Assessment of ventricular diastolic function.

A large number of patients suspected of having congestive heart failure have normal left ventricular systolic function and may, therefore, have primary diastolic heart failure. This diagnosis, however, should not be made unless there is also objective evidence of diastolic dysfunction, ie, signs of abnormal left ventricular relaxation and/or diastolic distensibility. The most useful noninvasive diagnostic approaches are the measurement of transmitral and pulmonary venous flow velocities by pulsed wave Doppler, and mitral annulus velocities by tissue Doppler echocardiography. In some patients, the assessment of intraventricular flow propagation by colour M-mode Doppler echocardiography provides additional information. Diastolic heart failure is most often due to coronary artery disease and/or hypertension; therefore, other noninvasive or invasive tests are needed to define the etiology of myocardial dysfunction. However, in the few patients who have constrictive pericarditis, the Doppler echocardiographic assessment of diastolic filling provides the most important clues to the etiology of the disease. Doppler echocardiographic assessment of left ventricular filling may also be used to obtain semiquantitative estimates of left ventricular diastolic pressure. Furthermore, left ventricular filling patterns, in particular, the deceleration time of early transmitral filling, are powerful predictors of patient prognosis. It is probably not cost effective to perform a comprehensive assessment of diastolic filling in every patient undergoing an echocardiographic examination. However, in selected patients, the assessment of diastolic filling provides information that is important for patient management.     

Doppler tissue imaging in congestive heart failure patients due to diastolic or systolic dysfunction: a comparison with Doppler echocardiography and the atrio-ventricular plane displacement technique

BACKGROUND: Doppler tissue imaging (DTI) is an echocardiographic technique by which regional contractility, relaxation properties and time intervals are obtained easily. DTI has been reported to be relatively pre-load independent and could, in comparison with the commonly used mitral pulse wave Doppler (MPWD) method, be of clinical interest for identification of patients with diastolic dysfunction. The atrio-ventricular plane displacement (AVPD) method is an established technique to assess left ventricular systolic function. AIMS: To determine the pulsed Doppler DTI-pattern in patients with heart failure and to examine whether it has a similar capacity as MPWD and AVPD to diagnose diastolic dysfunction. METHODS: We studied 15 controls without congestive heart failure (CHF), 15 patients with diastolic (EF>45%+CHF) and 15 patients with systolic (EF<35%+CHF) left ventricular dysfunction and CHF. RESULTS: The DTI maximal velocities during systole (s), early filling wave (e) and atrial filling wave (a), decrease with reduced left ventricular ejection fraction, r=0.75, r=0.56 and r=0.66 (P<0.001) and regional isovolumetric contraction and intraventricular relaxation time measured by DTI are prolonged, r=0.59 and r=0.73, respectively (P<0.001). The 15 patients with diastolic heart failure were identified by MPWD or DTI but only 11 by AVPD with 8, 10 and 9 false-positive, respectively (P<0.01, P<0.05 and NS). CONCLUSIONS: Regional DTI show a consistent pattern in patients with left ventricular dysfunction and heart failure. Regional DTI has similar accuracy as MPWD in identifying diastolic heart failure patients and is superior to the AVPD technique. DTI may be a useful diagnostic tool in diastolic heart failure patients.     

Echokardiographische Diagnostik der diastolischen Herzinsuffizienz

BACKGROUND: Left ventricular diastolic dysfunction can be diagnosed if clinical signs of heart failure and normal ejection fraction are found. Beside clinical signs of heart failure and criteria from catheterization studies like abnormal left ventricular relaxation, filling and/or compliance echocardiography provides valuable parameters for the assessment of diastolic dysfunction. ECHOCARDIOGRAPHIC DEGREES OF SEVERITY: By the use of various parameters diastolic dysfunction can be differentiated into four degrees of severity, which are of great prognostic importance. If more than one echocardiographic parameter is used, sensitivity for the assessment of diastolic dysfunction becomes nearly 100%. Conventional parameters include isovolumetric relaxation time (IVRT) measured by pulsed Doppler, the ratio of rapid filling and atrial filling velocity (E/A), deceleration time of rapid mitral inflow as well as the ratio of systolic and diastolic pulmonary venous flow velocities. In patients with signs of diastolic heart failure and a normal E/A ratio pulmonary venous flow pattern can help to unmask "pseudonormalization" as the transition from abnormal relaxation to restriction. These parameters, however, are preload-dependent and do not provide intrinsic left ventricular properties. Even in atrial fibrillation, left ventricular filling pressure can be assessed. NEW METHODS: Two novel approaches, color Doppler M-mode of left ventricular inflow and tissue Doppler of the mitral annulus, are relatively preload-independent and allow direct estimation of relaxation and filling pressure. By the means of real-time 3-D echocardiography we developed a new method for the non-invasive assessment of rapid filling rate (PFR), thereby completing the echocardiographic approaches to determine diastolic dysfunction. CONCLUSION: The broad spectrum of approaches available today makes echocardiography the first choice for the assessment of diastolic dysfunction.     

老年舒张性心力衰竭与收缩性心力衰竭患者左心形态及功能的超声评价

目的　探讨老年舒张性心力衰竭与收缩性心力衰竭患者超声左心形态、功能的特点。方法　对临床确诊的 30例老年左心室舒张性心力衰竭 (L VDHF)病例及 36例老年左心室收缩性心力衰竭 (L VSHF)病例进行超声检测 ,以2 0例正常人为对照组。结果　 1与 L VSHF组比较 ,L VDHF组左心房内径 (L AD)、左心室内径 (L VD)扩大程度小 ,但室间隔厚度 (IVST)、左心室后壁厚度 (PWT)增加。 2与对照组比较 ,L VDHF组 L AD、IVST、PWT增加 ,但L VD无显著性差异 ,L VSHF组 L VD显著性扩大。 3L VDHF组左心室射血分数 (L VEF)、心脏指数 (CI)与对照组比较无显著差异 ,而 L VSHF组 L VEF、CI减低。4与对照组比较 ,L VDHF组二尖瓣舒张早期流速峰值 (EPFV)、二尖瓣舒张早、晚期流速峰值比 (E/ A )、舒张早期减速度 (DC)减低 ,二尖瓣舒张晚期流速峰值 ((APFV )、等容舒张时间 (IRT)增高。L VDHF组上述指标与 L VSHF组无显著差异。结论　难以单纯从超声左心室舒张功能指标判断有无 L VDHF的存在 ,应综合分析判断。     

Modern evaluation of left ventricular diastolic function using Doppler echocardiography

The evaluation of left ventricular (LV) diastolic function is an essential component of the echocardiographic examination for dyspneic patients with impaired or preserved LV systolic function. Doppler echocardiography in combination with two-dimensional echocardiographic findings can assist the diagnosis of underlying cardiac dysfunction, give an estimate of LV filling pressures, guide heart failure treatment, and provide important prognostic information. This article reviews the essentials of modern Doppler assessment of diastolic function and highlights recent updates, areas of controversy, and future applications.     

Assessment of global and regional left ventricular diastolic function in hypertensive heart disease using automated border detection techniques

Acoustic quantification (AQ) and color kinesis (CK) are techniques that involve automated detection and tracking of endocardial borders. These methods are useful for the evaluation of global and regional left ventricular (LV) systolic function and more recently have been applied to evaluating LV diastolic performance. Assessment of diastolic dysfunction in hypertensive heart disease is a relevant clinical issue in which these techniques have proven useful. The diastolic portion of left atrium and LV AQ area waveforms are frequently abnormal in patients with left ventricular hypertrophy (LVH). Left ventricular AQ curves consistently demonstrate reduced rapid filling fraction (RFF) and peak rapid filling rate (PRFR), elevated atrial filling fraction (AFF), peak atrial filling rate (PAFR), and reductions in the ratio PRFR/PAFR. Acoustic quantification complements traditional Doppler echocardiographic evaluation of global diastolic function. Many patients with significant LVH and normal Doppler diastolic parameters can be identified as having diastolic dysfunction with AQ. In addition, CK has allowed the evaluation of regional diastolic performance in hypertensive patients. Regional filling curves obtained from CK have demonstrated that endocardial diastolic motion is commonly delayed and heterogeneous in patients with LVH.     

Left ventricular diastolic filling abnormalities identified by Doppler echocardiography in asymptomatic patients with sickle cell anemia

To determine whether left ventricular diastolic abnormalities are an early feature of sickle cell anemia, indexes of diastolic filling were obtained with pulsed Doppler echocardiography in 30 consecutive patients with this disease (mean age 29 years; range 19 to 39) who had not experienced symptoms of heart failure and had normal left ventricular systolic function. Data were compared with those in 30 normal control subjects of similar ages. Seventeen (57%) of the 30 patients with sickle cell anemia had evidence of abnormal left ventricular diastolic filling. Six of these 17 patients had a Doppler pattern consistent with "restrictive" filling, characterized by reduced early diastolic deceleration time (less than 110 ms) or an increased rate of decline of early flow velocity (EF slope greater than 7.4 m/s2), or both, as well as decreased late diastolic velocity-time integral (2.6 +/- 0.7 vs. 3.4 +/- 0.8 cm in normal subjects; p less than 0.05). Another 11 patients showed a Doppler waveform consistent with impaired relaxation, characterized by prolonged deceleration time (greater than 166 ms) or reduced EF slope (less than 3.8 m/s2), as well as increased late diastolic velocity-time integral (4.0 +/- 0.5 vs. 3.4 +/- 0.8 cm in normal subjects; p = 0.03). This Doppler echocardiographic analysis demonstrates that left ventricular diastolic filling patterns are altered in patients with sickle cell anemia and that these diastolic abnormalities may be present in the absence of symptoms of heart failure. These abnormal patterns suggest an intrinsic myocardial abnormality in patients with sickle anemia and may prove to be early markers of cardiac disease.     

Relation of atrial natriuretic peptides to left ventricular systolic and diastolic function in heart failure

BACKGROUND: Plasma concentrations of atrial natriuretic peptides are correlated with atrial pressures, as are left ventricular ejection fraction and left ventricular filling abnormalities. AIMS: This study investigated the relation of atrial natriuretic peptides to both left ventricular systolic and diastolic function in heart failure. METHODS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were measured in 63 patients with chronic heart failure and left ventricular systolic dysfunction. According to Doppler transmitral flow measurements, 19 patients had a restrictive and 44 patients had a non-restrictive left ventricular filling pattern. RESULTS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were higher in patients with a restrictive filling pattern than in patients with a non-restrictive filling pattern (197 vs. 75 pmol/l, P<0.0001 and 1.14 vs. 0.45 nmol/l, P<0.0001). In univariate analysis, atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide correlated with deceleration time, E/A ratio and left ventricular ejection fraction. In multivariate analysis, both peptides appeared independently related to left ventricular ejection fraction and left ventricular filling pattern. CONCLUSION: In patients with chronic heart failure, atrial natriuretic peptides provide information on left ventricular systolic as well as diastolic function.     

Echocardiographic predictors of change in left ventricular diastolic pressure in heart failure patients receiving nesiritide

Background: To evaluate the usefulness of currently accepted echocardiographic parameters of diastolic function to assess the acute change in left ventricular end‐diastolic pressure (LVEDP) following the administration of nesiritide in a heart failure population. Methods: In 25 heart failure patients (15 with systolic dysfunction, 10 with preserved ejection fraction [EF]), Doppler echocardiography, right and left heart catheterization, and invasive biventricular pressure hemodynamics were obtained at baseline and 30 minutes after nesiritide infusion. Results: Twenty‐four patients had sufficient echocardiographic images for analysis. The mean age was 60 ± 11 years, 48% were male, 56% had coronary artery disease, and 64% had hypertension. Right ventricular systolic pressure (RVSP) had the highest correlation with LV filling pressure: pulmonary capillary wedge pressure (PCWP), pre‐A wave LV, and LVEDP (r = 0.66, P = 0.0009; r = 0.63, P = 0.002; r = 0.72, P = 0.0002, respectively). Following nesiritide administration, the mean PCWP decreased from 17.1 ± 7.8 mmHg at baseline to 9.6 ± 6.2 mmHg (P < 0.001). Change in RVSP had the highest correlation with change in PCWP (r =?0.67, P = 0.10) and change in LVEDP (r =?0.71, P = 0.07). Conclusion: Echocardiographic parameters are frequently assessed in attempts to estimate left heart diastolic pressures. In heart failure patients, RVSP appears to be the best predictor of LVEDP, outperforming tissue Doppler E/E′. RVSP was found to be the best echocardiographic predictor of change in LV filling pressure with intravenous vasodilator therapy in heart failure patients. RVSP may provide a noninvasive means of assessing response to cardiac therapy.     

Diastology: 2020-A practical guide

Left ventricular (LV) diastolic function can be most conveniently assessed by echocardiography which provides reliable assessments of LV structure and function. Most patients with structural heart disease have variable degrees of myocardial dysfunction. LV structural changes as pathologic hypertrophy and systolic functional abnormalities as depressed LV long-axis systolic function are associated with diastolic dysfunction. The recognition of structural abnormalities and abnormal LV long-axis function as indices of diastolic dysfunction is an important difference between 2016 and 2009 guidelines. In addition, there are other Doppler findings indicative of diastolic dysfunction and abnormally elevated LV filling pressures. In the absence of clinical, 2D echocardiographic, and specific Doppler indices of diastolic dysfunction, mitral annulus early diastolic velocity (e’), left atrium (LA) maximum volume index, peak velocity of tricuspid regurgitation jet by continuous-wave Doppler, and ratio of mitral inflow early diastolic velocity to e’ velocity can be used to draw inferences about LV diastolic function. In the presence of diastolic dysfunction, mean LA pressure and grade of diastolic dysfunction should be determined. When LA pressure at rest is normal, it is reasonable to proceed to diastolic stress testing in an attempt to identify patients with dyspnea due to heart failure. There are specific algorithms recommended in patients with atrial fibrillation, moderate or severe mitral annular calcification, and noncardiac pulmonary hypertension.     

Dyspnoe bei normaler systolischer Funktion

30-50% of patients presenting with symptoms of congestive heart failure exhibit a near normal left ventricular systolic function at rest, and an impaired diastolic function of the heart may be causative. Despite a better prognosis than in systolic heart failure, frequency of hospitalizations due to diastolic heart failure is comparable with systolic heart failure. According to the criteria of Vasan and Levy diagnosis of diastolic heart failure is probable, if symptoms and signs of heart failure are accompanied in proximity (within 72 h) by objective evidence of normal left ventricular systolic function. Newer echocardiographic techniques (e. g., tissue Doppler) aid to confirm the diagnosis and to determine the severity of dysfunction and may substitute invasive demonstration of impaired left ventricular relaxation, filling, compliance or stiffness for standardized diagnosis. Incorporation of biochemical test (BNP [brain natriuretic peptide]) allows differential diagnosis and may increase the accuracy of diagnosis. Due to inconsistent diagnostic criteria, data from prospective randomized controlled trials for the treatment of diastolic heart failure are rare. Basic principles include treatment of the underlying disease, i. e., control of hypertension, diabetes, or obstructive airway disease. Angiotensin 1 antagonists (ARB) have proven effective in regression of left ventricular hypertrophy (LIFE) and may reduce morbidity, but not mortality (CHARM). Maintenance of sinus rhythm, heart rate control (beta-blockers, calcium channel blockers) and anti-ischemic therapy may be indicated in view of pathophysiological aspects. Diuretics should be administered with caution in patients with symptoms of congestion, digitalis is not useful in the treatment of isolated diastolic heart failure. The results of ongoing trials (e. g., I-Preserve) may offer new therapeutic options, and evidence-based guidelines for the so far often unsatisfactory treatment of diastolic dysfunction/heart failure are awaited.     

Usefulness of Doppler echocardiography in the diagnosis of congestive heart failure

One hundred fifty-one consecutive patients with a diagnosis of congestive heart failure (CHF) referred for echocardiography were prospectively evaluated to (1) define the frequency of normal left ventricular systolic function in a referral-based population with CHF; (2) establish cardiac mechanisms responsible for symptomatology in these patients; and (3) assess the ability to clinically differentiate these subsets of patients based on routine history and physical examination. Of the 151 total patients, 51 (34%) had normal left ventricular systolic function (left ventricular ejection fraction greater than or equal to 55%). Primary valvular disease was present in 4 of these 51 patients (8%), and Doppler echocardiographic evidence of abnormal left ventricular filling (diastolic dysfunction) was evident in 10 (20%). In addition, no predefined resting abnormality was noted in 34 (66%) of them. Despite this finding, 51% of all patients with normal left ventricular systolic function were being treated with digoxin therapy in the absence of atrial arrhythmia. Clinical differentiation of this group of patients from those with abnormal left ventricular systolic function was difficult and may have accounted for this apparently inappropriate treatment. Thus, evaluation of left ventricular function and of causative mechanisms of CHF before initiation of long-term treatment is mandatory.     

Left ventricular diastolic function in systemic sclerosis

OBJECTIVE: To assess left ventricular diastolic function in patients with systemic sclerosis (SSc) and to verify if a "primary" diastolic dysfunction might exist. METHODS: In total 124 patients and 41 healthy subjects underwent complete echocardiographic examination. The following pulsed wave Doppler variables were evaluated: peak velocity during early filling (E), peak velocity during late atrial filling (A), E/A ratio, and early filling deceleration time. RESULTS: Seventy-seven patients (62.1%) had conditions potentially affecting left ventricular diastolic function (Group A) and 47 patients (37.9%) formed a homogeneous group without cardiac involvement or other causes of abnormal diastolic function (i.e., systemic and/or pulmonary hypertension, ventricular hypertrophy, pericardial disease, systolic dysfunction, valvular heart disease, coronary artery disease) (Group B). The entire SSc population and Group A showed significant differences in the Doppler variables of diastolic function compared to the control group. No significant differences were found between Group B and controls. CONCLUSION: In patients with SSc, left ventricular diastolic dysfunction was found only in patients with conditions potentially affecting left ventricular diastolic function. In patients without conditions potentially affecting left ventricular diastolic function no differences were seen in comparison with controls. SSc does not seem to cause "primary" diastolic abnormalities.     

Abnormal diastolic filling patterns in chronic heart failure--relationship to exercise capacity.

Abnormal patterns of diastolic ventricular filling are well recognized in chronic heart failure, but their relationship to the severity of heart failure is not known. The present study evaluates the relationship of diastolic filling indices to the severity of heart failure and to exercise capacity. In 40 patients with chronic heart failure secondary to ischaemic left ventricular impairment, exercise capacity was measured as peak oxygen consumption (VO2max) by progressive treadmill exercise. Left ventricular function was assessed by M-mode and Doppler echocardiographic indices. Peak aortic velocity correlated weakly with VO2max (R = +0.38, P less than 0.05). VO2max did not correlate with other systolic indices, including mean aortic acceleration, time to peak velocity, or isovolumic contraction time. VO2max correlated with the mitral inflow E/A ratio (R = -0.57, P less than 0.005) and with the Doppler estimate of isovolumic relaxation time (R = -0.48, P less than 0.01). Two distinct patterns of diastolic filling were observed: subjects with mild-to-moderate heart failure (NYHA grade II, VO2max 15-20 ml.kg-1.min-1) had abnormally low E/A ratios and long isovolumic relaxation times, whereas those with severe heart failure (NYHA grade III-IV, VO2max less than 12 ml.kg-1.min-1) had abnormally high E/A ratios and short isovolumic relaxation times. Different patterns of abnormal diastolic filling with different degrees of severity of heart failure may explain some of the previous controversy as to the prevalence of abnormal diastolic function in chronic heart failure. Exercise capacity in chronic heart failure appears more closely related to abnormalities of diastolic filling pattern than to indices of systolic function.     

Plasma B-type natriuretic peptide levels in systolic heart failure: importance of left ventricular diastolic function and right ventricular systolic function

OBJECTIVES: This study was designed to characterize the importance of echocardiographic indexes, including newer indexes of diastolic function, as determinants of plasma B-type natriuretic peptide (BNP) levels in patients with systolic heart failure (SHF). BACKGROUND: Plasma BNP levels have utility for diagnosing and managing heart failure. However, there is significant heterogeneity in BNP levels that is not explained by left ventricular size and function alone. METHODS: In 106 patients with symptomatic SHF (left ventricular ejection fraction [LVEF] <0.35), we measured plasma BNP levels and performed comprehensive echocardiography with assessment of left ventricular diastolic function, including color M-mode (CMM) and tissue Doppler imaging (TDI), and of right ventricular (RV) function. RESULTS: Median plasma BNP levels were elevated and increased with greater severity of diastolic dysfunction. We found significant correlations (p < 0.001 for all) between BNP and indexes of myocardial relaxation (early diastolic velocity: r = -0.26), compliance (deceleration time: r = -0.55), and filling pressure (early transmitral to early annular diastolic velocity ratio: r = 0.51; early transmitral flow to the velocity of early left ventricular flow propagation ratio: r = 0.41). In multivariate analysis, overall diastolic stage, LVEF, RV systolic dysfunction, mitral regurgitation (MR) severity, age and creatinine clearance were independent predictors of BNP levels (model fit r = 0.8, p < 0.001). CONCLUSIONS: Plasma BNP levels are significantly related to newer diastolic indexes measured from TDI and CMM in SHF. Heterogeneity of BNP levels in patients with SHF reflects the severity of diastolic abnormality, RV dysfunction, and MR in addition to LVEF, age, and renal function. These findings may explain the powerful relationship of BNP to symptoms and prognosis in SHF.     

老年左室舒张性心力衰竭超声心动图观察

目的评价老年左室舒张性心力衰竭超声左心形态、功能的特点。方法对核素心室造影证实的４０例左室舒张性心力衰竭（ＬＶＤＨＦ）及３０例左室收缩性心力衰竭（ＬＶＳＨＦ）进行超声心动图检查，并以２０例正常人为对照组（ＣＧ）。结果ＬＶＤＨＦ组左房内径、室间壁及左室后壁厚度增加，左室内径不大，左室舒张功能参数减低，而左室收缩功能参数正常。ＬＶＳＨＦ组左室内径明显增加，左室收缩、舒张功能参数均异常。结论老年ＬＶＤＨＦ超声心动图特点为左房内径扩大、室壁增厚、左室内径不大，左室收缩功能正常，而左室舒张功能异常。     

"Pure" diastolic dysfunction is associated with long-axis systolic dysfunction. Implications for the diagnosis and classification of heart failure

AIMS: To investigate regional systolic function of the left ventricle, to test the hypothesis that "pure" diastolic dysfunction (impaired global diastolic filling, with a preserved ejection fraction > or = 50%) is associated with longitudinal systolic dysfunction. METHODS AND RESULTS: One hundred thirty subjects (31 patients with asymptomatic diastolic dysfunction, 30 with diastolic heart failure, 30 with systolic heart failure; and 39 age-matched normal volunteers) were studied by conventional and tissue Doppler echocardiography. Global diastolic function was assessed using the flow propagation velocity, and by estimating left ventricular filling pressure from the ratio of transmitral E and mitral annular E(TDE) velocities (E/E(TDE)); and global systolic function by measurement of ejection fraction. Radial and longitudinal functions were assessed separately from posterior wall and mitral annular velocities. Global and radial systolic function were similar in patients with "pure" diastolic dysfunction and normal subjects, but patients with either asymptomatic diastolic dysfunction or diastolic heart failure had impaired longitudinal systolic function (mean velocities: 8.0+/-1.2 and 7.7+/-1.5 cm/s, respectively, versus 10.1+/-1.5 cm/s in controls; p<0.001). In subjects with normal ejection fraction, global diastolic function correlated with longitudinal systolic function (r=0.56 for flow propagation velocity, and r=-0.53 for E/E(TDE) ratio, both p<0.001), but not with global systolic function. CONCLUSION: Worsening global diastolic dysfunction of the left ventricle is associated with a progressive decline in longitudinal systolic function. Diastolic heart failure as conventionally diagnosed is associated with regional, subendocardial systolic dysfunction that can be revealed by tissue Doppler of long-axis shortening. Diagnostic algorithms and definitions of heart failure need to be revised.     

Right ventricular diastolic function in beta-thalassemia major: echocardiographic and clinical correlates

BACKGROUND: Cardiac hemochromatosis remains the most frequent cause of death in beta-thalassemia major. Previous studies suggest an important right ventricular (RV) contribution to cardiac morbidity and mortality. Studies with Doppler echocardiography have shown contradictory results regarding left ventricular (LV) filling, whereas the RV filling characteristics have not been studied yet. We prospectively studied the pattern of RV filling and investigated echocardiographic and clinical correlates during baseline and follow-up examinations in patients with beta-thalassemia major. METHODS AND RESULTS: The study included 79 patients, aged 24.2 +/- 8.0 years, with homozygous beta-thalassemia major without symptoms of heart failure with normal LV function and 51 healthy control subjects, matched for age, sex, and body surface area. Doppler echocardiographic indexes of systolic and diastolic ventricular function were assessed. Hemodynamic measurements were obtained in 8 patients by right heart catheterization. An abnormal RV relaxation pattern was evident in the patient group. The LV filling characteristics indicated increased preload without abnormal alteration, whereas catheterization findings were consistent with a high cardiac output state. Short tricuspid deceleration time (DT) had the best predictive value for subsequent cardiac events. Repeat echocardiographic study in 35 asymptomatic patients at 19 +/- 7 months demonstrated deterioration of LV systolic function, chamber enlargement, and shortening of DT of tricuspid and mitral inflow. CONCLUSIONS: In patients with homozygous beta-thalassemia major without cardiac disease, the pattern of RV filling is abnormally altered, indicating impaired relaxation. In contrast, the LV filling is compatible with increased preload, as in chronic anemia. Short DT of early tricuspid inflow carries important prognostic value. LV remodeling occurs over time along with transition toward a restrictive ventricular filling pattern.     

Increased circulating atrial natriuretic factor concentrations in patients with chronic heart failure after inhibition of neutral endopeptidase: effects on diastolic function.

OBJECTIVE--+/- Candoxatrilat was used to raise atrial natriuretic factor (ANF) concentrations in patients with heart failure, and the effects on left ventricular systolic and diastolic function were studied to determine the contribution of peripheral and central mechanisms to the haemodynamic effects. DESIGN--This was a single blind, randomised comparison of +/- candoxatrilat and placebo in patients with mild heart failure. All patients received two intravenous doses of +/- candoxatrilat and two placebo doses on four consecutive days. SETTING--A teaching hospital department of cardiology. PATIENTS--Six men (mean age 52 years) with mild heart failure (New York Heart Association class II) due to ischaemic heart disease (four patients) or dilated cardiomyopathy (two patients) were included. Mean ejection fraction was 37.5% and mean peak oxygen consumption was 20.4 ml/min/kg. MAIN OUTCOME MEASURES--Plasma ANF concentrations, haemodynamic indices and left ventricular diastolic function measured by early to atrial filling rate (E:A ratio) with Doppler echocardiography were determined before and after +/- candoxatrilat and placebo. RESULTS--+/- Candoxatrilat caused a threefold rise of plasma ANF compared with placebo (p < 0.005), but there was no significant change in heart rate, blood pressure, or cardiac output. Mean right atrial pressure fell from 6.7 to 4.7 mmHg (NS) and pulmonary artery wedge pressure fell from 9.2 to 6.7 mmHg (p < 0.05). Doppler echocardiographic measurements of transmitral blood flow showed a significant fall in peak early left ventricular filling velocity from 39.5 to 34.2 cm/s (p < 0.05), along with a non-significant rise in peak atrial filling velocity from 39.7-41.6 cm/s after +/- candoxatrilat. The E:A ratio, a Doppler index of left ventricular diastolic function, fell from a mean of 1.04 to 0.87 (p < 0.05). CONCLUSIONS--+/- Candoxatrilat increased plasma ANF concentrations and reduced right atrial and pulmonary artery wedge pressures. No evidence of an improvement in left ventricular systolic or diastolic function was found, so the fall in preload was due to peripheral effects, either an increase in venous capacitance or a fall in circulating blood volume.