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Role of intraventricular dispersion of early diastolic filling in indicating left ventricular diastolic dysfunction: assessment by color M-mode inflow propagation velocity.

The intraventricular to mitral E velocity ratio (IvE/MvE) and the color M-mode Doppler inflow propagation velocity (LVIPV) were evaluated in 36 healthy controls and 33 patients with hypertension and/or ischemic heart disease. The intraventricular E velocity was significantly lower than the mitral E velocity in the control group (52 vs. 68 cm/s, p < 0.001), but they are similar in the disease group (59 vs. 63 cm/s, p = nonsignificant). Compared with the control group, the disease group had a higher IvE/MvE (0.95 +/- 0.28 vs. 0.78 +/- 0.23, p < 0.01). Nevertheless, the LVIPV was not significantly different between the disease and control groups (53 +/- 14 vs. 56 +/- 13 cm/s, p = nonsignificant). The LVIPV did not correlate with the IvE/MvE (r = 0.202, p = nonsignificant). Therefore, an intraventricular dispersion of early diastolic filling does not seem to indicate impaired left ventricular relaxation.

Adolescent↗

[Diastolic dysfunction in chronic renal failure patients under hemodialysis].

Myocardial hypertrophy due to volume and pressure overload is common in hemodialysis patients because renal failure is usually responsible for arterial hypertension. The left ventricular filling pattern often exhibits abnormalities denoting a relaxation disorder. These abnormalities increase after hemodialysis sessions, which are sometimes followed by severe hypotension. This sequence of left ventricular hypertrophy, altered relaxation, and severe postdialysis hypotension sometimes associated with severe ventricular rhythm disorders deserves to be studied in detail. The data gathered would help to determine the prognosis in this situation, which often depends on cardiac function.

Diastole↗

Cerebral oxygenation responses to standing in elderly patients with predominantly diastolic dysfunction.

Patients with left ventricular dysfunction may have different orthostatic responses of blood pressure (BP) and cerebral oxygenation than healthy elderly subjects. We investigated orthostatic changes in systemic haemodynamic variables and cerebral oxygenation in 21 elderly patients with heart failure New York Heart Association class I-III in stable condition (age 70-83 years) after withdrawal of furosemide and captopril for 2 weeks, and in 18 healthy elderly subjects (age 70-84 years). Frontal cortical concentration changes of oxyhaemoglobin ([O2Hb]) and deoxyhaemoglobin ([HHb]) were continuously measured by near-infrared spectrophotometry and BP changes by Finapres before and during 10 min of standing. Upon standing [O2Hb] reflecting blood flow, changed by -1.2 +/- 0.9 micromol L-1 (mean +/- SEM) in the patients, whereas it decreased by -4.5 +/- 0.6 micromol L-1 (P<0.01) in the healthy subjects after standing (P<0.05 between groups). [HHb] reflecting the sum of cerebral blood flow, arterial oxygen saturation and cerebral oxygen uptake, increased by 1.5 +/- 0.5 micromol L-1 (P<0.05) and 1.7 +/- 0.6 micromol L-1 (P<0.05), respectively. Compared with healthy elderly subjects, elderly patients with left ventricular dysfunction showed smaller orthostatic [O2Hb] decreases (P<0.01), in relation to higher orthostatic BP rises (P<0.05). These findings indicate that BP changes and an altered cardiovascular balance may influence orthostatic cortical haemodynamic responses in elderly subjects.

Aged↗

Coronary flow reserve and diastolic dysfunction in hypertrophic cardiomyopathy.

We studied 14 patients with hypertrophic cardiomyopathy during and after atrial pacing by simultaneous registration of left ventricular high fidelity pressure measurements and M-mode echocardiography together with great cardiac vein flow measured by thermodilution. Heart rate rose from 75 +/- 18 to 142 +/- 14 beats/minute with an increase of 93 +/- 30 to 127 +/- 46 milliliters/minute of great cardiac vein flow (increase of flow/beat: 0.8 versus 1.5 milliliters/beat in normal individuals; P less than 0.05). In addition, diastolic hemodynamic parameters (such as left ventricular end-diastolic pressure, T1 (time constant of relaxation) (of first 40 milliseconds) and T2 (of second 40 milliseconds) and LVdP/dt-) changed from, respectively, 27.4 +/- 7.1 to 24.0 +/- 10.3 mm Hg; (NS), 67.3 +/- 16.1 to 65.7 +/- 22.2 liters/second; (NS) 68.6 +/- 36.9 to 52.9 +/- 19.4 (P less than 0.05), and 1592 +/- 75 to 1302 +/- 48 mm Hg/sec; P less than 0.05. Left ventricular end-diastolic dimensions decreased whereas end-diastolic wall thickness increased from, respectively, 37 +/- 3 to 34 +/- 4 millimeters; (P less than 0.05) and 14 +/- 2 to 17 +/- 1 millimeters (P less than 0.05). Eleven of the 14 patients experienced angina pectoris concomitant with ST-T depression of 1 millimeter or more on the electro-cardiogram. No correlations were found between great cardiac venous flow and hemodynamically or ultrasonically derived diastolic parameters of left ventricular function.

Adolescent↗

A point mutation (R192H) in the C-terminus of human cardiac troponin I causes diastolic dysfunction in transgenic mice.

Cardiac troponin I (cTnI) mutations have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. We modeled one mutation in human cTnI C-terminus, arginine192-->histidine (R192H) by cardiac specific expression of the mutated protein (cTnI(193His) in mouse sequence) in transgenic mice. Heart tissue sections revealed neither significant hypertrophy nor ventricular dilation in cTnI(193His) mice. The main functional alteration detected in cTnI(193His) mice by ultrasound cardiac imaging examinations was impaired cardiac relaxation manifested by a decreased left ventricular end diastolic dimension (LVEDD) and an increased end diastolic dimension in both atria. The cardiac ejection fraction (EF) was not significant changed in 6- to 8-week-old cTnI(193His) mice, however, the EF was significantly decreased in cTnI(193His) mice at age of 11 months. These data indicate that individual genetic conditions and environmental factors participate together in the development of the cTnI mutation based-cardiac muscle disorders. This mouse model provides us with a tool to further investigate the pathophysiology and the development of RCM.

Animals↗

Increased systolic performance with diastolic dysfunction in adult spontaneously hypertensive rats.

Hypertensive heart disease is characterized by early development of hypertrophy and fibrosis that leads to heart failure (HF). HF develops in spontaneously hypertensive rats (SHR) after 18 months; however, it is not clear whether hypertrophy leads to altered cardiac performance at an earlier age in these rats. We studied cardiac performance in 10- to 11-month-old SHR and age-matched Wistar-Kyoto rats (WKY), using presssure-volume (PV) conductance catheter system to evaluate systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), +dP/dt, and its relation to end-diastolic volume (+dP/dt-EDV) and preload-adjusted maximal power (PWR(max)-EDV(2)) as well as the time constant of left ventricular pressure decay, tau (tau), as an index of relaxation. The slope of the end-diastolic pressure-volume relation (EDPVR) and the ex vivo PV relation, both indexes of stiffness, were also calculated for each heart, and the Doppler E/A ratio was determined. In addition, plasma samples were obtained to assess B-type natriuretic peptide levels (BNP). We found that PRSW was higher in SHR than in WKY (174.5+/-15.6 versus 92.6+/-18.9 mm Hg; P<0.01). +dP/dt and +dP/dt-EDV were also enhanced in SHR versus WKY (9125+/-662 versus 6633+/-392 mm Hg/sec, P<0.01, and 28.14+/-4.35 versus 12.7+/-2.8 mm Hg/s per micro L, P<0.02). In addition, PWR-EDV(2) was elevated in SHR (7.3+/-1.5 versus 3.1+/-0.6 mW/ micro L(2)). Tau was prolonged in SHR (14.5+/-1 ms versus 10.8+/-0.8 for WKY, P<0.02) and EDPVR was significantly greater in SHR than in WKY (0.01+/-0.005 versus 0.004+/-0.001, P<0.05). The ex vivo pressure-volume relation was also steeper for SHR and the E/A ratio was 2.53+/-0.15 for SHR versus 1.67+/-0.08 for WKY (P<0.02). BNP was 45+/-2.5 pg/mL for SHR and 33.3+/-1.8 pg/mL for WKY (P<0.02). Taken together, these data suggest that at 10 to 11 months of age, before HF develops, SHR have increased systolic performance accompanied by delayed relaxation and increased diastolic stiffness.

Animals↗

Diastolic dysfunction and pulmonary hypertension in sickle cell anemia: is there a role for L-carnitine treatment?

Clinical manifestations of cardiovascular abnormalities in patients with sickle cell (SC) anemia are well documented. Many variables were assessed in our study before and after administration of L-carnitine to randomly selected 37 SC disease (SCD) children for a period of 6 months. Variables such as weight, height, serum ferritin levels, units of blood transfused and the number of veno-occlusive crises all showed significant improvement after the 6 months of therapy with L-carnitine. Our study also showed that cardiac diastolic function and pulmonary hypertension are common in pediatric SCD patients. These two disorders showed some improvement after L-carnitine administration. Therefore, L-carnitine deserves a rigorous large-scale randomized clinical trial to evaluate its potential benefits as treatment for SCD patients with cardiac complications.

Adolescent↗

Diastolic dysfunction in hypertensive heart disease is associated with altered myocardial metabolism.

BACKGROUND: Hypertension is an important clinical problem and is often accompanied by left ventricular (LV) hypertrophy and dysfunction. Whether the myocardial high-energy phosphate (HEP) metabolism is altered in human hypertensive heart disease and whether this is associated with LV dysfunction is not known. METHODS AND RESULTS: Eleven patients with hypertension and 13 age-matched healthy subjects were studied with magnetic resonance imaging at rest and with phosphorus-31 magnetic resonance spectroscopy at rest and during high-dose atropine-dobutamine stress. Hypertensive patients showed higher LV mass (98+/-28 g/m2) than healthy control subjects (73+/-13 g/m2, P<0.01). LV filling was impaired in patients, reflected by a decreased peak rate of wall thinning (PRWThn), E/A ratio, early peak filling rate, and early deceleration peak (all P<0. 05), whereas systolic function was still normal. The myocardial phosphocreatine (PCr)/ATP ratio determined in patients at rest (1. 20+/-0.18) and during stress (0.95+/-0.25) was lower than corresponding values obtained from healthy control subjects at rest (1.39+/-0.17, P<0.05) and during stress (1.16+/-0.18, P<0.05). The PCr/ATP ratio correlated significantly with PRWThn (r=-0.55, P<0.01), early deceleration peak (r=-0.56, P<0.01), and with the rate-pressure product (r=-0.53, P<0.001). CONCLUSIONS: Myocardial HEP metabolism is altered in patients with hypertensive heart disease. In addition, there is an association between impaired LV diastolic function and altered myocardial HEP metabolism in humans. The level of myocardial PCr/ATP is most likely determined by the level of cardiac work load.

Adenosine Triphosphate↗

The relationship of cardiac diastolic dysfunction to concurrent hormonal and metabolic status in type I diabetes mellitus.

The presence of diabetic cardiomyopathy and its relationship to concurrent hormonal and metabolic status have not been defined in patients with uncomplicated type I diabetes mellitus. Accordingly, radionuclide left ventricular angiograms and simultaneous metabolic profiles were obtained in 8 type I diabetic patients who had no major diabetic complications and in 11 normal subjects. Occult coronary artery disease was excluded by electrocardiogram exercise testing. Hemodynamics and systolic function did not differ between the groups. However, the peak filling rate (PFR; end-diastolic volumes per s) was less in the diabetic patients at rest [mean, 4.1 +/- 0.2 (+/- SE) vs. 4.8 +/- 0.2; P less than 0.05] and during aerobic (6.8 +/- 0.2 vs. 8.30 +/- 0.3; P less than 0.01) and anaerobic exercise (8.8 +/- 0.3 vs. 9.8 +/- 0.4; P less than 0.05). The time to PFR was prolonged in the diabetic patients at rest (174 +/- 10 vs. 133 +/- 7 ms; P less than 0.01) and during anaerobic exercise (126 +/- 5 vs. 103 +/- 6 ms; P less than 0.01). Plasma glucose and insulin levels were elevated in the diabetic patients at rest and during exercise. Otherwise, the metabolic and hormonal levels did not differ between the groups. In the diabetic patients, no single metabolic or hormonal parameter correlated with PFR or time to PFR. Impairment of diastolic filling also did not correlate with level of glycosylated hemoglobin or duration of diabetes. The alteration in diastolic filling present in type I diabetic patients who have no other diabetic complications may represent the earliest functional effect of diabetic cardiomyopathy.

Adult↗

[Regional left ventricular diastolic dysfunction in patients with apical hypertrophy].

Differences in cardiac function between the apical and the chordal parts of the left ventricle in apical hypertrophy (APH) were investigated by M-mode echocardiography. The subjects consisted of 10 patients with APH (APH Group) and 10 normal controls (N Group). The M-mode echocardiograms of the interventricular septum (IVS) and left ventricular posterior wall (LVPW), both in the apical and chordal parts were simultaneously recorded with the electrocardiogram and phonocardiogram. There were no significant differences in the blood pressures, heart rates, left ventricular end-diastolic internal diameters, and left ventricular end-systolic internal diameters between the APH Group and the N Group. The hypertrophy was localized to the IVS and LVPW of the apical part in the APH Group. In the chordal part, there were no significant differences in the peak negative dD/dt (-dD/dt) and the time to the peak filling rate (TPFR) between the APH Group and N Group. In the apical part, -dD/dt of the APH Group tended to increase compared with that of the N Group. The TPFR of the APH Group was significantly longer than that of the N Group (APH Group: 167 +- 33 msec and N Group: 126 +- 19 msec, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Late left ventricular diastolic flow propagation velocity determined by color M-mode Doppler in the assessment of diastolic dysfunction.

BACKGROUND: Early color M-mode Doppler flow propagation (Ep) through the left ventricle (LV) has been proposed as a useful noninvasive index for assessing LV relaxation, whereas data concerning late velocity propagation (Ap) is lacking. METHODS: We studied 51 patients with delayed relaxation (group I) and 50 with pseudonormal filling pattern (group II). Another 51 aged-matched healthy persons served as the control group. RESULTS: Patients showed increased left atrial dimensions, atrial wave of the pulmonary vein flow, and Ap, and reduced LV ejection fraction, Ep, and Ep/Ap ratio compared with the control group. Patients in group II revealed increased left atrial dimensions (P =.001), atrial wave of the pulmonary vein flow (P <.001), and Ep/Ap ratio (P <.001), and reduced LV ejection fraction and Ap (P <.001) compared with group I. Regression analysis showed that the strongest independent variable distinguishing normal from pseudonormal filling pattern was the Ep/Ap ratio. CONCLUSION: Ap evaluation offers a new diagnostic diastolic index, especially in the field of the pseudonormal pattern where the separation from normal is difficult.

Adult↗

Systolic and diastolic heart failure in the community.

CONTEXT: The heart failure (HF) syndrome is heterogeneous. While it can be defined by ejection fraction (EF) and diastolic function, data on the characteristics of HF in the community are scarce, as most studies are retrospective, hospital-based, and rely on clinically indicated tests. Further, diastolic function is seldom systematically assessed based on standardized techniques. OBJECTIVE: To prospectively measure EF, diastolic function, and brain natriuretic peptide (BNP) in community residents with HF. MAIN OUTCOME MEASURES: Echocardiographic measures of EF and diastolic function, measurement of blood levels of BNP, and 6-month mortality. DESIGN, SETTING, AND PARTICIPANTS: Olmsted County residents with incident or prevalent HF (inpatients or outpatients) between September 10, 2003, and October 27, 2005, were prospectively recruited to undergo assessment of EF and diastolic function by echocardiography and measurement of BNP. RESULTS: A total of 556 study participants underwent echocardiography at HF diagnosis. Preserved EF (> or =50%) was present in 308 (55%) and was associated with older age, female sex, and no history of myocardial infarction (all P<.001). Isolated diastolic dysfunction (diastolic dysfunction with preserved EF) was present in 242 (44%) patients. For patients with reduced EF, moderate or severe diastolic dysfunction was more common than when EF was preserved (odds ratio, 1.67; 95% confidence interval [CI], 1.11-2.51; P = .01). Both low EF and diastolic dysfunction were independently related to higher levels of BNP. At 6 months, mortality was 16% for both preserved and reduced EF (age- and sex-adjusted hazard ratio, 0.85; 95% CI, 0.61-1.19; P = .33 for preserved vs reduced EF). CONCLUSIONS: In the community, more than half of patients with HF have preserved EF, and isolated diastolic dysfunction is present in more than 40% of cases. Ejection fraction and diastolic dysfunction are independently related to higher levels of BNP. Heart failure with preserved EF is associated with a high mortality rate, comparable to that of patients with reduced EF.

Aged↗

[Ischemic left ventricular diastolic dysfunction at females: clinical aspect].

UNLABELLED: The prevalence of the coronary heart disease at females becomes close to that of the male gender at older ages. However, studies of the assessment of ischemic cardiac disfunction include a few women. The objective of the paper is the analysis of the clinical profile of women with ischemic heart disfunction. METHODS: There have been studied 189 patients with coronary heart disease (chronic myocardial infarction, stable angina, ischemic cardiomyopathy): 63 females and 126 males. The prevalence of the coronary diseases, risk factors, symptoms, lipidic profile, radiologic and echocardiographic alterations were analysed. RESULTS: Mean age of the male group was 56.8 +/- 12.2, and of the female was 66.3 +/- 10.9 years, significantly older (p = 0.00001). Ischemic cardiomyopathy had a greater prevalence at women (33.3% vs 11.9%, p = 0.0004), while myocardial infarction dominated at the male gender (61.9% vs 28.6%, p = 0.0001); stable angina had similar rates (20.6%, respectively 19%). Episodes of cardiac decompensation were more often at women (20.6% vs 7.1%, p = 0.0003). Arterial hypertension prevailed at females (77.8% vs 60.3%, p = 0.01), and smoking at males (72.2% vs 7.5%, p = 0.00001). Women declared more often dyspnoea (p = 0.02) and the resting heart rate was higher (87 +/- 23/min vs 75 +/- 13/min, p = 0.0007). Mean values of cholesterol were higher at women, particularly LDL: 165 +/- 49 mg% vs 149 +/- 46 mg%, p = 0.04. At X-ray examination, cardiomegaly and pulmonary congestion were dominant at females. At echo examination, the ejection fraction had similar values (52.3 +/- 9.3% at women and 51.2 +/- 11.6% at men), but left ventricular hypertrophy and diastolic disfunction were prevalent at women (87.3% vs 69.1%, p = 0.01). CONCLUSIONS: Ischemic heart disfunction at females appears at older ages, with the dominance of ischemic cardiomyopathy and angina. At similar levels of sistolic disfunction, the diastolic disfunction, the left ventricular hypertrophy and the cardiac decompensations are more frequently at female gender.

Aged↗

Diastolic dysfunction and myocardial energetics.

Myocardial relaxation is an energy-dependent process. Indeed, adenosine triphosphate (ATP) is required to pump free myoplasmic calcium back into the sarcoplasmic reticulum. It is also necessary to extrude the calcium ions which enter the cell during the plateau phase of the action potential. The calcium-sodium exchange mechanism does not seem to require energy in itself, but sodium exchanged for calcium eventually needs to be extruded via sodium/potassium ATPase and there is also an ATP-dependent calcium pump. Thus, when ATP production is limited, calcium may remain fixed to troponin for part or for the whole of diastole, resulting in a slower rate of isovolumic relaxation and reduced distensibility of the myocardium. Alterations in diastolic function caused by inadequate energy production occur in the high-demand type of myocardial ischaemia. There is also growing evidence that most forms of heart failure are accompanied by a state of energy depletion. Alterations in mitochondrial density and enzymatic activity are common in the failing myocardium and may partially explain the reduction in ATP production. Inadequate growth of the capillary network in hypertrophied myocardium, impaired subendocardial perfusion due to increased diastolic wall stress and/or coronary artery disease, probably also contribute to an imbalance between energy production and utilization. As relaxation is intrinsically a much slower process than activation and since changes in ATP concentration may also affect calcium efflux by allosteric effects, impaired relaxation and reduced diastolic distensibility are almost universal in chronic congestive heart failure. Optimal therapy of heart failure should, therefore, also aim at improving this phase of the cardiac cycle.

Animals↗

Increased myocardial collagen and ventricular diastolic dysfunction in relaxin deficient mice: a gender-specific phenotype.

OBJECTIVE: To investigate cardiac phenotypes in mice deficient in the peptide hormone relaxin by gene targeting. METHODS: Echocardiography and cardiac catheterization were performed on male and female relaxin deficient (Rlx(-/-)) mice as well as heterozygous (Rlx(+/-)) and wildtype (Rlx(+/+)) littermates aged between 8 and 24 months. Collagen expression and content in the heart were analysed by real-time PCR, hydroxyproline assay and histology. RESULTS: Heart rate, blood pressures, left ventricular (LV) dimensions, fractional shortening and maximal and minimal dP/dt did not differ significantly between the three genotypes of either gender at any age. However, 8-10-month-old Rlx(-/-) males exhibited a greater transmitral flow velocity (A-wave) at the late LV diastolic phase. Male Rlx(-/-) mice aged between 12 and 24 months had significantly higher LV end-diastolic pressures, a 30% increase in atrial weight and 10-30% increases in lung and liver weights. Male mice also showed an age-dependent increase (P<0.01) in LV collagen content that was more pronounced in Rlx(-/-) than control littermates (P<0.01). Procollagen type-1 expression was also significantly higher in the LV of Rlx(-/-) males compared with either Rlx(+/-) or Rlx(+/+) males at 6, 9 and 12 months of age. Age-matched female Rlx(-/-) mice did not display any of these cardiac phenotypes seen in Rlx(-/-) males. CONCLUSIONS: Male Rlx(-/-) mice had impeded LV diastolic filling and increased atrial weights, most likely due to an increase in ventricular collagen content and chamber stiffness. These phenotypes in the Rlx(-/-) males were not observed in Rlx(-/-) females, indicating the importance of other gender-related factors in cardiovascular function.

Animals↗

Chronic inhibition of fatty acid oxidation: new model of diastolic dysfunction.

The proportion of cardiac energy derived from fatty acid oxidation decreases and that derived from glucose increases during ischemia. This biochemical profile of cardiac energy production is achieved in rats and mice without ischemia by pharmacological agents such as tetradecylglycidic acid. Chronically this leads to increased cardiac stiffness, and hypertrophy in the rodent models. Elements of human cardiac dysfunction are hypothesized to develop from and/or cause similar changes in substrate utilization for energy production. For some individuals treatment that would prevent or reverse these changes may be appropriate.

Animals↗