Longer Isovolumic Relaxation Time Research Articles

Diastolic Dysfunction in Neonates With Hypoxic-Ischemic Encephalopathy During Therapeutic Hypothermia: A Tissue Doppler Study.

Diastolic dysfunction often complicates myocardial ischemia with increased mortality rates. However, less is known about diastolic function after perinatal asphyxia in neonates with hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia (TH) and rewarming.AimThe aim of this study was to assess diastolic function with tissue Doppler imaging (TDI) in neonates with moderate–severe HIE during TH and rewarming.MethodNewborns at >36 weeks' gestation with moderate–severe HIE treated with TH were evaluated with targeted neonatal echocardiography (TNE), including TDI, within 24 h of TH initiation (T1), at 48–72 h of treatment (T2), and after rewarming (T3). These retrospective data were collected and compared with a control group of healthy babies at >36 weeks' gestation that was prospectively evaluated following the same protocol.ResultsA total of 21 patients with HIE + TH and 15 controls were included in the study. Myocardial relaxation before the onset of biventricular filling was prolonged in the HIE + TH group during TH with significantly longer isovolumic relaxation time (IVRT') in the left ventricle (LV), the septum, and the right ventricle (RV). This was associated with slower RV early diastolic velocity (e') and prolonged filling on T1. Total isovolumic time (t-IVT; isovolumic contraction time [IVCT'] + IVRT') and myocardial performance index (MPI') were globally increased in asphyxiated neonates. All these differences persisted after correction for heart rate (HR) and normalized after rewarming. TDI parameters assessing late diastole (a' velocity or e'/a' and E/e' ratios) did not differ between groups.ConclusionTDI evaluation in our study demonstrated a pattern of early diastolic dysfunction during TH that normalized after rewarming, whereas late diastole seemed to be preserved. Our data also suggest a possible involvement of impaired twist/untwist motion and dyssynchrony. More studies are needed to investigate the impact and therapeutic implication of diastolic dysfunction in these babies, as well as to clarify the role of TH in these findings.

Signs of diastolic dysfunction are graded by serum testosterone levels in aging C57BL/6 male mice

We investigated whether maladaptive, age-associated changes in heart structure and function were linked to circulating testosterone levels. Male C57BL/6 mice had a gonadectomy (GDX) or sham surgery at 4 weeks and effects of GDX on the heart were examined with echocardiography. Serum testosterone was measured with ELISA. Left ventricular (LV) mass increased with age but was smaller in GDX mice than sham at 18 months (144.0 ± 8.7 vs 118.2 ± 11.9 mg; p = 0.009). The isovolumic relaxation time (IVRT) declined with age but was prolonged in GDX mice at 18 months (10.5 ± 0.8 vs 12.5 ± 0.5 msec, p = 0.008). Ejection fraction did not change with age or GDX, but E/A ratios were lower in GDX mice than controls at 18 months (1.6 ± 0.2 vs 1.3 ± 0.1, p = 0.021). When links between serum testosterone and cardiac parameters were examined longitudinally in 18−24-month-old mice, LV mass declined with decreasing testosterone (β = 37.70, p = 0.016), however IVRT increased as testosterone decreased (β=−2.69, p = 0.036). Since longer IVRT and lower E/A ratios are signs of diastolic dysfunction, low circulating testosterone may promote or exacerbate diastolic dysfunction in older males. These findings suggest that lower testosterone directly modifies heart structure and function to promote maladaptive remodeling and diastolic dysfunction in the aging heart.

Evaluation of Cardiac Functions in Children and Adolescents with Type 1 Diabetes.

BackgroundCardiac dysfunction in patients with type 1 diabetes (T1D) represents one of the serious complications. To evaluate the cardiac function in children with T1D by conventional echocardiography and tissue Doppler imaging (TDI).MethodsThe study included 40 T1D patients (age between 6 and 16 years) with > 5 years duration of diabetes and 42 healthy control children. The patients were subjected to clinical evaluation and laboratory investigations [glycosylated hemoglobin A1c (HbA1c), serum lipids and lipoproteins]. Conventional echocardiography and TDI were performed to patients and controls.ResultsThe patients had lower early diastolic filling velocity (E wave) of the tricuspid valve and mitral valves with a p value of (0.000 and 0.006, respectively). TDI revealed that patients had lower S′velocity of the T1D, shorter isovolumic contraction time, longer isovolumic relaxation time and lower E/E′ of the right ventricle than controls (p value 0.002, 0.001, 0.004, 0.003, and 0.016, respectively). The left ventricle (LV)-T1D of the patients was significantly higher (p value 0.02). Twenty eight patients had poor glycemic control without significant differences between them and those with good glycemic control regarding echocardiographic data. Patients with dyslipidemia (13 patients) had higher late diastolic filling velocity of the mitral valve (A) and the lower LV late tissue velocity (A′) (p wave 0.047 and 0.015). No correlation existed between the duration of illness or the level of HbA1c and the echocardiographic parameters.ConclusionDiabetic children have evidence of echocardiographic diastolic dysfunctions. Periodic cardiac evaluation with both conventional and tissue Doppler echocardiography is recommended for early detection of this dysfunction.

Predictors of respiratory instability in neonates undergoing patient ductus arteriosus ligation after the introduction of targeted milrinone treatment

IntroductionThe postoperative course of preterm babies undergoing surgical closure of a patent ductus arteriosus (PDA) is often complicated by postligation cardiac syndrome (PLCS). Despite targeted milrinone prophylaxis, some infants continue to experience postoperative respiratory deterioration. Our objective is to describe the immediate postoperative course and identify risk factors for respiratory instability when preterm infants undergoing PDA ligation are managed with targeted milrinone treatment. MethodsA retrospective review of a cohort of infants undergoing PDA ligation between January, 2010 and August, 2013 was conducted. All infants had a targeted neonatal echocardiogram performed 1 hour after surgery. Infants received prophylactic milrinone treatment if the left ventricular output was <200 mL/kg/min. The primary outcome measure was the development of respiratory instability within 24 hours of surgery. Multivariable logistic regression was performed to identify predictors of respiratory instability. ResultsEighty-six infants with a median gestational age of 25 weeks (interquartile range [IQR], 24-26) and a birth weight of 740 g (IQR, 640-853) were included in this study. Forty-nine (57.0%) received milrinone prophylaxis. There were 44 (51.2%) infants who developed oxygenation or ventilation failure, and 7 (8.1%) neonates developed PLCS. Infants with longer isovolumic relaxation time (IVRT ≥30 milliseconds) were more likely to develop either oxygenation or ventilation failure. ConclusionsAlthough the incidence of PLCS has declined after the introduction of targeted milrinone prophylaxis, many preterm infants continue to develop respiratory instability after surgical ligation. In this population, diastolic dysfunction manifested by prolonged IVRT could be associated with an adverse postoperative respiratory course.

The effect of L-thyroxine treatment on left ventricular functions in children with subclinical hypothyroidism

ObjectiveThe aim of this study was to search for evidence suggesting treatment for childhood subclinical hypothyroidism (SH) by evaluating left ventricular (LV) functions of children with SH by using M-mode...

Left ventricular function in Nigerian diabetics with or without hypertension

Objectives: This study evaluated left ventricular function, using echocardiographic methods, in Nigerian diabetics with additional aim of assessing the effect of coexisting hypertension. Design: A descriptive cross sectional study Setting: Hospital based study Subjects: Ninety five subjects aged 30-60 years comprising 31 hypertensive diabetics, 30 normotensive diabetics, and 34 age- and sex- matched non diabetic non hypertensive subjects as control. Main Outcome measures: All subjects had transthoracic 2D/Mmode and Doppler flow echocardiography performed to determine left ventricular systolic and diastolic functions. Results: Age and sex of the subjects were comparable. Duration of diabetics for hypertensive diabetics and normotensive diabetics were 36.78 ±31.26 months and 36.12 ± 47.50 months respectively. Mean fasting blood glucose was significantly higher in the normotensive diabetics (8.94 ± 2.13 mmol/L) than hypertensive diabetics (6.04 ± 2.01 mmol/L); p=0.038. There was stepwise reduction in Left Ventricular Ejection Fraction(LVEF) from normal controls (71.77 ± 8.26 %) to normotensive diabetics (65.34 ± 9.75 %) and hypertensive diabetics (64.29 ±10.99 %); p= 0.005. The diabetic subjects had impaired LV diastolic function, as shown by their significantly longer Isovolumic relaxation time (IVRT) and deceleration time and lower transmitral E: A ratio compared with controls. No statistically significant difference existed in these indices of LV diastolic function between the normotensive and hypertensive diabetics, though hypertensive diabetics had higher LVMI than the normotensive diabetics. Conclusion: Left ventricular function is impaired in diabetics. This may be independent of coexisting hypertension, though presence of hypertension appears to worsen it. Key words : diabetes, echocardiography, left ventricular function.

Three-dimensional echocardiographic assessment of left ventricular remodeling in predialysis chronic kidney disease patients

The aim of this study was to investigate the relations of left ventricular (LV) mass and geometry to LV function in patients with predialysis chronic kidney disease (CKD), by real-time 3-dimensional echocardiography (RT3-DE). Echocardiography was performed on 76 consecutively enrolled patients (51 men) with different stages of CKD, including 26 patients with mild CKD (CKD stages 1-2) and 50 patients with moderate-to-severe CKD (CKD stages 3-5). LV mass and LV end-diastolic volume were measured by RT3-DE. Greater prevalence of LV diastolic dysfunction and higher mitral E/myocardial velocities in early diastole (Em) values were noted in patients with moderate-to-severe CKD. In the moderate-to-severe CKD group, patients with increased LV mass had lower myocardial velocities in peak systole (Sm) and longer isovolumic relaxation time (IVRT). In the mild CKD group, patients with increased LV mass to volume ratios had lower Em. Moderate-to-severe CKD was associated with lower Sm and Em and higher mitral rapid filling to Em (E/Em) ratios by LV mass quartile stratification. Using LV mass/volume quartile stratification, moderate-to-severe CKD was associated with longer IVRT, lower Sm and higher mitral E/Em. Multivariable logistic regression analysis showed that CKD severity was the most independent predictor of elevated LV filling pressure (odds ratio = 2.96, p=0.019). Increased LV mass impaired LV contraction and relaxation in patients with moderate-to-severe CKD. Concentric remodeling impaired LV diastolic function in patients with mild CKD. CKD severity was positively associated with elevated LV filling pressure.

Increased relative wall thickness is a marker of subclinical cardiac target-organ damage in African diabetic patients : cardiovascular topic

To assess the prevalence and covariates of abnormal left ventricular (LV) geometry in diabetic outpatients attending Muhimbili National Hospital in Dar es Salaam, Tanzania. Echocardiography was performed in 61 type 1 and 123 type 2 diabetes patients. LV hypertrophy was taken as LV mass/height(2.7) > 49.2 g/m(2.7) in men and > 46.7 g/m(2.7) in women. Relative wall thickness (RWT) was calculated as the ratio of LV posterior wall thickness to end-diastolic radius and considered increased if ≥ 0.43. LV geometry was defined from LV mass index and RWT in combination. The most common abnormal LV geometries were concentric remodelling in type 1 (30%) and concentric hypertrophy in type 2 (36.7%) diabetes patients. Overall, increased RWT was present in 58% of the patients. In multivariate analyses, higher RWT was independently associated with hypertension, longer isovolumic relaxation time, lower stress-corrected midwall shortening and circumferential end-systolic stress, both in type 1 (multiple R(2) = 0.73) and type 2 diabetes patients (multiple R(2) = 0.66), both p < 0.001. These associations were independent of gender, LV hypertrophy or renal dysfunction. Increased RWT is common among diabetic sub-Saharan Africans and is associated with hypertension and LV dysfunction.

Impaired Cardiac Function Among Obese Adolescents

To measure cardiac function before and after 3 months of aerobic interval training in obese adolescents and to compare the findings with those in lean counterparts. Exercise intervention study. Cardiac function was assessed by echocardiography and maximal oxygen uptake by ergospirometry. The obese adolescents were referred from general practice to the St Olav University Hospital, Trondheim, Norway, and the control group was recruited from 2 schools. Ten obese adolescents (mean [SD] age, 14.8 [1.2] years; mean [SD] body mass index {BMI; calculated as weight in kilograms divided by height in meters squared}, 33.5 [4.3]) and 10 lean counterparts (mean [SD] age, 14.9 [1.3] years; mean [SD] BMI, 20.4 [3.0]) participated. Intervention Aerobic interval training (4 x 4 minutes at 90% of maximal heart rate, 40 minutes of training in total) was performed twice per week for 13 weeks among the obese adolescents, whereas the lean counterparts only performed the tests. Left ventricular end-diastolic volume, stroke volume, and maximal oxygen uptake. Maximal oxygen uptake was 41.4% lower among the obese adolescents compared with the lean counterparts, but the maximal oxygen uptake increased by 8.6% (P = .008) after intervention. Obese adolescents initially had 7.8% and 14.5% lower left ventricular end-diastolic and stroke volumes, 21.3% reduced global strain rate and 16.3% global strain, reduced mitral annulus excursion and systolic/diastolic tissue velocity, longer isovolumic relaxation time, and longer deceleration time compared with the lean counterparts. No group difference was observed after the intervention. Aerobic interval training increased the ejection fraction but was lower compared with the lean counterparts. Aerobic interval training reduced fat content by 2.0% (P = .005) among the obese adolescents. Aerobic interval training almost restored an impaired systolic and diastolic cardiac function among obese adolescents when compared with lean counterparts. These results may have implications for future treatment programs for obese adolescents.

Left ventricular diastolic function in patients with treated haemochromatosis

Objectives. We recently demonstrated reduced exercise capacity in phlebotomy treated genetic haemochromatosis in spite of normal systolic function. The present objective was to investigate diastolic function at rest. Design. Diastolic function was echocardiographically assessed in 132 phlebotomy treated genetic haemochromatosis patients and 50 controls. Results. Patients had higher body mass index and heart rate, higher transmitral early (E) (11.2±2.6 versus 10.4±2.2 cm) and atrial (A) (5.7±1.6 versus 5.0±1.6) velocity time integrals, pulmonary venous systolic peak velocity (0.58±0.12 versus 0.54±0.13 m/s) and ratio of E to spectral tissue Doppler E′ velocity (6.3±1.6 versus 5.6±1.4, all p <0.05). Independently of age, heart rate, systolic blood pressure and body weight, having haemochromatosis remained statistically significantly associated with higher E (β =0.27) and A (β =0.18) velocity time integrals, pulmonary venous systolic peak velocity (β =0.21), and E/E′-ratio (β =0.25) in separate multivariate analyses (all p <0.05). In the youngest age tertile, patients had longer isovolumic relaxation time and lower E′ than controls. Conclusion. Our findings are compatible with mildly impaired diastolic function in treated haemochromatosis, with delayed relaxation in the younger tertile, and an elevated filling pressure and pseudonormalisation with increasing age.

Independent Association of Coronary Flow Reserve with Left Ventricular Relaxation and Filling Pressure in Arterial Hypertension

It has been recognized that "cross-talk" occurs between coronary flow and left ventricular (LV) function. This study tested the hypothesis that impairment of coronary flow reserve (CFR) in arterial hypertension is associated with LV systolic and diastolic dysfunction, independent of abnormalities in LV geometry. We studied 59 newly diagnosed, never-treated hypertensive patients, using transthoracic Doppler echocardiography including pulsed Tissue Doppler of mitral annulus and CFR on left anterior descending artery (low-dose dipyridamole). The study population was divided into two groups on the basis of age-normalized relative wall thickness (RWTn): 36 patients with normal LV geometry (RWTn < or = 0.41) and 23 patients with LV concentric geometry (RWTn > 0.41). Patients with LV concentric geometry (RWTn > 0.41) had significantly lower values of midwall shortening (but not of endocardial shortening), longer isovolumic relaxation time (IVRT), lower Tissue Doppler-derived early diastolic velocity (Em), higher ratio of transmitral E velocity to Em, and lower CFR as compared to patients with normal LV geometry (RWTn < or = 0.41). In the whole population, a lower CFR was significantly associated with lower values of midwall shortening and Em, longer IVRT, and higher E/Em ratio. After controlling for heart rate, mean blood pressure, and RWTn, only the relation of CFR with IVRT, Em, and E/Em ratio remained significant. Reduced midwall mechanics is associated with lower CFR, a relationship that depends on LV concentric geometry. A reduced CFR is associated with both impaired relaxation and increased filling pressure, a relation that is independent of LV geometry and pressure load.

AT1receptor antagonism attenuates target organ effects of salt excess in SHRs without affecting pressure

Our recent studies have demonstrated that salt excess in the spontaneously hypertensive rat (SHR) produces a modestly increased arterial pressure while promoting marked myocardial fibrosis and structural damage associated with altered coronary hemodynamics and ventricular function. The present study was designed to determine the efficacy of an angiotensin II type 1 (AT(1)) receptor blocker (ARB) in the prevention of pressure increase and development of target organ damage from high dietary salt intake. Eight-week-old SHRs were given an 8% salt diet for 8 wk; their age- and gender-matched controls received standard chow. Some of the salt-loaded rats were treated concomitantly with ARB (candesartan; 10 mg kg(-1) day(-1)). The ARB failed to reduce the salt-induced rise in pressure, whereas it significantly attenuated left ventricular (LV) remodeling (mass and wall thicknesses), myocardial fibrosis (hydroxyproline concentration and collagen volume fraction), and the development of LV diastolic dysfunction, as shown by longer isovolumic relaxation time, decreased ratio of peak velocity of early to late diastolic waves, and slower LV relaxation (minimum first derivative of pressure over time/maximal LV pressure). Without affecting the increased pulse pressure by high salt intake, the ARB prevented the salt-induced deterioration of coronary and renal hemodynamics but not the arterial stiffening or hypertrophy (pulse wave velocity and aortic mass index). Additionally, candesartan prevented the salt-induced increase in kidney mass index and proteinuria. In conclusion, the ARB given concomitantly with dietary salt excess ameliorated salt-related structural and functional cardiac and renal abnormalities in SHRs without reducing arterial pressure. These data clearly demonstrated that angiotensin II (via AT(1) receptors), at least in part, participated importantly in the pressure-independent effects of salt excess on target organ damage of hypertension.

Excessive increase in left ventricular mass identifies hypertensive subjects with clustered geometric and functional abnormalities

Left ventricular mass (LVM) exceeding needs to sustain haemodynamic load has been termed 'inappropriate left ventricular mass'. We hypothesized that inappropriate LVM identifies hypertensive patients with clustered cardiac geometric and functional abnormalities. For this purpose, 359 hypertensive individuals without prevalent cardiovascular disease underwent Doppler echocardiography. Observed LVM exceeding more than 28% of the value predicted for individual cardiac work, body size and sex was defined as inappropriate LVM. Concentric left ventricular geometry was defined as age-adjusted relative wall thickness (RWT) greater than 0.40. Systolic dysfunction was defined as ejection fraction less than 50% or midwall shortening less than 14.7%. Diastolic dysfunction was defined as isovolumic relaxation time (IVRT) greater than 100 ms, E-velocity deceleration time greater than 220 ms or age and heart rate-normalized early/late (E/A) ratio less than 0.66. Left ventricular hypertrophy (LVH) was defined as an LVM index greater than 49.2 g/m2.7 in men and 46.7 g/m2.7 in women. As expected, inappropriate LVM was associated with higher RWT, lower left ventricular systolic function, longer IVRT and prolonged E-deceleration time (all P < 0.05). Patients with inappropriate LVM had a higher prevalence of concentric geometry (65.5 versus 40.4%), systolic dysfunction (67.9 versus 47.4%) and diastolic dysfunction (46.4 versus 39%; all P < 0.001) than those with LVH. Inappropriate LVM had greater sensitivity (0.89 versus 0.54) and specificity (0.82 versus 0.62; both P < 0.01) than LVH in identifying patients with clustered left ventricular concentric geometry, systolic and diastolic dysfunction. Inappropriate LVM is associated with a cluster of concentric left ventricular geometry, delayed left ventricular relaxation and reduced systolic performance. Compared with LVH, inappropriate LVM is more accurate at identifying patients with clustered left ventricular geometric and functional abnormalities.

Echocardiography as a Noninvasive Swan-Ganz Catheter

Diwan and co-investigators report in this issue of Circulation that the interval between onset of mitral E and annular early diastolic velocity (Ea) by tissue Doppler, TE−Ea, can be used to estimate left ventricular (LV) filling pressure in patients with mitral valve disease.1 Garcia and colleagues were the first to report that the onset of Ea occurred 7.5±3.5 ms after peak mitral inflow velocity in 7 patients with restrictive cardiomyopathy, whereas Ea started 22±19 ms earlier than did E in the normal group.2 Subsequently, TE−Ea has been shown to correlate with the time constant of LV relaxation (τ) demonstrated by Hasegawa and associates in their elegant animal experiment.3 With worsening of heart failure by rapid pacing, Ea progressively decreased in velocity and delayed in onset. Mitral E occurred coincidently with the termination of the early diastolic left arterial (LA) and LV pressure gradient at baseline and all stages of heart failure. In contrast, with increasing heart failure, Ea was progressively delayed after LA to LV pressure crossover, and TE−Ea was related to τ. Rivas-Gotz, Nagueh, and their associates also demonstrated that TE−Ea was prolonged after constriction of the circumflex coronary artery in dogs.4 In patients with heart failure, LV myocardial relaxation and compliance are decreased. See p 3281 Although LV filling is initiated and enhanced by augmentable myocardial relaxation in healthy individuals, it is driven by high filling pressure in patients with heart failure because myocardial relaxation remains reduced, not being sensitive to preload. Myocardial relaxation also affects the isovolumic relaxation time (IVRT). As relaxation becomes abnormal, LV pressure falls more slowly and the opening of the mitral valve is delayed, resulting in a longer IVRT. IVRT, however, becomes shorter as LA pressure increases; hence, IVRT∝τ/LA pressure. Because TE−Ea∝τ, …

Prognostic significance of the left ventricular contractility index in patients with essential hypertension

The aim of the study was to assess the relationship between the left ventricular (LV) contractility index, cardiac function and extracardiac organ damage in essential hypertension (EH). We have studied 142 patients (pts) with EH, age 43–52 years, free of signs of heart failure, normal values of the LV ejection fraction and fractional shortening. From M-mode Echo midwall fractional shortening (mFS)(de Simone method), end-systolic stress ESS (Reichek method) were calculated. LV contractility index was assessed as mFS in relation to ESS(mFS/ESS). Early filling velocity (E), late filling velocity (A), E/A ratio, isovolumic relaxation time (IVRT) and deceleration time (DT) were determined by Doppler-Echo. Albuminuria was measured as albumin to creatinine ratio (ACR). Retinal vascular changes were evaluated by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of LV hypertrophy and depressed LV contractility were 68.0 and 43.0%, respectively. The pts with depressed LV contractility index showed high prevalence of LV hypertrophy (86.7% vs 32.3%, p<0.001), especially eccentric hypertrophy (58.0% vs 14.2%, p<0.001). Pts with depressed mFS/ESS had longer IVRT and DT with significant difference in peak E-, A-wave and E/A ratio (IVRT-157.5±9.40 vs 120.0±10.0 ms; 292.5 ±23.4 vs 214.0±6.1 ms; E-60.5±2.43 vs 70.2±1.28 cm/s; A-71.2±2.70 vs 52.0±1.64 cm/s; E/A-0.96 ±0.04 vs 1.20 ±0.08, p<0.01 for all). IVRT and DT showed a strong relation to mFS/ESS (r=−0.67 and r=−0.69, respectively, p<0.01 for both). Moreover hypertensives with depressed mFS/ESS showed early signs of extracardiac damage namely increased ACR (3.2±0.6 vs 1.2 ±0.08, p<0.01) and serum creatinine (3.6±1.2 vs 1.0±0.06 mg%, p<0.05), a higher prevalence of retinopathy (fundoscopy grade II or beyond) compared with subjects with preserved contractility (89.0% vs 40.0%, p<0.001). Furthermore, mFS/ESS was strongly associated with ACR and serum creatinine level in an univariate analysis (r=−0.59 and r=−0.62, respectively, p<0.01 for both) and these associations were still present after stepwise multivariate analysis. Pts with depressed contractility show a higher prevalence of LV hypertrophy, diastolic dysfunction and early signs of extracardiac vascular damage. The evaluation of LV contractility index might improve the prognostic stratification of hypertensive pts and it might be suitable to recognize subset of pts at higher risk.

Left ventricular diastolic function after anthracycline chemotherapy in childhood: relation with systolic function, symptoms, and pathophysiology.

To examine left ventricular (LV) diastolic function in patients previously treated with anthracycline drugs for childhood malignancy. To consider clinical relevance, relations with systolic dysfunction, and the pathophysiology of anthracycline cardiotoxicity. Cross sectional echocardiographic study of LV function. Supraregional centre for paediatric cardiology, principal centre for the treatment of childhood malignancy in southwest England. 226 of 236 patients surviving between 6.5 months and 17 (median 5.3) years from initial anthracycline treatment for childhood malignancy attended for clinical and echocardiographic examination. Cumulative anthracycline doses were between 50 and 750 (median 300) mg/m2. 22 patients had also received cardiac irradiation. Detailed assessment of transmitral diastolic pulsed wave Doppler flow patterns along with LV dimensions and systolic function measured by M mode echocardiography. Peak early (E) and atrial (A) phase filling velocities and EA ratio, time and acceleration and deceleration to and from peak E velocity, velocity integrals and ratio, isovolumic relaxation time (IVRT), and heart rate were measured. Results were examined in relation to LV cavity and posterior wall dimensions and shortening fraction (SF), and compared with paired control data matched for body surface area. Eleven (5%) patients had abnormal effort tolerance. Fifty one (23%) had SF < 30% and SF was inversely correlated with cumulative dose and time from treatment. The relative risk of symptomatic cardiac failure was greatly increased by prior irradiation; > 60% of irradiated patients who received > 400 mg/m2 of anthracycline were symptomatic. Early diastolic filling was relatively normal or enhanced at low anthracycline doses or when SF was preserved, with a shorter IVRT and increased atrial phase filling. Early filling was reduced at higher doses or with reduced SF, with longer IVRT and a further increase in atrial phase filling. A more "restrictive" pattern of diastolic filling (with high E and low A velocities) was seen in some patients, particularly after cardiac irradiation. Significant abnormalities of diastolic function are associated with anthracycline induced cardiac damage. These are not linearly related to anthracycline dose but appear to reflect the underlying myocardial pathophysiology associated with anthracycline toxicity, which is not demonstrated by the standard M mode echocardiogram. Although the overall clinical significance of such diastolic dysfunction is uncertain, some individual abnormalities may have significant management and therapeutic implications.

Use of Valsalva maneuver to unmask left ventricular diastolic function abnormalities by Doppler echocardiography in patients with coronary artery disease or systemic hypertension

It has been suggested that changes in left atrial pressure may mask or mimic left ventricular diastolic function abnormalities detected by Doppler echocardiography. The effect of the Valsalva maneuver on the transmitral flow velocity profile was therefore studied in 28 patients without evidence of coronary artery disease (group 1, mean age ± standard deviation 50 ± 8 years) and in 94 patients with evidence of coronary artery disease or systemic hypertension (group 2, mean age 54 ± 10 years). At baseline, group 2 patients had higher peak late diastolic filling velocity (A), lower peak early (E) to late diastolic filling velocity ( E A ) ratio and longer isovolumic relaxation time than group 1, whereas heart rate, E velocity and E deceleration time were similar in both groups. During Valsalva, both groups had similar increases in heart rate and similar decreases in E velocity but E A ratio decreased significantly only in group 2 because of a lesser decrease in A velocity. The E A ratio was ≥1.0 both before and during Valsalva in all but 1 patient in group 1, whereas in group 2, 32 patients had E A ≥1.0 at rest and during Valsalva, 33 patients had E A ≥1.0 at rest but <1.0 during Valsalva and 29 patients had E A <1.0 both at rest and during Valsalva. Using group 1 as controls, prevalence, specificity and positive predictive value of E A <1.0 in group 2 were 31, 100 and 100% at rest and 66, 96 and 98% during Valsalva. The correct classification of patients in groups 1 and 2 on the basis of E A ratio <1.0 was 47% at rest and 73% during Valsalva. This study shows that the Valsalva maneuver is an easy means of obtaining a reduction in left atrial pressure during Doppler echocardiography and helps unmask otherwise unsuspected diastolic function abnormalities.