Impact of left ventricular size on pharmacologic reverse remodeling in heart failure

BACKGROUND AND HYPOTHESIS: Although medical therapy may normalize echocardiographic left ventricular (LV) systolic function in selected patients with cardiomyopathy, other patients experience no change or a further deterioration in heart failure remodeling. Our aim was to determine what clinical or echocardiographic parameters predict a beneficial therapeutic response. METHODS: We prospectively followed biannual clinical and echocardiographic assessments in 215 patients. Forty-six of these patients ("Nonresponders") experienced no change or a decline in LV ejection fraction at 6 months. Of the 148 patients who improved LV function, 21 ("Responders") normalized LV systolic function at 6 months. Only Responders (n = 21) and Nonresponders (n = 46) were compared. RESULTS: On average, these 67 patients were 54 +/- 12 years old with 4.5 +/- 3.3 years of heart failure. At 6 months, following up-titration of angiotensin-converting enzyme inhibitors and nitrates, Responder LV ejection fraction rose from 22 +/- 6 to 50 +/- 5% with improvement in New York Heart Association classification (2.6 +/- 0.8 to 1.5 +/- 0.8, p = 0.001). These patients had significantly more favorable clinical and echocardiographic outcomes versus Nonresponders despite comparable medical therapy. All baseline demographic, clinical, and echocardiographic variables were equivalent, except for initial LV end-diastolic diameter which differentiated Nonresponders (7.1 +/- 0.7 cm) from Responders (6.1 +/- 0.8 cm), p = 0.007. CONCLUSION: Thus, although heart failure therapy improves LV systolic function in a majority of patients, with normalization in up to 10% of patients, significant LV enlargement may render remodeling unresponsive to pharmacologic intervention, with a potential future need for alternative mechanical or surgical intervention.     

Effects of quinapril on myocardial function,ventricular remodeling and cardiac cytokine expression in congestive heart failure in the rat

Inflammatory cytokines have been shown to be activated in congestive heart failure (CHF). This activation is likely the result of the convergence of a number of factors, several of which could be attenuated with the use of an Angiotensin converting enzyme (ACE) inhibitor. In order to assess this, rats had a myocardial infarction (MI) created by coronary artery ligation and were followed for 28 days without treatment to permit the development of CHF. At that time, the ACE inhibitor quinapril was started, or rats remained untreated and were followed a further 56 days for a total of 84 days. Half of the untreated rats had quinapril started 3 days prior to sacrifice, on day 81. Starting quinapril at either 28 or 81 days had little effect on cardiac hemodynamics, or ventricular remodeling. Quinapril did however attenuate the MI-induced rise in cardiac cytokine expression (tumor necrosis factor- [TNF-], interleukin-1, -5 and -6). Thus, in CHF, ACE inhibitors attenuate the rise in cardiac cytokine expression. This study helps to identify a new mechanism by which ACE inhibitors may exert their beneficial effects in CHF.     

Comparison of left and right ventricular end-systolic pressure-volume relations in congestive heart failure

A hemodynamic-radionuclide study was performed to compare the relations between end-systolic pressure and volume in the left and right ventricles in 10 patients with biventricular failure, and to correlate the end-systolic pressure-volume slope with baseline variables of systolic function. During nitroprusside or nitroglycerin infusion, or a combination of both, linear relations were found between end-systolic pressure and volume for both ventricles. In 9 of 10 patients, the end-systolic pressure-volume slope was greater for the left ventricle (mean +/- SD 1.12 +/- 0.36 mm Hg X m2/ml) than for the right ventricle (0.46 +/- 0.27 mm Hg X m2/ml) (p less than 0.001). In all 10 patients, the volume-axis intercept of the pressure-volume relation was greater for the left ventricle (82 +/- 66 ml/m2) than for the right ventricle (2 +/- 30 ml/m2) (p less than 0.005). Right ventricular pressure-volume slope correlated weakly with baseline right ventricular ejection fraction (r = 0.69, p less than 0.05), strongly with the baseline right ventricular end-systolic pressure-volume ratio (r = 0.89) and inversely with baseline right ventricular end-systolic volume (r = -0.86). In conclusion, 1) in patients with severe biventricular failure, changes in systolic pressure influence end-systolic volume more strongly in the right than in the left ventricle. 2) For the right ventricle, the slope of the end-systolic pressure-volume relation is directly related to rest indexes of systolic function. 3) The greater the end-systolic volume at rest, the greater the predicted improvement in right ventricular emptying for any vasodilator-induced reduction in pulmonary artery end-systolic pressure.     

Rationale for the use of angiotensin II receptor blockers in patients with left ventricular dysfunction (part I of II)

Almost 5 million individuals in the United States are diagnosed with chronic heart failure (HF), and the prevalence is increasing. Angiotensin-converting enzyme (ACE) inhibitors and beta blockers, neurohormonal antagonists that block the renin-angiotensin system (RAS) and the sympathetic nervous system, respectively, have been shown in clinical trials to reduce morbidity and mortality in patients with HF, and these therapies are now integral components of standard HF treatment. Yet, morbidity and mortality rates in HF remain unacceptably high, and the limitations of current standard therapies are becoming increasingly apparent. About 10% of patients with HF are unable to tolerate ACE inhibitors, often because of cough. In addition, ACE inhibition may not completely block the RAS because angiotensin II, the main end product of the RAS, can be generated via non-ACE enzymatic pathways. Angiotensin II receptor blockers (ARBs) may exert more complete RAS blockade than ACE inhibitors by interfering with the binding of angiotensin II at the receptor level, regardless of the enzymatic pathway of production. They are also better tolerated than ACE inhibitors and have been shown to improve symptoms and function in clinical trials in patients with HF. These factors provide a strong rationale for the study of the clinical effects of ARBs in patients with HF.     

Effect of heart failure program on cardiovascular drug utilization and dosage in patients with chronic heart failure

BACKGROUND: Utilization and dosage of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF) remain low. Recent data suggest that care of patients with CHF in specialized heart failure programs is associated with improved clinical outcomes. HYPOTHESIS: Specialized heart failure care is associated with better utilization and higher dose of cardiovascular drugs. METHODS: Data from 133 patients with CHF referred to a heart failure program were analyzed. Mean functional class 3.1 +/- 0.5, left ventricular ejection fraction 19 +/- 8. Utilization and doses of cardiovascular drugs were examined at initial evaluation and at last visit, after an average period of 17 +/- 14 months. Hospitalization and survival data were determined. RESULTS: Utilization of ACE inhibitors and angiotensin-receptor blockers increased from 87 to 100% (p < 0.001). Average daily dose increased by 60%, from the equivalent of captopril 105 +/- 78 mg to 167 +/- 86 mg (p < 0.001). Utilization of the following drugs increased significantly: beta blockers (16-37%, p < 0.001), metolazone (10-23%, p = 0.007), spironolactone (1-36%, p < 0.001), amiodarone (7-15%, p = 0.05), hydralazine (1-9%, p = 0.004), and nitrates (20-33%, p = 0.03). One-year survival was 90%. The 3- and 6-month hospitalization rates for heart failure were 4 and 7%, and for all cardiovascular causes they were 6 and 11%, respectively. CONCLUSIONS: Care of patients with CHF in a specialized heart failure program was associated with significant increase in the utilization and doses of all beneficial cardiovascular drugs, especially ACE inhibitors. It was also associated with excellent clinical outcomes.     

Clinical update: the role of angiotensin II receptor blockers in patients with left ventricular dysfunction (Part II of II)

Almost 5 million individuals in the United States have chronic heart failure (HF), which is increasing in prevalence. Angiotensin-converting enzyme (ACE) inhibitors are standard therapies for HF, although more than 10% of patients with HF are unable to tolerate these agents. Furthermore, ACE inhibitors may not provide complete blockade of the renin-angiotensin system (RAS) in the long term. Because angiotensin II receptor blockers (ARBs) may block the RAS more completely than ACE inhibitors and are better tolerated, several large-scale ARB trials have been performed exploring their potential role in treating patients with symptomatic HF and left ventricular systolic dysfunction. The Losartan Heart Failure Survival Study (ELITE II) demonstrated no significant differences in morbidity and mortality between the ARB losartan and the ACE inhibitor captopril among elderly patients with HF. The Valsartan Heart Failure Trial (Val-HeFT) demonstrated reductions in hospitalizations for HF with the ARB valsartan when added to standard HF therapy, with no effect on mortality. Both trials suggested a potential negative interaction between ARB and beta-blocker therapy. The Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program demonstrated significant reductions in morbidity and mortality with the ARB candesartan in patients with HF due to systolic dysfunction, with or without ACE inhibitors and with or without beta blockers. Thus, the addition of ARBs to the treatment regimen of patients with symptomatic HF should be strongly considered.     

Linearity of the left ventricular end-systolic pressure-volume relation in patients with severe heart failure

The left ventricular end-systolic pressure-volume relation is a relatively load-independent measure of left ventricular contractile function. Linearity of the relation derived from full left ventricular pressure-volume loops has not previously been demonstrated for patients with severe heart failure. Therefore, nine patients with markedly depressed left ventricular systolic function (ejection fraction 0.14 +/- 0.08) were studied with micromanometer left ventricular pressure measurement and simultaneous radionuclide ventriculography. Afterload was reduced with graded infusions of nitroprusside, allowing construction of pressure-volume loops under four afterload conditions in four patients and three afterload conditions in the other five patients. The end-systolic pressure-volume relation derived from the pressure-volume loops was found to be linear for the range of pressures and volumes examined, with correlation coefficients in individual patients ranging from 0.936 to 0.999 (mean 0.981). The mean slope of the relation (or end-systolic elastance) was 0.71 mm Hg/ml (range 0.42 to 1.52), and the extrapolated volume intercept at zero pressure was positive in all patients. An exponential relation between end-systolic elastance and ejection fraction was demonstrated for this group of patients. Approximations of end-systolic elastance obtained from measurements other than the full pressure-volume loops correlated variably with "true" elastance obtained from the pressure-volume loops. The relation between stroke work and end-diastolic volume was nonlinear in most patients. Thus, the end-systolic pressure-volume relation is linear in the "physiologic" range in patients with severe heart failure. This finding should permit construction of the relation from two loading conditions in clinical studies, facilitating its use as an index of contractile function in patients with heart failure.     

Effect of angiotensin-converting enzyme inhibition on functional class in patients with left ventricular systolic dysfunction--a meta-analysis

BACKGROUND: The effect of angiotensin converting enzyme (ACE) inhibitors on symptoms in patients with left ventricular systolic dysfunction (LVSD) is controversial. AIMS: To perform a meta-analysis of studies evaluating effect of ACE inhibitors on New York Heart Association (NYHA) class in patients with LVSD. METHODS: Individual data from 10389 patients in NYHA classes I-IV from four large long-term studies (2-4-year follow-up) and summary data from 2302 patients in NYHA classes II-IV from 16 short-term studies (3 months follow-up) were meta-analysed to assess changes in NYHA class. RESULTS: The large long-term studies showed a significant improvement in the worst NYHA classes (classes II-IV compared to class I) in the ACE inhibitor arm versus placebo, odds ratio (OR) = 0.875 (0.811-0.943) p = 0.0005. This effect was only present in studies which included patients with chronic heart failure and was particularly pronounced on deterioration to the worst NYHA class IV, OR = 0.66 (0.52-0.84) p = 0.001. There was no effect in the studies which included patients after myocardial infarction. The short-term chronic heart failure studies showed a significant improvement in NYHA class; OR for improvement of at least one NYHA class was 2.11 (1.48-2.98, 95% CI) p < 0.0001. CONCLUSION: ACE inhibition significantly improves symptomatic status measured as NYHA classification in patients with chronic heart failure.     

Effect of acute cardiac tamponade on left ventricular pressure-volume relations in anaesthetised dogs

STUDY OBJECTIVE--The aim was to determine whether depressed myocardial contractility is responsible for the decline in stroke volume that occurs with cardiac tamponade. DESIGN--Left ventricular contractile performance was assessed before and after beta adrenergic blockade using the end systolic pressure-volume relation, the left ventricular dP/dtmax-end diastolic volume relation, and the left ventricular stroke work-end diastolic volume relation during acute cardiac tamponade in dogs. EXPERIMENTAL MATERIAL--In eight pentobarbitone anaesthetised dogs (15.7-24.8 kg), transducer tipped and volume impedance catheters were positioned in the left ventricle. Through a median sternotomy incision, a pericardial catheter was inserted to produce varying stages of cardiac tamponade. By the use of transient bicaval occlusions, variably loaded pressure-volume loops were recorded. MEASUREMENTS AND RESULTS--Incremental tamponade reduced mean arterial pressure from 105(SEM 3) to 89(2) mm Hg (mild tamponade), 75(2) mm Hg (moderate tamponade), and 59(10) mm Hg (severe tamponade). The slope of the end systolic pressure-volume relation was 6.3(1.2) mm Hg.ml-1 at baseline and increased slightly to 7.7(1.8), 8.5(1.3), and 9.2(1.5) mm Hg.ml-1 with the progressive levels of tamponade (NS). The role of autonomic reflexes was assessed by repeating the tamponade sequence after beta adrenergic blockade with 10 mg of metoprolol intravenously. The slope of the end systolic pressure-volume relation was reduced by metoprolol, at 4.9(1.0) mm Hg.ml-1 (p less than 0.01), but was not significantly altered by the sequence of tamponade following beta blockade [5.6(0.9), 6.0(1.0), and 5.5(7.0) mm Hg.ml-1, respectively (NS)]. Neither were changes found indicative of depressed contractile function with progressive tamponade in the slopes of the left ventricular dP/dtmax-end diastolic volume and stroke work-end diastolic volume relations. CONCLUSIONS--Left ventricular contractility was not altered during acute cardiac tamponade in an anaesthetised, closed chest canine model. Depressed left ventricular contractile function was not responsible for the observed haemodynamic deterioration.     

Ability of left ventricular stress-shortening relations, end-systolic stress/volume ratio and indirect indexes to detect severe contractile failure in ischemic or idiopathic dilated cardiomyopathy

The ability of several proposed indirect and direct indexes of left ventricular LV) systolic performance and contractility to detect clinically important LV dysfunction was evaluated in 42 patients with refractory dilated cardiomyopathy studied with right-sided heart catheterization and M-mode echocardiography. Hemodynamic evaluation demonstrated elevated filling pressure (mean pulmonary artery wedge pressure 24 +/- 6 mm Hg) and depressed function (cardiac index 1.68 +/- 0.43 liters/min/m2). Echocardiographic LV end-diastolic dimension (7.3 +/- 1.0 cm), mass (182 +/- 60 gm/m2) and end-systolic stress (163 +/- 44 x 10(3) dynes/cm2) were increased whereas fractional shortening was depressed in all (mean 12 +/- 4%). During follow-up 88% of patients died at a median interval of 16 months after study. Indirect measurements of LV function (mitral E point-septal separation and the ratio of preejection period to LV ejection time) were abnormal in 100 and 88% of patients, respectively. Contractility was classified as depressed in 36 (86%) patients by the end-systolic stress volume index ratio and in 31 (74%) by the relation between fractional shortening and end-systolic stress. In contrast, the relation between end-systolic stress and velocity of circumferential shortening identified only 7 (17%) patients as having subnormal contractility and classified 9 (21%) as having supernormal contractility. Rate correction of velocity of circumferential shortening only modestly improved the ability of the relation to identify depressed contractility (abnormal in 16 patients or 38 percent).     

氯沙坦钾和盐酸苯那普利对老年高血压患者左室肥厚和左室功能的作用

目的　应用多普勒超声心动图评价氯沙坦钾和盐酸苯那普利对老年原发性高血压患者左室肥厚 (LVH)的逆转作用和应用心肌作功指数 (MPI)评价药物对左室功能的改善作用。　方法　6 9例患者随机分组 ,分别选用氯沙坦钾 5 0mg(38例 )或盐酸苯那普利 10mg(31例 )每天 1次口服 ,疗程 2 4周。治疗前、后测定左室室壁厚度和收缩舒张功能 ,并根据等容舒张期和等容收缩期之和与射血期的比值计算MPI。　结果　LVH患者经盐酸苯那普利治疗后左室重量指数降低 ,由治疗前的(14 6 9± 15 1) g/m2 降至治疗后的 (130 1± 17 5 ) g/m2 ,P <0 0 5。两组射血分数均在正常范围 ,药物治疗后二尖瓣舒张早期E峰加速度均显著增加〔分别为 (5 89 6± 176 9)cm/s2 和 (74 0 8± 2 4 2 7)cm/s2 ,(6 6 4 7± 2 5 7 5 )cm/s2 和 (85 3 6± 2 6 9 1)cm/s2 〕 ,均为P <0 0 1。氯沙坦钾组患者治疗后等容舒张时间和射血时间改善 ,分别为 (12 1 8± 2 4 1)ms和 (95 5± 2 4 6 )ms、(2 5 8 8± 38 7)ms和 (2 95 5± 37 5 )ms,均为P <0 0 1,MPI由 0 6 1± 0 13降至 0 4 5± 0 12 (P <0 0 1)。　结论　盐酸苯那普利对左室肥厚有逆转作用 ,并能改善心肌的松弛性 ;氯沙坦钾能更有效改善老年高血压患者的左室功能。MPI能早期综合     

Aspirin alters arterial function in patients with chronic heart failure treated with ACE inhibitors: a dose-mediated deleterious effect

BACKGROUND: By inhibiting prostaglandin synthesis, aspirin can interfere with both arterial functional and angiotensin-converting enzyme inhibitor (ACEI) properties and be deleterious in chronic heart failure (CHF). AIM: Our aim was to prospectively evaluate the effect of aspirin on arterial functional properties in CHF patients treated with ACEIs. METHODS AND RESULTS: Over three consecutive treatment periods of 7 days, 18 patients received placebo, followed by aspirin 100 mg/day, and then aspirin 325 mg/day. Single blind prospective assessment of reflected wave and time reflection by radial applanation tonometry; pulse wave velocity; blood pressure; thromboxane B2 (TxB2) and prostaglandins in plasma and urine was performed. Aspirin 325 mg/day induced a significant increase in augmentation index of reflected wave (P<0.0001 and P=0.0013 vs. placebo and aspirin 100 mg, respectively) and a significant decrease in reflected wave traveling times (P=0.0007 vs. placebo). Aspirin 100 mg/day produced a similar, though non-significant, trend in these parameters compared with placebo. Both aspirin treatments produced a statistically significant decrease in serum TxB2 (P<0.0001) but did not have an effect on the metabolite of prostaglandin I2 (P=0.136). CONCLUSION: This study demonstrates the existence of a dose-mediated deleterious effect of aspirin upon arterial functional properties in CHF patients treated with ACEI.     

Inotropic effect of enoximone in patients with severe heart failure: demonstration by left ventricular end-systolic pressure-volume analysis

Left ventricular end-systolic pressure-volume analysis was employed to assess the inotropic effect of the phosphodiesterase inhibitor enoximone (formerly MDL-17,043) in nine patients with severe heart failure (New York Heart Association class IV symptoms, mean ejection fraction = 0.22). Left ventricular pressure-volume loops were constructed using high fidelity left ventricular pressure measured with micromanometer-tipped catheters and simultaneous left ventricular volume obtained by gated blood pool imaging. Afterload was reduced with the vasodilator nitroprusside to generate the baseline left ventricular end-systolic pressure-volume relation, a relatively load-independent measure of contractile function. The intravenous administration of enoximone (mean dose 75 mg) shifted the end-systolic pressure-volume point upward and leftward from the baseline pressure-volume relation in eight of the nine patients, demonstrating a positive inotropic effect of this agent. The maximal rate of left ventricular pressure development (peak positive dP/dt) increased from 1,030 +/- 142 to 1,381 +/- 219 mm Hg/s (p less than 0.01) on enoximone despite a significant decrease in preload (as assessed by left ventricular end-diastolic pressure and volume) and a small, insignificant decrease in mean arterial pressure. Two patients developed angina after enoximone administration; both patients had coronary artery disease and experienced a greater than 30% increase in heart rate-systolic blood pressure product. Thus, enoximone has a significant inotropic effect in patients with severe heart failure. Like other inotropic drugs, it has the potential to increase myocardial oxygen demand and thereby precipitate ischemia.     

Effects of ramipril on the neurohormonal response to exercise in patients with mild or moderate congestive heart failure

Static measurements of plasma neurohormones at rest may notbe adequate to detect alterations in cardiovascular controlmechanisms in congestive heart failure (CHF). Therefore, itis of interest to study neurohormonal activation during differentphysiological conditions. Plasnw neurohormones were measuredin 54 patients on diuretic therapy for mild or moderate CHF.Samples were taken at rest and immediately after maximal bicycleexercise, before and after 12 weeks of treatment with ramiprilor placebo. There was a strong correlation between the plasmalevels of each hormone before and after exercise. An inversecorrelation existed at baseline between exercise duration andangiotensin II levels after maximal exercise (r= – 0·30,P=0·03), but not at rest. Plasma levels of angiotensinII, aldosterone, atrial natriuretic peptide (ANP) and noradrenalinewere increased after maximal exercise compared to rest. Plasmaangiotensin converting enzyme activity and ANP were reducedby ramipril compared to placebo, both at rest and after exercise,but levels of angiotensin II, aldosterone and nordrenaline werenot significantly affected Thus, exercise consistently activatesneurohormonal systems in patients with CHF. Patients with thelowest exercise duration had the highest angiotensin II levelsafter exercise. Measurements of plasma neurohormones after maximalexercise provide limited additional value to measurements atrest.     

Relative efficacy of angiotensin converting enzyme inhibitors on mortality of patients with congestive heart failure: implications of randomized trials and role of the aetiology (ischaemic or non-ischaemic) of heart failure.

We examined the influence of angiotensin converting enzyme inhibitors (ACE inhibitors) on mortality in patients with heart failure of both ischaemic or non-ischaemic origin. Eleven, randomized, placebo-controlled trials of ACE inhibitors involving 1266 patients were selected. The follow-up period varied from 3 to 6 months. Four different ACE inhibitors were used in the 11 clinical trials. A total of 679 patients presented with an ischaemic heart failure and 587 with a non-ischaemic heart failure. Meta-analysis, performed for both subgroups, showed that mortality was significantly decreased in the ischaemic subgroup only (ischaemic group: odds ratio 0.45; 95% confidence interval 0.28 to 0.71; non-ischaemic subgroup: odds ratio 0.7; 95% confidence interval 0.4 to 1.5). Although the two odds ratio are not significantly different, further randomized, placebo-controlled trials with ACE inhibitors are required in order to determine more precisely the benefit/risk ratio in patients with non-ischaemic heart failure.     

Accuracy of radionuclide ventriculography for estimation of left ventricular volume changes and end-systolic pressure-volume relations

Estimation of left ventricular end-systolic pressure-volume relations depends on the accurate measurement of small changes in ventricular volume. To study the accuracy of radionuclide ventriculography, paired radionuclide and contrast ventriculograms were obtained in seven dogs during a control period and when blood pressure was increased in increments of 30 mm Hg by phenylephrine infusion. The heart rate was held constant by atropine infusion. The correlation between radionuclide and contrast ventriculography was excellent. In the individual animals, the average r value for left ventricular volume was 0.96 +/- 0.03 (+/- SD) (p = 0.001, n = 7) and the mean r value for end-systolic volume changes was 0.90 +/- 0.08 (n = 7, range 0.76 to 0.99). For the entire series, there were 33 end-systolic volume changes, and there was an equally strong radionuclide-contrast correlation (r = 0.89, p less than 0.001, n = 33), even though the volume changes averaged only 11.9 +/- 8.2 ml (range 0.3 to 38.1). The systolic pressure-volume relations were linear for both radionuclide and contrast ventriculography (r = 0.98 and 0.97, respectively, n = 7). The mean slope for radionuclide ventriculography (2.9 +/- 1.4) was lower than the mean slope for contrast ventriculography (4.8 +/- 1.7) (p = 0.004); however, the slopes correlated well (r = 0.81, n = 7, p = 0.026). The radionuclide-contrast volume relation was compared using background subtraction, attenuation correction, neither of these or both. By each method, radionuclide ventriculography was valid for measuring small changes in left ventricular volume and for defining end-systolic pressure-volume relations.     

Preload-induced curvilinearity of left ventricular end-systolic pressure-volume relations. Effects on derived indexes in closed-chest dogs

End-systolic pressure-volume relations (ESPVRs) were analyzed in 10 closed-chest autonomically blocked dogs before and after volume loading that restored end-diastolic volume to its value measured in the control conscious state. Dogs had been previously instrumented with a left ventricular pressure micromanometer and ultrasonic crystals for measurements of major, anteroposterior, and septum-free wall diameters. Left ventricular volume was calculated with an ellipsoidal model in the left ventricular cavity. ESPVRs obtained during caval occlusion after volume loading were curvilinear as shown by the division of the relation into two parts. The initial part of the relation had a significantly smaller ESPVR slope (Ees, 12.0 +/- 1.8 mm Hg/ml) and ESPVR volume-axis intercept (Vd, - 3.5 +/- 0.8 ml) than the final part of the relation (19.5 +/- 3.1 mm Hg/ml and 0.0 +/- 0.6 ml, respectively, p less than 0.01). The end-diastolic volume-peak dP/dt relation showed a similar curvilinearity when end-diastolic volumes were larger than 1.5-1.7 times the minimal end-diastolic volume reached during caval occlusion. ESPVRs were not different during aortic constriction and caval occlusion when end-diastolic volume was small. In contrast, with large end-diastolic volumes, Ees and Vd were significantly smaller during caval occlusion than during aortic constriction. The final part of ESPVR (with small end-diastolic volume) had the same slope and intercept as that during aortic constriction. We conclude that preload produces a curvilinearity of ESPVR that significantly modifies derived indexes when the range of preload changes is large.     

Heart failure: Economic aspects of treatment with captopril for patients with asymptomatic left ventricular dysfunction in The Netherlands

OBJECTIVE: To estimate the costs and effects of preventive treatment withcaptopril compared with the current treatment policy in patientswith asymptomatic left ventricular dysfunction after a myocardialinfarction. METHODS: Estimates of effects are based on the results of the SAVE trial.Costs are estimated on the basis of current treatment patternsin four Dutch hospitals. All knowledge is incorporated in amathematical model extrapolating the SAVE results to 20 years. RESULTS AND CONCLUSIONS: Captopril treatment is expected to increase survival at certaincosts. The average additional costs per patient are estimatedat DFI 2 491 in 4 years and at DFI 8 723 in 20 years of treatment.Costs per additional survivor after 4 years are estimated atDFI 69 126. After extrapolation of the results of the SAVE trialto 20 years, costs per life-year gained can be estimated atDFI 15 799. From ursivariate sensitivity analysis it appearsthat the results are highly sensitive for the costs of treatmentwith captopril and the occurrence and prevention of clinicalheart failure. Varying all estimates randomly between upperand lower limits— in 5000 simulations—an estimateof costs per life-year gained of DFI 15 729 is made for 20 yearsof treatment, with 95% of all estimates between DFI 0 and DFI50 000. On a national level, undiscounted costs are expectedto increase up to approximately DFI 42 million annually duringthe first 40 years after introduction of the preventativae strategy.