Cardiac event rates after acute myocardial infarction in patients treated with verapamil and trandolapril versus trandolapril alone. Danish Verapamil Infarction Trial (DAVIT) Study Group

Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), but mortality may be as high as 10% to 15% after 1 year. Verapamil prevents cardiac events after an AMI in patients without CHF. We hypothesized that in postinfarct patients with CHF already prescribed diuretics and an ACE inhibitor, additional treatment with verapamil may reduce cardiac event rate. In this multicenter, double-blind study, patients with CHF receiving diuretic treatment were consecutively randomized to treatment with trandolapril 1 mg/day for 1 month and 2 mg/day the following 2 months (n = 49), or to trandolapril as mentioned plus verapamil 240 mg/day for 1 month and 360 mg/day for 2 months (n = 51). Trial medication started 3 to 10 days after AMI. All patients were followed for 3 months. End points in the trandolapril/trandolapril-verapamil groups were death 1/1, reinfarction 7/1, unstable angina 9/3, and readmission for CHF 6/2. The 3-month first cardiac event rate was 35% in trandolapril-treated patients and 14% in trandolapril-verapamil-treated patients (hazard ratio 0.35, 95% confidence interval 0.15 to 0.85, p = 0.015). These data suggest that verapamil reduces cardiac event rates in post-AMI patients with CHF when added to an ACE inhibitor and a diuretic.     

The DD genotype of the angiotensin-converting enzyme gene is associated with increased mortality in idiopathic heart failure

OBJECTIVES: The aim of the present study was to investigate the association between the homozygous DD (deletion) genotype of the angiotensin-converting enzyme gene and survival and cardiac function in patients with idiopathic congestive heart failure. BACKGROUND: The DD genotype gene is a linkage marker for an etiologic mutation at or near the angiotensin-converting enzyme gene and has been associated with increased risk for the development of coronary artery disease, left ventricular hypertrophy and left ventricular dilation after myocardial infarction. We investigated the association between this angiotensin-converting enzyme genotype and mortality in a population-based cohort of patients with idiopathic congestive heart failure. METHODS: The genotype was determined in 193 patients recruited from a large unselected population of patients with congestive heart failure (n = 2,711). The patients were studied with echocardiography, and survival data were obtained after 5 years of follow-up. A control group from the general population (n = 77) was studied by a similar procedure. RESULTS: The frequency of the D allele was not significantly different in the study and control groups (0.57 vs 0.56, p = NS). Long-term survival was significantly worse in the patients with the DD genotype than in the remaining patients (5-year survival rate 49% vs. 72%, p = 0.0011 as assessed by log rank test). The independent importance of the DD genotype for prognosis was verified by a multivariate Cox proportional hazards analysis, by which the odds ratio for mortality and the DD genotype was 1.69 (95% confidence interval 1.01 to 2.82). The only significant difference in cardiac function data between the two groups was an increase in left ventricular mass index in the DD group (153 +/- 57 vs 134 +/- 44 g/m2, p = 0.019). CONCLUSIONS: Angiotensin-converting enzyme gene DD polymorphism was associated with poorer survival and an increase in left ventricular mass in patients with idiopathic heart failure. The results suggest a possible pathophysiologic pathway between angiotensin-converting enzyme gene polymorphism, angiotensin-converting enzyme activity, myocardial hypertrophy and survival. Therefore, the DD genotype may be a marker of poor prognosis in patients with congestive heart failure.     

Coronary artery bypass grafting in cases with poor left ventricular function

From January 1987 through June 1992, 18 patients with poor left ventricular function (left ventricular ejection fraction [LVEF] less than 0.3) underwent elective isolated primary coronary artery bypass surgery. The mean age was 56.4 years (range, 46 to 72 years), and 15 were males and 3 were females. Mean pre-operative LVEF measured by ventriculography was 0.26 +/- 0.03 (range, 0.19 to 0.30). Sixteen patients (88.9%) had a prior myocardial infarction and 9 (50%) had a history of congestive heart failure. Complete revascularization was the goal for all patients, and the mean number of bypass grafts was 3.0 +/- 0.8 per patient. The left anterior descending coronary artery (LAD) was revascularized in all patients. There were no operative deaths. Post-operative LVEF improved significantly from 0.26 +/- 0.03 to 0.42 +/- 0.11 (p = 0.0002), and the regional left ventricular wall motion improved in the diaphragmatic and posterobasal regions (p < 0.01). The patency of the grafts was 93.9% in all, and 100% for LAD. The mean follow-up period was 77 months, and the overall actuarial survival rate was 88.9% at 10 years. During follow-up periods, two patients died of congestive heart failure (CHF), and two required three rehospitalizations because of CHF. The overall cardiac event free rate was 75.8% at 10 years. In patients with poor left ventricular function, surgical revascularization can be performed safely, but congestive heart failure sometimes occurs during follow-up periods and may be the cause of death. Therefore alternate forms of therapy such as cardiac transplantation and/or TMLR should be considered in selected patients.     

Heart rate variability index in congestive heart failure: relation to clinical variables and prognosis

AIM: To evaluate the clinical and prognostic value of the heart rate variability index in patients with congestive heart failure. METHODS: Sixty-four patients with chronic congestive heart failure and sinus rhythm underwent clinical assessment, 24-h ambulatory electrocardiography and echocardiography. Patients were followed for 6 to 30 months. Cardiac death or heart transplantation constituted the primary end-point of the study. RESULTS: The heart rate variability index was related to left ventricular ejection fraction (r=0.29, P=0.02) and New York Heart Association class (P=0.01). Patients with a restrictive left ventricular filling pattern had a lower heart rate variability index compared to patients with a non-restrictive pattern (26+/-11 vs 33+/-9 units, P=0.01). Patients who died (n=11) or underwent heart transplantation (n=4) had a lower heart rate variability index compared to survivors (21+/-10 vs 33+/-9 units, P<0.0001). In multivariate survival analysis, a reduced heart rate variability index was related to survival independent of parameters of left ventricular function. CONCLUSION: The heart rate variability index provides independent information on clinical status and prognosis in patients with chronic congestive heart failure.     

Congestive heart failure in patients with valvular aortic stenosis. A clinical and echocardiographic Doppler study

The aim of this study was to evaluate echographically anatomic and functional features of the left ventricle in adult patients with valvular aortic stenosis according to the presence or absence of congestive heart failure and the level of ventricular performance. Fifty-six adult patients with moderate-to-severe aortic stenosis underwent echocardiographic Doppler examination in order to evaluate left ventricular mass and dimensions, systolic function and filling dynamics. Twenty-seven patients had no heart failure and were symptomatic for angina (5), syncope (4) or were symptom-free (group I); the other 29 had heart failure (group II): 16 with normal left ventricular systolic performance (fractional shortening > 25%, group IIa) and 13 with systolic dysfunction (fractional shortening < or = 25%, group IIb). Despite a similar left ventricular mass, compared to group IIa, group IIb showed a significant left ventricular dilatation (end-diastolic diameter: 61 +/- 6.5 vs. 45.5 +/- 6.1 mm, p < 0.001) and mild or no increase in wall thickness (11.5 +/- 1.6 vs. 14.9 +/- 2 mm, p < 0.001). Indices of left ventricular filling on Doppler transmitral flow were also significantly different between the two groups, with a higher early-to-late filling ratio and a shorter deceleration time of early filling in group IIb (2.8 +/- 1.9 vs. 1.2 +/- 0.85, p < 0.01, and 122 +/- 66 vs. 190 +/- 87 ms, p < 0.05, respectively), both indirectly indicating higher left atrial pressure. Finally, heart failure was generally more severe in group IIb patients. In some patients with aortic stenosis, symptoms of heart failure may be present despite a normal left ventricular systolic function and seem to depend on abnormalities of diastolic function. The presence of systolic or isolated diastolic dysfunction appears to be related to a different geometric adaptation of the left ventricle to chronic pressure overload.     

Congenital hypoplasia of portions of both right and left ventricular myocardial walls. Clinical and necropsy observations in two patients with parchment heart syndrome

Clinical and morphologic findings are described in two patients with congenital hypoplasia of portions of both right and left ventricular free walls in the absence of associated coronary or valvular heart disease. One, a 61 year old man who had never had clinical evidence of cardiac dysfunction, died suddenly and unexpectedly. The second, a 55 year old woman, died of progressive, eventually intractable congestive heart failure of 29 months' duration. Although at least 22 necropsy patients have previously been reported to have "parchment-like" thinning of portions of the right ventricular free wall, only one patient has previously been described with such thinning of portions of both right and left ventricular free walls. The spectrum of right or right and left ventricular wall congenital hypoplasia is a broad one, with nearly half of described patients dying of congestive heart failure in the 1st year of life and the other half reaching adulthood with or without manifestations of cardiac dysfunction.     

Invasive pharmacodynamic characterization of combined ibopamine and calcium blocker therapy for heart failure

STUDY OBJECTIVE: To determine the acute hemodynamic response of single-dose coadministration of ibopamine plus nifedipine or diltiazem in patients with New York Heart Association functional class (NYHA FC) II-III congestive heart failure. DESIGN: A single-blind, placebo-controlled, two-paired, crossover study. SETTING: Cardiology clinics at two large teaching hospitals. PATIENTS: Eight patients with NYHA FC II-III congestive heart failure who met the inclusion criteria were selected randomly. INTERVENTIONS: All patients underwent right heart catheterization. Day 1 consisted of concomitant calcium channel blocker plus placebo, with cardiac and peripheral hemodynamic recordings from 30 minutes-24 hours. The design was equivalent on day 2, with single-dose administration of ibopamine plus calcium channel blocker. MEASUREMENTS AND MAIN RESULTS: Single-dose nifedipine-diltiazem augmented cardiac output and stroke volume secondary to decreasing systemic vascular resistance. The nifedipine-ibopamine and diltiazem-ibopamine subgroups demonstrated relatively equal hemodynamics, augmenting cardiac index (nifedipine 43%, p < 0.05; diltiazem 40%, p < 0.05 vs baseline) while decreasing systemic vascular resistance (nifedipine 41%, p < 0.05; diltiazem 28%, p NS vs baseline) 30 minutes after the dose. In contrast to single-dose diltiazem, the diltiazem-ibopamine subgroup exhibited an increased left ventricular filling pressure (122%, p < 0.05 vs baseline) and mean pulmonary artery pressure (43%, p < 0.05 vs baseline) at 30 minutes after the dose. One patient experienced a transient episode of chest pain associated with increased heart rate and blood pressure with diltiazem-ibopamine. CONCLUSION: Diltiazem and ibopamine should be coadministered with caution in patients with coronary artery disease and left ventricular dysfunction.     

Preventing congestive heart failure

The morbidity, mortality and health care costs associated with congestive heart failure make prevention a more attractive public health strategy than treatment. Aggressive management of etiologic factors, including hypertension, coronary artery disease, valvular disease and excessive alcohol intake, can prevent the left ventricular remodeling and dysfunction that lead to heart failure. Early intervention with angiotensin converting enzyme inhibitors in patients with chronic left ventricular dysfunction can prevent, as well as treat, the syndrome. Several intervention strategies in patients with acute myocardial infarction can slow or prevent the left ventricular remodeling process that antedates congestive heart failure. The primary care physician must be alert to the need for aggressive intervention to reduce the burden of heart failure syndrome on the patient and on society.     

In situ detection of DNA fragmentation and expression of bcl-2 in human neuroblastoma: relation to apoptosis and spontaneous regression

In patients with alcoholic cardiomyopathy there is evidence that mild heart failure is reversible if patients abstain from alcohol, but there is no consensus whether the disease is progressive once structural myocardial dilation has evolved. The aim of the present study was to compare the long-term course of congestive heart failure due to alcoholic and idiopathic dilated cardiomyopathy. Of 75 patients with overt congestive heart failure, 23 had alcoholic cardiomyopathy and were compared to 52 patients with idiopathic cardiomyopathy. The mean age was 48 +/- 12 years. Despite medical therapy, heart failure class New York Heart Association III-IV was present in 52% of patients with alcoholic and 47% of patients with idiopathic cardiomyopathy (not significant). Their mean left ventricular ejection fraction was 30 +/- 12% vs 28 +/- 12% and left ventricular end-diastolic volumes were 264 +/- 125 ml and 254 +/- 100 ml respectively (not significant). Overall survival at 1, 5 and 10 years was 100%, 81% and 81% for the group with alcoholic dilated cardiomyopathy and 89%, 48% and 30% for the group with idiopathic cardiomyopathy, respectively (P = 0.041), and the difference was even greater for transplant-free survival P = 0.005). Clinical and invasive signs of left and right heart failure as well as left ventricular dimensions were predictive of a fatal outcome; however, symptom duration and left ventricular volumes were only predictive in patients with idiopathic cardiomyopathy, suggesting that in the two patient groups different mechanisms may lead to death. Mortality in patients with severe congestive heart failure and left ventricular dilatation due to alcoholic cardiomyopathy is significantly lower than that in patients with idiopathic cardiomyopathy and similar degrees of heart failure. Thus, despite structural changes inherent in marked left ventricular dilatation, disease progression in alcoholic dilated cardiomyopathy is different from that in idiopathic cardiomyopathy and thus may have implications for the choice of therapy.     

Evaluation of a new bipyridine inotropic agent--milrinone--in patients with severe congestive heart failure

Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone. In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure. Significant increases occurred in cardiac index (from 1.9 +/- 0.1 to 2.9 +/- 0.2 liters per minute per square meter) and the peak positive first derivative of left ventricular pressure, with a slight increase in heart rate. Hemodynamic improvement was sustained during a 24-hour continuous infusion. Nineteen of the 20 patients subsequently received oral milrinone (29 +/- 2 mg per day) for up to 11 months (mean, 6.0 +/- 0.8), with sustained improvement in symptoms of heart failure. In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug. Four patients died after a mean of 4.8 months of therapy, and three patients with severe underlying coronary-artery disease and angina pectoris required additional antianginal therapy. No patient had fever, thrombocytopenia, gastrointestinal intolerance, or aggravation of ventricular ectopy. We conclude that milrinone shows promise for the longterm treatment of congestive heart failure.     

Corticosteroid therapy in cardiac sarcoidosis

Corticosteroid treatment of cardiac sarcoidosis is not conclusive, although sarcoid granulomas in the heart may be more responsive to steroid therapy than in other organs. Healing of sarcoidosis lesions in the heart results in fibrosis and sinning of the myocardium, which may lead to aneurysm formation causing congestive heart failure or sudden death. Congestive heart failure is the leading cause of death in patients with cardiac sarcoidosis in Japan. It is reasonable to initiate steroid therapy as soon as the diagnosis of cardiac sarcoidosis is established in order to prevent fibrosis. Early initiation of steroid therapy with conventional treatment for specific cardiac manifestations (antiarrhythmic therapy, pacemaker implantation and heart failure medication) should bring improvement in the left ventricular systolic and diastolic function with prevention from malignant arrhythmias. Systemic disorder represents a contraindication to organ transplantation, but heart transplantation is now a feasible treatment for patients with end-stage cardiac sarcoidosis with congestive heart failure.     

Incidence and significance of ventricular tachycardia and fibrillation in the absence of hypotension or heart failure in acute myocardial infarction treated with recombinant tissue-type plasminogen activator: results from the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial

OBJECTIVES: The purpose of this study was to determine the incidence of ventricular tachycardia and fibrillation without hypotension or heart failure after treatment with recombinant tissue-type plasminogen activator (rt-PA), anatomic correlates of their development, the effect of immediate intravenous metoprolol on their occurrence and the outcome of patients with these arrhythmias. BACKGROUND: Malignant arrhythmias after thrombolytic therapy have been reported to occur as a result of coronary reperfusion, which is associated with reduced mortality in patients receiving thrombolytic therapy. METHODS: We analyzed data from 2,546 patients in the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial without congestive heart failure or hypotension during the 1st 24 h after study entry. Forty-nine patients (1.9%) developed sustained ventricular tachycardia or ventricular fibrillation within 24 h of study entry (group 1), and 2,497 patients (98.1%) did not (group 2). RESULTS: Baseline characteristics and admission laboratory values were similar in the two groups. In patients undergoing protocol angiography 18 to 48 h after rt-PA, the infarct-related artery was patient in a greater percent of group 2 patients (87% [1,015 of 1,169]) than group 1 patients (68% [15 of 22], p = 0.01), although angiography was performed less frequently in group 1 than in group 2. More group 1 than group 2 patients died within 21 days (20.4%) (1.6%, p < 0.001). For patients surviving to 21 days, there was no difference in mortality between patients in the two groups in the following year. CONCLUSIONS: Ventricular tachycardia and fibrillation are not markers for reperfusion after thrombolytic therapy. These arrhythmias are associated with occlusion, not patency, of the infarct-related artery. Early mortality is increased in patients who develop ventricular tachycardia and fibrillation, even in the absence of congestive heart failure and hypotension.     

A placebo-controlled study of growth hormone in patients with congestive heart failure

AIM: Experimental data in heart failure models and an open trial of seven patients with idiopathic dilated cardiomyopathy have suggested beneficial effects of growth hormone on cardiac function. The aim of the present study was to evaluate growth hormone effects on cardiac function in a placebo-controlled study. METHODS: Twenty two patients with congestive heart failure of different aetiologies in NYHA II and III and an echocardiographic ejection fraction <0.45 were studied in a 3 month double-blind placebo-controlled study with growth hormone added to optimal heart failure therapy. Patients received either placebo (n=11) or recombinant human growth hormone (n=11) in an initial dose of 0.1 IU x kg(-1) week(-1) for 1 week, and thereafter 0.25 IU x kg(-1) week(-1) for the rest of the treatment period. Cardiac function was assessed by equilibrium radionuclide angiography and Doppler echocardiography. Functional capacity was evaluated by computerized bicycle exercise electrocardiography. RESULTS: Recombinant human growth hormone had no significant effect on systolic or diastolic cardiac function, exercise capacity or neuroendocrine activation. In addition, there was no overall improvement in functional class or dyspnoea grade. Insulin-like growth factor-I significantly increased demonstrating that the growth hormone had an endocrine effect. CONCLUSION: This is the first double-blind and placebo-controlled study of the administration, over 3 months, of recombinant human growth hormone in patients with congestive heart failure of different aetiologies. The treatment was safe and without serious side effects. However, no beneficial effects on cardiac function or structure could be detected.     

Experimental rat model representing both acute and chronic heart failure related to autoimmune myocarditis

The most important clinical manifestation of myocarditis is congestive heart failure. The precise mechanisms of heart failure during myocarditis have not been elucidated because no animal model that would permit in vivo study of hemodynamics in severe active myocarditis has been available. We monitored hemodynamics and left ventricular function in a rat model of experimental autoimmune myocarditis to determine if this model could be useful for the study of in vivo hemodynamics in severe active myocarditis. Lewis rats were immunized with human cardiac myosin suspended in complete Freund's adjuvant. Baseline hemodynamics were measured using an ultraminiature catheter pressure transducer via the right internal carotid artery, 4 weeks after immunization in one group of rats (acute phase) and 3 months after immunization in another group (chronic phase). Untreated rats served as the control group. Hemodynamic measurements were also obtained after infusion of dobutamine in the acute-phase and chronic-phase groups. The heart weight-to-body weight ratios were significantly higher in both the acute-phase group and the chronic-phase group compared with normal control rats. The baseline left ventricular systolic pressure was significantly lower in the chronic phase group than in the control group. Peak dP/dt and peak -dP/dt were significantly lower in both the acute-phase group and the chronic-phase group compared with the control group. Dobutamine significantly increased left ventricular systolic pressure, peak dP/dt, and peak -dP/dt in the chronic-phase group but caused only minor changes in hemodynamic variables in the acute-phase group. In vivo measurements of hemodynamic variables indicated the presence of left ventricular dysfunction in rats with experimental autoimmune myocarditis. This animal model may be useful for the study of both acute heart failure related to acute myocarditis and chronic heart failure due to diffuse myocardial fibrosis.     

Treatment of heart failure with beta-blockaders]

Since 1975 several studies have indicated that treatment with beta-adrenergic blocking drugs has a positive effect on prognosis in patients with left ventricular dysfunction. After myocardial infarction, treatment with timolol and propranolol improves prognosis in patients with symptoms of cardiomegaly and heart failure. In patients with idiopathic dilated cardiomyopathy, treatment with metoprolol improves the left ventricular ejection fraction and symptoms of heart failure, and may have a positive effect on prognosis. Recent studies of patients with chronic congestive heart failure also indicate that carvedilol has a positive effect on mortality and morbidity. The authors review some relevant studies, to stimulate the use of beta-adrenergic blocking drugs to treat certain types of heart failure.     

Short-term and long-term outcome of left heart function after cardioverter defibrillator implantation

The usefulness and problems of implantable cardioverter defibrillators (ICD) were examined in patients with reduced heart function. Of 36 patients who received ICD for refractory ventricular tachycardia (VT) or ventricular fibrillation (VF), VT and/or VF was associated with underlying heart disease in 26 patients, and VF without underlying heart disease in 10. Of the former 26 patients, 13 with left ventricular ejection fraction (LVEF) of less than 30% were assigned to group A, 13 with LVEF of greater than 30% to group B, and the other 10 with idiopathic VF to group C. Intraoperative death, cardiac death due to heart failure, sudden death, functional status of the ICD, exacerbation of heart failure symptoms and complications were compared between the three groups. There were no intraoperative deaths in any of the groups. During the median follow-up period of 36 +/- 22 months, there was only one sudden death in group A. There were no significant differences between the three groups. There were five cardiac deaths in group A, but none in groups B or C. The cardiac death-free rates 12, 24, and 36 months after implantation in group A were 83%, 60% and 50%, respectively. These values significantly differed from those in groups B and C (p < 0.05). The number of patients who received defibrillation therapy was higher in group A (p < 0.05). Defibrillation therapy was administered earlier in group A than in groups B and C (p < 0.05). The incidence of exacerbation of heart failure after implantation was 69%, 23% and 0% in groups A, B, and C, respectively. In group A, defibrillation therapy was administered in all patients with exacerbation of heart failure. The administration of defibrillation therapy significantly differed from that in patients without exacerbation of heart failure (p < 0.05). Exacerbation of heart failure during the postoperative acute stage occurred in both patients in group A in whom an epicardial lead system was used, but not in the four patients in group B or five in group C (p < 0.05). There were no differences in the incidence of other complications between the three groups. In group A, patients with reduced heart function, ICD greatly decreased the risk of sudden death. However, heart failure mortality remained high. Therefore, ICD may have limitations for improved prognosis. In group A patients, defibrillation therapy was administered in all patients with exacerbation of heart failure or death due to heart failure. In patients with reduced heart function, treatment for heart failure and prophylaxis of VT and/or VF should be administered.     

Effects of continuous positive airway pressure on obstructive sleep apnea and left ventricular afterload in patients with heart failure

BACKGROUND: The objectives of this study were to determine the effects of continuous positive airway pressure (CPAP) on blood pressure (BP) and systolic left ventricular transmural pressure (LVPtm) during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). In CHF patients with OSA, chronic nightly CPAP treatment abolishes OSA and improves left ventricular (LV) ejection fraction. We hypothesized that one mechanism whereby CPAP improves cardiac function in CHF patients with OSA is by lowering LV afterload during sleep. METHODS AND RESULTS: Eight pharmacologically treated CHF patients with OSA were studied during overnight polysomnography. BP and esophageal pressure (Pes) (ie, intrathoracic pressure) were recorded before the onset of sleep and during stage 2 non-rapid eye movement sleep before, during, and after CPAP application. OSA was associated with an increase in systolic BP (from 120.4+/-7.8 to 131.8+/-10.6 mm Hg, P<0.05) and systolic LVPtm (from 124.4+/-7.7 to 137.2+/-10.8 mm Hg, P<0.05) from wakefulness to stage 2 sleep. CPAP alleviated OSA, improved oxyhemoglobin saturation, and reduced systolic BP in stage 2 sleep to 115.4+/-8.5 mm Hg (P<0.01), systolic LVPtm to 117.4+/-8.5 mm Hg (P<0.01), heart rate, Pes amplitude, and respiratory rate. CONCLUSIONS: In CHF patients with OSA, LV afterload increases from wakefulness to stage 2 sleep. By alleviating OSA, CPAP reduces LV afterload and heart rate, unloads inspiratory muscles, and improves arterial oxygenation during stage 2 sleep. CPAP is a nonpharmacological means of further reducing afterload and heart rate during sleep in pharmacologically treated CHF patients with OSA.     

Effects of exercise on plasma level of brain natriuretic peptide in congestive heart failure with and without left ventricular dysfunction

This study was designed to determine whether plasma brain natriuretic peptide (BNP) increases in response to exercise in patients with congestive heart failure and to show what kind of hemodynamic abnormalities induce increased secretion of BNP during exercise. Plasma levels of atrial natriuretic peptide (ANP) and BNP and hemodynamic parameters were measured during upright bicycle exercise tests in seven patients with dilated cardiomyopathy and nine with mitral stenosis. At rest, there were no intergroup differences in cardiac output or pulmonary capillary wedge pressure; however, the group with dilated cardiomyopathy had higher left ventricular end-diastolic pressures and lower left ventricular ejection fractions than did the group with mitral stenosis. Plasma ANP levels were comparable between the dilated cardiomyopathy group (170 +/- 77 [SE] pg/ml) and the mitral stenosis group (106 +/- 33 pg/ml) (p, not significant), whereas BNP was significantly higher in the dilated cardiomyopathy group (221 +/- 80 pg/ml) than in the other group (37 +/- 10 pg/ml) (p < 0.05). The plasma concentration of BNP but not of ANP significantly correlated with left ventricular end-diastolic pressure and volume. Exercise increased plasma ANP and BNP in the two groups. The dilated cardiomyopathy group had a larger increment in BNP (+157 +/- 79 pg/ml) than did the mitral stenosis group (+17 +/- 5 pg/ml) (p < 0.05), although the increase in pulmonary capillary wedge pressure was greater in the mitral stenosis group. Thus exercise increases plasma levels of BNP, and impaired left ventricular function may be a main factor in the greater increment in BNP during exercise in patients with congestive heart failure.     

Value of right ventricular ejection fraction in predicting short-term prognosis of patients with severe chronic heart failure

BACKGROUND: The prognosis of chronic heart failure has been studied extensively, but factors predicting short-term outcome in patients with severe chronic heart failure are still poorly defined, and the current indications for heart transplantation as a treatment for end-stage heart failure need on objective analysis. METHODS: Purpose of the study was to identify the determinants of short-term prognosis in a group of 142 consecutive ambulatory patients (mean age 49.8 +/- 11 years). Referred for heart transplantation because of severe chronic heart failure, the patients were admitted with left ventricular ejection fraction markedly depressed and had had symptoms in spite of an optimal standardized medical therapy for at least 1 month. Baseline clinical and instrumental evaluation included right-sided heart catheterization with a flow-directed multilumen thermodilution catheter, which enables determination of pressures, cardiac output, right ventricular volumes, and ejection fraction. RESULTS: Most patients were in New York Heart Association class III (61%) and IV (24%), and the hemodynamic profile was characterized by mean left ventricular ejection fraction of 20.2% +/- 6%, cardiac index of 2.13 +/- 0.6 l/min/m2, pulmonary capillary wedge pressure of 23.1 +/- 11 mm Hg, right atrial pressure of 7.9 +/- 6 mm Hg, right ventricular ejection fraction of 23.2% +/- 12.4%. During a mean follow-up of 11.1 +/- 9.4 months, 33 patients underwent transplantation (23.4%), 41 died (28.8%), and 68 were still alive (47.8%). There was a substantial overlap in left ventricular ejection fraction between patients divided on the basis of outcome, whereas right ventricular ejection fraction was significantly lower in patients who died or underwent transplantation. Cox multivariate analysis showed three independent prognostic variables: cause (p = 0.03), heart failure score (p = 0.001), and right ventricular ejection fraction (p = 0.000). Short-term survival (10 months) was significantly (p = 0.000) different in patients with > or = 24% or < 24% right ventricular ejection fraction. Statistical analysis identified right ventricular ejection fraction as the single variable to be highly correlated with an increased risk of early death. CONCLUSIONS: This study suggests that right ventricular function is a crucial determinant of short-term prognosis in severe chronic heart failure. Statistical analysis identified right ventricular ejection fraction, determined by thermodilution during right-sided heart catheterization, as the single most important predictor of short-term prognosis in a large cohort of patients who had symptoms in spite of a standardized, optimized, multipharmacologic treatment. The variable allows a useful risk stratification in patients with severe chronic heart failure and uniformly depressed left ventricular ejection fraction and provides guidance in the assessment of indications and timing for transplantation.     

Evaluation of acute dual-chamber pacing with a range of atrioventricular delays on cardiac performance in refractory heart failure

OBJECTIVES: This study evaluated how variations in atrioventricular (AV) delay affect hemodynamic function in patients with refractory heart failure being supported with intravenous inotropic and intravenous or oral inodilating agents. BACKGROUND: Although preliminary data have suggested that dual-chamber pacing with short AV delays may improve cardiac function in patients with heart failure, detailed Doppler and invasive hemodynamic assessment of patients with refractory New York Heart Association class IV heart failure has not been performed. METHODS: Nine patients with functional class IV clinical heart failure had Doppler assessment of transvalvular flow and right heart catheterization performed during pacing at AV delays of 200, 150, 100 and 50 to 75 ms. RESULTS: Systemic arterial, pulmonary artery, right atrial and pulmonary capillary wedge pressures, cardiac index, systemic and pulmonary vascular resistances, stroke volume index, left ventricular stroke work index (SWI) and arteriovenous oxygen content difference demonstrated no significant changes during dual-chamber pacing with AV delays of 200 to 50 to 75 ms. There were also no changes in the Doppler echocardiographic indexes of systolic or diastolic ventricular function. The study was designed with SWI as the outcome variable. Assuming a clinically significant change in the SWI of 5 g/min per m2, a type I error of 0.05 and the observed standard deviation from our study, the observed power of our study is 85% (type II error of 15%). CONCLUSIONS: Changes in AV delay between 200 and 50 ms during dual-chamber pacing do not significantly affect acute central hemodynamic data, including cardiac output and systolic or diastolic ventricular function in patients with severe refractory heart failure due to dilated cardiomyopathy.