The impact of angiotensin-converting enzyme inhibitor therapy on the extracellular collagen matrix during left ventricular assist device support in patients with end-stage heart failure.

OBJECTIVES: We hypothesized that angiotensin-converting enzyme inhibition (ACE-I) during left ventricular assist device (LVAD) support in patients with end-stage heart failure prevents potentially deleterious effects on the extracellular matrix. BACKGROUND: Left ventricular assist device-induced mechanical unloading increases myocardial collagen and stiffness and may contribute to the low rate of recovery. METHODS: Heart samples obtained before and after LVAD implantation were divided into groups depending on whether the patients received (n = 7) or did not receive (control; n = 15) ACE-I. At transplant, ex vivo pressure-volume relationships were measured and chamber and myocardial stiffness constants determined. Myocardial tissue content of angiotensin (Ang) I and II, matrix metalloproteinase (MMP)-1, tissue inhibitor of MMPs (TIMP)-1, and total and cross-linked collagen was measured. RESULTS: Duration of support was comparable between ACE-I and control subjects (96 +/- 65 days vs. 109 +/- 22 days). Pre-LVAD Ang I and II and total and cross-linked collagen were similar between groups. Post-LVAD, Ang II was reduced in the ACE-I group but increased in control subjects (181 +/- 7 fmol/g vs. 262 +/- 41 fmol/g; p < 0.05). Similarly, cross-linked collagen decreased during LVAD support in the ACE-I group. Left ventricular (LV) mass and myocardial stiffness were lower in the ACE-I group. ACE-I normalized the LV and right ventricular (RV) MMP-1/TIMP-1 ratio. Collagen content and characteristics of the RV were not affected by ACE-I. CONCLUSIONS: ACE-I therapy was associated with decreased Ang II, myocardial collagen content, and myocardial stiffness during LVAD support. This is the first demonstration of a pharmacologic therapy that can impact myocardial properties during mechanical unloading, and it could foster new lines of investigation in strategies of enhancing myocardial recovery during LVAD support.     

Angiotensin II-forming pathways in normal and failing human hearts

Reduced preload and afterload to the heart are important effects of angiotensin converting enzyme (ACE) inhibitors in the treatment of congestive heart failure. However, since angiotensin II (Ang II) directly increases the strength of myocardial contraction, suppression of Ang II formation by ACE inhibitors could potentially reduce the beneficial effects of Ang II on the failing heart. To study how ACE inhibition suppresses cardiac Ang II formation in man, we characterized ACE-dependent and ACE-independent Ang II-forming pathways in eight normal and 24 failing human hearts obtained at cardiac transplantation. Ang II-forming activity in left ventricular (LV) membrane preparations was assessed by measuring the conversion of [125I]angiotensin I (Ang I) to [125I]Ang II. LV [125I]Ang II-forming activity in normal hearts (35.5 +/- 2.7 fmol/min/mg, n = 8) was not different from that in hearts from patients with ischemic cardiomyopathy (25.5 +/- 2.9 fmol/min/mg, n = 9) and was 48% lower (p less than 0.001) in hearts from patients with idiopathic cardiomyopathy (18.5 +/- 1.9 fmol/min/mg, n = 15).(ABSTRACT TRUNCATED AT 250 WORDS)     

Enalapril-induced cough is associated with non-severe heart failure

The incidence of enalapril-induced cough was evaluated in 199 patients with congestive heart failure. Cough was more frequent in class I or II patients (28%) than in class III (4.1%, p<0.01) and class IV (0%, p<0.01) patients. Brain natriuretic peptide level was lower in patients in the cough (+) group than in the cough (-) group (170+/-107 vs. 538+/-637 pg/ml, p<0.01). The incidence of enalapril-induced cough is low in patients with severe congestive heart failure and a cough can be a marker of non-severe heart failure.     

Plasma hormones in patients with chronic heart failure before and early after orthotopic heart transplantation.

The aim of this prospective study was to investigate both vasoconstricting and vasodilating plasma hormones and plasma factors regulating the circulatory homeostasis in patients with endstage congestive heart failure before and early after orthotopic heart transplantation and to evaluate factors which may influence their regulation. 19 patients with endstage congestive heart failure were analyzed serially before and 3-4 weeks after orthotopic heart transplantation. A significant decrease in plasma concentrations of noradrenaline (457 +/- 202 vs. 204 +/- 88 pg/ml; p less than 0.001), adrenaline (43 +/- 32 vs. 26 +/- 11 pg/ml), atrial natriuretic peptide (341 +/- 218 vs. 139 +/- 64 pg/ml; p less than 0.005), cyclic guanosine monophosphate (13.8 +/- 7.8 vs. 6.6 +/- 2.2 pmol/ml, p less than 0.05) and in plasma renin activity (16.6 +/- 13.0 vs. 2.0 +/- 2.4 ng AI/ml/h; p less than 0.01) was found after transplantation. The data indicate that the marked increase in plasma catecholamine concentrations and renin activity in endstage congestive heart failure is reversible as early as 3-4 weeks after heart transplantation. This is most likely the consequence of normalization of cardiac function. While elevation of atrial natriuretic peptide and cyclic guanosine monophosphate as well as increased vasoconstrictor activity in heart failure appear to be related to impaired ventricular function, the persistent moderate elevation of both vasodilating agents after transplantation may be compensatory to counteract cyclosporin-induced arterial hypertension after heart transplantation.     

Uncoupling of atrial natriuretic peptide extraction and cyclic guanosine monophosphate production in the pulmonary circulation in patients with severe heart failure.

OBJECTIVES. This study was designed to evaluate the role of endogenous atrial natriuretic peptide in the pulmonary circulation in patients with chronic heart failure. BACKGROUND. Plasma atrial natriuretic peptide concentrations in patients with heart failure have been reported to be higher than those in normal subjects and to increase as the severity of heart failure progresses. Although endogenous atrial natriuretic peptide is thought to improve the condition of patients with heart failure by reducing preload and afterload, recent findings have indicated that a high plasma atrial natriuretic peptide level is a prognostic predictor in patients with heart failure. METHODS. To evaluate the pathophysiologic role of endogenous atrial natriuretic peptide in the pulmonary circulation, plasma atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP) levels were determined in the main pulmonary artery and pulmonary capillary wedge region in 80 patients with chronic congestive heart failure (New York Heart Association functional classes II to IV). RESULTS. The plasma atrial natriuretic peptide level decreased significantly from the main pulmonary artery to the pulmonary capillary wedge region, whereas the plasma cGMP level increased significantly from the main pulmonary artery to the pulmonary capillary wedge region. In patients with mild chronic heart failure (n = 50), the plasma atrial natriuretic peptide level correlated with the cGMP level in the main pulmonary artery (gamma = 0.71, p less than 0.001). The atrial natriuretic peptide extraction level, calculated as (Atrial natriuretic peptide in the main pulmonary artery--Atrial natriuretic peptide in the pulmonary capillary wedge region) x Cardiac output x (1-hematocrit/100) (ng/min), also correlated with the cyclic guanosine monophosphate production level, calculated as (cGMP in the pulmonary capillary wedge region--cGMP in the main pulmonary artery) x Cardiac output x (1-hematocrit/100) (nmol/min) (gamma = 0.78, p less than 0.001). In contrast, such correlations were not found in patients with severe chronic heart failure (n = 30). In these patients, the atrial natriuretic peptide extraction level was significantly higher but there was no significant difference in the cGMP production level between the two groups (mild and severe chronic heart failure). Therefore, the molar ratio of cGMP production to atrial natriuretic peptide extraction in the pulmonary circulation was significantly lower in patients with severe chronic heart failure (88 +/- 16 vs. 480 +/- 41, p less than 0.001). CONCLUSIONS. These results indicate that down-regulation of atrial natriuretic peptide receptors coupled to guanylate cyclase may occur in the pulmonary vascular beds of patients with severe chronic heart failure.     

Responsiveness of atrial natriuretic factor to reduction in right atrial pressure in patients with chronic congestive heart failure

In patients with congestive heart failure, atrial natriuretic factor may serve as a counter-regulatory hormone, offsetting the vasoconstrictive and volume-retentive effects of the sympathetic nervous system, the renin-angiotensin-aldosterone system and vasopressin. Indeed, the plasma levels of atrial natriuretic factor and the vasoconstrictor hormones are often simultaneously elevated in these patients. It is not known, however, whether atrial natriuretic factor remains responsive to sudden reductions in atrial pressure in patients with chronic heart failure, or is unresponsive like the vasoconstrictor systems. To examine this issue, the plasma concentrations of atrial natriuretic factor and the vasoconstrictor hormones were measured in 20 normal subjects and 12 patients with chronic congestive heart failure during incremental lower body negative pressure, an intervention that lowers atrial pressure. In the normal subjects, incremental lower body negative pressure at -10, -20 and -40 mm Hg decreased central venous pressure and pulse pressure. At maximal lower body negative pressure, plasma atrial natriuretic factor levels decreased from 51 +/- 5 to 27 +/- 3 pg/ml (p less than 0.01), whereas increases occurred in plasma levels of norepinephrine (194 +/- 11 to 385 +/- 70 pg/ml, p less than 0.01), renin activity (1.4 +/- 0.2 to 3.9 +/- 0.1 ng/ml per h, p less than 0.01) and vasopressin (1.3 +/- 0.1 to 6.4 +/- 2.4 pg/ml, p less than 0.05). In the patients with congestive heart failure, lower body negative pressure also reduced central venous pressure. Baseline plasma atrial natriuretic factor levels were markedly elevated, averaging 438 +/- 138 pg/ml, and decreased to 317 +/- 87 pg/ml at maximal lower body negative pressure (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure. Evidence for abnormalities unrelated to blood flow

Previous studies with 31P nuclear magnetic resonance have demonstrated that patients with chronic congestive heart failure often exhibit increased glycolytic metabolism and impaired oxidative phosphorylation in exercising skeletal muscle, but the mechanism for these changes remains unresolved. This study was conducted to determine whether these abnormalities result from impaired blood flow or oxygen delivery. Nine patients with mild-to-moderate congestive heart failure and nine age- and size-matched, healthy control volunteers were studied during repetitive submaximal finger flexion exercise under aerobic and ischemic conditions. Skeletal muscle metabolism was assessed by 31P nuclear magnetic resonance of the flexor digitorum superficialis muscle. During steady-state aerobic exercise at 33% of each subject's predetermined maximum workload, the patients with congestive heart failure exhibited significantly lower pH values (6.65 +/- 0.22 vs. 6.97 +/- 0.09, p less than 0.002) and phosphocreatine concentrations, expressed as [phosphocreatine]/([phosphocreatine] + [inorganic phosphate]) (0.59 +/- 0.14 vs. 0.79 +/- 0.08, p less than 0.002). Similar differences were also present throughout ischemic exercise at the same workload. Based upon these measurements, calculated lactate production and adenosine 5'-triphosphate consumption rates were significantly higher in the patients with congestive heart failure. These results indicate that in many patients with congestive heart failure exercising muscle exhibits increased glycolytic metabolism and appears to be metabolically less efficient in relation to external work performed. These changes cannot be explained by impaired blood flow or oxygen delivery alone.     

The N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of the atrial natriuretic factor prohormone each circulate in humans and increase in congestive heart failure

Two peptides consisting of amino acids 1-30 and 31-67 of the N-terminus of the prohormone of atrial natriuretic factor (pro-ANF) that have vasodilatory and natriuretic properties were investigated to determine if they circulate in humans. Specific and sensitive radioimmunoassays were developed to amino acids 1-30, 31-67, and 99-126 of pro-ANF. Evaluation of human plasma that had been subjected to reverse-phase high-pressure liquid chromatography suggested that pro-ANFs 1-30 and 31-67 as well as ANF were distinct peaks in human plasma corresponding exactly to pure synthetic peaks of these peptides on high-pressure liquid chromatography. Molecular weight determination of the endogenous immunoreactive peptides measured in plasma by G-50 Sephadex gel permeation chromatography revealed that the pro-ANF 1-30 radioimmunoassay recognized a peptide of 10,000 MW, which is consistent with it measuring the whole N-terminus of pro-ANF (amino acids 1-98) but without ANF (C-terminus) attached to it. The pro-ANF 31-67 radioimmunoassay recognized mainly (more than 95%) a peptide of 3,900-4,000 MW, which corresponds closely with its actual molecular weight of 3,878. Our ANF radioimmunoassay recognizes a peptide in plasma of 3,000 MW with the known molecular weight of ANF being 3,081. The mean circulating concentrations of immunoreactive pro-ANF 1-98, pro-ANF 31-67, and ANF in 54 control subjects were 531 +/- 25, 371 +/- 18, and 22 +/- 1 fmol/ml (+/- SEM), respectively. Thirty patients with varying severity of congestive heart failure were also studied. The N-terminus, C-terminus, and pro-ANF 31-67 increased: twofold for New York Heart Association functional Class II, threefold to ninefold for Class III, and 10- to 20-fold for Class IV patients with congestive heart failure. Thus, the N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of pro-ANF as well as ANF circulate normally and increased proportionately to the increasing severity of congestive heart failure. However, because the pro-ANF 31-67 radioimmunoassay was the only assay that discriminated between patients with Class I congestive heart failure and control subjects, this assay may be the most useful to accurately classify the severity of congestive heart failure.     

Angiotensin II type 1 receptor antagonist decreases plasma levels of tumor necrosis factor alpha, interleukin-6 and soluble adhesion molecules in patients with chronic heart failure

OBJECTIVES: To evaluate the effects of an angiotensin (Ang II) type 1 receptor antagonist on immune markers in patients with congestive heart failure (CHF). BACKGROUND: Ang II stimulates production of immune factors via the Ang II type 1 receptor in vitro, and the long-term effects of Ang II type 1 receptor antagonists on plasma markers of immune activation are unknown in patients with CHF. METHODS: Twenty-three patients with mild to moderate CHF with left ventricular dysfunction were randomly divided into two groups: treatment with Ang II type 1 receptor (candesartan cilexetil) (n = 14) or placebo (n = 9). We measured plasma levels of immune factors such as tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). We also measured plasma levels of the neurohumoral factors such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP), a biological marker of ANP and BNP. RESULTS: Plasma levels of TNFalpha, IL-6, sICAM-1 and sVCAM-1 were increased in the 23 CHF patients compared with normal subjects and significantly decreased after 14 weeks of candesartan cilexetil treatment, but did not change in the placebo group. Plasma levels of BNP, which is a marker of ventricular injury, significantly decreased, and the molar ratio of plasma cGMP to cardiac natriuretic peptides (ANP + BNP) was significantly increased after candesartan cilexetil treatment, but did not change in the placebo group. CONCLUSIONS: These findings suggest that 14 weeks of treatment with an Ang II type 1 receptor antagonist (candesartan cilexetil) decreased plasma levels of the immune markers such as TNFalpha, IL-6, sICAM-1 and sVCAM-1 and that it improved the biological compensatory action of endogenous cardiac natriuretic peptides in patients with mild to moderate CHF.     

Secretion of human atrial natriuretic peptide in response to atrial pacing and its function in patients with ventricular septal defect

The capacity to secrete human atrial natriuretic peptide (hANP) in response to atrial pacing and the resulting changes in diuresis and urinary electrolyte excretion were compared in children with and without a ventricular septal defect (VSD). The subjects examined were 9 children with a history of Kawasaki disease (as controls) and 11 patients with a VSD, including 5 patients with congestive heart failure (CHF). Their ages ranged from 6 to 40 months old. Atrial pacing resulted in a significant increase in the plasma hANP level from 40 +/- 19 to 140 +/- 37 pg/ml in the controls and from 757 +/- 762 to 1540 +/- 1160 pg/ml in the VSD patients. In control children, the urinary flow rate increased 2.3-fold, urinary sodium excretion increased 6.2-fold and urinary chloride excretion increased 7.6-fold, but these values increased only slightly in VSD patients, especially in those patients with CHF, in spite of the marked increase in their plasma hANP level. These results indicate that the capacity for hANP secretion was increased in VSD patients who had chronic volume overloading of the left atrium, but that their diuresis and urinary electrolyte excretion in response to hANP were attenuated.     

Sympathetic response to ventricular extrasystolic beats in hypertension and heart failure

Provoked premature ventricular contractions (PVCs) evoke, in concomitance with an early and late blood pressure fall and overshoot, an early sympathoexcitation and a later period of sympathoinhibition, respectively. The present study was designed to examine whether in healthy subjects this is the case for spontaneous PVCs. Because of their pathophysiological relevance for arrhythmogenesis, it was also designed to determine whether the sympathetic responses are different from those seen in essential hypertension and congestive heart failure. In 14 untreated mild essential hypertensives (EH; age, 53.8+/-2.6 years; mean+/-SEM), 20 untreated congestive heart failure patients (CHF; age, 56.7+/-2.5 years; New York Heart Association class, II or III), and 16 age-matched healthy subjects (control) in Lown class 相似文献   

Differential effects of direct antagonism of AII compared to ACE inhibitors on serum potassium levels and azotemia in patients with severe congestive heart failure

OBJECTIVES. The present study was undertaken to determine if direct blockade of angiotensin II receptors by losartan potassium as compared to ACE inhibition might result in greater tolerability in patients with congestive heart failure in whom ACE inhibition resulted in hyperkalemia and azotemia. BACKGROUND. Blockade of angiotensin II receptors by losartan potassium may produce similar benefits in congestive heart failure as ACE inhibition. However, some observations suggest losartan potassium may have different effects on renal function than ACE inhibition. METHODS. Five consecutive patients with severe congestive heart failure were identified in whom treatment with ACE inhibition was complicated by hyperkalemia (K>5.7) and azotemia. In three of these patients losartan potassium was substituted for ACE inhibition while losartan potassium was added to treatment with ACE inhibition in the remaining two. The mean of four serial values of potassium, blood urea nitrogen, and creatinine were compared before and after change in treatment using a two-tailed t test. RESULTS. The addition or substitution of losartan potassium resulted in statistically insignificant reductions in blood urea nitrogen and creatinine and a significant reduction in potassium from 5.7+/-0.1 to 4.9+/-0.3, p<0.03. Two patients who had required kayexalate were withdrawn. In all patients, hyperkalemia resolved and did not reoccur. CONCLUSIONS. There appear to be fundamental differences between the effects of losartan potassium and ACE inhibitors on potassium excretion in congestive heart failure patients with mild to moderate renal insufficiency. Losartan potassium may also be associated with less azotemia in such patients. These differences may have important clinical implications, particularly in the subset of patients in whom ACE inhibition is poorly tolerated as a result of hyperkalemia and azotemia. (c)2000 by CHF, Inc.     

Possible vascular role of increased plasma arginine vasopressin in congestive heart failure

BACKGROUND: The present study was undertaken to determine the relation of cardiac dysfunction with hormonal release in patients with congestive heart failure. METHODS: Seventy-two patients with congestive heart failure were examined, who were divided into four subgroups classified by the criteria of the New York Heart Association (NYHA). Also, 10 age-matched subjects were served as a control. Plasma arginine vasopressin (AVP), norepinephrine, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined. Cardiac index and pulmonary capillary wedge pressure (PCWP) were measured in 51 of 72 patients. RESULTS: Plasma AVP levels were significantly increased according to the severity of NYHA classes; control: 1.7 +/- 0.2; NYHA I: 4.9 +/- 0.8, NYHA II: 5.5 +/- 0.9, NYHA III: 13.4 +/- 2.6 (p < 0.05), NYHA IV: 26.9 +/- 5.6 pmol/l (p < 0.001). Similar results were obtained with plasma norepinephrine, ANP and BNP. Plasma AVP levels had negative correlation with cardiac index (r = -0.36, p < 0.01), but did not with PCWP and plasma osmolality. Plasma BNP levels positively correlated with PCWP (r = 0.44, p < 0.001), but did not with cardiac index. There was no correlation between plasma AVP and BNP. Intensive therapy profoundly reduced all the hormones according to the improvement of cardiac index in the patients with NYHA class III and IV. The percent decrease in plasma AVP was 60.0%, a value greater than that in plasma BNP. CONCLUSION: The present study indicates that increased AVP may deteriorate cardiac function through V(1a) as well as V(2) action, and that plasma AVP level is also a proper marker for the presence and severity of congestive heart failure.     

Use of aspirin in conjunction with angiotensin-converting enzyme inhibitors does not worsen long-term survival in heart failure

BACKGROUND: A negative interaction has been shown to exist between aspirin and angiotensin-converting enzyme inhibitors (ACE-I) in subjects with heart failure. We explored the effect of combined ACE-I and aspirin therapy compared to ACE-I without aspirin on clinical outcomes in patients with heart failure. METHODS: 430 consecutive subjects (70+/-14 years, 55% male, 41% with coronary artery disease) released from the hospital with a primary diagnosis of heart failure were classified into three groups based on the use of aspirin and ACE-I at discharge: ACE-I without aspirin (group I, n=134), ACE-I with aspirin (group II, n=138) and no ACE-I (group III, n=158). Follow-up (all-cause mortality and the composite end-point of mortality or emergent heart transplant) was available in 406 (94%) patients at a median duration of 28 months. Differences in outcomes between patient groups were compared using contingency tables, Kaplan-Meier survival, and Cox regression analyses. Similar analyses were conducted in four predefined subsets (patients with and without coronary artery disease, and those with left ventricular ejection fraction 45%). RESULTS: Death and the composite end-point occurred in 155 (38%) and 165 (41%) patients, respectively. In the total cohort as well as in the four subsets, the treatment group showed no association with clinical outcomes in univariate or multivariate analyses. CONCLUSIONS: In patients with a principal discharge diagnosis of heart failure, the use of aspirin, in combination with ACE-I, does not worsen long-term survival compared to the use of ACE-I without aspirin.     

慢性心力衰竭患者血浆激素水平动态变化及其临床意义

目的观察慢性心力衰竭(CHF)患者血浆N端脑钠素原(NtproBNP)水平和肾素血管紧张素系统的动态变化及其临床意义。方法选择CHF病人44例,随机接受β阻滞剂比索洛尔或卡维地洛治疗共7个月。测定血管紧张素原、肾素、血管紧张素Ⅱ、醛固酮水平和NtproBNP水平。结果基线血管紧张素原、肾素、血管紧张素Ⅱ、醛固酮水平在正常参考值范围内;NtproBNP明显高于正常参考值上限,且随着心功能分级的增加而明显增加。与用药前相比,血管紧张素原、肾素、血管紧张素与醛固酮药后各时点无显著变化(P值均>0.05);用药后达标时的血浆NtproBNP水平明显减低(P<0.01)。事件组NtproBNP明显高于非事件组。多元回归结果显示:基线时左室射血分数与NtproBNP水平负相关(β=-0.389,P=0.009),与血管紧张素Ⅱ正相关(β=0.341,P=0.020),用药后左室射血分数剂量与调整期结束后NtproBNP水平明显负相关(β=-0.424,P=0.020),与NYHA分级呈正相关(β=0.410,P=0.024)。结论NtproBNP水平比肾素血管紧张素醛固酮系统在定量评价心功能受损程度、疗效及预后判定等方面更加敏感及准确。     

Echocardiographic abnormalities in acute rheumatic fever.

The echocardiographic velocity of circumferential fiber shortening and left atrial dimension were measured serially in two groups of children with acute rheumatic fever: Group I, six patients with valve regurgitation without congestive heart failure, and Group II, seven patients with regurgitation and congestive heart failure. In Group I, the initial velocity of circumferential fiber shortening was increased to 1.90 +/- 0.31 circumferences per second (circ/sec) (mean +/- standard deviation). In group II, it was decreased (1.18+/-0.25). In group I velocity of circumferential fiber shortening subsequently decreased but remained above the normal level; in Group II it increased to exceed the expected normal value. Concurrent changes in left atrial dimension were observed in both groups. The initial left atrial dimension of Group I (2.2 +/- 0.75 cm/m2) was slightly increased and returned to normal (1.70 +/- 0.32) on follow-up study. The left atrial dimension of Group II was greatly increased initially (2.70 +/- 0.81 cm/m2) and remained large (2.50 +/- 0.67). Three patients in Group II experienced rebound during corticosteroid withdrawal. In each the velocity of circumferential fiber shortening decreased, suggesting impaired cardiac contractility. The echocardiogram thus facilitates serial assessment of the severity of carditis in acute rheumatic fever.     

Clinical characteristics, treatment, and outcome of tachycardia induced cardiomyopathy

Tachycardia-induced cardiomyopathy is characterized by ventricular systolic dysfunction and congestive heart failure resulting from persistent or highly frequent tachyarrhythmias with uncontrolled heart rate. While reversible and often considered benign, few studies have examined the outcome of the disorder. The clinical characteristics, treatment, and long-term outcomes of 12 consecutive patients with tachycardia-induced cardiomyopathy (9 men, age, 51.9 +/- 17.6 years) were studied. The mean period between the occurrence of tachyarrhythmias and the development of congestive heart failure was 26.0 +/- 34.3 days. The mean heart rate on admission was 156.3 +/- 28.7 beats/min. All patients had severe heart failure with a NYHA functional class of 2.3 +/- 0.5, left ventricular ejection fraction of 0.32 +/- 0.10, and brain natriuretic peptide level of 505.7 +/- 449.1 pg/mL. In all patients, cardiac dysfunction recovered after 53.5 +/- 61.3 days. During the follow-up of 53 +/- 24 months, 2 patients had a recurrence of heart failure with uncontrolled tachyarrhythmia and 1 patient died suddenly. In tachycardia-induced cardiomyopathy, recurrent heart failure with uncontrollable tachyarrhythmia and sudden death were observed after recovery from cardiac dysfunction. A substrate for heart failure and/or life-threatening arrhythmia might persist, and careful, long-term follow-up seems required.     

Plasma atrial natriuretic factor concentration during maximal cardiopulmonary exercise in men with mild heart failure

The response in terms of production of atrial natriuretic factor to maximal cardiopulmonary exercise was investigated in 13 patients with mild heart failure (New York Heart Association function class II) secondary to previous myocardial infarction. Exercise induced a rapid and gradually increasing production of atrial natriuretic factor. The concentration at the termination of the test was statistically higher than at rest (64.5 +/- 9.7 versus 119.4 +/- 18.3 pmol/l. P = 0.001). Resting levels of the natriuretic factor correlated well to levels at peak exercise (r = 0.797, P = 0.001). The increase in concentration from rest to peak exercise (atrial natriuretic factor delta) was inversely correlated to the peak consumption of oxygen (r = -0.584, P = 0.036), indicating that the response to exercise is not attenuated in the patients with most marked functional impairment. The relationship between resting levels of atrial natriuretic factor and peak consumption of oxygen did not reach statistical significance (r = -0.421, P = 0.152), but a significant inverse relationship was observed between concentration at peak exercise and peak consumption of oxygen (r = -0.671, P = 0.012). Levels of atrial natriuretic factor during peak exercise are related to functional impairment in mild heart failure and may discriminate between the functional capacity of patients belonging in the same class of clinical function.     

Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure.

Impaired endothelial-dependent vasodilation has been demonstrated in two animal models of congestive heart failure and in the coronary circulation of patients with idiopathic dilated cardiomyopathy. To determine whether this impairment contributes to the abnormal peripheral vasomotor tone in patients with congestive heart failure, the local vascular response to intraarterial infusions of graded concentrations (10(-8) M to 10(-5) M) of acetylcholine (an endothelial-dependent vasodilator) and nitroglycerin (a direct-acting vasodilator) was studied in the superficial femoral artery of 19 patients with congestive heart failure (New York Heart Association classes I to IV) and 6 age-matched normal control subjects. The local vascular response was determined from the arterial blood flow velocity pattern obtained by transcutaneous Doppler ultrasonography. Acetylcholine, 10(-5) M, induced a pattern characteristic of vasodilation in all six normal subjects; mean blood flow velocity for the group significantly increased from 11.9 +/- 2.7 to 44.8 +/- 20.9 cm/s (p less than 0.05). In contrast, the same dose of acetylcholine induced a blood flow velocity pattern characteristic of vasodilation in only 4 of the 19 patients with congestive heart failure. Group mean blood flow velocity did not change significantly. Nitroglycerin, 10(-7) M, induced vasodilation in all 6 normal subjects but in only 1 of 19 patients. Nitroglycerin, 10(-5) M, was administered to 10 patients; all 10 demonstrated a pattern characteristic of vasodilation. Thus, acetylcholine-mediated endothelial-dependent vasodilation appears to be impaired in the peripheral vasculature of patients with congestive heart failure. Both endothelial dysfunction and abnormal vascular smooth muscle responsiveness may contribute to abnormal peripheral vasomotor tone.     

Angiotensin inhibition and atrial natriuretic peptide release after acute volume expansion in rats with aortocaval shunt.

OBJECTIVE: In heart failure atrial natriuretic peptide (ANP) release in response to volume expansion is impaired while the renin-angiotensin system is activated. This study was designed to test the hypothesis that ANP release in heart failure is dependent on an activated angiotensin system. METHODS: We studied the ANP and renin-angiotensin systems in a rat model of shunt-induced high-output heart failure, in which we rapidly increased circulating fluid volume with a 5 ml, hyperoncotic infusion, and evaluated the effects of acute inhibition of the angiotensin converting enzyme as well as of the blockade of the angiotensin II type 1 receptors on the ANP release and on renal excretory function. RESULTS: ANP and angiotensin II plasma concentrations prior to volume expansion were elevated (p < 0.05) in rats with aortocaval shunt compared to controls. The diuretic response to acute volume expansion (18.5 +/- 1.5 vs. 48.2 +/- 2.4 microliters/min, p < 0.001) was markedly blunted. ANP release was attenuated in rats with aortocaval shunt, as was the increase of its second messenger cGMP in plasma and urine. The blunted increase in ANP plasma levels was not due to depleted cardiac stores as cardiac ANP content, as well as ANP synthesis, were increased (p < 0.05). Acute inhibition of the angiotensin converting enzyme as well as blockade of the angiotensin II type 1 receptors restored ANP release in response to volume expansion (p < 0.01). Moreover, acute inhibition of the renin-angiotensin system completely normalized the diuretic response. CONCLUSIONS: Our data suggest that the ANP system is impaired in rats with aortocaval shunt. The activation of the angiotensin system contributes to the impairment of the ANP system. Acute inhibition of the angiotensin II system significantly improved the ability of the ANP system to respond to acute volume expansion. Our findings indicate a hitherto fore unappreciated interaction between both systems and suggest additional mechanisms for the beneficial effects of angiotensin converting enzyme inhibition or angiotensin II type 1 receptor antagonists in heart failure.