Effects of positive inotropic stimulation (post-extrasystolic potentiation) on non-uniformity of left ventricular contraction in patients with coronary artery disease

In patients with chronic coronary artery disease, post-extrasystolicpotentiation (PESP) slightly worsens relaxation, increasingthe constant of ventricular pressure decay. However, it doesnot negatively influence left ventricular (LV) diastolic filling.To our knowledge, no data are available on the effects of PESPon segmental relaxation in chronic coronary artery disease. The effects of PESP on the LV pressure–volume (P/V) relationshipand on segmental pressure–length loops (P/L) were studiedin eight patients with coronary artery disease submitted toLV angiography. P/V loops were constructed by means of frame-to-frame analysisof ventriculograms and simultaneous high-fidelity LV pressuretracings; P/L loops were calculated by the endocardial movementof 45 chords intersecting the LV outline (centreline method).PESP was produced by programmed stimulation during ventriculography.P/V and P/L loops were studied in basal conditions and afterPESP. Results showed enhanced LV pump function (ejection fractionfrom 0.45 ± 0.14 to 0.54 ± 0.13, P<0.01; LVstroke work index from 62±29 to 79±28 g. m^–1.m^–2,P<0.01; the LV end-systolic pressure–volume relationfrom 2.9±1 to 3.2±2 mmHg.ml^–1, P<0.05)associated with impaired relaxation (time constant _w, from 40±9to 48±8 ms, P<0.01; time constant _m from 53±11to 61±10 ms, P<0.05;peak filling rate from 3.7 ±1 to 2.3 ± 1 EDV.s^–1, P<0.01; minimal diastolicpressure from 6±6 to 7.5±6 mmHg, P<0.05) andwith increased preload (EDVI from 97±27 to 106±27ml.m^–2, P<0.01; LVEDP from 16 ± 9 to 19 ±7 mmHg, P<0.01). P/L loops showed increased non-unformityof LV relaxation after PESP. The effects were more evident inthe segments showing P/L loops inclined to the left, where PESPincreased or caused the appearance of post-systolic shortening.PESP showed only slight or no effect in the segments showingP/L loops inclined towards the right. PESP slightly impaired early left ventricular filling by decreasingthe rate of fall of intraventricular pressure and increasingthe non-unformity of contraction and relaxation. However, itdid not change the isovolumic phases of pressure–lengthloops of normal segments, while worsened relaxation of hypokinetic(probably ischaemic) segments with the appearance of post-systolicshortening in the loops inclined to the left.     

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.     

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.     

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.     

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.     

Short-term haemodynamic effects of dopexamine in patients with chronic congestive heart failure

Dopexamine (FPL 60278) is a new dopamine analogue which possessesa combination of dopamine receptor and beta-2-adrenoreceptoragonist properties. The aim of our study was to evaluate theshort-term haemodynamic effects of dopexamine administered byintravenous infusion at different dosage rates. Eight patientswith chronic congestive heart failure were studied. A dose of1 µg kg^–1 min^–1 produced a 27% decrease insystemic vascular resistance index (32.6 to 23.9 res. unitsm², P<0.001 and a significant increase in cardiac index (2.7to 3.61min^–1 m^–2, P<0.001). Stroke volume indexand heart rate increased significantly by 22% and 7%, respectively.An increase in left ventricular stroke work index was also seenat the dose level inducing the maximum cardiac output. Leftventricular filling pressures and arterial blood pressures werenot affected. We conclude that administration of dopexamineto patients with congestive heart failure augments cardiac performanceat rest.     

Left ventricular volume determination in dogs: a comparison between conductance technique and angiocardiography

Left ventricular (LV) volume was determined simultaneously bymonoplane cineangiocardiography and conductivity using a multielectrodeconductance catheter at rest and during pressure loading inseven mongrel dogs (mean body weight 22 kg). LV volumes werecalculated frame-by-frame (75 frames s^–1) by angiocardiographyand matched with instantaneous volumes obtained by conductivity.There was an excellent correlation between the two techniquesat rest (correlation coefficient, r = 0.96) and during pressureloading (r = 0.92) when the data of each dog were pooled. Thestandard error of estimate of the mean angiographic volume was4%. The slope of the regression analysis showed a small butsignificant (P <0.01) decrease from 0.365 at rest to 0.289during pressure loading, whereas the intercept remained unchanged(24 versus 26 ml). Since no calibration for parallel conductivityof the surrounding tissue was performed, LV end-systolic volumewas significantly over- and LV ejection fraction significantlyunderestimated whereas LV end-diastolic volume was estimatedcorrectly by the conductance technique. It is concluded that LV end-diastolic volume can be determinedaccurately by the conductance technique in dogs. However, LVend-systolic volume is significantly over- and ejection fractionsignificantly under-estimated. Since there is a good correlationbetween angiocardiography and conductivity, exact determinationOf LV volumes and ejection fraction is feasible using a correctionfactor. The change is slope of the regression equation betweenangiocardiography and conductivity suggests a change in conductivityof the surrounding tissue during pressure loading which limitsthe application of the conductance catheter to stable haemodynamicsituations or calls for repeated calibrations by an independenttechnique during acute interventions.     

Relation of left ventricular dilation during acute myocardial infarction to systolic performance, diastolic dysfunction, infarct size and location

The quantification of left ventricular (LV) volumes and assessment of their relation to systolic and diastolic dysfunction, infarct size and anatomic location were performed in 54 patients with a first acute myocardial infarction (AMI). Blood pool radionuclide angiography was used to assess LV end-diastolic, end-systolic, and stroke volume indexes, ejection fraction and peak diastolic filling rate. Infarct size was estimated from plasma MB creatine kinase activity. Substantial LV dilation occurred within the initial 24 hours of AMI. The peak diastolic filling rate was low, even in those patients with a normal ejection fraction. In comparison with inferior AMI (n = 25), patients with anterior AMI (n = 29) had a larger end-diastolic volume index (105 +/- 8 vs 81 +/- 4 ml/m2, p less than 0.01) and end-systolic volume index (64 +/- 7 vs 37 +/- 4 ml/m2, p less than 0.001), but similar stroke volume index (41 +/- 3 vs 43 +/- 2 ml/m2, difference not significant). No significant relation was noted between infarct size estimated by MB creatine kinase and any volumetric index. On repeat study (day 10 after AMI), end-diastolic and end-systolic volume indexes increased further (p less than 0.05 vs day 1) but ejection fraction and peak diastolic filling rate were unchanged. It was concluded that: (1) LV dilation occurs within hours of AMI in both inferior and anterior AMI, but is more marked in the latter; (2) significant LV diastolic dysfunction is the rule, even in patients with preserved LV systolic function; and (3) LV dilation is an early compensatory mechanism that maintains normal stroke volume, even in patients with severely reduced LV function.     

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.     

Effect of flecainide on left ventricular ejection fraction

Antiarrhythmic agents may depress cardiac contractility andworsen heart failure. Flecainide is an effective antiarrhythmicdrug, but when administered orally in patients with left ventricular(LV) dysfunction, its effect on LV function is unknown. To assessthe effects of flecainide on cardiac function, LV ejection fraction(LVEF) was measured by radionuclide ventriculography in 36 patientswith LV dysfunction (LVEF 40%), prior to and 7 days after drugtherapy was initiated. To analyse the possibility of a dose-dependenteffect on LVEF, 18 patients received 200 mg day^–1 of flecainideand 18 patients with an identical initial LVEF (27±8vs 27±9) (NS) received 300 mg day^–1. The studywas stopped in 7 patients because of severe cardiac adverseeffects; in these patients the LVEF was significantly lower(15±7) than that of the 29 patients who completed theprotocol (27±8) (P<0.01). In patients who completedthe protocol, there was no significant change in LVEF eitherwith a daily dosage of flecainide of 200 mg day^–1 (27±8vs 27±8) or with 300 mg day^–1 (27±9 vs 28±13).Thus, in the patients with LV dysfunction studied, oral flecainidedid not significantly affect LV function either with a low orwith the ususal daily dosage. However in patients with severeimpairment of LV function (LVEF<30%) flecainide must be usedcarefully owing to a higher incidence of adverse effects oncardiac rhythm.     

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.     

Felodipine in ventricular dysfunction

The systemic and coronary haemodynamic effects of felodipinewere evaluated at rest and during stress induced atrial pacingin fourteen patients with chronic cardiac failure, secondaryto coronary heart disease. Felodipine was an effective arteriolarvasodilator producing increases in cardiac index from 2.6 ±0.l to 3.5 ± 0.2 l min^–1 m^–2 (P<0.001)and stroke volume 35.3 ± 2.7 to 41.4 ± 2.4 mlbeat^–1 m^–2 (P<0.002). Coronary venous flow also increased significantly (126 ±8 to 168 ± 13 ml min^–1) (P<0.005) and this didnot appear to be accompanied by an increase in myocardial oxygenusage, as myocardial oxygen consumption was essentially unchanged.When the myocardium was stressed by atrial pacing the increasein cardiac output and stroke volume was maintained—25%and 23%, respectively (P<0.01). These results suggest thatfelodipine may well have a significant role in the managementof patients with congestive cardiac failure.     

The acute response of left ventricular filling dynamics to intravenous verapamil predicts the changes in exercise tolerance after oral verapamil therapy in patients with hypertrophic cardiomyopathy

We studied the correlation between changes in left ventricularfilling dynamics induced by acute intravenous administrationof verapamil and the changes in exercise tolerance induced byoral administration of the agent in 30 patients with hypertrophiccardiomyopathy. Diastolic cardiac function was measured by meansof a nuclear stethoscope before and 10 min after intravenousadministration of verapamil, 0.15mg. kg^–1 over 2 min.Treadmill exercise tests using a modified Bruce protocol wereperformed before the initiation of oral verapamil treatmentand after 4 weeks of oral therapy at a dose of 320–360mg. day^–1 (mean±SD 332±17mg. day^–1). Peak filling rate (PFR) increased in 21 patients, 18 of whom(86%) also had an increase in exercise duration. PFR showedno increase in nine patients, eight of whom (89%) had no changein exercise duration (sensitivity 95%, specificity 73%, predictivevalue of the positive result 86%, predictive value of the negativeresult 89%). Acute changes in time from the beginning of rapidfilling to PFR (t-PFR) and in left ventricular end-diastolicvolume (EDV) were less useful in predicting improvement in exercisetolerance. In 19 patients the changes in PFR and EDV parallelled.Twelve of the 13 patients (92%) will an increase in both parametersalso had an increase in exercise duration, whereas all six inwhom these parameters were reduced showed no increase in exerciseduration (sensitivity 100%, specificity 86%, predictive valueof positive results 92%, and predictive value of negative results100%). In conclusion, the response of PFR, and even more so the combinedresponse of PFR and EDV to intravenous verapamil, accuratelyidentify patients with hypertrophic cardiomyopathy who are likelyto show improvement in exercise tolerance after oral verapamiltherapy.     

Cardiac function and maximal exercise capacity early after acute myocardial infarction

The purpose of the study was to assess the relationship betweenleft and right ventricular function measured at rest and maximalexercise capacity in patients with recent acute myocardial infarction(AMI). Forty-three male patients (Killip Class I, n=36; KillipClass II, n=7) with a wide range of left ventricular (LV) functionand size underwent graded bicycle exercise testing less than4 weeks after AMI (mean 21 days, 17–27). None of the patientshad exercise limiting factors other than dyspnoea and fatigue.Left and right ventricular ejection fractions were determinedby a radionuclide ventriculo graphic method which also alloweddetermination of absolute LV volumes and actual LV peak fillingrate. LV ejection fraction had a tt weak association to estimatedmaximal oxygen uptake (VO₂ max) (r=0·37). No associationwas found between LV size, LV stroke volume, or LV peak fillingrate and estimated VO₂ max. Similarly, right ventricular ejectionfraction showed no correlation to estimated VO₂ max. Patientswith well preserved LV function had a higher exercise inducedincrease in systolic blood pressure than patients with reducedLV function, but the increase in systolic blood pressure couldnot be used to estimate LV function with any reasonable accuracy. We conclude that the maximal exercise capacity of patients withrecent AMI is virtually independent of their left and rightventricular function determined at rest, and that exercise testingand radionuclide ventriculography should be regarded as complementaryprocedures in the evaluation of patients with AMI.     

Left ventricular function in children with the Marfan syndrome

Aortic dilatation and heart valve lesions are common in theMarfan syndrome but whether primary alterations occur in leftventricular (LV) function has not been studied hitherto. LVsize, mass and systolic as well as diastolic function were studiedby M-mode and Doppler echocardiography and cine magnetic resonanceimaging in 22 Marfan children aged 3.0–15.4 years andin 22 age-matched healthy children. No child had significantvalve disease. Heart rate and systolic blood pressure were comparablein the groups but diastolic blood pressure was higher in thecontrols (67 ± 7 mmHg vs 62 ± 8 mmHg, P=0.030).No statistically significant differences were found in LV size,mass or systolic function. The Marfan children had slower LVpeak diameter lengthening rates (106 ± 27 mm s^–1vs 132 ± 29 mm. s^–1, P=0.004), prolonged relaxationtimes (155 ± 22 ms vs 140 ± 19ms, P=0.023), slowerdeceleration of the early transmitral velocity (580 ±144 cm.s^–2 vs 720 ± 160 cm. s^–2, P=0.006),and smaller early-to-late peak velocity ratios (1.99 ±0.40 vs 2.29 ± 0.46, P=0.031). These data indicate thatI.V early diastolic function (relaxation) is impaired in theMarfan syndrome. Weakened elastic recoil due to the underlyingconnective tissue abnormality may best explain this novel observation.     

Left ventricular end-systolic pressure volume relations in healthy young men

The purpose of the present study was to establish the relationshipof left ventricular end-systolic volume vs. mean systemic pressurein variously afterloaded beats in a group of healthy, young,men (n=6, age 24±0.9 years). The relationship was expressedby the slope (E_max) of the line connecting pressure-volume co-ordinatesand its extrapolated intercept (V_d) of the volume axis. Theslope was calculated by linear regression of mean systemic arterialpressure (mean SAP, measured by catheter in the radial artery)vs. end-systolic left ventricular volume (ESV, estimated fromcross-sectional, 4-chamber echocardiographic images). Recordingswere obtained at resting, reduced (nitroglycerin infusion),and elevated (metaoxedrin infusion) blood pressure. IndividualE_max values ranged from 1.05 to 2.01 mmHg ml^–1; Vd wasconsistently found to be negative, ranging from –4.7 to–54.8 ml. All individual relations were statisticallysignificant (P<005 to P<0001). Group values were E_max=1.27±0.25(SE) mmHg ml^–1, V_d=–43.3±7.5 (SE) ml, andE_max indexed for body surface area, E_{max ind} ±=2.54±0.49(SE) mmHg ml^–1 m^–2. We further examined the validityof proposed optimal relations among E_max, heart rate (HR) andsystemic resistance (R_s): E^max/HR=R_s, and among ejection fraction(EF), EDV and V_d: EF=0.5 (1–EDV/V_d). For the group E_max/HR/0023±0.003and R_s=0016±0004 (mmHg ml^–1 min^–1), i.e.,a deviation from equivalence of 30% (P<0.001). EF (=0.72±0.02)deviated by 18% (P<0001) from its proposed optimum (0.5 (1–V_d/EDV)=0.61=006).     

Influence of haemodynamics and myocardial ischaemia on Doppler transmitral flow in patients undergoing dobutamine echocardiography

To examine whether pulsed Doppler left ventricular filling indicescan reliably detect myocardial ischaemia in patients with coronaryartery disease undergoing dobutamine stress echocardiographywe studied three groups matched for age and global indices ofleft ventricular function. Group 1 patients (n=10) had normalcoronary arteries whereas those in Groups 2 (n=12) and 3 (n=15)had significant coronary disease (70% diameter stenosis) atangiography. After stopping cardiouctive treatment, patientsunderwent incremental dobutamine stress (5, 10, 15 and 20 µg.kg^–1. min^–1) during pulsed Doppler interrogationof diastolic filling with simultaneous heart rate and bloodpressure measurements. Only Group 3 patients developed myocardialischaemia using electrocardiographic and cross sectional echocardiographiccriteria, subset 3A (n=4) comprised those with inducible mitralregurgitation on colour Doppler. Electrocardiographic R-R intervaldecreased (–311 ± 123 ms, P<0·001) andmean blood pressure altered (5±17 mmHg, P=ns) uniformlyacross groups. The respective changes in peak early velocity,peak atrial velocity and their ratio for Groups 1 (0·08± 0·09 m. s^–1, 0·26 ± 0·18m.s^–1 and – 0·32 ± 0·36), 2(0·07 ± 0·07 m.s^–1 0·18±0·15m.s^–1 and –0·13±0·21) and 3(0·09±0·12 m.s^–1, 0·20±0·13m.s^–1 and –0·17±0·21) weresimilar (all P=ns between groups). Corresponding data for subset3A (0·23 ± 0·04 m.s^–1 0·20± 0·10 m.s^–1and 0·00 ± 0·16)revealed a significantly greater increase in peak early velocityand normalized velocity ratio in these patients. Overall, changesin peak early (r= –0·47, P<0·01) andatrial velocity (r–0·65, P<0·001) andtheir ratio (r=0·35, P<0·05) correlated withreduction in R-R interval but not alterations in blood pressure.In conclusion, tachycardia during dobutamine stress masks theeffects of myocardial ischaemia on Doppler diastolic indicesalthough a minority of patients with inducible mitral regurgitationmanifest a relatively distinct filling profile.     

Short-term cardiac adaptation to severe haemodilution: an echocardiographic study in normal and hypertensive subjects

In order to avoid transfusion risks and optimize blood bankresources, in recent years many blood sparing techniques havebeen proposed, including severe haemodilution. The aim of thisstudy is to assess the pattern of normal haemodynamic and cardiacadaptation to severe haemodilution in patients undergoing majororthopaedic surgery and refusing blood transfusions for religiousreasons (the patients were Jehovah's Witnesses). Two-dimensionally guided M-mode echocardiograms were performedat baseline and 4 days after major orthopaedic surgery in 26Jehovah's Witnesses (age 61±11 years), with normal regionaland global baseline left ventricular function and no valvulardisease. Left ventricular (LV) volumes were estimated by usingthe Teichholz formula. From the latter, we calculated ejectionfraction and stroke volume, cardiac output (stroke volumex heartrate), and total peripheral resistance estimated as mean arterialpressure by cuff sphygmomanometer x 80/cardiac output. On thebasis of LV mass (ASE-cube corrected by Devereux), two groupswere identified: non-hypertrophic (LV mass index <110 g.m^–2 in women and <130g. m^–2 in males) and hypertrophic. In the 19 patients without LV hypertrophy, haemoglobin decreasedfrom 13.5±1.6 (mean ± standard deviation) g. dl^–1(at baseline) to 8.7 ± 1.3 post-operation (P<0.01),and peripheral vascular resistances fell from 2131 ±450 to 1278±310 (dyne. s. cm^–5) (P<0.01). Therewas an increase in heart rate (from 68±9 to 87±9beats. min^–1, P<0.01) and cardiac output (from 3.8±0.7 to 6.7 ±1.41 min^–1, P<0.01), witha rise in ejection fraction (from 62 ± 5 to 66 ±6%, P<0.01) and a decrease in relative wall thickness (from0.42 ± 0.03 to 0.35 ± 0.04, P<0.01). In theseven hypertensive hypertrophic patients, haemoglobin went from12.4 ± 1 (at baseline) to 8.4 ± 1.5 post-operation(P<0.01) and peripheral vascular resistances fell from 2551± 845 to 1363 ± 413 (P<0.01). There was anincrease in heart rate (+38%) and cardiac output (+46%) comparableto that found in non-hypertrophic patients, but with no significantvariation in LV relative wall thickness (from 0.50 ±0.08 to 0.48 ± 0.05, P=ns) and no increase in ejectionfraction (from 62 ±8 to 62.3 ±9%, P=ns). Therewas an inverse correlation between haemoglobin levels and LVcardiac output in both the normal (r= - 0.74; P<0.01) andthe hypertrophic (r= -0.63, P<0.05) group. In conclusion, severe haemodilution induces a high output statewith a fall in peripheral vascular resistance. This haemodynamicadaptation is accompanied by an eccentric remodelling in normal,but not in hypertrophic, hearts. In normal patients, but muchless so in the hypertrophic ones, LV geometry is a dynamic variablewhich can be profoundly modified by a few days of severe haemodilutionand can thus significantly contribute to the overall adaptationto altered haemodynamics.     

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.     

Haemodynamic and cardiac metabolic effects of the new {beta}1 agonist prenalterol in patients with cardiac failure

Prenalterol, a ß₁ selective agonist, exerts a positiveinotropic action in animal studies as well as in human volunteersand is effective when administered orally. To assess its immediatehaemodynamic and myocardial metabolic effects, we studied theresponse to prenalterol (50 and 100 µg kg^–1 givenintravenously by cardiac catheterization) in 15 patients withcongestive heart failure secondary to coronary artery diseaseor non-ischaemic cardiomyopathy. At peak effect, cardiac indexincreased from 2.6 ± 0.5 to 3.2 ± 0.81 min^–1m² (mean ± S.D.) (P <0.001); peak rate of left ventricularpressure development rose from 963 ± 242 to 1335 ±411 mmHg s^–1 (P < 0.001); left ventriuclar end-diastolicpressure fell from 25 ± 6 to 17 ± 7 mgHg (P <0.001);coronary sinus blood flow increased from 113 ± 39 to148 ± 55 ml min^–1 (P <0.01); myocardial oxygenconsumption was augmented from 12.7 ± 3.9 to 16.4 ±5.8 ml min^–1 (P < 0.001); and heart rate increasedslightly (from 76 ± 12 to 86 ± 14 beats min^–1;(P <0.05)). No significant changes occurred in left ventricularsystolic pressure, stroke volume index, myocardial lactate extractionrate and myocardial arteriovenous oxygen difference, and nopatients developed angina, ECG changes or ventricular arrhythmias.Infusion of prenalterol effectively improved haemodynamic functionand cardiac metabolism in cardiomyopathy. Therefore this agentdeserves further investigation to evaluate its possible rolefor the long-term therapy of patients with chronic heart failure.