Factors of importance to Doppler indices of left ventricular filling in 50-year-old healthy subjects

Age is an important determinant of Doppler indices of left ventriculardiastolic filling in normal subjects. To define reference valuesand factors of importance to Doppler indices of left ventricularfilling in subjects of similar age, 58 men and 76 women aged50 years underwent Doppler echocardiography. All those takingpart in the study were healthy. When gender was analysed ina multivariate model it showed a significant independent correlationwith the peak velocity of early diastolic filling (E wave) (P<0·00l)and the early to atrial peak velocity (E/A) ratio (P<0·0l).The peak E wave velocity was 0·75±0·11m . s^–1 vs 0·66±0·10 m . s^–1(P<0·0O1) and the E/A ratio was 1·24±0·25vs 1·14±0·20 (P<0·05) in womenand men, respectively. In multivariate analyses, heart rate,diastolic blood pressure and body mass index correlated independentlywith the E/A ratio in women (P<0·00l for all), whereasin men, heart rate, diastolic blood pressure, body mass indexand left ventricular diameter correlated independently withthe E/A ratio (P<0·00l for all). Doppler measurementsof left ventricular filling in 50-year-old healthy subjectsshowed a wide variation and were significantly associated withheart rate, diastolic blood pressure, body mass index and gender.     

Age-related transmural peak mean velocities and peak velocity gradients by Doppler myocardial imaging in normal subjects

Doppler myocardial imaging is a new cardiac ultrasound techniquebased on the principles of colour Doppler imaging which candetermine myocardial velocities by detecting the changes ofphase-shift of the ultrasound signal returning directly fromthe myocardium. To determine the normal range of transmuralvelocities in healthy hearts a prospective study was carriedout involving 42 normal subjects (age from 21 to 78, mean 47±16years). Using M-mode Doppler myocardial imaging the peak valuesof the mean velocity and velocity gradient across the left ventricularposterior wall were measured during standardized phases of thecardiac cycle. Peak mean velocities had the following valuesduring the cardiac cycle: isovolumic contraction –1·3±1·2cm.s^–1, early ventricular ejection 4·2±1·2cm.s^–1, late ventricular ejection 1·8±1·1cm.s^–1, isovolumic relaxation –2·0±0·8cm.s^–1, rapid ventricular filling –6·6±2·2cm.s^–1, atrial contraction –2·8±1·8cm.s^–1, atrial relaxation 1·2±1·1cm.s^–1. Peak velocity gradients were: isovolumic contraction1·3±1·9 s^–1, early ventricular contraction4·7±1·9s^–1, late ventricular contraction1·1 ±1·0 s^–1, isovolumic relaxation–0·6±0·5 s^–1, rapid ventricularfilling 6·1±3·4 s^–1, atrial contraction2·6±1·7 s^–1, atrial relaxation 0·0±0·3s^–1. Linear regression analysis showed that with the increaseof age, peak velocity gradient decreases during rapid ventricularfilling (r=0·83; P<0·0001) and increases duringatrial contraction (r=0·86; P<0·0001) whilepeak mean velocity increases only during atrial contraction(r=0·80, P<0·0001). Thus, there was no correlationbetween increasing age and systolic peak mean velocity and peakvelocity gradient but both diastolic filling phases rapid ventricularfilling and atrial contraction demonstrated age-related changes. In summary, this study has determined the age-related rangeof normal transmural myocardial velocities within the left ventricularposterior wall in healthy hearts during the cardiac cycle. Weconclude that these measurements of peak mean velocities andpeak velocity gradients, should form the baseline for subsequentDoppler myocardial imaging clinical studies on myocardial diseasesprocesses.     

Effects of antianginal therapy with a calcium antagonist and nitrates on dobutamine--atropine stress echocardiography: Comparison with exercise electrocardiography

BACKGROUND: Anti-ischaemic therapy with nitrates and/or calcium channelblockers profoundly affects the results of pharmacological stressechocardiography with coronary vasodilators but the influenceon catecholamine stress testing remains unsettled. AIMS: The present study aimed to assess the effects of non-beta-blockerantianginal therapy on dobutamine (up to 40 µg.kg^–1.min^–1)-atropine(up to 1 mg) stress echocardiography and to evaluate whetherdrug-induced changes in the dobutamine-atropine stress echocardiographyresponse may predict variations in exercise tolerance. METHODS: Twenty six patients with angiographically assessed coronaryartery disease (seven patients with single-, 10 with double-,and nine with triple-vessel disease) performed a dobutamine-atropinestress echocardiography and an exercise electrocardiographytest in random order both off and on antianginal drugs (nitratesand calcium antagonists). In dobutamine-atropine stress echocardiography,we evaluated: dobutamine time (i.e. the time from initiationof the dobutamine infusion to obvious dyssynergy), wall motionscore index (in a 16-segment model of the left ventricle, eachsegment ranging from 1=normal, to 4=dyskinetic), and rate-pressureproduct at peak stress. RESULTS: Dobutamine-atropine stress echocardiography positivity occurredin 26 out of 26 patients off and in 23 patients on therapy (100vs 88%, P=ns). Atropine coadministration was needed to evokeecho positivity in no patient off and in five out of 26 on therapy(0 vs 19%, P<0·01). The achieved rate-pressure productduring dobutamine-atropine stress echocardiography was comparableon and off therapy (17±4 vs 19±5x10³ mmHgxheartrate. min^–1, Pns). Therapy induced an increase in dobutaminetime (on=16±3 vs off=13±3 min, P<0·01)and a decrease in peak wall motion score index (on=1·3±0·2vs off=1·5±0·3, P<0·01). Thetherapy-induced changes in exercise time during the exerciseelectrocardiography test were not significantly correlated todobutamine-atropine stress echocardiography variations in eitherdobutamine time (r=0·07, P=ns), or peak rate-pressureproduct (r=0·24, P=ns), or peak wall motion score index(r=0·02, P=ns). CONCLUSION: (1) non-beta-blocker antianginal therapy only modestly reducesdobutamine-atropine stress echocardiography sensitivity, althoughatropine coadministration is more often required to reach stressecho positivity under therapy; (2) therapy reduces the severityof dobutamine-atropine stress echocardiography ischaemia stratifiedin the time and space domain, but these changes are only poorlycorrelated to variations in exercise tolerance.     

Effect of altered loading conditions during haemodialysis on left ventricular filling pattern

Changes in the circulating volume associated with haemodialysisresult in modification of left ventricular loading conditions.To determine the influence of haemodialysis on Doppler indicesof left ventricular filling, 12 patients (mean age 40.8 ±2.7(SEM) years) with renal insufficiency but without overt heartdisease were studied by Doppler-echocardiography immediatelybefore and after haemodialysis. Haemodialysis resulted in adecrease in body weight from 68.0±3.8 kg to 65.0 ±3.7kg (P< 0.01). Heart rate and blood pressure did not changesignificantly during haemodialysis. Left ventricular diastolicdimension (M-mode) decreased from 53.5±1.1 mm to 49.5±1.9mm (P < 0.05), whereas the shortening fraction did not change.Haemodialysis elicited marked changes in the early diastolicrapid filling wave (E wave) recorded by pulsed Doppler at thelevel of the mitral annulus. Peak velocity of the early rapidfilling phase (peak E) decreased significantly from 95.3 ±8.2 cm .s^–1 to 63.0 ±5.7cm .s^–1 (P< 0.001)and mid-diastolic deceleration of transmitral velocity decreasedfrom 437.3 ±54.2 cm . s^–2 to 239.7 ±54.4cm . s^–2 (P<0.01). The peak filling velocity duringatrial contraction (peak A) did not change (79.7 ±6.3cm .s^–1 vs 74.1±4.7 cm.s^–1;P=NS). The ratiopeak E/peak A decreasedfrom 1.19±0.06 to 0.85 ±0.04 (P < 0.01) during haemodialysis. The results providefurther evidence for the pronounced preload-dependence of Dopplerindices of left ventricular diastolic function.     

Pattern of left ventricular filling in hypertrophic cardiomyopathy: Assessment by Doppler echocardiography and radionuclide angiography

Aims The left ventricle in hypertrophic cardiomyopathy is anatomicallyand functionally non-uniform. This study was undertaken to verifywhether a heterogeneity in the pattern of diastolic fillingcan be detected along the left ventricular inflow tract in hypertrophiccardiomyopathy. Methods and results Early (E) and late (A) diastolic velocitieswere recorded by Doppler echocardiography at mitral and at mid-ventricularlevel in 16 normal volunteers and 30 patients with hypertrophiccardiomyopathy. Patients with hypertrophic cardiomyopathy alsounderwent radionuclide angiography to assess left ventricularfunction. E wave decreased significantly in normal volunteers(80±15 to 60±14cm.s^–1;P<0·001),but it increased in hypertrophic cardiomyopathy (76±22to 87±28cm.s^–1;P=0·04), whereas the A wavedecreased similarly in both. By multivariate analysis, systolicasynchrony and the ejection fraction of left ventricular lateralwall were directly related to the pattern of early filling progression(r=0·656; F=9·467;P<0·002). Moreover,systolic asynchrony showed a univariate direct correlation withchanges in E velocity (r=0·42;P=0·02). Conclusion Many patients with hypertrophic cardio-myopathy havean acceleration of filling within the left ventricular inflowtract; this phenomenon is directly related to systolic asynchronyand ejection fraction of the left ventricular lateral wall,suggesting increased suction.     

Left ventricle filling abnormalities prior to and following treatment of thyrotoxicosis -- is diastolic dysfunction implicated in thyrotoxic cardiomyopathy?

Despite cardiac failure being a well recognised complicationofthyrotoxicosis, systolic function has generally been reportedas maintained or enhanced. In this study, left ventricular diastolicfunction was assessed in 16 thyrotoxic patients and 18 age-matchedcontrols by pulsed-Doppler echocardiography. Patients were re-studiedafter 3 and 12 months of treatment. Prior to treatment all standardDoppler-;derived indices of diastolic function were significantlydifferent to control (isovolumic relaxation time (IVRT) 63±18.9vs 84.0±14.8 ms, peak early filling velocity (E_max) 79.2±15.2vs 61.9±10.7 cm . s^–1, peak atrial filling velocity(A_max) 68.2±17.9 vs42.2±9.4 cm . s^–1, decelerationof early filling (E/F slope) 6.1±1.8 vs3.7±1.1m . s^–1, thyrotoxic vs control). However, these fillingabnormalities appear likely to reflect the tachycardia and reducedsystemic vascular resistance (SVR) found in the patients (heartrate 102±15 vs 76 ± 9, SVR 874 ± 207 vs1293 ± 362 dynes .s^–1. cm^–5, both P<0.001).After 3 months of treatment haemodynamics were similar in thetwo groups but filling remained abnormal in patients with apattern suggesting increased transmitral pressure gradients(E_max 73.1 ± 15.1 cm.s^–1, A_max 55.8 ± 19.2cm.s^–1,E/F slope 4.9 ± 2.0m . s^–1, all P<0.05 comparedto controls). After 12 months of treatment most parameters hadreturned to normal but the atrial contribution to left ventricularfilling remained high (A_max54.7 ± 13.9 vs control 42.2± 9.4 cm . s^–1 .flow velocity integral of atrialfilling 4.7 ± 1.3 vs 3.6±11 control, both P0.01).Left ventricular filling is therefore highly abnormal beforeand during the treatment ofthyrotoxicosis. However, these changesappear unlikely to reflect an intrinsic thyrotoxic cardiomyopathyand are more likely to represent a combination of prolongedincreases in left ventricular filling pressures along with abnormalitiesof left atrial function. The abnormal Doppler parameters emphasisethe importance of sinus rhythm in maintaining left ventricularfilling in thyrotoxicosis and may explain why marked haemodynamicdeterioration may result from the development of atrial fibrillationin these patients.     

Left ventricular diastolic filling alterations in subjects with mitral valve prolapse: a Doppler echocardiographic study

To assess left ventricular diastolic filling in mitral valveprolapse (MVP), we studied 22 patients with idiopathic MVP and22 healthy controls matched for sex, age, body surface areaand heart rate. A two-dimensional, M-mode and Doppler echocardiographicexamination was performed to exclude any cardiac abnormalities.The two groups had similar diastolic and systolic left ventricularvolumes, left ventricle mass and ejection fraction. Dopplermeasurements of mitral inflow were; E and A areas (the componentsof the total flow velocity-time integral in the early passiveperiod of ventricular filling, E; and the late active periodof atrial emptying, A), the peak E and A velocities (cm. s^–1),acceleration and deceleration half-times (ms) of early diastolicrapid inflow, acceleration time of early diastolic flow (AT),total diastolic filling time (DFT) (ms), and the decelerationof early diastolic flow (cm. s^–2). From these measurementswere calculated: peak A/E ratio (A/E), E area/A area, the earlyfilling fraction, the atrial filling fraction, AT/DFT ratio.All the Doppler measurements reported are the average of threecardiac cycles selected at end expiration. The mean peak A velocity,A/E velocity ratio, deceleration half time and atrial fillingfraction were each significantly higher for subjects presentinga MVP (60±12cm. s^–1 vs 49±14, P <0.00898±13% vs 64±12%, P <0.0001; 120±36ms vs 92±11, P <0.002; 0.45±0.14 vs 0.36±0.08P <0.02). The opposite was found for the mean decelerationof early diastolic flow, which was significantly lower (290±150cm.s^–2vs 410±122, P <0.007). None of the remaining parameterswas significantly different. In conclusion, we have documenteda different pattern of ventricular filling in patients withMVP compared to healthy subjects. Other investigations are neededto clarify the significance and the causes of these observations.     

Vascular and systemic diseases: Use of transthoracic Doppler echocardiography combined with clinical and electrocardiographic data to predict acute pulmonary embolism

Transthoracic echocardiography and continuous wave Doppler wereprospectively performed in 132 out-patients with suspicion ofpulmonary embolism, and who had no previous history of severecardiac or pulmonary disease. Bedside echocardiography determineddiagnosis other than pulmonary embolism in 55 patients. Furtherstudy was completed in 70 patients; pulmonary embolism was foundin 31 and excluded in 39. Significant differences were foundas regards right ventricular diameter (27±8 vs 22±5mm, P<0·001), left ventricular diameter (41±9vs 49±7 mm, P<0·001), right over left ventriculardiameter ratio (0·67±0·23 vs 0·43±0·15,P<0·0001), tricuspid regurgitant flow peak velocity(2·9±0·4 vs 2·4±0·7m. s^–1P<0·0001), and abnormal septum motion(12 vs 4, P<0·01). Multivariate analysis of echocardiographicdata included a tricuspid regurgitant flow peak velocity greaterthan 2·5 m . s^–1 and a right over left ventriculardiameter ratio greater than 0·5 in a logistic model (sensitivity93%, specificity 81%). The combination of echocardiographicand non-echocardiographic data included the two previous echocardiographicvariables, together with signs of deep vein thrombosis, a deepS wave in lead D1, and a Q wave in lead D3 on the electrocardiogramin a logistic model (sensitivity 96%, specificity 83%). It canbe concluded that emergency echocardiography, alone or combinedwith clinical examination and electrocardiogram, satisfactorilypredicts acute pulmonary embolism.     

Determinants of exercise capacity in patients with coronary artery disease and mild to moderate systolic dysfunction: Role of heart rate and diastolic filling abnormalities

BACKGROUND: To test the hypothesis that diastolic filling abnormalitiesare an important cause of exercise limitation in some patientswith coronary artery disease we assessed the factors limitingexercise capacity in a group of patients with coronary arterydisease in whom exercise limitation was greater than expectedfrom the degree of resting left ventricular systolic dysfunction. METHODS AND RESULTS: We assessed the relationship between exercise capacity (maximaloxygen consumption) during erect cycle ergometry, heart rate,radionuclide indi ces of left ventricular systolic function(ejection fraction) and diastolic filling (peak filling rate,and time to peak filling) during semi-erect cycle ergometryin 20 patients (15 male, five female) who were aged 42–72years (mean 61 years) and had angiographically proven coronaryartery disease and evidence of reversible myocardial ischaemiaon thallium scintigraphy. All patients exhibited marked exerciselimitation (maximal oxygen consumption 8.7–22.4 ml. min^–1.kg^–1— mean 15.9 ml. kg^–1. min^–1, whichwas 611 ± 16% of age and gender predicted maxi mum) dueto breathlessness or fatigue rather than angina, in spite ofa mean ejection fraction for the group of 465% (range 30–67%).We also compared the diastolic filling characteristics of thesepatients during exercise with 10 healthy controls (age 38–66,mean 58 years; eight male, two female). Comparing diastolicfilling characteristics, peak filling rate was higher and timeto peak filling shorter both at rest and peak exercise in controlsthan patients (peak filling rate 3.1± 0.5 vs 2.2±0.9 EDV. s^–1 P =0.01 at rest and 8.3± 0.8 vs 5.2±1.9 EDV. s^–1 , P< 0.0000l on exercise; time to peakfilling 115.2± 29.8 vs 228.9± 71.7 ms, p< 0.0001.atrest and 52.8± 16.2 vs 139.6± 4.48 ms, P<0.0000lon exercise respectively). On univariate analysis in the patientsstudied, maximal oxygen consumption was correlated with peakheart rate (r=0.45 P=0.04), peak exercise time to peak filling(r=– 0.85 P< 0.0001 peak exercise peak filling rate(r = 0.58, P=0.019), and the relative increase in cardiac outputi.e. cardiac output peak/cardiac output rest (r=0.58, P=0.008).There was no correlation between maximal oxygen consumptionand resting indices of diastolic filling (peak filling rateand time to peak filling) or with resting or peak exercise ejectionfraction. On multiple regression analysis, only peak exercisetime to peak filling was significantly related to maximal oxygenconsumption. CONCLUSION: We have observed a strong correlation between exercise capacityand indices of exercise left ventricular diastolic filling,and have confirmed previous studies showing a poor correlationwith resting and exercise indices of systolic function and restingdiastolic filling, in patients with coronary artery disease.     

Left ventricular filling pattern in {beta}-thalassaemia major -- a Doppler echocardiographic study

The pattern of left ventricular filling was assessed by Dopplerechocardiography in 38 adult ß-thalassaemia majorpatients; 28 with normal (age 25.2±5.3 years) and 10with abnormal (age 24.5±8.8 years) left ventricular systolicfunction. The findings were compared with those obtained from38 age and sex matched normal individuals. In patients with normal left ventricular systolic function,peak flow velocity in early diastole was higher than in thecontrols (94±16 vs 79±12 cm. s^–1 P <0.001).The peak flow velocity in late diastole was also greater (60±18vs 46±9cm. s^–1 P <0.001) but the ratio betweenthe early and late (atrial) peaks was approximately the samein both groups (1.74±0.72 vs 1.70±0.30 There wasno difference in deceleration time and rate between the twogroups (152±32 vs 151±21 ms and 504±93vs 508±115 cm. s^–2 respectively). None of the patientshad atrial predominant left ventricular inflow pattern. In patients with congestive heart failure the peak flow velocityin early diastole was greater than in the controls (96±10vs 79±2 cm. s^–1 P < 0.001) while in late diastoleit was smaller (39±6 vs 44±2 cm. s^–1 P <0.05).The ratio between the early and late peaks was greater in thepatients than in the controls (2.5±0.35 vs 1.8±0.08,P <0.001). The deceleration time and rate were not significantlydifferent in the two groups (153±33 vs 152±17msand 617±219 vs 550±56 cm. s^–2 respectively),until the end stage of congestive heart failure. Thus, leftventricular filling pattern in ß-thalassaemia majorpatients with normal left ventricular systolic function, issimilar to that seen in conditions of an increased preload.Patterns compatible with abnormally prolonged relaxation orrestriction do not appear.     

Functional characteristics of myocardial bridging: A combined angiographic and intracoronary Doppler flow study

AIMS: Combined quantitative coronary angiography and intracoronaryDoppler flow velocity measurements were performed to study theunderlying haemodynamic mechanisms leading to myocardial ischaemiain patients with myocardial bridging in the absence of coronaryartery disease. METHODS AND RESULTS: In 42 symptomatic patients with myocardial bridging of the leftanterior descending coronary artery, quantitative coronary angiographywas used to measure absolute and relative vessel diameters duringsystole and diastole. In 14 patients, serial frame-by-framediameter quantification during a complete cardiac cycle wasperformed. Intracoronary blood flow velocities were determinedusing a 0·014 inch Doppler flow guide wire proximal,within, and distal to myocardial bridges, and coronary flowreserve was calculated. Quantitative coronary angiography revealeda maximal systolic lumen diameter reduction of 71 ± 16%with a persistent diameter reduction of 35 ± 13% duringmid-diastole. Flow velocities revealed increased average diastolicpeak flow velocities within myocardial bridges of 38·6± 19 cm. s^–1 vs 22·4 ± 7·7cm. s^–1 proximal and 18·6±4·6cm.s^–1 distal (P<0·001), which increased duringrapid pacing (64·7 ± 25 cm. s^–1, P<0·001vs baseline). Coronary flow reserve distal to myocardial bridgeswas 2·3 ± 0·9 (vs 2·9 ± 0·9proximal, P<0·05). There was a characteristic Dopplerflow profile within myocardial bridges with an early diastolicovershoot, which was further augmented during rapid pacing. CONCLUSION: Myocardial bridging is characterized by a delay in diastoliclumen gain and a concomitant increase in diastolic intracoronaryDoppler flow velocities, which are enhanced by rapid pacing.In combination with a reduced coronary flow reserve and anginalsymptoms these findings support the concept of a haemodynamicallysignificant obstruction to coronary flow due to myocardial bridgingin a selected subset of patients.     

Doppler echocardiographic assessment of left ventricular filling dynamics in patients with coronary heart disease and normal systolic function

The purpose of this study was to assess altered left ventriculardiastolic filling by noninvasive means in patients with coronaryartery disease and normal systolic pump function. Mitral inflowvelocity was measured by pulsed Doppler, and left ventricularvolumes were obtained from cross-sectional echocardiographyat rest and during upright bicycle exercise. Peak and integratedearly and late diastolic filling velocities were calculatedfrom Doppler-derived time-velocity curves. Studies were performedin normal subjects (group I, n = 8) and in patients with angiographicallyproven coronary artery disease (Group II, n = 18). The ejectionfraction was not significantly different in group II as comparedto group I (group 1, 60 ± 7%; group II, 55 ± 11%).During exercise, ejection fraction increased significantly ingroup I by 7·6%, but did not increase in group II. Inall cases, diastolic filling showed a biphasic pattern. At rest,the major part of diastolic filling occurred during early diastole:the ratio of early filling velocity integral (E) to the latefilling velocity integral (L) was significantly greater in groupI than in group II (group I, 1·74 ± 37; groupII, 1·19 ±·3, P<0·001). Duringexercise, early diastolic filling was unchanged in normal subjectsbut decreased in patients, with a significant decrease in E/Lindex of 34% (P < 0·001). Thus, pulsed Doppler echocardiography provides a useful methodfor assessing noninvasively exercise-induced changes in leftventricular diastolic filling dynamics in patients with coronaryartery disease.     

Infra-low dose dipyridamole test: A novel dose regimen for selective assessment of myocardial viability by vasodilator stress echocardiography

Low (0·56 mg.kg^–1 over 4 min) and high (0·48mg.kg^–1 over 10 min) doses of dipyridamole can identifyviable myocardium through the contractile recovery of basallydyssynergic regions; however, it also induces ischaemia in susceptiblepatients. The aim of this study was to assess the potentialof an ‘infra-low’ dose of dipyridamole to selectivelyidentify myocardial viability, independently evaluated by lowdose dobutamine. Forty patients with resting dyssynergy andangiographically assessed coronary artery disease (1-vesselin 18, 2-vessel in 12, and 3-vessel in 10 patients) separatelyunderwent a low dose dobutamine (5–10µg. kg^–1min for 3 min) echo test and an infra low dose (0·28mg.kg^–1 over 4 min) dipyridamole echo test. Systolic bloodpressure (rest: 131±19 mmHg) changed slightly after dobutamine(137±21, P<0·05 vs rest) and remained stableafter dipyridamole (130± 17, p=ns vs rest). Heart rate(rest: 68±13 beats. min^–1) was also unchanged afterdipyridamole (69±12, P=ns vs rest) and increased slightlyafter dobutamine (71±15, P<0·05 vs rest andvs dipyridamole). No patient developed echocar diographic orelectrocardiographic signs of ischaemia after either dipyridamoleor dobutamine. Of the 243 segments with baseline dyssynergy,70 were responders (i.e. they showed an improvement of I gradeor more, from I normalIhyperkinetic to 4=dyskinetic in a 16-segmentmodel of the left ventricle) by both dipyndamole and dobutamine,157 were non-responders (i.e. they showed no change) by bothdipyridamole and dobutamine, and 16 showed discordant results(five responders by dipyridamole only; 11 by dobutamine only).The overall concordance of dipyridamole and dobutamine was 93%.An echocardio graphic follow-up could be obtained >6 weeksafter suc cessful revascularization (achieved with angioplastyin 17, with by pass surgery in 3) in 19 patients and showedan improvement of one grade or more in 50 segments (viable)and no improvement in 50 segments (necrotic). The sensi tivityof dobutamine and dipyridamole for predicting recov ery was76 and 78% respectively (p=ns); the specificity of both testswas 94%. In conclusion, infra-low dose dipyridamole is a haemody namicallyneutral stress test which does not affect either heart rateor systolic blood pressure; it allows myocardial viability tobe explored selectively, without eliciting ischae mia; it showsexcellent overall concordance with low dose dobutamine and hasgood sensitivity and excellent specifi city for predicting functionalrecovery following successful revascularization.     

Impact of dietary sodium intake on left ventricular diastolic filling in early essential hypertension

Aims Dietary sodium intake modulates left ventricular hypertrophyin established essential hypertension independent of blood pressurelevel. We conducted this study to elucidate the relationshipbetween sodium intake and left ventricular structural or functionalchanges in early essential hypertension. Methods Forty-four young male patients (age 25·9±2·6years) with mild essential hypertension that had never beentreated and 45 normotensive male control subjects of similarage were examined. Dietary sodium intake was measured from 24hurinary sodium excretion, blood pressure from 24h ambulatorymonitoring (SpaceLabs 90207), left ventricular structure from2-D guided M-mode echocardiography, and diastolic filling ofthe left ventricle (as the main compound of diastolic functionin a young population) by pulse-wave Doppler sonography. Results In hypertensive patients, daily sodium excretion correlatedwith the ratio of late (A) to early (E) maximum velocity (VmaxA/E; r=+0·27,P=0·07), velocity time integrals(A/E; r=+0·54,P<0·001) as well as atrial contribution,as a percent of left ventricular filling (VH ATCO; r=+0·52,P<0·001)independent of heart rate, whereas the opposite correlationswere observed in normotensives (allP<0·001). Stepwisemultiple regression analysis confirmed these results. Sodiumexcretion emerged as the strongest independent determinant ofimpaired diastolic filling in hypertensive patients (velocitytime integrals A/E: R²=0·49, ß=+0·57,P=0·0001;VH ATCO: R²=0·48, ß=+0·56,P<0·0001;Vmax A/E: ns). In normotensive subjects, sodium excretion wasa similar strong, but inverse deter-minant of diastolic filling(velocity time integrals A/E: R²=0·40, ß=–0·43,P=0·0028).Heart rate was a strong determinant of diastolic filling inhypertensive patients (ß=+0·55,P=0·0002)and in normotensive subjects (ß=+0·34,P=0·011).Left ventricular mass and end-diastolic volume index were notrelated to diastolic filling in either group. Conclusion In early essential hypertension, sodium excretion is correlatedwith impaired left ventricular diastolic filling independentof left ventricular mass. The renin-angiotensin-aldosteronesystem might be a mediator of the observed correlation.     

Doppler haemodynamic assessment of clinically and echocardiographically normal mitral and aortic Allcarbon valve prostheses

Doppler echocardiographic characteristics of normally functioningAllcarbon prostheses were studied in 149 consecutive patientswith 157 valves in the mitral (n=73) and aortic (n=84) positionswhose function was considered normal by clinical and echocardiographicevaluation. In the mitral position, the mean gradient and theeffective mitral orifice area were not significantly differentin either the 25-mm or the 31-mm size valves (from 5±1to 4±1 mmHg and from 2.2±0.6 to 2.8±0.9cm², respectively; P=ns for both). Conversely, peak gradientwas significantly and inversely correlated to actual orificearea (r=–0.70; P<0.0006), decreasing from 15±3mmHg in the 25-mm size valve to 9±1 mmHg in the 31-mmsize. In the aortic position, the mean gradient was 29±8 mmHgin the 19-mm size valve; it decreased to 8±2 mmHg inthe 29-mm size. Effective prosthetic aortic valve area, calculatedusing the continuity equation, ranged between 0.9±0.1cm² for the 19-mm size valve to 4.1±0.7 cm² for the 29-mmsize. By analysis of variance, effective prosthetic aortic valvearea differentiated various valve sizes (F=25.3; P<0.0001)better than peak (F=5.34; P=0.012) or mean (F=4.34; P=0.0052)gradients alone, and it correlated better with actual orificearea (r=0.89, r=–0.70 and r=–0.65, respectively).This study provides the normal range for Doppler haemodynamiccharacteristics of the various sizes of the Allcarbon valvein the mitral and aortic positions so that prosthetic malfunctioncan be identified.     

Skeletal muscle lactate accumulation and creatine phosphate depletion during heavy exercise in congestive heart failure: Cause of limited exercise capacity?

OBJECTIVE: To study the mechanisms of limited exercise capacity and skeletalmuscle energy production in male patients with congestive heartfailure. DESIGN: Muscle biopsy study. PATIENTS: Skeletal muscle metabolic response to maximal bicycle exercisewas studied in 10 patients with chronic congestive heart failure(ejection fraction 0·22±0·05; peak oxygenconsumption, Vo₂ 15·1±4·9 ml. min^–1.kg^–1) and in nine healthy subjects (peak Vo₂ 33·5±6·7ml. min^–1. kg^–1). Activities of skeletal muscleenzymes were measured from the vastus lateralis muscle of 48patients (ejection fraction 0·24±0·06,peak Vo₂ 17·4±5·4 ml. min^–1. kg^–1)and 36 healthy subjects (peak Vo₂ 38·3±8·4ml. min^–1. kg^–1). RESULTS: Although blood lactate levels were lower in patients than inhealthy subjects (2·2±0·3 vs 5·2±0·6mmol. 1^–1; P<0·001) at peak exercise (96±11W for patients and 273±14 W for controls), skeletal musclelactate was similarly elevated (25·6±3·2vs 22·7±2·7 mmol.kg^–1) and creatinephosphate was equally depressed (P<0·02) to low levels(7·0±1·9 vs 6·7±0·9mmol.kg^–1). The muscle ATP decreased by 21% (P<0·05)and 8% (P<0·01) in the patients and controls, respectively.Activities of rate limiting enzymes of the citric acid cycle(alpha-ketoglutarate dehydrogenase) and oxidation of free fattyacids (carnitine palmitoyltransferase II) were 48% and 21% lowerthan in controls, but the mean phosphofructokinase activitywas unchanged in congestive heart failure. CONCLUSIONS: It seems that the main limiting factor of exercise performanceduring heavy exercise is the same in congestive heart failureand healthy subjects, a high rate of skeletal muscle lactateaccumulation and high-energy phosphate depletion. In congestiveheart failure, the low activity of aerobic enzymes is likelyto impair energy production and lead to lactate acidosis atlow workloads.     

Mechanisms of adenosine-induced epicardial coronary artery dilatation

BACKGROUND: In order to ascertain whether human adenosine-induced dilatationof epicardial arteries is direct or flow-mediated, we comparedthe effects of intracoronary adenosine infusion on epicardialcoronary arteries with those produced by dypiridamole, a selectivearteriolar vasodilator. METHODS AND RESULTS: In 24 patients with angiographically normal coronary arteries,coronary blood flow velocity was measured by a Doppler wireduring intracoronary infusion of adenosine or dipyridamole,which is known to increase intramyocardial adenosine concentration.Coronary angiograms were obtained at baseline and immediatelyafter the end of each infusion period; coronary diameters 5mm distal to the wire tip were measured by computer-assistedquantitative coronary angiography. Peak coronary blood flowvelocities during adenosine or dipyridamole infusions were similar(52·0 ± 15·5 and 47·9 ± 24·2cm. s^–1, P=ns). Coronary diameters immediately after adenosineand dipyridamole infusions were similar and both higher thanthat at baseline (2·80 ± 0·63 and 2·80± 0·64 vs 2·44 ± 0·69 mm,P<0·05). The absolute and percentage increases ofcoronary artery diameters in response to adenosine were highlycorrelated to coronary blood flow velocity (R=0·622,intercept –0·10 ± 0·14, P=0·002and R=0·617 intercept –15·2 ± 9·9,P=0·001, respectively); similar correlations were foundin response to dipyridamole (R=0·708, intercept –0·44± 0·19, P<0·001 and R=0·649,intercept –13·5 ± 8·7, P<0·001,respectively). Finally the absolute and percentage changes ofcoronary artery diameters caused by adenosine were highly correlatedto those caused by dipyridamole (R=0·840, P<0·001and R=0·836, P<0·001 respectively). CONCLUSIONS: A significant correlation exists between epicardial coronaryvasodilation and coronary blood flow velocity during intracoronaryadenosine infusion, thus suggesting that epicardial coronaryvasodilation induced by adenosine is predominantly flow-mediatedrather than direct. This conclusion is supported by the observationthat similar findings were obtained using dipyridamole, whichcan only dilate epicardial coronary arteries indirectly, throughthe increase in coronary blood flow velocity caused by the inhibitionof intramyocardial adenosine re-uptake.     

The influence of muscle mass, strength, fatigability and blood flow on exercise capacity in cachectic and non-cachectic patients with chronic heart failure

BACKGROUND: The influence of age, skeletal muscle function and peripheralblood flow on exercise capacity in chronic heart failure patientsis controversial, possibly due to variations in skeletal muscleatrophy. METHODS AND RESULTS: To assess predictors of exercise capacity in patients with clinicalcardiac cachexia, we studied 16 cachectic and 39 non-cachecticmale chronic heart failure patients of similar age and ejectionfraction. All cachectic patients were wasted (% ideal body weight:81 1·9 vs 105·2±2·1, P<0·mean±SEM) and had documented weight loss (5–30kg). Peak oxygen consumption (14·9±1·4vs 16·3±0·6 ml.kg^–1, min ^–1,resting, and peak blood flow (plethysmography) and 20 min fatigability(% baseline strength) were all similar between the two groups.Quadriceps strength, muscle size (all P<0·0001), strengthper unit muscle (right: P<0·05; left: P<0·0·01)and 5 min fatigability (P<0·05) were all lower incachectic patients. In non-cachectic patients, age (R=0·48and quadriceps strength (R=0·43, all P<0·01)predicted peak oxygen consumption. Only in cachectic patientsdid peak blood flow predict peak oxygen consumption significantly(R=0·72, P0·005), whereas age and strength didnot. Similar findings were confirmed using other previouslypublished definitions of cardiac cachexia. CONCLUSION: The predictors of exercise capacity change with the developmentof cardiac cachexia from age and strength to peak blood flow.This shift may be caused by additional endocrine or catabolicabnormalities active in end stage heart failure.     

Dobutamine stress-Doppler echocardiography before and after coronary angioplasty

To determine if dobutamine-induced myocardial ischaemia causesabnormalities in Doppler parameters of left ventricular ejectionand filling and to assess early effects of successful coronaryangioplasty (PTCA) on these parameters, dobutamine stress echocardiographyand Doppler studies were performed once in 11 normal volunteersand twice in 17 patients (within 1 day pre- and post-PTCA).Dobutamine induced wall motion abnormalities, ST changes andangina in 11, five and five patients, respectively, before andthree, two and one patients. respectively, after PTCA. Dopplerindices of both systolic and diastolic function were comparableat rest, before and after PTCA. Dobutamine induced similar increasesin peak aortic velocity and average acceleration in healthyindividuals (39% and 53%) and in patients with one-vessel diseaseboth before (38% and 39%) and after PTCA (39% and 40%). In thethree patients with multivessel disease, peak aortic velocityshowed a blunted response (–0.3%) before PTCA but increasedby 17% after PTCA, while acceleration decreased both before(12%) and after PTCA (14%). There were significant differences(P<0.0001) between healthy individuals and pre-PTCA patientsin the effect of dobutamine on peak early (E) filling velocity(+34% vs –19%), E-acceleration (+ 35% vs –26%),peak early to atrial filling velocity ratio (E/A) (–0.7%vs – 37%) and diastolic time velocity integral (TVI) (+34% vs –22%). After PTCA, the response of Doppler diastolicindices improved during dobutamine, as shown by the increasein E and E-acceleration (+ 8%, + 24%, respectively) and by thedecline in the reduction of E/A and TVI (–17% and –10%,respectively). Thus, the response of Doppler diastolic parametersto dobutamine stress is a sensitive indicator of significantcoronary disease and is superior to changes in ejection indices.Successful PTCA resulted in an improved diastolic filling responseto dobutamine stress.     

Doppler echocardiographic characteristics of the Carpentier-Edwards xenograft

In order to define ranges of normal velocities for the Carpentier-Edwardsxenograft, 38 mitral, 24 aortic and 9 tricuspidprostheses werestudied with pulsed or continuous wave Doppler at a mean intervalof 38 months following surgery. All patients had clinicallynormal prosthetic valve function and no clinical or radiographicsigns of heart failure. Mean peak velocity across aortic prostheseswas 244 cm s^–1 (SD 48). There was weak correlation (r= 0.54, P < 0.01) between peak velocity and time since valveimplantation, but no significant difference in peak velocityacross valves of different size. In the mitral position, meanpeak velocity was 164 cm s^–1 (SD 24) and mean pressurehalf time 90 ms (SD 23). There was again no significant differencebetween valves of different size. There was a weak correlationbetween pressure half time and time since implantation (r =0.44, P <0.01), but there was no relationship between thelatter and peak velocity. In the tricuspid position, mean peakvelocity was 150 cm s^–1 (SD 12) and mean pressure halftime 163 ms (SD 50). The Doppler indices of obstruction to bloodflow for prostheses in the mitral and aortic positions showeda significant increase with time after implantation.