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Natriuretic peptides as markers of preclinical cardiac disease in obesity.

BACKGROUND: Aim of the study was to evaluate the role of atrial (ANP) and brain natriuretic peptides (BNP) as markers of preclinical cardiac disease in obesity. METHODS: We selected 26 obese (BMI > 29 kg m(-2)) never-treated hypertensives (24-h BP > 140 and/or 90 mmHg), 26 obese normotensives (24-h BP < 130/80 mmHg) and 25 lean (BMI < or = 25 kg m(-2)) never-treated hypertensives. Each subject underwent measurements of ANP and BNP plasma levels, 24-h ambulatory blood pressure (BP) monitoring, digitized M-mode and Doppler echocardiography. RESULTS: Mean values of ANP and BNP were similar among the three groups. All the subjects had normal left ventricular (LV) systolic function. Within each group ANP levels were higher in patients with LV diastolic dysfunction than in patients with normal diastolic function, and BNP levels were higher in patients with LV hypertrophy and in patients with LV diastolic dysfunction. Within each group, ANP levels were inversely correlated with LV diastolic indices, whereas BNP levels were directly correlated with LV mass index and inversely correlated with LV diastolic indices. ANP and BNP levels were not correlated with other echocardiographic parameters, age, BMI or 24-h BP values. CONCLUSION: In normotensive and hypertensive obese subjects the relationships of ANP and BNP levels with LV morpho-functional characteristics follow the same trend as in lean hypertensives, with ANP mainly influenced by diastolic dysfunction and BNP influenced by both LV hypertrophy and LV diastolic dysfunction. Therefore ANP and BNP can be considered useful markers of preclinical cardiac disease in obesity.

Adult↗

Clinical aspects of left ventricular diastolic function assessed by Doppler echocardiography following acute myocardial infarction.

LV systolic function and dilation after Ml have been extensively studied and have been related to heart failure and cardiac mortality. In recent years, it has been increasingly apparent that LV diastolic dysfunction contributes to signs and symptoms of heart failure and LV diastolic dysfunction is associated with increased mortality rates in patients chronic heart failure independent of systolic function. LV diastolic dysfunction is difficult to assess on basis of clinical examination including chest radiography and electrocardiography. LV diastolic filling has traditionally been evaluated by cardiac catherization with direct measurement of filling pressures and relaxation. However, the invasive approach describing LV compliance and relaxation as the major determinants of LV diastolic function, is not feasible and suitable for routine investigations of diastolic function. Two-dimensional and Doppler echocardiography has become a well accented practical and safe non-invasive method for diagnosis of LV diastolic dysfunction. Combined invasive and echocardiographic studies have shown that analysis of mitral and pulmonary venous flow velocities relate to invasively measured filling pressures and relaxation rate in cardiac diseases. Based on Doppler analysis of mitral and pulmonary venous flow three abnormal LV filling patterns are identified: impaired relaxation, "pseudonormalization" and restrictive. These LV filling patterns have been related to symptoms, relaxation rate, filling pressure and prognosis in patients with restrictive and dilated cardiomyopathy. The Doppler flow profiles are influenced by several factors including age, heart rate, load conditions and valve heart diseases which must be taken into consideration during evaluation. During the last decade information about LV diastolic function assessed non-invasively by Doppler echocardiography has gained in patients with CAD. Myocardial ischemia induced by brief coronary artery occlusion or pacing leads to abnormal myocardial relaxation which can be reversed to normal by restoring normal myocardial blood flow. The diastolic abnormality is present within seconds and a characteristic impaired relaxation filling pattern are identified by mitral and pulmonary venous flow analysis. Diastolic dysfunction has been recognized during the early as well during the post-MI phase with or without LV systolic dysfunction. In the acute phase both an abnormal relaxation pattern and restrictive LV filling pattern are present which has been related to in-hospital heart failure. The identification of a pseudonormal or restrictive LV filling pattern are associated with later readmission to hospital with heart failure and cardiac death. Abnormal relaxation filling is the most pronounced filling pattern after one year which might be related to the remodeling process including compensatory hypertrophy, scarring of the infarct zone leading to a non-uniform relaxation of the LV. Remodeling of the LV following a MI is subject to several factors which might involve diastolic function. This is supported by the presence of an impaired relaxation and restrictive filling pattern are associated with progressive LV dilatation following Ml. Furthermore, the LV remodeling process following the very early phase includes the scarring process with collagen deposition in the infarcted and non-infarcted myocardium. The extent and quality of the repair process involving collagen deposition are believed to influence the remodeling process. Increased collagen deposition in the subacute phase of Ml indicated by elevated values of the collagen marker PIIINP is found to be related to LV dilation, depressed systolic function and restrictive LV filling. Development of a restrictive filling in patients with increased collagen deposition might be due to increasing LV volume but also to increased myocardial stiffness. Regarding prognosis diastolic dysfunction seems to be an important marker of outcome as abnormal diastolic properties are related to progressive LV dilatation, development of heart failure and cardiac death following MI. The beneficial effects of BB on morbidity and mortality in post-MI patients are well established. Recently, it has been demonstrated that BB has beneficial effects on progressive CHF and cardiac mortality in patients with chronic heart failure and moderate to severe systolic dysfunction. The mechanisms behind these effects are not fully understood. However, improvement of both systolic and diastolic function during BB therapy are demonstrated in patients with CHF. A few studies in patients with MI indicates that long-term BB therapy improves LV diastolic function which seems to be followed by improvement in systolic function. BB has the potential to lengthening diastole, improving subendocardial myocardial perfusion and affecting symptomatic amd neurohumoral activation following MI which might affect LV systolic and diastolic function and thereby improving outcome. Functional capacity following Ml is a well known predictor for outcome in MI patients. LV diastolic function a closely related to exercise capacity in contrast to measures of systolic function. BB therapy in patients with mild to moderate systolic dysfunction seems to improve exercise capacity which is related to improvement in LV diastolic function. Thus, BB improves exercise capacity and diastolic function by increasing LV compliance which might have prognostic implications. Even though LV systolic and diastolic dysfunction coexist, few two-dimensional and Doppler echocardiographic variables combine measurements of both phases of the cardiac cycle. Recently, the MPI has been suggested as a measure of combined systolic and diastolic myocardial performance which is based on Doppler time intervals of the systolic and diastolic phases. The MPI is easily obtained, reproducible, non-geometric and seems less dependent on heart rate and load conditions compared to traditional Doppler measurements. In patients with MI is has shown to reflect disease severity and contain prognostic information. The assessment of MPI seems therefore to be a relevant attractive alternative to established measurements of LV function following MI.

Diastole↗

Usefulness of B-type natriuretic peptide in hypertensive patients with exertional dyspnea and normal left ventricular ejection fraction and correlation with new echocardiographic indexes of systolic and diastolic function.

B-type natriuretic peptide (BNP) levels increase in systolic heart failure (HF). However, the value of BNP in hypertensive patients with suspected diastolic HF (symptoms suggestive of HF but normal ejection fraction) and its relation to myocardial function in these patients is unclear. We prospectively studied 72 ambulatory hypertensive subjects (40 women, mean age 58 +/- 8 years) with exertional dyspnea and ejection fraction > or =50%. Diastolic function was evaluated with transmitral and pulmonary venous Doppler, mitral annular velocities (pulsed-wave tissue Doppler), and flow propagation velocity (color M-mode). Systolic function was assessed with strain and strain rate derived from color tissue Doppler imaging. BNP was related to myocardial function and the presence or absence of global diastolic dysfunction. By conventional Doppler criteria, 34 patients had normal left ventricular diastolic function and 38 had isolated diastolic dysfunction. BNP values were higher in patients with diastolic dysfunction (46 +/- 48 vs 20 +/- 20 pg/ml, p=0.004) and were related independently to blood pressure, systolic strain rate, left atrial function (p<0.01 for all), and age (p=0.015). Patients with diastolic dysfunction and pseudonormal filling had higher BNP levels compared with impaired relaxation (89 +/- 47 vs 35 +/- 42 pg/ml, p=0.001). However, 79% of patients with diastolic dysfunction had BNP levels within the normal range. We conclude that in ambulatory hypertensive patients with symptoms suggestive of mild HF and normal ejection fraction, BNP is related to atrial and ventricular systolic parameters, blood pressure, and age. Although elevated in the presence of diastolic dysfunction, the BNP level mostly is in the normal range and, therefore, has limited diagnostic value in stable patients with suspected diastolic HF.

Biomarkers↗

A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction.

BACKGROUND: Although echocardiography is the gold standard test for suspected left ventricular dysfunction, its cost and availability limits its use as a routine screening tool. The high negative predictive value of B-natriuretic peptide (BNP) in dyspneic patients suggests its possible utility in screening patients prior to echocardiography. Determining an appropriate BNP level below which the need for echocardiography is precluded would be valuable. We hypothesized that a fixed plasma BNP level of 20 pg/mL and simple clinical parameters are an effective pre-echocardiographic screening tool for left ventricular dysfunction. METHODS: Two hundred and two patients at a Veterans Administration facility with symptoms suggestive of heart disease (male to female ratio 193:9, mean age 65 years) were screened prior to echocardiography. Patients with known cardiac dysfunction were excluded. RESULTS: BNP levels of > or =20 pg/mL were 79% sensitive and 44% specific in screening for any abnormality of ventricular function. The negative predictive value was 69%. When broken down into categories of dysfunction, the cutoff point of 20 pg/mL had a better negative predictive value for those with systolic dysfunction (96%) or systolic plus diastolic dysfunction (100%) if patients with diastolic dysfunction were excluded. The majority of patients with falsely low BNP levels (<20 pg/mL with positive echocardiographic findings) had mild diastolic dysfunction, with 3 patients exhibiting mild systolic dysfunction. CONCLUSIONS: BNP may be a useful screening tool for left ventricular dysfunction in patients with history suggestive of heart disease and be used to assist in forming a pretest probability, which in turn could greatly assist in appropriateness of patient referral and in optimization of drug therapy.

Adult↗

Early Doppler echocardiographic dysfunction is associated with an increased mortality after orthotopic cardiac transplantation.

BACKGROUND: Doppler echocardiographic (DE) diastolic dysfunction has been correlated with rejection after orthotopic cardiac transplantation (Tx). However, the relationship of early diastolic dysfunction to late outcome is unknown. The purpose of this study was to assess the correlation between early DE diastolic dysfunction and outcome after heart Tx. METHODS AND RESULTS: Of 133 patients undergoing heart Tx between October 1990 and April 1994, 83 were identified with > or = 4 routine DE performed during the first 6 months. Assessment of diastolic function included measurement of isovolumic relaxation time (IVRT), pressure half-time (PHT), and peak early mitral inflow velocity (M1). Diastolic dysfunction was defined as a decrease of 15% from baseline (IVRT and PHT) or an increase of 20% (M1). A mean dysfunction score (MDS) was calculated for each patient (number of episodes of dysfunction by Doppler total number of echocardiograms performed). The population diastole MDS was determined and two groups established (group 1, MDS < mean; group 2, MDS > mean). Actuarial survival, rejection, and transplant coronary artery disease (TxCAD) were compared between groups. Actuarial survival was significantly reduced in patients with greater early diastolic dysfunction (P < .05). There were 17 deaths overall: 5 in group 1 (mean, 786 days) and 12 in group 2 (mean, 384 days). There were no significant differences in treated rejection episodes, actuarial freedom from rejection or TxCAD, immunosuppression, sex, donor age, donor ischemic time, or cytomegalovirus between the two groups. CONCLUSIONS: Diastolic dysfunction within 6 months of transplant was associated with an increased late mortality.

Adult↗

Systolic and diastolic cardiac dysfunction early after the initiation of doxorubicin therapy: significance of gender and concurrent mediastinal radiation.

Diastolic and systolic left ventricular (LV) function may be affected early after the initiation of doxorubicin therapy. However, the role of mediastinal radiation and other cytotoxic agents in the production of these early cardiac effects is unclear. In this study LV diastolic and systolic function were assessed before and after doxorubicin (223+/-122 mg.m-2; range, 40-618) in 33 patients. After doxorubicin, LV ejection fraction declined (0.61+/-0.08 to 0.56+/-0.08, P=0.0008), peak filling rate decreased (3.38+/-1.10 to 2.82+/-0.62 end diastolic volumes/s, P=0.006), and time to peak filling rate increased (162+/-39 to 182+/-45 ms, P=0.04). The changes in LV systolic and diastolic function were not related to doxorubicin dose and the use of other cytotoxic agents; the decrease in LV ejection fraction with doxorubicin was more notable in men and in patients who received mediastinal irradiation concurrently with doxorubicin. It is concluded that the use of doxorubicin was associated with the simultaneous early development of LV systolic and diastolic dysfunction. Male gender and concurrent mediastinal irradiation were independent influences, but doxorubicin dose and the use of other cytotoxic agents were not associated with worse cardiac dysfunction.

Antineoplastic Agents↗

Systolic and diastolic heart failure are associated with different plasma levels of B-type natriuretic peptide.

Previous studies have found that plasma B-type natriuretic peptide (BNP) is elevated during left ventricular systolic or diastolic dysfunction. It is unclear whether the ventricular systolic and diastolic function is associated with different levels of plasma BNP. Plasma BNP was measured in 149 heart failure patients by a rapid point-of-care assay. The patients were divided into left ventricular diastolic dysfunction (n = 48), left ventricular systolic dysfunction (n = 62) and right ventricular systolic dysfunction group (n = 39). The mean BNP level in the left ventricular diastolic dysfunction, left ventricular systolic dysfunction and right ventricular systolic dysfunction was 115 +/- 80 pg/ml, 516 +/- 445 pg/ml and 345 +/- 184 pg/ml, respectively (p < 0.05). We concluded that ventricular systolic and diastolic dysfunction increases plasma BNP levels to a different extent. Left and right ventricular systolic dysfunction is associated with a higher level of plasma BNP than left ventricular diastolic dysfunction.

Adult↗

Diagnosing diastolic heart failure.

BACKGROUND: increasing evidence supports the existence of left ventricular diastolic dysfunction as an important cause of congestive heart failure, present in up to 40% of heart failure patients. AIM: to review the pathophysiology of LV diastolic dysfunction and diastolic heart failure and the currently available methods to diagnose these disorders. RESULTS: for diagnosing LV diastolic dysfunction, invasive hemodynamic measurements are the gold standard. Additional exercise testing with assessment of LV volumes and pressures may be of help in detecting exercise-induced elevation of filling pressures because of diastolic dysfunction. However, echocardiography is obtained more easily, and will remain the most often used method for diagnosing diastolic heart failure in the coming years. MRI may provide noninvasive determination of LV three-dimensional motion during diastole, but data on correlation of MRI data with clinical findings are scant, and possibilities for widespread application are limited at this moment. CONCLUSIONS: in the forthcoming years, optimal diagnostic and therapeutic strategies for patients with primary diastolic heart failure have to be developed. Therefore, future heart failure trials should incorporate patients with diastolic heart failure, describing precise details of LV systolic and diastolic function in their study populations.

Diastole↗

Biventricular diastolic filling patterns after coronary artery bypass graft surgery.

OBJECTIVE: We sought to study the evolution of biventricular filling properties after coronary artery bypass grafting. BACKGROUND: The evolution of diastolic function as defined with newer echocardiographic modalities after coronary artery bypass grafting surgery is unknown in patients with preoperative left ventricular diastolic dysfunction. METHODS: Transthoracic echocardiography was performed preoperatively and 48 hours and 6 months after coronary artery bypass grafting in 49 patients (randomized to milrinone [n = 25]) or placebo [n = 24]) with preoperative left ventricular diastolic dysfunction classified according to published criteria. Mild right ventricular diastolic dysfunction was defined as the ratio of early to atrial filling velocity of less than 1 in transtricuspid flow or the velocity of reversed atrial flow of greater than 50% of that of systolic flow in hepatic venous flow or the ratio of tricuspid annulus velocity during early and atrial filling of less than 1 if both the ratio of early to atrial filling velocity and the ratio of systolic to diastolic velocity was greater than 1 in hepatic venous flow. Moderate right ventricular diastolic dysfunction was diagnosed when there was a ratio of early to atrial filling velocity of greater than 1 with a ratio of systolic to diastolic velocity of less than 1. Severe right ventricular diastolic dysfunction was defined as a ratio of early to atrial filling velocity of greater than 1 associated with reversed systolic wave in hepatic venous flow. RESULTS: Moderate and severe left ventricular diastolic dysfunction increased from preoperatively to 48 hours after coronary artery bypass grafting from 8.2% to 53.7% and from 2.0% to 9.7%, respectively (P < .0001, 48 hours vs preoperatively for both), and the patterns at 6 months were similar to those observed preoperatively. Similar evolution over time was found for right ventricular diastolic dysfunction. CONCLUSIONS: In patients with preoperative left ventricular diastolic dysfunction, biventricular filling patterns are impaired initially but return to preoperative status 6 months after coronary artery bypass grafting.

Aged↗

Correction of intraoperative diastolic myocardial dysfunction with nifedipine.

We report the case of a 62-year-old man with severe aortic stenosis and hypertrophic cardiomyopathy, who could not be weaned from cardiopulmonary bypass after aortic valve replacement until buccal administration of the calcium-blocking agent nifedipine led to achievement of adequate hemodynamics. These observations demonstrate the importance of diastolic dysfunction in patients with hypertrophic cardiomyopathy, and suggest an important peri- and intraoperative role for calcium-blocking agents in their management. Recent hemodynamic studies have shown the importance of diastolic myocardial dysfunction in patients with hypertrophic cardiomyopathy, and demonstrated that calcium-blocking agents may enhance myocardial performance by reducing this dysfunction (Goodwin, 1982; Lorell et al., 1980, 1982; Sanderson et al., 1977). Although this new class of drugs has been increasingly used as an adjunct to cardioplegia, there is little information thus far on their application as treatment of intraoperative diastolic abnormalities. We report the case of a 62-year-old man with severe aortic stenosis and hypertrophic cardiomyopathy, who could not be weaned from cardiopulmonary bypass after aortic valve replacement until buccal administration of the calcium-blocking agent nifedipine led to an increase in cardiac output and blood pressure.

Aortic Valve Stenosis↗

[Left ventricular diastolic function in normal pregnancy. A prospective study using M-mode echocardiography and Doppler echocardiography].

BACKGROUND AND OBJECTIVE: During pregnancy many substantial changes occur in the cardiovascular system. Aim of this study was to examine how physiological preload alterations influence left ventricular haemodynamic parameters. PATIENTS AND METHODS: During the 9th, 24th and 33rd weeks of pregnancy and 8 weeks after childbirth 36 patients underwent echocardiographic studies. 36 young not pregnant women (25 +/- 7 years) served as controls. The following Doppler echocardiographic parameters were measured: peak early diastolic flow velocity (VE, ms); acceleration (AT; ms) and deceleration time (DT; ms) of flow velocity in early diastole; peak late diastolic flow velocity (VA; m/s) and isovolumetric relaxation time (IVRT; ms). In all women the left ventricular muscle mass index (LVMMI), fractional shorting (FS; %) and the ratio between septum and posterior ventricular wall were calculated. RESULTS: During pregnancy all women showed an elevation of the left ventricular muscle mass index (LVMMI: from 66 +/- 6 to 100 +/- 9 g/m2; p < 0.01) and a decrease of fractional shortening (FS: from 38 +/- 4 to 31 +/- 3%). All patients developed a relevant diastolic dysfunction: reduced early diastolic flow velocity (VE: from 0.89 +/- 0.11 to 0.83 +/- 0.19 m/s; P < 0.01), reduced E/A ratio (1.7 +/- 0.4 to 1.2 +/- 0.4; P < 0.01), prolonged IVRT (72 +/- 12 to 114 +/- 12 ms; P < 0.01) and deceleration time (DT: to 189 +/- 17 to 227 +/- 18 ms; P < 0.01). Eight weeks after childbirth all parameters of left ventricular systolic and diastolic functions were normal. CONCLUSION: Preload alterations during normal pregnancy lead to reversible physiological left ventricular hypertrophy. Furthermore, we found a short-time reduction of systolic function just before childbirth and a significant alteration of the left ventricular diastolic filling pattern (abnormal relaxation pattern). While left ventricular systolic function was normal in all patients one week after childbirth, left ventricular hypertrophy and left ventricular diastolic dysfunction persisted for nearly two months.

Adult↗

Diagnosis and treatment of diastolic heart failure.

Up to 40% of patients with heart failure have isolated diastolic dysfunction. With proper management, the prognosis is generally more favorable than in systolic dysfunction. Distinguishing diastolic from systolic dysfunction is essential since the optimal therapy for one condition may aggravate the other. New echocardiographic methods enable accurate diagnoses.

Adult↗

Which left ventricular function is impaired earlier in the evolution of diabetic cardiomyopathy? An echocardiographic study of young type I diabetic patients.

OBJECTIVE: To determine whether diastolic dysfunction preceded systolic dysfunction in the evolution of diabetic cardiopathy. RESEARCH DESIGN AND METHODS: A total of 157 young (mean age 26.6 years) cardiac asymptomatic type I diabetic patients and 54 age- and sex-matched healthy (nondiabetic) subjects were studied. The severity of diabetic complications (retinopathy, nephropathy, and cardiac autonomic neuropathy) was evaluated by the diabetic complication index (DCI), a sum of individual scores for each complication. Left ventricular (LV) function was studied by M-mode echocardiography. Impaired systolic and diastolic functions were presumed if at least two echocardiographic variables for systolic function (fractional shortening [FS], mean velocity of circumference fiber shortening, and stroke index) and for diastolic function (slope of anterior mitral leaflet in early diastole, isovolumic relaxation time [IRT], and left atrium emptying index) were out of the control range (mean +/- 2 SD). RESULTS: Diastolic dysfunction was twice as common as systolic dysfunction (27% and 12%, respectively, P < 0.001). Of diabetic patients with systolic dysfunction, 83% had impaired diastolic function, whereas only 30% of diabetic patients with diastolic dysfunction had systolic damage (P < 0.001). On the other hand, only 3 of 157 diabetic patients (1.9%) had systolic dysfunction with preserved diastolic function (P > 0.05). Diastolic dysfunction, represented by the interval from minimal LV dimension to mitral valve opening, was seen in diabetic patients approximately 8 years after onset of diabetes and systolic dysfunction represented by FS after approximately 18 years. Diastolic dysfunction, represented by IRT, was found in the presence of mild complications (DCI = 2), and systolic dysfunction, represented by FS, was found in the presence of more severe complications (DCI = 4). CONCLUSIONS: Our findings indicate that myocardial damage in patients with diabetes affects diastolic function before systolic function. The intentional assessment of diastolic function is advisable for early detection of LV dysfunction before clinical symptoms appear, with follow-up to detect further deterioration of cardiac status.

Adult↗

[Doppler echocardiographic assessment of diastolic function of left ventricle].

Approximately half of the patients with overt congestive heart failure (CHF) have diastolic dysfunction without reduced ejection fraction (LVEF>50%). Diastolic dysfunction is an abnormality in left ventricular myocardial relaxation and/or compliance that alters the ease with which blood is accepted into the left ventricle during diastole. Elevated pressures in the left atrium are compensatory, ensuring adequate filling. All patients with systolic dysfunction have concomitant diastolic dysfunction. Indeed, in patients with CHF and reduced systolic function the level of diastolic dysfunction influences the severity of symptoms. It is now clear that hypertension, coronary artery disease and other diseases and conditions commonly produce diastolic dysfunction in the absence of significant systolic dysfunction. Accurate noninvasive Doppler-echocardiographic assessment of the presence and severity of diastolic impairment is crucial to the broad application and understanding of this common condition. This review discusses the clinical impact of classic and recent echocardiographic contributions to the field of diastology.

Diastole↗

Role of mechanical and hormonal factors in cardiac remodeling and the biologic limits of myocardial adaptation.

Patients with chronic congestive heart failure manifest > or = 1 of the following abnormalities: diastolic dysfunction, systolic dysfunction, and arrhythmias. Diastolic dysfunction, one of the first symptoms to occur during hypertensive cardiopathy, depends on both active relaxation of the cardiac muscle and passive ventricular compliance. The ability of the ventricles to relax depends on normal calcium metabolism and adenosine triphosphate concentration. Ability to extrude intracellular calcium is depressed in the hypertrophied, overloaded heart as compared with the normal myocardium. Myocardial fibrosis is the major cause of increased diastolic ventricular stiffness. Left ventricular (LV) hypertrophy and myocardial fibrosis also greatly increase the likelihood of ventricular arrhythmias, in particular by prolonging the QRS interval and facilitating the occurrence of reentry arrhythmias. Findings in animal studies have indicated that such fibrosis, which involves excessive collagen deposition, is independent of LV hypertrophy and that LV hypertrophy does not necessarily result in myocardial fibrosis. Instead, the development of myocardial fibrosis is sensitive to circulating levels of both angiotensin II and aldosterone, and the fibrotic response to each of these substances is independent. The aldosterone antagonist spironolactone prevents myocardial fibrosis in several animal models, thus confirming the importance of aldosterone in the genesis of excessive collagen deposition.

Adaptation, Physiological↗

Valsartan, an angiotensin II type-I receptor blocker, and left ventricular diastolic function--a case report.

Impaired diastolic function is related to subjective symptoms, reduced exercise capacity, and poor prognosis in patients with congestive heart failure, and an angiotensin II type-I receptor blocker might have a beneficial effect on diastolic function in such patients with heart failure. A 53-year-old woman underwent valvuloplasty of the mitral valve and later presented with heart failure symptoms, including exertional dyspnea and easy fatigue. Although no pathological changes could be identified by radiography of the chest, electrocardiography, or routine echocardiography, the assessment of diastolic function with Doppler echocardiography revealed left ventricular diastolic dysfunction. Her neurohumoral parameters and left ventricular diastolic dysfunction improved after 1 month of treatment with Valsartan, an angiotensin II type-I receptor blocker, accompanied by improvement of her subjective symptoms. This case implies that angiotensin II type-I receptor blocker could improve left ventricular diastolic dysfunction and that Doppler echocardiography might be useful for detecting diastolic dysfunction in high-risk patients undergoing cardiac surgery.

Angiotensin II Type 1 Receptor Blockers↗

The relationship between altered load and impaired diastolic function in conscious dogs with pacing induced heart failure.

The complexities of diastolic dysfunction are being recognized with increasing frequency. Prior studies of diastolic dysfunction in both clinical disease states and experimental models have overlooked the major role which altered loading conditions may play in the evolution of diastolic dysfunction. In order to determine the relative importance of the multiple determinants of diastolic dysfunction in disease states requires a large animal model, suitable for chronic study in which the determinants can be controlled independently. This manuscript reviews recent work from our laboratory in which we investigated the mechanisms of diastolic dysfunction in conscious dogs with dilated cardiomyopathy induced by rapid ventricular pacing.

Animals↗

Lack of relationship between Doppler indices of diastolic function and left ventricular pressure transients in patients with definite diastolic heart failure.

OBJECTIVES: The purpose of this study was to compare invasive with noninvasive indices of diastolic function in a well-defined group of patients with diastolic dysfunction and a history of diastolic heart failure. BACKGROUND: Patients with heart failure and a normal left ventricular (LV) ejection fraction comprise a very large portion of the heart failure population and most are thought to have diastolic heart failure. While clinical and Doppler criteria for diastolic dysfunction and diastolic heart failure have been developed, there remains some controversy about the need for invasive cardiac catheterization and/or echo-Doppler evaluation of LV diastolic function. To date, there is no consensus as to the utility of these 2 methods in the diagnosis of diastolic heart failure. METHODS: Forty-seven patients (mean age 58 +/- 11 years) with a history of congestive heart failure and preserved ejection fraction (> or =50%) by echocardiography underwent a combined hemodynamic/echo-Doppler study. Patients with coronary disease were excluded. Invasive parameters of LV diastolic function (tau, LV diastolic pressures) and Doppler parameters (peak E, peak A, E/A ratio, isovolumic relaxation time, and E deceleration time) were measured using standard techniques. RESULTS: There was a close correlation between invasively-determined parameters (tau vs end diastolic pressure: r = 0.62, P <.001). The relationships between standard Doppler parameters and LV diastolic pressures were uniformly poor. However, the relationship between Doppler isovolumic relaxation time and tau improved considerably when patients were subgrouped by hemodynamic load. CONCLUSIONS: Standard echo-Doppler indices of diastolic function correlate poorly with LV diastolic pressure transients. The diagnosis of diastolic heart failure cannot be made on the basis of a single echo-Doppler parameter but, rather, all parameters must be examined in concert and used in combination with clinical observations.

Cardiac Catheterization↗