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Natriuretic peptides and cyclic guanosine 3',5'-monophosphate in asymptomatic and symptomatic left ventricular dysfunction.

BACKGROUND: Screening for patients with asymptomatic left ventricular dysfunction is of considerable importance because they may benefit from early treatment with angiotensin converting enzyme inhibitors. It has been suggested that atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and cyclic guanosine 3',5'-monophosphate (cGMP) might be useful markers for screening. OBJECTIVE: To compare directly the power of the three immunoreactive forms of ANP (CT-ANP, beta-ANP, NT-ANP) and BNP and cGMP to detect asymptomatic left ventricular dysfunction. METHODS AND RESULTS: Radionuclide ventriculography was used to study left ventricular ejection fraction in 37 patients with asymptomatic left ventricular dysfunction, 32 patients with mild to moderate congestive heart failure, and 38 controls. CT-ANP, NT-ANP, beta-ANP, BNP, and cGMP were measured at rest and 3 minutes after exercise. Plasma BNP was the most sensitive marker for patients with asymptomatic left ventricular dysfunction but it reached only a sensitivity of 58% and a specificity of 76% at rest and a sensitivity of 65% and a specificity of 84% after exercise. Combined measurements of all natriuretic peptides and cGMP did not improve the power to detect asymptomatic left ventricular function above that of a single BNP measurement. CONCLUSIONS: Although natriuretic peptides and cGMP measured at rest and three minutes after ergometry may be useful for monitoring left ventricular dysfunction they are unlikely to be suitable for more general routine screening for completely asymptomatic left ventricular dysfunction.

Adult

Hemodynamic effects of dilevalol in patients with systemic hypertension and left ventricular dysfunction.

Hemodynamic and left ventricular function parameters were measured in patients with mild to moderate hypertension and compromised left ventricular function who were given dilevalol, an antihypertensive agent with selective beta 2-agonism and nonselective beta-antagonist activity. After a 2- to 3-week placebo washout period, 9 patients were given dilevalol titrated upward from 100 to 600 mg twice daily over a 7-week period to achieve a supine diastolic blood pressure of less than 90 mm Hg with a decrease of greater than or equal to 10 mm Hg from baseline. Multigated radionuclide ventriculography and systolic and diastolic time intervals were performed after the pretreatment placebo washout, at the end of 2 weeks' maintenance dosing, and after a 7- to 10-day post-treatment discontinuation and placebo washout period. At an average daily dose of dilevalol, 444 mg, heart rate at rest decreased significantly (p less than 0.01) during treatment and increased during post-treatment placebo. Systolic and diastolic blood pressures at rest decreased significantly (p less than 0.01) during treatment and increased during post-treatment placebo. At maximal exercise, changes in blood pressure and heart rate were significantly blunted (p less than 0.05) during treatment. Ejection fraction at rest increased significantly (p less than 0.01) during treatment, with no significant change occurring during exercise, and decreased during post-treatment placebo. Preejection period decreased significantly during treatment (p less than 0.005) and increased during post-treatment placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Pulmo cardialis: effect of inhaled bronchodilators on airway resistance of acute left ventricular dysfunction].

Disturbance of left ventricular function leads to an impairment of ventilation: airway resistance increases, while pulmonary compliance is reduced. We therefore studied the effect of inhalable bronchodilators (Fenoterol, Ipratropium bromide) on oscillatory airway resistance in 16 patients with an acute left heart failure. The results show that the resistance can be significantly reduced to normal values by the bronchodilators. Fenoterol has the greatest spasmolytic potency, but Ipratropium bromide is also effective. Recompensation of left heart function alone does not lead to comparable acute effects on airway resistance. The possibility of immediate improvement of ventilation through the use of inhalable bronchodilators should therefore be considered in the treatment of acute left heart failure.

Airway Resistance

Recent preoperative myocardial infarction increases the risk of surgery for unstable angina.

Patients with postinfarction angina undergoing surgery for unstable angina face an increased risk of operative mortality. Between January 1982 and December 1987, clinical, angiographic, and operative data was collected prospectively in 588 unstable patients with a prior myocardial infarction within 30 days of surgery (MI) and 5951 unstable patients without preoperative damage (NONMI). MI patients were characterized as being older (age greater than or equal to 70 years: MI, 19.7%; NONMI, 11.6%; p less than 0.001) and having more left ventricular dysfunction (left ventricular ejection fraction less than 40%: MI, 34.8%; NONMI, 26.4%; p less than 0.001). Semi-elective surgery was performed in 82.0% of NONMI patients while 76.9% of MI patients underwent urgent surgery. Operative mortality was increased in MI patients (MI, 11.1%; NONMI, 4.0%; p less than 0.001) which was related to the extent of preoperative MI (non-Q wave, 8.3%; Q wave, 17.5%; p less than 0.001). Stepwise logistic regression analysis identified preoperative MI as an independent risk variable of operative mortality for unstable angina. Separate multivariate analyses were performed to identify the independent predictors for MI and NONMI patients. The multivariate predictors of operative death for MI patients were left ventricular dysfunction, reoperative coronary surgery, nonuse of the internal mammary, age, transmural MI (relative risk 2.11 vs non-Q wave infarction) and left main stenosis. For NONMI patients, the independent variables were urgent operation, left ventricular dysfunction, reoperation, female gender, left main stenosis, and age. The results of this study indicate that recent preoperative MI adversely influences the surgical results in patients with unstable angina. Alternative treatment strategies are warranted for high risk patients, particularly those with transmural MIs and impaired ventricular function.

Adult

Clinical characteristics of patients in studies of left ventricular dysfunction (SOLVD).

The Studies of Left Ventricular Dysfunction (SOLVD) trials were designed to evaluate the effects of enalapril on long-term mortality in patients with severe left ventricular (LV) dysfunction. Patients with LV ejection fractions less than or equal to 0.35 and symptoms of congestive heart failure (CHF) were enrolled in the treatment trial, whereas those with no history of overt CHF and taking no treatment directed for LV dysfunction were enrolled in the prevention trial. The baseline clinical characteristics of SOLVD patients were compared to characterize differences between patients in these 2 separate but concurrent trials. From over 70,000 patients screened with LV dysfunction, 4,228 patients were enrolled in the prevention trial and 2,569 patients in the treatment trial. Ischemic heart disease was the primary cause of LV dysfunction in both prevention (83%) and treatment (71%) trial patients. Prior myocardial infarction was present in 80% of the prevention and 66% of the treatment trial patients (p less than 0.001). In the prevention trial, infarction was recent (less than or equal to 6 months) in 27% patients and remote (greater than 6 months) in 57% patients. Treatment trial patients had proportionately more women (20 vs 13%; p less than 0.001) and non-Caucasians (20 vs 14%; p less than 0.001), as well as the coexisting risk factors of hypertension (42 vs 37%; p less than 0.001) and diabetes (26 vs 15%; p less than 0.001) than did prevention trial patients. Clinical characteristics of patients in both trials were influenced by the gender and race of enrolled patients. Similarly, coronary artery bypass surgery was performed less often in women and non-Caucasians.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Left ventricular diastolic filling in patients with left ventricular dysfunction.

The pattern of abnormal left ventricular diastolic filling and its specificity in coronary disease patients with severe left ventricular dysfunction has received little attention. We evaluated the left ventricular diastolic filling curve derived from gated blood pool scans in 21 normals, 61 coronary disease patients with ejection fractions less than or equal to 30%, and 51 congestive cardiomyopathy patients with ejection fraction less than or equal to 30%. The peak filling rate (PFR), peak ejection rate (PER), PFR/PER and the % stroke volume filled at 1/3 of diastole (%SV-1/3 DT) and at the end of the rapid filling period (%SV-RFP) were determined for each group. The PFR and PER were reduced in both coronary disease and congestive cardiomyopathy groups. The PFR/PER was increased in the coronary disease group (1.19 +/- 0.28) and congestive cardiomyopathy group (1.21 +/- 0.32) as compared to normals (0.93 +/- 0.20, P less than 0.001). A greater %SV-1/3 DT and %SV-RFP were noted in both coronary disease and congestive cardiomyopathy groups. Coronary disease and congestive cardiomyopathy patients with a mean pulmonary capillary pressure (PCP) greater than or equal to 18 mm Hg had a greater PFR/PER, %SV-1/3 DT, and %SV-RFP than patients with a PCP less than 18 mm Hg. An abnormal and nonspecific pattern of left ventricular diastolic filling is present in both coronary disease and congestive cardiomyopathy patients and is characterized by an increased PFR/PER, a greater %SV-1/3 DT, and a greater %SV-RFP. This pattern may be related to elevated PCPs.

Cardiac Output

[Coronary heart disease and impaired left ventricular function in patients over 80 years of age--is bypass operation justified?].

Between April 1988 and February 1995, 35 patients aged 80 years or older underwent elective coronary artery bypass grafting. Concomitant aortic valve replacement was performed in eight patients. Fifteen patients with moderate to severe left ventricular dysfunction (left ventricular ejection fraction (EF) 20 to 45%) (group I) were compared to 20 patients with an EF > 45% (group II). There were no differences according to age, NYHA classification and associated diseases. Group I patients had significantly more myocardial infarctions compared to group II (1.3 +/- 1.1 vs. 0.5 +/- 0.8; p < 0.05). Also more bypass grafts per patient were used in group I (3.1 +/- 0.9 vs. 2.3 +/- 0.9; p < 0.01). No differences between the groups were observed in the postoperative course. One patient of group II died from multiorgan failure (hospital mortality 2.2%). A follow-up could be performed in 32 of 34 hospital survivors (94%) 12.0 +/- 11.2 months (1-41 months) postoperatively. There was one non-cardiac death in each group. All hospital survivors improved by at least one NYHA functional class. Actuarial survival at 3 years is 91% in both groups. In patients aged 80 years or older with or without left ventricular dysfunction coronary artery bypass surgery can be performed with an acceptable risk and a functional benefit. Thus, elective operations should be performed in this age group despite left ventricular dysfunction.

Aged

Relation between left ventricular shape and exercise capacity in patients with left ventricular dysfunction.

OBJECTIVES: The aim of this study was to identify dynamic predictors of exercise duration in patients with systolic left ventricular dysfunction and to test the hypothesis that left ventricular shape is an independent determinant of exercise duration in these patients. BACKGROUND: Measurements of left ventricular volumes and ejection fraction at rest do not predict exercise capacity in patients with systolic left ventricular dysfunction. Left ventricular shape at rest has been reported to be an independent determinant of exercise duration in these patients. The significance of alterations in left ventricular shape that occur during dynamic exercise has not been investigated. METHODS: Twenty-one patients with a documented ejection fraction < 40% performed symptom-limited graded upright bicycle exercise with simultaneous quantitative two-dimensional echocardiography. End-diastolic volume, end-systolic volume, stroke volume, ejection fraction and sphericity index were measured at rest and peak exercise. RESULTS: Eleven patients exercised beyond stage II (6 min, 50 W), averaging 8.9 +/- 1.9 min; 10 patients were unable to complete stage II, averaging 4.9 +/- 0.9 min. No patient developed clinical evidence of ischemia during the exercise period. Of the echocardiographic variables considered, only end-systolic and end-diastolic sphericity indexes at peak exercise (r = 0.809 and 0.711, respectively) and the change in end-systolic sphericity index during exercise (r = 0.697) were strongly correlated with exercise duration. CONCLUSIONS: Conventional descriptors of left ventricular function are poor predictors of exercise capacity. Dynamic changes in heart shape correlate strongly with exercise duration and may be important determinants of exercise capacity in patients with systolic left ventricular dysfunction.

Adult

Use of electrophysiological studies in the diagnosis and treatment of cardiac patients with left ventricular dysfunction and high grade ventricular ectopy.

We studied the sudden death occurrence in 28 patients (23 males, age 59.2 +/- 15.6 years) who had a documented cardiac disease with left ventricular dysfunction (ejection fraction < or = 0.4) and high grade ventricular ectopy. None had suffered from spontaneous sustained ventricular arrhythmia and/or syncope. Their diagnosis and treatment were guided by electrophysiological studies. Electrophysiological studies were performed in the antiarrhythmic drug-free state. In cases when sustained ventricular arrhythmias could be induced, antiarrhythmic treatment was prescribed according to the results of the electrophysiological studies. In cases of non-inducibility, no antiarrhythmic treatment was prescribed. The patients were followed up for a period of 20.6 +/- 11.2 months. The end points were occurrence of documented spontaneous sustained ventricular arrhythmia and sudden death. None of the 19 non-inducible patients experienced sudden death or spontaneous sustained ventricular arrhythmia. Two of the nine inducible patients died suddenly (P = 0.1). The 3-year sudden death mortality rate of the whole group was 7.5%. We conclude that when cardiac patients with high grade ventricular ectopy and left ventricular systolic dysfunction are treated according to the results of electrophysiological studies, it can be expected that their 3-year mortality rate will be low and significantly inferior to that reported for conventionally treated patients.

Adult

Left ventricular dysfunction after intravenous tartar emetic.

Left ventricular dysfunction had been reported in many patients suffering from schistosomal cor pulmonale. The nocuous agents affecting the left ventricle have not been defined. Antischistosomal therapy is suspected to contribute in the adverse effects on the myocardium, particularly antimonials and niridazole. In this study, the left ventricular performance was studied in 29 patients suffering from schistosomiasis before and 30 min after i.v. therapeutic dose of a tartar emetic. After the injection, the PEPI and PEPI/LVETI were increased, the LVETI was abbreviated, EF. was reduced, the LVEDP was raised, the peak dp/dt and the Vmax were reduced. Toxic effects of the T.E. on the myocardium and diminished contractility of the left ventricle were presumed to be caused by T.E. Other factors adversely affecting the myocardium in patients suffering from schistosomiasis cannot be excluded.

Adolescent

Circulating N-terminal atrial natriuretic peptide as a marker for symptomless left-ventricular dysfunction.

Early identification of patients with symptomless left-ventricular dysfunction and early pharmacologic intervention may have an impact on the outlook of patients with heart failure. Atrial natriuretic peptide (ANP) is a cardiac hormone that is released as a C-terminal (C-ANP) and an N-terminal peptide (N-ANP). Since N-ANP has reduced clearance rates compared with C-ANP, N-ANP circulates at higher concentrations. Based on the known increased concentration of C-ANP in symptomatic congestive heart failure, our study was designed to evaluate prospectively N-ANP profile and left-ventricular function in subjects with symptomless and symptomatic heart failure, and the role of plasma N-ANP as a marker for early identification of patients with heart failure. 180 patients who were referred for rest and exercise radionuclide angiography for evaluation of left-ventricular function were studied. Blood was taken for measurement of C-ANP and N-ANP before angiography. Patients were grouped according to New York Heart Association (NYHA) heart failure classification and left-ventricular function. Mean (SD) plasma N-ANP concentration in patients with symptomless left-ventricular dysfunction (NYHA class I, n = 70) was 243 (256) pmol/L (range 27-922 pmol/L), and was higher (p < 0.001) than in 25 control subjects (28 pmol/L). A plasma N-ANP concentration above 54 pmol/L (mean +/- 1.96SD of the control group) had a sensitivity of 90% and a specificity of 92% for detection of patients with symptomless left-ventricular dysfunction. We have shown that plasma N-ANP concentrations are significantly increased in patients with symptomless left-ventricular dysfunction and that this peptide can serve as a marker for diagnosis of such patients.

Adult

Use of impedance cardiography in evaluating the exercise response of patients with left ventricular dysfunction.

Invasive studies in patients with left ventricular dysfunction show that data at rest (e.g. ejection fraction-EF) are poor predictors of the changes in cardiac output (CO) which occur with exercise. This investigation was undertaken to determine whether impedance cardiography could be used in such patients to assess CO response to exercise. The method was compared with the direct Fick method. Over a range of COs between 4 and 18 min-1 there was no systematic error. Reproducibility for CO over one week was highly significant (r = 0.94; P less than 0.001). Impedance cardiography was incorporated into routine exercise testing on a bicycle ergometer for a group of 15 patients (mean age 53.2 +/- 3.0 yrs, SEM) who had sustained a major myocardial infarct 6 to 12 months previously, (EF 38.1 +/- 3.5%, SEM). CO was measured at the end of each 3-min stage. In eight patients (EF 40.0 +/- 3.4%, SEM) CO response was abnormal with either a decrease or a failure to increase with increasing workloads. Conventional end-points i.e. angina, attainment of 85% of predicted maximum heart rate, abnormal blood pressure response or excessive dyspnoea did not indicate consistently a need to terminate the test. It is suggested that impedance cardiography is a useful non-invasive method of evaluating patients with left ventricular dysfunction.

Adult

Myocarditis in beta-thalassemia major. A cause of heart failure.

BACKGROUND: Although acute pericarditis is a common complication of beta-thalassemia major, the prevalence and consequences of myocarditis in this disease have not been investigated. METHODS AND RESULTS: A prospective 5-year follow-up study was carried out in all patients with beta-thalassemia major in whom the diagnosis of acute infectious myocarditis could be established between 1977 and 1986. A similar number of age- and sex-matched control subjects with beta-thalassemia and normal left ventricular function and no evidence of myocarditis were also followed for 5 years. Of 1048 patients with beta-thalassemia major, 47 patients (age, 15 +/- 2.5 years) with precordial chest pain were diagnosed as having acute infectious myocarditis. Myocardial biopsy was diagnostic in 26 patients, border-line in 14 patients, and nondiagnostic in 7 patients. Acute heart failure with left ventricular dysfunction (left ventricular ejection fraction, 25 +/- 11%) developed in 11 patients (23.4%) with myocarditis, and 8 of them died within 1 month to 1 year after diagnosis. Thirteen patients with myocarditis (27.6%) developed chronic heart failure (left ventricular ejection fraction, 26 +/- 13%) within 3 +/- 1.3 years, and 10 of them died within 8 +/- 3 months. Left ventricular systolic and diastolic functions of the control subjects did not change significantly during the 5-year period (left ventricular ejection fraction, 63 +/- 11% versus 65 +/- 7%; P = NS). However, left ventricular restrictive abnormalities (early diastole/late diastole, > 2.2; deceleration time, < 110 milliseconds) combined with right ventricular dilatation (> 30 mm internal diameter) and right-sided heart failure developed in 3 patients with extremely high mean serum ferritin levels. No significant difference was found in mean levels of serum ferritin and pretransfusion hemoglobin between patients with and those without myocarditis. CONCLUSIONS: In patients with beta-thalassemia, myocarditis appears to be involved in the pathogenesis of left ventricular systolic dysfunction, being the main cause of death. Iron overload appears to provoke left ventricular restrictive abnormalities combined with right ventricular enlargement and dysfunction.

Adolescent

Improvement in left ventricular dysfunction after aortic reimplantation in 11 consecutive paediatric patients with anomalous origin of the left coronary artery from the pulmonary artery. Early results of a serial echocardiographic follow-up.

To study the potential for recovery of left ventricular function in patients with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) after aortic reimplantation, serial two-dimensional echocardiographic examinations were performed before and up to 9 months after operation in 11 consecutive paediatric patients (group 1: six infants; group 2: five children above the age of 1 year). End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), myocardial volume (MV), ratio of myocardial volume/end-diastolic volume (MVI), and regional wall motion of the left ventricle (LV) were studied. Pre-operatively, mean LVEDV was 339% of normal in group 1 and 289% in group 2 (P < 0.001); mean LVMV was about twice the normal value in both groups (P < 0.001); LVMVI was 0.79 +/- 0.23 in group 1 and 0.83 +/- 0.3 in group 2; LVEF was 28 +/- 10% in group 1 and 46 +/- 18% in group 2; regional wall motion was normal in two group 2 patients, the other showed uniform reduction in segmental shortening fraction. Postoperatively, mean LVEDV tended to become normal after 2 weeks in group 1 and after 3 months in group 2. In both groups mean LVEF reached the normal range after 3 months; LVMV as well as LVMVI normalized after 9 months. Three months after the operation, all infants had a nearly normal pattern of regional wall motion, while in three group 2 children a residual reduced shortening fraction could be observed in anterior or lateral segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta, Thoracic

Left ventricular dysfunction due to stunning and hibernation in patients.

Left ventricular dysfunction is in most cases the consequence of myocardial ischemia. It may occur transiently during an attack of angina and usually it is reversible. It may persist over hours or even days in patients after an episode of ischemia followed by reperfusion, leading to the so-called condition of stunning. In patients with persistent limitation of coronary flow, left ventricular dysfunction may be present over months and years, or indefinitely in subjects with fibrosis, scar formation, and remodeling after myocardial infarction. However, chronic left ventricular dysfunction does not mean permanent or irreversible cell damage. Hypoperfused myocytes can remain viable but akinetic. This type of dysfunction has been called hibernating myocardium. The dysfunction due to hibernation can be partially or completely restored to normal by reperfusion. It is, therefore, important to clinically recognize a hibernating myocardium. In the present article we evaluate stunning and hibernation with respect to clinical decision making and, when possible, we refer to our ongoing clinical experience.

Humans

Effect of inotropic and vasodilator therapy on left ventricular diastolic filling in dogs with severe left ventricular dysfunction.

Inotropic and vasodilator therapy for congestive heart failure improve left ventricular systolic performance by different mechanisms. However, the nature and extent to which diastolic filling is altered have not been well described. Acute severe left ventricular dysfunction was induced in 21 dogs by severe left ventricular global ischemia produced by left main coronary artery microsphere embolization until left ventricular end-diastolic pressure was greater than or equal to 18 mm Hg. Dobutamine was infused in seven dogs until the peak positive first derivative of left ventricular pressure (dP/dt) increased by greater than or equal to 33%. Nitroprusside was infused in seven dogs until left ventricular end-diastolic pressure was less than 15 mm Hg. Seven dogs were observed for 1 h after the induction of acute severe left ventricular dysfunction and served as the control group. In all groups of dogs, severe left ventricular dysfunction resulted in left ventricular dilation, reduction in area ejection fraction, elevation of left ventricular end-diastolic pressure and an early redistribution of diastolic filling (increased 1/3 and 1/2 filling fractions) despite a markedly abnormal time constant of relaxation. No changes were noted in any variable after 1 h of observation in the seven control dogs. Nitroprusside reduced left ventricular size and filling pressure, increased cardiac output, improved relaxation and redistributed diastolic filling to later in diastole as characterized by a reduced 1/3 filling fraction (19.4 +/- 7.4% versus 51.4 +/- 10%, p less than 0.001). The pressure-area curve was shifted downward and leftward.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Reversal of left ventricular dysfunction after renal transplantation.

We report the cases of four patients with end-stage renal disease and New York Heart Association class III or IV heart failure of nonischemic origin as documented by coronary angiography. Because of left ventricular dysfunction (left ventricular end-diastolic pressure, 23 to 30 mm Hg; ejection fraction, 20% to 35%), all four patients were initially considered poor surgical candidates for renal transplantation. These same four patients became asymptomatic, however, with markedly improved cardiac function (ejection fraction, 43% to 69%) detected as early as 6 and 14 days after renal engraftment. Therefore, there exists a subset of patients with end-stage renal disease in whom congestive heart failure should not be considered a contraindication to renal transplantation. We conclude that some dialysis-dependent patients who manifest symptomatic heart failure of nonischemic origin have a reversible cardiomyopathy and should not be denied renal transplantation.

Adult