Improved metabolic control does not reverse left ventricular filling abnormalities in newly diagnosed non-insulin-dependent diabetes patients

In this study left ventricular diastolic function at rest was evaluated in ten newly diagnosed, non-insulin-dependent diabetic patients by Doppler echocardiography, performed at the onset of disease and after 6 and 12 months of adequate glycaemic control. Glycosylated haemoglobin A1C, total cholesterol and triglyceride levels were assessed at the same time. The control group consisted of ten healthy subjects of matching age and body mass index. The following parameters of left ventricular function were evaluated: ejection fraction (EF), peak velocity of the early (E) and late atrial (A) mitral flow, A/E ratio, duration of the early (Ei) and of the atrial (Ai) filling phase, and heart rate. The diabetic patients had significantly higher total cholesterol and triglyceride levels compared with healthy subjects. These remained elevated throughout the follow-up period, in spite of improved glycaemic control. A significantly shorter duration of Ei (0.15 +/- 0.008 vs 0.18 +/- 0.004, P < 0.01) and a higher value of A (0.51 +/- 0.02 vs 0.39 +/- 0.01, P < 0.001) and A/E (1.06 +/- 0.05 vs 0.73 +/- 0.02, P < 0.001) were found in the diabetic patients before treatment. The parameters did not significantly change after 1 year of adequate glycaemic control. These results indicate a left ventricular filling abnormality which is present in newly diagnosed non-insulin-dependent diabetic patients and does not reverse with improved glycaemic control.     

Differences in myocardial velocity gradient measured throughout the cardiac cycle in patients with hypertrophic cardiomyopathy, athletes and patients with left ventricular hypertrophy due to hypertension

OBJECTIVES: We sought to compare the myocardial velocity gradient (MVG) measured across the left ventricular (LV) posterior wall during the cardiac cycle between patients with hypertrophic cardiomyopathy (HCM), athletes and patients with LV hypertrophy due to systemic hypertension and to determine whether it might be used to discriminate these groups. BACKGROUND: The MVG is a new ultrasound variable, based on the color Doppler technique, that quantifies the spatial distribution of transmyocardial velocities. METHODS: A cohort of 158 subjects was subdivided by age into two groups: Group I (mean [+/-SD] 30 +/- 7 years) and Group II (58 +/- 8 years). Within each group there were three categories of subjects: Group Ia consisted of patients with HCM (n = 25), Group Ib consisted of athletes (n = 21), and Group Ic consisted of normal subjects; Group IIa consisted of patients with HCM (n = 19), Group IIb consisted of hypertensive patients (n = 27), and Group IIc consisted of normal subjects (n = 33). RESULTS: The MVG (mean [+/-SD] s-1) measured in systole was lower (p < 0.01) in patients with HCM (Group Ia 3.2 +/- 1.1; Group IIa 2.9 +/- 1.2) compared with athletes (Group Ib 4.6 +/- 1.1), hypertensive patients (Group IIb 4.2 +/- 1.8) and normal subjects (Group Ic 4.4 +/- 0.8; Group IIc 4.8 +/- 0.8). In early diastole, the MVG was lower (p < 0.05) in patients with HCM (Group Ia 3.7 +/- 1.5; Group IIa 2.6 +/- 0.9) than in athletes (Group Ib 9.9 +/- 1.9) and normal subjects (Group Ic 9.2 +/- 2.0; Group IIc 3.6 +/- 1.5), but not hypertensive patients (Group IIb 3.3 +/- 1.3). In late diastole, the MVG in patients with HCM (Group Ia 1.3 +/- 0.8; Group IIa 1.4 +/- 0.8) was lower (p < 0.01) than that in hypertensive patients (Group IIb 4.3 +/- 1.7) and normal subjects (Group IIc 3.8 +/- 0.9). An MVG < or = 7 s-1, as a single diagnostic approach, differentiated accurately (0.96 positive and 0.94 negative predictive value) between patients with HCM and athletes when the measurements were taken during early diastole. CONCLUSIONS: In both age groups, the MVG was lower in both systole and diastole in patients with HCM than in athletes, hypertensive patients or normal subjects. The MVG measured in early diastole in a group of subjects 18 to 45 years old would appear to be an accurate variable used to discriminate between HCM and hypertrophy in athletes.     

Observation on left ventricular diastolic function of patients with heart-deficiency syndrome of cardiovascular diseases

In this paper, left ventricular diastolic function (LVDF) of 99 Heart-Deficiency Syndrome (HDS) patients was observed with pulse Doppler echocardiogram and was compared with normal group. The results showed that different LVDF abnormalities occurred in the HDS patients. When E, Ei DC were decreased and A, Ai, A/E, Ai/Ei, IRT increased, the degree of HDS deteriorated, the pattern was Heart Qi-Yin Deficiency > Heart Yang Deficiency > Heart Qi Deficiency > Heart Yin Deficiency. In conclusion, the above parameters of LVDF could be important indices for evaluation of HDS.     

Three-dimensional left ventricular deformation in hypertrophic cardiomyopathy

BACKGROUND: In hypertrophic cardiomyopathy, ejection fraction is normal or increased, and force-length relations are reduced. However, three-dimensional (3D) motion and deformation in vivo have not been assessed in this condition. We have reconstructed the 3D motion of the left ventricle (LV) during systole in 7 patients with hypertrophic cardiomyopathy (HCM) and 12 normal volunteers by use of magnetic resonance tagging. METHODS AND RESULTS: Transmural tagging stripes were automatically tracked to subpixel resolution with an active contour model. A 3D finite-element model was used to interpolate displacement information between short- and long-axis slices and register data on a regional basis. Displacement and strain data were averaged into septal, posterior, lateral, and anterior regions at basal, midventricular, and apical levels. Radial motion (toward the central long axis) decreased slightly in patients with HCM, whereas longitudinal displacement (parallel to the long axis) of the base toward the apex was markedly reduced: 7.5 +/- 2.5mm (SD) versus 12.5 +/- 2.0 mm, P < .001. Circumferential and longitudinal shortening were both reduced in the septum (P < .01 at all levels). The principal strain associated with 3D maximal contraction was slightly depressed in many regions, significantly in the basal septum (-0.18 +/- 0.05 versus -0.22 +/- 0.02, P < .05) and anterior (-0.20 +/- 0.05 versus -0.23 +/- 0.02, P < .05) walls. In contrast, LV torsion (twist of the apex about the long axis relative to the base) was greater in HCM patients (19.9 +/- 2.4 degrees versus 14.6 +/- 2.7 degrees, P < .01). CONCLUSIONS: HCM patients had reduced 3D myocardial shortening on a regional basis; however, LV torsion was increased.     

31P NMR spectroscopy detects metabolic abnormalities in asymptomatic patients with hypertrophic cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) often causes sudden, unexpected death in adolescents and young adults. Alterations in myocardial metabolism are considered to be causes for contractile dysfunction. We examined the question of whether metabolic abnormalities antedate the manifestation of symptoms in patients with HCM. METHODS AND RESULTS: Proton-decoupled 31P NMR spectroscopy of the anterior left ventricular wall of the heart of 14 young, asymptomatic patients with HCM was performed with a 1.5-T whole-body imager. Spectra of the phosphate metabolites were compared with those of normal control subjects. The patients exhibited a significantly reduced (P<0.02) ratio of phosphocreatine (PCr) to ATP of 1.98+/-0.37 (mean+/-SD), compared with 2.46+/-0.53 obtained in 11 normal control subjects. In addition, the group of patients with severe hypertrophy of the interventricular septum (n=8) showed a significantly increased (P<0.05) Pi-to-PCr ratio, with a Pi x 100/PCr of 20.0+/-8.3 versus 9.7+/-7.2 in control subjects. Both abnormalities are similar to those found in ischemic myocardium. This view is also supported by a significantly increased (P<0.01) phosphomonoester (PME)-to-PCr ratio, with a PME x 100/PCr of 20.7+/-11.2 compared with 8.4+/-6.7 in control subjects, indicating altered glucose metabolism. CONCLUSIONS: 31P NMR spectroscopy detects alterations of myocardial metabolism in asymptomatic patients with HCM. These alterations may contribute to the understanding of the pathophysiology and natural history of the disease.     

Changes in left ventricular diastolic function 6 months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy

BACKGROUND: Nonsurgical septal reduction therapy (NSRT) decreases left ventricular outflow tract (LVOT) gradient and improves symptoms in patients with hypertrophic obstructive cardiomyopathy (HOCM). NSRT effects on LV/left ventricular diastolic function are currently unknown. METHODS AND RESULTS: HOCM patients (n=29) had Doppler echocardiography at baseline and 6 months after NSRT to evaluate changes in LV volume, pre-A-wave pressure, early diastolic mitral annulus velocity (Ea) by tissue Doppler, and tau. At 6 months, a significant reduction in LVOT gradient (from 53.6+/-15 to 6+/-5 mm Hg; P<0.001) was accompanied by improvement in exercise duration (from 284+/-147 to 408+/-178 seconds; P=0.04) and New York Health Association class (from III to I; P<0.001). Pre-A pressure (18+/-6 to 14+/-5 mm Hg; P<0.01) and tau (62+/-8 to 51+/-8 ms; P<0.01) decreased, whereas Ea (5.8+/-1.8 to 8+/-1.8 cml/s; P<0.01) and LV end-diastolic volume (117+/-16 to 130+/-22 mL; P<0.01) increased. CONCLUSIONS: NSRT improves LV relaxation and compliance, which contributes to the symptomatic relief seen at 6 months.     

Bronchodilator response to salbutamol after chronic dosing with salmeterol or placebo

OBJECTIVES: We report the occurrence of cardiac events during long-term follow-up in patients with hypertrophic cardiomyopathy (HCM) after cardioverter-defibrillator implantation. BACKGROUND: The identification of patients at high risk for sudden death and the prevention of recurrence of sudden death in HCM represents a difficult problem. METHODS: We retrospectively analyzed the occurrence of cardiac events during follow-up of 13 patients with HCM who received an implantable cardioverter-defibrillator (ICD) because of aborted sudden death (n = 10) or sustained ventricular tachycardia (n = 3) (group I). Findings were compared with those in 215 patients with an ICD and other structural heart disease or idiopathic ventricular fibrillation (group II). RESULTS: After a mean (+/-SD) follow-up period of 26+/-18 months, 2 of 13 patients in group I received appropriate shocks. The calculated cumulative incidence of shocks was 21% in group I and 66% in group II after 40 months (p < 0.05). We observed a low incidence of recurrence of ventricular tachycardia/fibrillation during follow-up in patients with HCM. No deaths occurred. CONCLUSIONS: Our data suggest that ventricular tachyarrhythmias may not always be the primary mechanism of syncope and sudden death in patients with HCM. The ICD seems to have a less important impact on prognosis in patients with HCM than in patients with other etiologies of aborted sudden death.     

Cerebrovascular and cardiovascular responses to graded tilt in patients with autonomic failure

BACKGROUND AND PURPOSE: Patients with autonomic nervous system failure often experience symptoms of orthostatic intolerance while standing. It is not known whether these episodes are caused primarily by a reduced ability to regulate arterial blood pressure or whether changes in cerebral autoregulation may also be implicated. METHODS: Eleven patients and eight healthy age- and sex-matched control subjects were studied during a graded-tilt protocol. Changes in their steady state middle cerebral artery mean flow velocities (MFV), measured by transcranial Doppler, brain-level mean arterial blood pressures (MABPbrain), and the relationship between the two were assessed. RESULTS: Significant differences between patients and control subjects (P < .05) were found in both their MFV and MABPbrain responses to tilt. Patients' MFV dropped from 60 +/- 10.2 cm/s in the supine position to 44 +/- 14.0 cm/s at 60 degrees head-up tilt, whereas MABPbrain fell from 109 +/- 11.7 to 42 +/- 16.9 mm Hg. By comparison, controls' MFV dropped from 54 +/- 7.8 cm/s supine to 51 +/- 8.8 cm/s at 60 degrees, whereas MABPbrain went from 90 +/- 11.2 to 67 +/- 8.2 mm Hg. Linear regression showed no significant difference in the MFV-MABPbrain relationship between patients and control subjects, with slopes of 0.228 +/- 0.09 cm.s-1.mm Hg-1 for patients and 0.136 +/- 0.16 cm.s-1.mm Hg-1 for control subjects. CONCLUSIONS: The present study found significant differences between patients and control subjects in their MFV and MABPbrain responses to tilt but no difference in the autoregulatory MFV-MABPbrain relationship. These results suggest that patients' decreased orthostatic tolerance may primarily be the result of impaired blood pressure regulation rather than a deficiency in cerebral autoregulation.     

Familial hypertrophic cardiomyopathy. Cardiac ultrasonic abnormalities in genetically affected subjects without echocardiographic evidence of left ventricular hypertrophy

AIMS: It is not known whether the apparent normality of echocardiographic examination results, in subjects bearing a mutation for hypertrophic cardiomyopathy but without ultrasonic left ventricular hypertrophy, is due to incomplete phenotypic expression, or inaccurate echocardiographic criteria. The aim of this study was to search for echocardiographic abnormalities in these patients. METHODS AND RESULTS: Echocardiography was performed in 100 subjects from two families with a mutation in the beta-MHC (720) or My-BPC (714) genes. We compared genetically affected subjects with an apparently normal left ventricle (thickness < 13 mm) (20 patients), and nonaffected first-degree relatives (61 normal subjects). (1) Patients had a thicker left ventricular wall (9.7 +/- 1.4 vs 8.9 +/- 1.4 mm, P = 0.03), a greater indexed mass (107 +/- 18 vs 97 +/- 17 g. m-2, P = 0.03), a larger left atrium (27 +/- 9 vs 23 +/- 10 mm3, P = 0.09) and lower wall stress (78 +/- 11 vs 89 +/- 15 10(3) dynes. cm-2, P = 0.002); these differences were highly significant after adjustment for height, age and systolic blood pressure either for wall thickness (P = 0.000003), mass (P = 0.005) or atrial volume (P = 0.001), and the ventricular systolic dimension appeared smaller (P = 0.01); (2) results remained significant (P < 0.01) when a lower cut-off value (< or = 11 mm) or only adults (> or = 18 years) were considered; (3) a subanalysis of Family 714 (13 patients, 25 normals matched for sex, age and height) showed the same trends. CONCLUSION: In familial hypertrophic cardiomyopathy, genetically affected subjects with an apparently normal heart by echocardiography show slight ultrasonic structural and functional left ventricular modifications, suggesting that the phenotype of the disease is a continuous spectrum from normal structure to typical hypertrophy.     

Echocardiography-guided ethanol septal reduction for hypertrophic obstructive cardiomyopathy

BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is frequently responsible for symptoms in hypertrophic obstructive cardiomyopathy (HOCM). Medical therapy is often not sufficient to control these symptoms, and surgical myotomy-myomectomy is required. METHODS AND RESULTS: We enrolled 33 symptomatic patients with HOCM and obstruction (>/=40 mm Hg gradient at rest or >/=60 mm Hg dobutamine-provoked). By contrast echocardiography, the bulging septum was localized and infarcted by injection of 2 to 5 mL of absolute ethanol into the septal artery(ies) supplying the hypertrophied area. Baseline echocardiograms with Doppler, myocardial perfusion tomograms, and treadmill exercise or pharmacological testing were compared with those at 6 weeks and 6 months. The mean rise in creatine kinase was 1964+/-796 U. All patients experienced symptomatic relief; NYHA class decreased from 3. 0+/-0.5 to 0.9+/-0.6 (P<0.001). Exercise time increased from 286+/-193 to 421+/-181 seconds (P=0.03). The resting and dobutamine-provoked gradient decreased from 49+/-33 and 96+/-34 mm Hg to 9+/-19 (P<0.001) and 24+/-31 mm Hg (P<0.001), respectively. Echocardiograms repeated at 6 weeks after the procedure showed a 28% reduction in septal thickness and 17% reduction in left ventricular mass. Myocardial perfusion imaging showed a "septal amputation pattern," with scarring in the upper and middle septal areas. Complete heart block developed in 11 patients, who then required permanent pacemaker implantation. CONCLUSIONS: Echocardiography-guided ethanol septal reduction in patients with HOCM is a safe, minimally invasive procedure that provides symptomatic relief with improved hemodynamic and left ventricular parameters.     

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index

Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. 'Up BRS' sequences-increases in systolic blood pressure associated with lengthening of R-R interval, and 'down BRS' sequences-decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. 'Up BRS' when supine was 11.2 +/- 1.5 ms/mmHg (mean +/- SEM) compared with 20.4 +/- 1.95 in control subjects (p < 0.003) and when standing was 4.1 +/- 1.9 vs 7.6 +/- 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 +/- 1.2 vs 22 +/- 2.6 (p < 0.001) and standing was 4.4 +/- 1.9 vs 7.3 +/- 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05-0.15 Hz as low-frequency and 0.2-0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 +/- 62.8 vs 746.6 +/- 77.6 ms2 p = 0.002) and high frequency bands 125.2 +/- 12.9 vs 459.3 +/- 89.8 ms2 p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 +/- 0.53 vs 4.6 +/- 0.55, p < 0.002 supine: 3.8 +/- 0.49 vs 6.6 +/- 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients.     

Clinical course of hypertrophic cardiomyopathy in a non selected population. The Experience of the Italian Multicenter Cardiomyopathy Study

BACKGROUND: Most of the information available on the clinical course and prognosis of hypertrophic cardiomyopathy (HCM) is based on data generated from international referral centres and as a result, it constitutes a potentially biased perspective of the disease process in this complex and diverse condition. A multicentric study was therefore set up with the aim of providing information on unselected patient populations with HCM. METHODS: The study group comprised 330 patients from 5 non-referral hospitals (mean age 42 +/- 16 years, M/F 226/104, 74-22%-obstructive, 299-91%-in NYHA class I-II) who were followed up regularly for 9.5 +/- 5.6 years. RESULTS: The vast majority of patients (n = 272, 82%) remained asymptomatic or mildly symptomatic during the follow-up period, whereas the remaining patients (n = 58, 18%) experienced clinical deterioration or died. Of the 18 patients (5%) who died of cardiovascular causes related to hypertrophic cardiomyopathy, 14 had progressive congestive heart failure and only 4 died suddenly. The annual mortality rate for cardiovascular disease was 0.57%, while the mortality rate due to sudden cardiac death was only 0.1%. The cumulative survival rate was 98, 95 and 93%, at 5, 10 and 15 years of follow-up respectively. Atrial fibrillation proved to be a relatively common (n = 81, 24%) and particularly unfavourable clinical feature, with higher mortality rate for cardiovascular causes related to hypertrophic cardiomyopathy. Syncope occurred in 47 patients (14%) but did not appear to have prognostic significance. CONCLUSIONS: In an unselected population, hypertrophic cardiomyopathy had a relatively benign prognosis that was inconsistent with its prior characterization as a generally progressive disorder, based primarily on the experience of selected referral institutions. Sudden unexpected cardiac death was distinctly uncommon, although a sizable proportion of patients, particularly the subset prone to atrial fibrillation, did experience clinical deterioration.     

How dangerous is genetic technology?]

Nonuniform hypertrophy of the left ventricle is an important factor in regional diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM). However, the effect of myocardial perfusion abnormalities on regional diastolic dysfunction has not been established in patients with HCM. We investigated the relationship between regional myocardial perfusion abnormalities and regional early diastolic function in 31 patients with HCM and 8 control patients. Short-axis images of the left ventricle recorded by cine magnetic resonance imaging were divided into ten blocks. The time-to-peak-wall-thickness-thinning rate (TPWR) and the wall thickness were measured in each block. Of the 310 blocks from the patients with HCM, 242 (78%) showed normal thallium-201 uptake (group 1), 40 (13%) showed slightly decreased uptake (group 2), and 28 (9%) showed markedly decreased uptake (group 3). There was no difference in the regional wall thickness among the three groups. The TPWR was longer in patients with HCM than in control patients. It was significantly longer in group 3 (190+/-45ms) than in group 1 (167+/-36 ms) and group 2 (160+/-31 ms). (P < 0.01). The linear regression slope of the relationship between the TPWR and the regional wall thickness was significantly steeper in group 3 than in groups 1 and 2 (P < 0.05). In conclusion, abnormalities in regional myocardial perfusion, in addition to regional hypertrophy, contributed to the regional early diastolic dysfunction in patients with HCM.     

Cloning, characterisation and expression of the alpha-tubulin genes of the leech, Hirudo medicinalis

BACKGROUND: Exercise testing has long been employed in patients with hypertrophic cardiomyopathy (HCM), although concerns have constantly been expressed regarding its safety. This study reviews a large number of exercise tests performed in a community-based population with HCM, in terms of safety and clinical utility. METHODS: We analyzed a total of 243 maximal symptom-limited cycloergometer exercise tests performed at our institution in 138 patients with HCM (age 42 +/- 14 years, M/F 99/39), who were followed systematically for 9.4 +/- 6.5 years. RESULTS: In none of the 243 exercise tests did cardiac arrest, hemodynamic collapse or malignant arrhythmia occur, although 53 of the study patients (38%) had > or = 1 risk factors including previous cardiac arrest, recurrent syncope, malignant family history and resting left ventricular outflow obstruction. Early termination of the test was necessary in only 8 patients due to symptomatic hypotension with dizziness, but none had syncope. Mean predicted functional capacity achieved by the study group was 77 +/- 22%. Poor performance (< 60% of predicted functional capacity) was observed in 32 patients (23%), and it was associated with a NYHA functional class > 1 and an abnormal blood pressure response to exercise. Non-malignant arrhythmias occurred in 41 patients (30%), including multiple premature ventricular beats (PVB), paroxysmal atrial fibrillation, non-sustained ventricular (NSVT) and supraventricular tachycardia. The combined presence of multiple exercise-induced PVB and NSVT on Holter ECG had a 14% positive but a 97% negative predictive value for sudden death or cardiac arrest. CONCLUSIONS: 1) Exercise testing is safe in a community-based population of patients with HCM, and provides useful information regarding functional capacity, efficacy of treatment, blood pressure response to exercise and inducible ischemia. Thus, ergometry should routinely be included in the standard evaluation and follow-up protocols of HCM patients. 2) Conversely, the utility of ergometry in the evaluation of the arrhythmic risk in HCM patients appears to be limited to the identification of low-risk patients.     

Evaluation of left atrial contribution to left ventricular filling in aortic stenosis by velocity-encoded cine MRI

Velocity-encoded cine MRI (VEC-MRI) can measure volume flow at specified site in the heart. This study used VEC-MRI to measure flow across the mitral valve to compare the contribution of atrial systole to left atrial filling in normal subjects and patients with left ventricular hypertrophy. The study population consisted of 12 normal subjects (mean age 34.5 years) and nine patients with various degrees of left ventricular hypertrophy resulting from aortic stenosis (mean age 70 years). VEC-MRI was performed in double-oblique planes through the heart to measure both the mitral inflow velocity pattern (E/A ratio) and the volumetric flow across the mitral valve. The left atrial contribution to left ventricular filling (AC%) was calculated. The results were compared with Doppler echocardiographic parameters. The VEC-MRI-derived mitral E/A ratios showed a significant linear correlation with E/A ratios calculated from Doppler echocardiography (r = 0.94), and the VEC-MRI-derived E/A ratios (2.1 +/- 0.5 vs 1.0 +/- 0.4) and AC% values (24.9 +/- 7.2 vs 45.7 +/- 16.4) were significantly different between normal subjects and patients with aortic stenosis (p < 0.01 in both groups). The same differences were seen in the Doppler echocardiographic parameters. The VEC-MRI-derived E/A ratio and AC% showed significant hyperbolic and linear correlations with left ventricular mass indexes (r = 0.95 and 0.86). In addition, the VEC-MRI-determined E/A ratio and the volumetric AC% displayed a highly significant hyperbolic correlation (r = 0.95). Thus VEC-MRI can be used to evaluate left ventricular diastolic filling characteristics in normal subjects and patients with abnormalities of diastolic filling.     

Alveolar oxygen uptake and femoral artery blood flow dynamics in upright and supine leg exercise in humans

We tested the hypothesis that the slower increase in alveolar oxygen uptake (VO2) at the onset of supine, compared with upright, exercise would be accompanied by a slower rate of increase in leg blood flow (LBF). Seven healthy subjects performed transitions from rest to 40-W knee extension exercise in the upright and supine positions. LBF was measured continuously with pulsed and echo Doppler methods, and VO2 was measured breath by breath at the mouth. At rest, a smaller diameter of the femoral artery in the supine position (P < 0. 05) was compensated by a greater mean blood flow velocity (MBV) (P < 0.05) so that LBF was not different in the two positions. At the end of 6 min of exercise, femoral artery diameter was larger in the upright position and there were no differences in VO2, MBV, or LBF between upright and supine positions. The rates of increase of VO2 and LBF in the transition between rest and 40 W exercise, as evaluated by the mean response time (time to 63% of the increase), were slower in the supine [VO2 = 39.7 +/- 3.8 (SE) s, LBF = 27.6 +/- 3.9 s] than in the upright positions (VO2 = 29.3 +/- 3.0 s, LBF = 17.3 +/- 4.0 s; P < 0.05). These data support our hypothesis that slower increases in alveolar VO2 at the onset of exercise in the supine position are accompanied by a slower increase in LBF.     

Augmented exercise plasma noradrenaline with impaired chronotropic responsiveness in patients with hypertrophic cardiomyopathy

1. There is controversy regarding plasma catecholamine levels in patients with hypertrophic cardiomyopathy (HCM) and few data exist on serial plasma catecholamine measurements during exercise. The present study determined whether cardiovascular and plasma catecholamine responses to exercise were altered in patients with HCM. 2. Plasma noradrenaline (NA) and adrenaline were measured at rest, at the end of each stage during exercise and immediately and 5 min after submaximal treadmill exercise in 15 patients with non-obstructive HCM (13 males, two females; mean (+/- SEM) age 54 +/- 3 years) and in 15 age- and sex-matched controls. The ratio of the increment in heart rate (HR) divided by the increment in plasma NA during exercise (delta HR/delta NA) was used as an index of chronotropic sympathetic responsiveness to exercise. 3. Exercise duration was shorter (11.2 +/- 0.6 vs 8.7 +/- 0.6 min for control vs HCM, respectively; P < 0.01) and diastolic blood pressure was significantly higher at stages I and II of modified Bruce protocol HCM. 4. Resting plasma NA levels (149 +/- 17 vs 167 +/- 28 pg/mL for control vs HCM, respectively; NS) were not different, but plasma NA levels at stages I and II were significantly higher in HCM than in controls (243 +/- 26 vs 399 +/- 69 pg/mL (P < 0.05) and 308 +/- 30 vs 548 +/- 110 pg/mL (P < 0.05), respectively). 5. Peak plasma NA levels were not significantly higher in HCM than in controls (578 +/- 59 vs 918 +/- 184 pg/mL, respectively; NS). 6. The ratio delta HR/delta NA was significantly lower in HCM compared with control at stages I and II (0.49 +/- 0.10 vs 0.21 +/- 0.05 (P < 0.05) and 0.38 +/- 0.06 vs 0.20 +/- 0.05 (P < 0.05), respectively). There were no differences in plasma adrenaline responses during exercise between the two groups. 7. Patients with HCM had augmented plasma NA levels during submaximal exercise with a higher diastolic blood pressure response. Chronotropic sympathetic responsiveness was impaired during the early stages of exercise in patients with HCM.     

Isolation and partial characterization of chromoprotein from the larval hemolymph of the Japanese oak silkworm (Antheraea yamamai)

OBJECTIVES: To investigate by urodynamic study position-related changes in uroflowmetry and postvoid residual urine volume (PVR) in men because altered bladder function in the supine position may be a predisposing factor for urinary tract infections in the institutionalized elderly. METHODS: Two healthy men, 34 and 59 years of age and living at home, and 53 nursing home residents (mean age 71.8 years, range 46 to 92) were evaluated with uroflowmetry in the standing and recumbent positions (lying on the left or right side); corresponding PVRs were measured by transabdominal ultrasonic bladder scanning. The two healthy men were monitored longitudinally with multiple recordings in both voiding positions, and the nursing home residents were subjected to two observations: one measurement of the variable parameters in either position. Differences were considered to be significant at P < 0.05. RESULTS: The 34-year-old man performed 51 3 flows (368 standing and 145 recumbent). The mean of all the peak flow rates in the upright (28.2 +/- 4.2 mL/s) versus the recumbent (16.8 +/- 4.1 mL/s) position revealed a highly significant difference (P = 0.0001). Sixteen urinary flows and corresponding PVRs were completed by this subject in either voiding position. The difference between PVRs in the standing (13.1 +/- 14.7 mL) versus recumbent (15.3 +/- 17.5 mL) position was not statistically significant. The 59-year-old man completed 156 flows (128 standing and 28 recumbent). A highly significant difference was noted between the mean of all peak flows in the upright (18.9 +/- 4.1 mL/s) versus recumbent (12.6 +/- 2.0 mL/s) position (P = 0.0001). Thirty-seven urinary flows and corresponding PVRs were completed by this individual (10 PVRs were determined after voiding in the standing and 27 after voiding in the recumbent position). No significant difference was noted between PVRs in the standing (24.6 +/- 34.4 mL) versus recumbent (16.5 +/- 60.0 mL) position. In the nursing home residents, the difference between the mean peak flow rates in the standing (14.5 +/- 8.6 mL/s) versus recumbent (12.4 +/- 6.7 mL/s) position also reached statistical significance (P = 0.0084). The difference between PVRs in the standing (60.5 +/- 125.6 mL) versus recumbent (84.8 +/- 186.2 mL) position barely reached statistical significance (P = 0.0497). CONCLUSIONS: The urinary flow rate decreases in the recumbent position. Bedridden residents may be predisposed to urinary tract infections because of alterations in voiding dynamics in the supine position. This area needs further study.     

Diastolic dysfunction in patients with chronic kidney failure on a hemodialysis program

OBJECTIVE: The aim of this study was to analyse different ultrasound parameters for the assessment of isolated left ventricular diastolic dysfunction (LVDD) in patients with chronic renal failure (CRF) on periodic hemodialysis (HD), comparing pulsed wave Doppler with pulsed tissue Doppler. MATERIALS AND METHODS: Forty-seven patients with CRF on HD (61% were male; mean age was 51.0 +/- 16.5 years, mean HD time--3.7 +/- 3.8 years, 38% had hypertension, 17% had diabetes) were studied by echocardiography (bidimensional, M-Mode, flow pulsed Doppler and tissue Doppler imaging). All patients had symptoms of left heart failure-class II NYHA, were in sinus rhythm and had no symptoms of ischemic heart disease. The presence of abnormal LV regional contractility was the exclusion criteria. According to their mitral inflow profile Doppler characteristics, patients were included in two groups: Group A (E/A > 1; n = 21) and B (E/A < 1; n = 26). We compared: LV dimensions and function, left atrial (LA) dimension. Gaasch index, LV mass index. E and A wave velocities (in flow pulsatile Doppler and tissue Doppler). E/N ratio in tissue Doppler, isovolumetric relaxation time (IVRT) and deceleration time (DT). RESULTS: There were no significant differences in the prevalence of age > or = 65 years male sex, hypertension or diabetes between group A and B patients, and almost all patients were on hemodialytic treatment for more than one year (81% vs 85%: NS). LV hypertrophy was present in almost all group A and B patients (A--95% vs B--85.5%; NS). Group A, compared with group B, had a difference in the Gaasch index (2.45 +/- 0.3 vs 2.08 +/- 0.4; p < 0.05), E wave velocity in flow pulsatile Doppler and tissue Doppler (cm/sec) (110 +/- 27 vs 62 +/- 20; p < 0.001 and 41 +/- 15 vs 28.5 +/- 16; p < 0.05), E/A ratio in tissue Doppler (1.3 +/- 0.4 vs 0.8 +/- 0.3; p < 0.001). IVRT (msec) (80.7 +/- 15.2 vs 113.5 +/- 28.3; p < 0.001) and DT (msec) (189.7 +/- 24 vs 278.2 +/- 17.9; p < 0.001). According to the E'/A' ratio in tissue Doppler, group A patients were divided in another two groups: E'/A' > 1 (13/21--62%) and < 1 (8/21--38%) and a significantly longer IVRT (75.8 +/- 9.3 vs 100.9 +/- 3.2; p < 0.001) and DT (178 +/- 15 vs 240 +/- 20; p < 0.001) and a greater LA dimension (37.6 +/- 6.9 vs 44.6 +/- 6.9; p < 0.05) were found. CONCLUSIONS: Pulsed wave Doppler is the most useful non invasive method for assessment of global diastolic dysfunction. In our study, 17% of the patients had E/A < 1 only in the tissue Doppler study. These patients probably had a pseudonormal mitral pattern.     

ACE inhibitors unmask incoordinate diastolic wall motion in restrictive left ventricular disease

OBJECTIVE: To assess the effect of ACE-inhibition on left ventricular filling and wall motion in patients with a clinical diagnosis of heart failure. DESIGN: Prospective examination of left ventricular systolic and diastolic function using M mode echocardiography and pulsed and continuous wave Doppler before and three weeks after starting an ACE inhibitor. SETTING: A tertiary referral centre for cardiac disease equipped with non-invasive facilities. SUBJECTS: 30 outpatients with a clinical diagnosis of heart failure in whom treatment with an ACE inhibitor was started; age 61 (SD 11) years; 27 male; 3 female; 21 healthy controls of similar age. RESULTS: Left ventricular cavity was dilated both at end systole and end diastole, and fractional shortening reduced. Although mean isovolumetric relaxation time (IVRT) and transmitral E (early) to A (late) filling velocity (E/A) ratio were not different from normal, a value of 1.0 on the normal frequency plot of the E/A ratio divided the patients bimodally into two groups: 20 patients (group A) with E/A ratio > 1.0 and 10 patients (group B) < 1.0. In group A patients, IVRT was short as was transmitral E wave deceleration time compared to normal (P < 0.001), fulfilling the criteria of restrictive left ventricular physiology. Left ventricular wall motion during IVRT was coordinate and left ventricular end diastolic pressure was raised on the apex-cardiogram (P < 0.001). In group B, E wave deceleration time was longer, relaxation incoordinate, and apexcardiogram normal. With an ACE inhibitor: in group A, left ventricular dimensions fell at end diastole (P < 0.05) and end systole (P < 0.01) but fractional shortening did not change; long axis total excursion (P < 0.01) and peak rate of shortening (P < 0.05) both increased; IVRT increased (P < 0.001) with the appearance of markedly incoordinate wall motion, minor axis lengthening, and long axis shortening (P < 0.001 for both); A wave amplitude also consistently increased (P < 0.001); finally, transmitral E wave velocity fell and A wave velocity increased. ACE inhibition did not alter any of the left ventricular minor and long axis or transmitral Doppler variables in patients in group B. CONCLUSIONS: Patients with a clinical diagnosis of heart failure differ in their presentation and response to ACE inhibition according to baseline haemodynamics. In restrictive left ventricular physiology, ACE inhibition reduces cavity size and prolongs IVRT, compatible with a fall in left atrial pressure. At the same time, ventricular relaxation becomes very delayed and incoordinate, greatly reducing early diastolic left ventricular filling velocity. Thus ACE inhibition unmasks major diastolic abnormalities in patients with restrictive left ventricular disease.