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Left ventricular diastolic dysfunction induced by cyclophosphamide in blood stem cell transplantation.

Cardiac complications are major limiting factors regarding the success of high-dose chemotherapy supported by blood stem cell transplantation (BSCT). The cardiotoxicity of cyclophosphamide remains obscure relative to that of anthracyclines. The aim of this study was to estimate noninvasively the cardiotoxicity of cyclophosphamide administered during the pretransplant conditioning of BSCT for patients with various hematological diseases. A total of 27 consecutive patients were divided into two groups depending on the conditioning regimen, ie, group A (n=15) which received cyclophosphamide (median dose of 120 mg/kg; range 100 to 200 mg/kg) and group B (n=12) which did not. Ultrasound cardiograms (UCG) and signal-averaged electrocardiograms (SAECG) were recorded in the two groups both preceding and following the BSCT. There were no statistical intergroup or intragroup differences in left ventricular (LV) dimensions or contractile function. Significant (P<0.01) posttransplant increases in interventricular septal wall thickness and Ap/Ep ratio were noted in group A. Moreover, the filtered QRS duration as estimated by SAECG was prolonged (P<0.05) whereas the summated LV voltage (S(V1)+R(V5)) was reduced in the posttransplant period only in group A. These results suggest that early cyclophosphamide cardiotoxicity was characterized by LV diastolic rather than systolic dysfunction. These findings may contribute to acute hemodynamic deterioration observed after cyclophosphamide-containing conditioning chemotherapy.

Adolescent↗

Systolic and diastolic dysfunction of the left ventricle induced by dietary taurine deficiency in cats.

Isovolumic left ventricular (LV) preparations were used to assess myocardial failure associated with dietary taurine deficiency in cats. Adult female cats (n = 12) were fed a purified diet devoid of taurine for 6-8 mo. Six of the cats received 1,000 mg of crystalline taurine orally once daily. The remaining six cats were not provided taurine replacement. Compared with control preparations, hearts isolated from taurine-deficient cats generated significantly lower values for developed LV systolic pressure (107 +/- 6 vs. 66 +/- 15 mmHg; P less than 0.05), maximal rate of LV pressure rise (+dP/dtmax; 1,103 +/- 38 vs. 718 +/- 172 mmHg/s; P less than 0.05), and fall (-dP/dtmax; 930 +/- 46 vs. 587 +/- 129 mmHg/s; P less than 0.05). LV function curves generated by hearts from taurine-deficient cats were shifted downward and to the right of control curves, demonstrating inotropic depression. In addition, end-diastolic pressure-volume (compliance) relationships in hearts from taurine-deficient cats were shifted downward and to the right of controls in the direction of increased chamber compliance or distensibility. Ten millimolar taurine significantly improved inotropic indexes only in hearts from taurine-deficient cats but failed to affect diastolic compliance. Myocardial contractile dysfunction and LV chamber dilatation in hearts from taurine-deficient cats verify a causal association between dietary deficiency of this amino acid and dilated cardiomyopathy in this species.

Animals↗

[Reduced distensibility of the hypertensive heart under stress as an early sign of diastolic dysfunction].

BACKGROUND: Hypertensive patients often present with exertional dyspnoea. However it is questioned whether it results from a systolic, early- or late diastolic impairment of left ventricular function. PATIENTS AND METHODS: Our study included 21 hypertensive patients (7 female; 14 male, median age 56 years) and 12 controls (4 female; 8 male, median age 52 years). All patients had normal epicardial coronary arteries. Parameters of systolic and diastolic heart function at rest and during exercise were analyzed using a combined hemodynamic and radionuclid-angiographic approach. RESULTS: One principal finding was that the investigated hypertensive patients had a normal ejection fraction during exercise (72 % +/- 11 vs 71 % +/- 10 in the control group). However these patients showed an exercise induced increase of pulmonary capillary wedge pressure (17.4 +/- 8 vs 11.5 +/- 5; p = 0.005), a fixed end diastolic volume (82 +/- 21 vs 104 +/- 23 ml/m (2), p = 0.01) and a reduced stroke volume index (58 +/- 1.2 vs 73 +/- 1.4 ml/m (2); p = 0.007). Radionuclid angiography revealed an increased exercise peak filling rate (6.1+/-1.6 vs 4.8+/-1.8 EDV/s; p = 0.04) in hypertensive patients. We assume that exercise capacity (cardiac index = 8.1 +/- 1.8 vs 8.4 +/- 2.2 l/min x m (2); ns) in hypertensive patients without excessive LV hypertrophy is predominantly preserved by an enhanced contractile state and its favorable effects on early diastolic filling. CONCLUSION: An increased left ventricular stiffness during exercise is an early manifestation of hypertensive heart disease.

Antihypertensive Agents↗

Severe diastolic dysfunction after endoventriculoplasty.

Endoventriculoplasty with pericardial patch has been advocated to repair anteroseptal ventricular aneurysm, but not studies have reported the influence of this technique on diastolic left ventricular function. We have evaluated the changes on ventricular filling by means of pulsed Doppler recording of diastolic transmitral flow. Doppler analysis reveals three distinct spectral patterns: (1) normal, (2) inverted, and (3) restrictive. We have found an abrupt change from a preoperative normal to postoperative restrictive pattern in a significant minority of patients (8%) who underwent endoventriculoplasty. These patients had clinical and hemodynamic signs (New York Heart Association class, time from anterior myocardial infarction, left ventricular end-diastolic pressure, pulmonary hypertension, and mitral regurgitation) of severe impairment but no differences were found in ejection fraction, aneurysmal extension, or remote myocardial function. Moreover, after operation they had a satisfactory ejection fraction, a low end-diastolic volume, and an apex-base length shorter than the predicted value for a normal population. The presence of a postoperative restrictive pattern of diastolic filling is a strong predictor of 3-month mortality and makes the medical treatment difficult. Caution must be taken to perform endoventriculoplasty in patients who are severely ill, especially those recently affected by myocardial infarction. When the clinical conditions dictate the operation, a nonenthusiastic volume reduction seems to be a prudent option.

Coronary Aneurysm↗

[Early diastolic dysfunction of the left ventricle and its relation to histopathological findings in patients with diabetes mellitus].

The relation of left ventricular diastolic function and the histopathological findings of the myocardium in patients with diabetes mellitus were observed using echocardiography and endomyocardial biopsy. The subjects consisted of six diabetic patients (mean age 49.3 years) and eight normal control subjects (mean age 44.8 years). Coronary angiography had no significant stenotic lesions in their coronary arteries. Their diabetic complications were mild to moderate in severity. Echoes from the left ventricular margin of the septum and from the posterior left ventricular wall were traced on a digitizing board; then the isovolumic relaxation period, rapid filling period, slow filling period and atrial contraction period were determined to calculate fractional shortening (FS), isovolumic relaxation time (IRT), and three filling volumes (RFV, SFV and ACV). The quotients of the left ventricular filling volume and stroke volume were also determined. Right ventricular endomyocardial biopsies were performed to determine the diameters of myocytes, the percentage of fibrosis and the eccentricity e, as a parameter of the degree of myocardial dysarrangement. The results were as follows: IRT was significantly longer and RFV/SV was significantly greater in patients with diabetes mellitus than those among the controls. Also the diameters of myocytes and the percentage of fibrosis were significantly greater, while the eccentricity e was less compared to that of the controls. There were no significant correlations, among IRT, RFV/SV, the diameters of myocytes, and eccentricity e, but the percentage of fibrosis significantly correlated with IRT and RFV/SV (r = 0.62, r = -0.63). IRT and RFV/SV were mainly responsible for the percentage of fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Normotensive offspring of hypertensive parents: no evidence of left ventricular diastolic dysfunction in a cross-sectional study.

Left ventricular filling alterations occur early in the development of systemic hypertension. We tested the hypothesis that alteration of diastolic filling might be present in a normotensive population with increased genetic risk for hypertension in the absence of increased left ventricular mass. In a blinded study we compared 31 lean, normotensive offspring of hypertensive parents having normal left ventricular mass (risk group) with 30 matched individuals without family history of hypertension (control group). Left ventricular diastolic function was assessed using Doppler echocardiography. Transmitral flow velocities showed no significant differences between the two groups. Peak early diastolic flow was 0.79+/-0.12 m/s and 0.79+/-0.13 m/s in the risk group and control group, respectively. Peak late diastolic flow was 0.44+/-0.08 in the risk group and 0.42+/-0.11 m/s in the control group. The ratio of early to late diastolic velocity was 1.85+/-0.32 and 1.94+/-0.37. The deceleration time of the early diastolic flow was identical in both groups: 138+/-24 ms and 138+/-23 ms. There was no significant prolongation of the isovolumic relaxation time in the risk group: 75+/-17 compared to 73+/-17 ms in the control group. Doppler measurements showed no correlation with left ventricular mass. We conclude that, in this cross-sectional study, young normotensive offspring of hypertensive parents do not exhibit Doppler echocardiographic signs of diastolic filling alteration in the absence of increased left ventricular mass.

Adult↗