, left ventricular (LV) end-diastolic pressure (LVEDP), volume (LVV), weight (LVW) and septal thickness (STh) were all significantly increased, while +/- dp/dt was significantly decreased in the AMI group (all P < 0.001). Compared with the AMI group, heart rate was significantly decreased in all except the LD-car treatment groups (P < 0.05-0.01); LVEDP, LVV, LVW, and STh in the four treatment groups were also significantly decreased (P < 0.05-0.001) except LVW and STh in the Meto group (both P > 0.05)(LVEDP: 14.5 +/- 4.6, 12.1 +/- 2.4, 7.7 +/- 1.9 and 13.0 +/- 6.7 mmHg vs 24.1 +/- 5.2 mmHg; LVV: 0.82 +/- 0.1, 0.79 +/- 0.1, 0.72 +/- 0.1 and 0.72 +/- 0.1 mL vs 0.92 +/- 0.1 mL; LVW: 666 +/- 57, 622 +/- 70, 589 +/- 57 and 699 +/- 78 mg vs 730 +/- 79 mg; STh: 1.14 +/- 0.12, 1.18 +/- 0.21, 1.19 +/- 0.15 and 1.35 +/- 0.20 mm vs 1.33 +/- 0.29 mm; P < 0.05-0.001); while +/- dp/dt was significantly increased in each therapy group (P < 0.05-0.001). There were dose-effect relations in LVEDP and LVV in the carvedilol groups. The results indicate that low, middle and high dose carvedilol has dose-related effects in the prevention of postinfarction LVRM with respect to volume expansion and segmental hypertrophy in rats, while metoprolol prevents only LV dilatation but not hypertrophy.     

Gender-related differences in left ventricular chamber function

OBJECTIVES: While women have lower rates of atherosclerotic disease than men, they are more likely to suffer cardiac failure following infarction or cardiac surgery, despite typically having a greater left ventricular (LV) ejection fraction. We hypothesised that gender differences in systolic chamber function and ventriculo-vascular coupling may contribute to these clinical findings. METHODS: LV chamber function was determined in a cohort of 30 patients (16 women) aged 48-75 years with normal LV function using pressure-volume loops obtained by simultaneous conductance catheter volumetry and micromanometer pressure. End-systolic and end-diastolic pressure volume (ESPVR, EDPVR) and preload recruitable stroke work relations (PRSWR) were derived. Results were analysed according to gender, and the effects of body size and chamber dimensions were examined. RESULTS: The groups were closely matched for age (60+/-6 vs. 60+/-8 years) and co-morbid conditions. Women had higher end-systolic blood pressure (139.7+/-21.1 vs. 123.6+/-12.6 mmHg, P=0.001), and smaller LV cavity volume (end-diastolic volume 96.4+/-30.6 vs. 139+/-30.7 ml, P=0.001). Women had significantly higher LV end-systolic elastance (Ees, 2.65+/-0.10 vs. 1.96+/-0.09 mmHg ml(-1), P<0.002), arterial elastance (2.41+/-1.13 vs. 1.54+/-0.55 mmHg ml(-1), P=0.01) and lower passive LV diastolic compliance (slope EDPVR, 6.12+/-0.37 vs. 10.0+/-0.50 ml mmHg(-1), P<0.001). While there was a strong relationship between end-systolic elastance and chamber volume (r=0.69, P<0.001), gender differences in chamber function all persisted after indexing to body size. Higher LV systolic function in women was also shown in PRSWR analysis (slope, M(SW); 101.4+/-3.8 vs. 90.4+/-2.8 mmHg, P<0.05), which is independent of chamber size. After normalising volumes to resting diastolic volume, the greater systolic and diastolic elastance in women was accounted for. The ratio of end-systolic to arterial elastance, a measure of ventriculo-vascular coupling, was similar in women and men (1.19+/-0.40 vs. 1.54+/-0.30, respectively, P=0.23). CONCLUSIONS: This study demonstrates greater systolic chamber function and lower diastolic compliance in women. Within the range of chamber dimensions seen in patients with normal LV function, a strong relationship was found between cardiac size and end-systolic elastance. While these differences were not accounted for by indexing to body size, the greater ventricular elastance in women was removed after normalising to chamber size. Despite differences in resting ventricular elastance, appropriate ventriculo-vascular coupling was maintained in both genders as the greater end-systolic elastance in women was matched by similarly elevated arterial elastance.     

Impact of atrial septal defect closure on right ventricular performance.

BACKGROUND: Atrial septal defect (ASD) closure is one of the most representative cardiac operations, but there have been few assessments of right ventricular (RV) performance during the perioperative period. METHODS AND RESULTS: Using transesophageal echocardiography with automated border detection system, the RV pressure - area (P-A) loops were measured in 6 patients immediately before and after an ASD closure. Multiple RV P-A loops obtained by the inferior vena cava occlusion technique were used to evaluate end-systolic maximal elastance (Ees), preload recruitable stroke work (MEW), external work (EW) and the systolic P-A area (PAA). Ees and MEW are indices of contractility, and PAA represents the total mechanical energy. RV Ees and MEW did not change after the operation (from 3.36 +/- 2.20 to 3.70 +/- 2.04 mmHg/cm2, p = 0.4; and from 10.3 +/- 5.0 to 10.5 +/- 4.5 mmHg, p = 0.8, respectively), whereas EW and PAA were significantly reduced (from 121.4 +/- 77.4 to 48.7 +/- 26.6 mmHg/cm2, p < 0.05; and from 274.8 +/- 212.8 to 92.7 +/- 52.8 mmHg/cm2, p < 0.05, respectively). ASD closure reduced the EW and total mechanical energy of the right ventricle without influencing contractility. CONCLUSIONS: These results indicate that ASD closure preserved RV function and reduced RV myocardial oxygen consumption. Assessment of the RV P-A relationship in the operating room demonstrates the beneficial effects of ASD closure on RV performance.