Coronary vasodilator reserve in primary and secondary left ventricular hypertrophy: A study with positron emission tomography

Objectives Coronary vasodilator reserve is reduced in hypertrophiccardiomyopathy and secondary left ventricular hypertrophy despiteangiographically normal coronaries. The aim of the present studywas to assess whether quantitative differences exist betweenthese conditions. Methods Using positron emission tomography with H₂¹⁵O, myocardialblood flow was measured at baseline and following intravenousdipyridamole (0·56 mg. kg ^–1) in 12 hypertrophiccardiomyopathy patients (age 34 (11) years, mean (SD), all male),16 secondary left ventricular hypertrophy patients (age 58 (20)years, P<0·01 vs hypertrophic cardiomyopathy; 10 female)and 40 normal controls (age 54 (20), 13 female). In view ofthe known decline of post-dipyridamole myocardial blood flowwith age, myocardial blood flow was compared between the patientgroups and appropriately matched subsets of the total controlgroup. Results Baseline myocardial blood flow in the hypertrophic cardiomyopathypatients was 0·82 (0·23) ml. min^–1 . g^–1vs 0·94 (0·14) ml. min^–1 . g^–1 inits matched control group, P=ns. For the secondary left ventricularhypertrophy patient group, baseline myocardial blood flow was1·17 (0·40) ml . min^–1 . g^–1 vs 1·06(0·28) ml . min^–1 . g^–1 for the secondaryleft ventricular hypertrophy matched control group, P=ns. Followingdipyridamole, myocardial blood flow was 1·64 (0·44)ml . min^–1 . g^–1 in hypertrophic cardiomyopathypatients vs 3·50 (0·95) ml . min^–1 . g^–1forthe hypertrophic cardiomyopathy matched control group, P=0·0001.For the left ventricular hypertrophy patients, post-dipyridamolemyocardial blood flow was 2·27 (0·60)ml . min^–1. g^–1 vs 2·94(1·29) ml . min^–1 . g^–1for the left ventricular hypertrophy controls, P 0·06.Coronary vasodilator reserve (dipyridamole-myocardial bloodflow/baseline-myocardial blood flow) was 2·05 (0·61)for hypertrophic cardiomyopathy patients vs 3·81 (0·98)for the hypertrophic cardiomyopathy controls (P=0 0001, patientsvs controls) and 2·06 (0·62) for left ventricularhypertrophy patients vs 2·90 (1·38) for the leftventricular hypertrophy controls, P<0·03 patientsvs controls. After correction of baseline myocardial blood flowfor baseline heart rate x systolic pressure product, coronaryvasodilator reserve for the hypertrophic cardiomyopathy patientswas 2·06 (1·06) vs 4·34 (1·54) forthe hypertrophic cardiomyopathy controls, P=0·0002 andin the secondary left ventricular hypertrophy patients, thevalues were 2·13 (0·64) vs 2·89 (1·42)in the secondary left ventricular hypertrophy controls, P<0·05. Conclusions In both hypertrophic cardiomyopathy and secondaryleft ventricular hypertrophy, the computed coronary vasodilatorreserve is impaired, even after correction for baseline cardiacwork. However, the extent of the reduction is greater in thehypertrophic cardiomyopathy patients. In the blunting of vasodilatorreserve of secondary left ventricular hypertrophy, the patients'greater hyperaemic response is partly offset by the higher baselinemyocardial blood flow.     

Altered autonomic cardiac control in hypertrophic cardiomyopathy: Role of outflow tract obstruction and myocardial hypertrophy

Aim The goal of this study was to investigate the role of leftventricular outflow tract obstruction and myocardial hypertrophyon autonomic cardiac function in patients with hypertrophiccardiomyopathy. Methods and results The sympatho-vagal function was evaluatedby spectral analysis of heart rate variability in 28 patientswith hypertrophic obstructive cardiomyopathy, 22 patients withhypertrophic non-obstructive cardiomyopathy, 12 with systemichypertension and left ventricular hypertrophy and 28 healthysubjects. Left ventricular outflow tract pressure gradient inpatients with hypertrophic cardiomyopathy was evaluated by echo-Dopplermethods and the quantitative assessment of left ventricularhyper-trophy was based on an echocardiographic index. At rest,patients with hypertrophic non-obstructive cardiomyop-athy showednormal spectral patterns, while in patients with hypertrophicobstructive cardiomyopathy and in patients with systemic hypertensionwe observed, respectively, a significant reduction and increasein the low frequency component relative to the control (P<0·05).During tilt, the physiological increases in the low frequencycomponent, and in the low to high frequency ratio were markedlyblunted, or even reverted, only in patients with hypertrophicobstructive cardiomyopathy. In these patients, the heart rateincrease during tilt was delayed in comparison to the othergroups. Finally, in the hypertrophic obstructive cardiomyopathygroup, the impairment of sympathetic activation (lack of increasein the low frequency component during tilt) was significantlycorrelated to the echocardiographic index of left ventricularhypertrophy (r=–0·800,P<0·001) ratherthan to the left ventricular outflow tract pressure gradient(r=0·295,P: ns). Conclusion Among patients with hypertrophic cardiomyopathy,only those with outflow tract obstruction show spectral signsof altered autonomic cardiac control. Within this group, theautonomic dysfunction appears to be correlated to myocardialhypertrophy rather than to left ventricular outflow tract obstruction.     

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.     

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.     

Left ventricular function after repeated episodes of ventricular fibrillation and defibrillation assessed by transoesophageal echocardiography

Background Investigators studying the effects of cardioverter-defibrillatorson left ventricular systolic function have given only minorattention to the diastolic effects. Objectives The purpose of this study was to investigate theimpact of repeated episodes of ventricular fibrillation anddefibrillation on systolic function and diastolic filling ofthe left ventricle during non-thoracotomy implantation of acardioverter-defibrillator. Methods Systolic function and diastolic filling of the leftventricle were assessed peri-operatively on a beat-by-beat basisusing a transoesophageal echo-Doppler technique in 12 patientsduring 4 episodes of ventricular fibrillation and defibrillation.Systolic function was assessed from the fractional area changeand diastolic filling from the E/A ratio. Arterial blood pressureand the ECG were recorded continuously. Results Blood pressure and heart rate did not change significantlythroughout the procedure. The systolic function, similarly,was not significantly affected; the only changes were seen inthe first two beats after defibrillation when the mean fractionalarea increased from 0·2±0·01 to 0·4±0·02and 0·3±0·02, respectively (P<0·001).Diastolic filling was, however, impaired as reflected by a decreasein the E/A ratio from 2·6±0·5 before to1·6±0·4 (P<0·01) after repeatedthreshold tests. Conclusions. While the combined ischaemic and electrical traumacaused by repeated episodes of ventricular fibrillation anddefibrillation during the implantation of a cardioverter-defibrillatordid not cause any systolic dysfunction, diastolic filling wassignificantly impaired.     

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.     

Syncope and ventricular arrhythmias in hypertrophic cardiomyopathy are not related to the derangement of coronary microvascular function

Non-sustained ventricular tachycardia on Holter and syncopehave been considered risk factors for sudden death in hypertrophiccardiomyopathy. AIMS: In these patients the coronary vasodilator reserve is impaireddespite normal coronaries, so we evaluated the correlation betweenthe severity of coronary vasodilator reserve impairment andthe occurrence of syncope and non-sustained ventricular tachycardia. METHODS AND RESULTS: Eighty-four patients with hypertrophic cardiomyopathy (62 males,age 43±12 years) had a two-dimensional echocardiographicstudy and a 48-h Holter. Myocardial blood flow was measuredby positron emission tomography, at baseline and after dipyridamole,and the coronary vasodilator reserve was computed as dipyridamolemyocardial blood flow/baseline myocardial blood flow. In 27patients, subendocardial and subepicardial myocardial bloodflow was measured in the septum and the subendocardial/subepicardialratio was computed. Twenty of 84 patients had at least one syncopalepisode, and 26 had at least one run of non-sustained ventriculartachycardia on Holter. Baseline and dipyridamole myocardialblood flow, coronary vasodilator reserve, and baseline and dipyridamolesubendocardial/subepicardial myocardial blood flow ratio weresimilar in patients with and without syncope and with and withoutnon-sustained ventricular tachycardia on Holter. However, patientswith non-sustained ventricular tachycardia had larger left ventricularend-diastolic (47±6 vs 44±5 mm, P<0·05)and end-systolic diameters (30±6 vs 27±4 mm, P<0·05). CONCLUSIONS: (1) Coronary vasodilation is not more severely impaired in patientswith hypertrophic cardiomyopathy and syncope or non-sustainedventricular tachycardia. (2) The left ventricle is more dilatedin hypertrophic cardiomyopathy with non-sustained ventriculartachycardia.     

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.     

Influence of the force--frequency relationship on haemodynamics and left ventricular function in patients with non-failing hearts and in patients with dilated cardiomyopathy

In isolated human myocardium it was shown that a positive force-frequencyrelationship occurs in non-failing myocardium; however, theforce-frequency relationship was found to be inverse in myocardiumfrom failing human hearts. In order to investigate the clinicalrelevance of these experimental findings, the influence of heartrate changes on haemodynamics and left ventricular functionwas studied in eight patients without heart failure and in ninewith failing dilated cardiomyopathy (NYHA II–III). Rightventricular pacing was performed at a rate slightly above sinusrate and at 100, 120 and 140 beats. min^–1 Haemodynamicparameters were obtained by right heart catheterization andby high-fidelity left ventricular pressure measurements. Leftventricular angiography was performed at basal pacing rate andat 100 and 140 beats. min^–1 With increasing heart rate,cardiac index increased in patients with normal left ventricularfunction from 2·9 ± 0·2 to 3·5 ±0·21. min^–1. m^–2 (P<0·01) and decreasedcontinuously in patients with dilated cardiornyopathy from 2·6± 0·1 to 2·2 ± 0·11. min^–1. m^–2 (P<0·05). With increasing heart rate,the maximum rate of left ventricular pressure rise increasedin non-failing hearts from 1388 ± 86 to 1671 ±88 mmHg. s^–1 (P<0·01) and did not change infailing hearts. Ejection fraction decreased from 27 ± 3% to 19 ±2% in patients with dilated cardiomyopathy (P<0·05)when the pacing rate was changed from 84 ± 2 beats. min^–1to 140 beats. min^–1, which was associated with a significantlyincrease in end-systolic volume without significantly changesin end-diastolic volume. In patients with normal left ventricularfunction, when the pacing rate was changed from 85 ±3 beats. min^–1 to 140 beats. min^–1, end-diastolicvolume decreased significantly by 13%, whereas left ventricularend-systolic volume and ejection fraction did not significantlychange. Left ventricular systolic and end-diastolic pressuresdid not significantly change with pacing tachycardia in eithergroup. The frequency-related changes in left ventricular volumesand pressures indicate that the differrent haemodynamic effectsof pacing tachycardia in both groups of patients result predominantlyfrom frequency effects on myocardial function and not from frequencyeffects on preload or afterload. These data indicate that recentexperimental findings of positive force-frequency effects innon-failing and negative force-frequency effects in failinghuman myocardium are relevant for the intact heart.     

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.     

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.     

Doppler flow and echocardiography in functional cardiac insufficiency: Assessment of nisoldipine therapy: Results of the DEFIANT-II study

Aims A multicentre, double-blind, placebo-controlled trial wasconducted in 542 patients, randomized 7–10 days aftermyocardial infarction, to study the effect of nisoldipine coat-core(nisoldipine-CC) on exercise after 6 months. Secondary endpointsincluded exercise-induced ischaemia, left ventricular functionmeasured by Doppler echocardiography, adverse cardiac eventsand clinical outcome. Methods and results Patients had reduced left ventricular ejectionfraction between 25 and 50%, but no heart failure. Exercisetime was not different in the two groups. Nisoldipine-CC prolongedtime to 1 mm ST deviation (P=0·03). There was an effectof nisoldipine-CC of +3·6cm. s^–1 on early peakvelocity (P=0·01 and of –6·2 ms on isovolumicrelaxation time (P=0·005), but no effects on left ventricularvolumes or ejection fraction. There was a trend towards reducedmortality (one death in the nisoldipine-CC group vs seven inthe placebo group, P0·07) and the combined end-pointof mortality and cardiac events (P0·09). Peripheral oedemaoccurred in 49 patients assigned to nisoldipine-CC and two assignedto placebo (P0·001). There were no differences in non-cardiacevents. Conclusions Nisoldipine-CC did not improve exercise time butincreased time to 1 mm ST deviation, and improved diastolicleft ventricular function. It is safe and well tolerated inpost-infarction patients with impaired left ventricular function.     

Beneficial effect of enalapril on left ventricular remodelling in patients with a severe residual stenosis after acute anterior wall infarction

OBJECTIVE: The present study was designed to evaluate the effects of earlyangiotensin converting enzyme (ACE) inhibition on left ventricularenlargement in patients with anterior wall infarction followingreperfusion therapy. METHODS: Seventy-one consecutive patients with an anterior wall myocardialinfarction were randomly allocated to enalapril (n=36) or placebo(n=35). All patients received either thrombolytic therapy (n=46)or underwent primary coronary angioplasty (n=25). Medicationwas started within 48 h admission to hospital and continuedfor 48 weeks. The process of left ventricular remodelling wasassessed with two-dimensional echocardiography at 3 weeks and1 year after the acute onset, and was related to the severityof the residual stenosis of the infarct-related artery. RESULTS: Baseline left ventricular ejection fraction was 39·2±8·7%.During the study period, left ventricular end-diastolic volumeindex increased from 48·2±9·9 ml. m^–2to 54·6±12·2 ml. m^–2 at 3 weeks,and to 59·4±170 ml. m^–2 after 1 year incontrol patients (P<0·001). In the enalapril-treatedpatients, left ventricular end-diastolic volume index increasedfrom 50·0±16·1 to 57·7±19·3ml. m^–2 at 3 weeks, and to 61·9±22·7ml. m^–2 after 1 year (P<0·001). Both at 3 weeksand after 1 year, no overall differences in left ventricularvolumes were observed between the enalapril and the placebogroup (both ns). However, patients with a residual stenosisseverity of 70% in the infarct-related artery (n=43) showedsignificant attenuation of remodelling by enalapril (n=22) whencompared to placebo (n=21). In patients on enalapril, left ventricularend-diastolic volume index increased from 470±130 to53·7±17·7 ml. m^–2 compared to 48·0±9·6to 60·3±16·3 ml . m^–2 in controlpatients (P<0·03). Also diastolic filling parameterswere significantly improved in patients with 70% residual stenosis. CONCLUSION: In patients with an anterior wall infarction and a severe residualinfarct-related coronary artery stenosis following reperfusion,treatment with enalapril prevents the process of left ventricularremodelling. As left ventricular dilatation is an early processwe suggest that treatment with ACE inhibition should be startedas soon as possible in this group of patients.     

Hyperleptinaemia in chronic heart failure: Relationships with insulin

Background Leptin, a product of theobgene, is known to increaseenergy expenditure. Given that chronic heart failure is a hypercatabolicstate, we sought to determine whether congestive heart failureinvolves elevations in plasma leptin levels. Since leptin secretionis up-regulated by insulin, we also explored whether in congestiveheart failure, a hyperinsulinaemic state, plasma leptin levelsrelate to plasma insulin levels. Methods Male patients with weight-stable congestive heart failure(n=25, aged 55·5±2·0, mean±SEM,body mass index=27·4±0·8, radionuclideleft ventricular ejection fraction=29·3±3·0%)and 18 controls, matched for age, sex and body fat (dual energyX-ray absorp-tiometry), underwent measurement of fasting plasmaleptin (radioimmunoassay) and insulin levels. Results Compared to controls, patients with congestive heartfailure had higher plasma leptin [8·12 (–1·12,+1·31)vs 4·48 (–0·61,+0·70) ng.ml^–1,mean±asymmetrical SEM,P=0·003], 41·5% higherplasma leptin per percent body fat mass (P<0·001),and higher fasting insulin levels [67·8 (–11·1,+13·3)vs 32·9 (–5·7,+6·9) pmol.l^–1,P=0·010].In the congestive heart failure group, plasma leptin correlatedwith total body fat (r=0·66) and fasting insulin (r=0·68)(bothP<0·001). In multivariate regression analysesof the congestive heart failure group, fasting insulin (standardizedcoefficient=0·41,P=0·011) emerged as a predictorof plasma leptin levels, independent of total body fat (standardizedcoefficient=0·73,P=0·002, R²=0·66,P<0·001). Conclusions Plasma leptin levels are raised in patients withcongestive heart failure. The observation of a positive relationshipbetween plasma leptin and insulin concentrations suggests thatthe insulin–leptin axis may be related to the increasedenergy expenditure observed in patients with congestive heartfailure.     

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.     

Myocardial structure as a determinant of pre- and postoperative ventricular function and long-term prognosis after valve replacement for aortic stenosis

Background Long-term results after aortic value replacement for aorticstenosis can be correlated to a cardiac-related pre-operativerisk profile. This predictability indicates that there is acommon basis in subtle or overt structural abnormalities ofleft ventricular myocardium. Methods and Results Forty-nine patients aged 24–82 (mean 61) years, with aorticstenosis had a full wall thickness transmural biopsy of theleft ventricular antero-lateral free wall during aortic valvereplacement. Echocardiography and radionuclide ventriculographywere performed prior to, and 18 months (n=41) after, the operation.Postoperative follow-up to a maximum of 7·7 years was100% complete. Pre-operatively, all patients had an increasein both the left ventricular mass index (202±67g.m^–2)and the muscle cell diameter (41±8µm); other morphologicaldata included a muscle cell nucleus volume of 752±192µm³,a muscle cell mass index of 163±54g.m^–2, and afibrous tissue mass index of 39±16g.m^–2. Patientswith a pre-operative episode of clinical left ventricular failure(n=19) had significantly greater morphological variables thanthose without. Pre-operative ejection fraction and other measuresof systolic function correlated inversely with the morphologicaldata, except for the fibrous tissue mass index; diastolic functionindices correlated inversely with all the morphological variables.At the 18-month re-study, the same general picture was noted,but with an underlying strengthening, especially of the musclecell mass index. Overall, the mass index dropped to 152±51g.m^–2(P<0·0001),but in 17% of the patients it became normal; the mass indexat 18 months was directly correlated to morphological variables.A high muscle cell nucleus volume was identified as an independentpredictor of early and late mortality. Conclusion Abnormalities of the hypertrophied left ventricular muscle celland the degree of muscle hypertrophy are, to some degree, underlyingdeterminants of pre-operative symptomatology, pre- and postoperativeventricular function, and early and late mortality after valvereplacement for aortic stenosis. Incomplete hypertrophy regressionafter valve replacement, being indicative of impaired results,was related to pre-operative myocardial structural abnormalities.     

Metabolic syndrome is associated with abnormal left ventricular diastolic function independent of left ventricular mass

Aim To characterize the extent to which metabolic syndrome criteriapredict left ventricular (LV) structure and function. Methods and results Metabolic syndrome criteria were assessedin 607 adults with normal LV function. The cohort was groupedaccording to the number of criteria satisfied: (1) Absent (0criteria, n = 110); (2) Pre-Metabolic Syndrome (1–2 criteria,n = 311); and (3) Metabolic Syndrome (3 criteria, n = 186).Echocardiography was used to assess LV structure (LV mass) andsystolic (LVEF, Vs) and diastolic function, by pulse-wave Doppler(E/A ratio) and tissue Doppler imaging (Ve). LV volumes andLVEF were similar between groups. However, LV mass increasedsignificantly and progressively (LVM/Ht^2.7, in g/m^2.7: 34.9± 6.7, 41.0 ± 9.5, 46.3 ± 11.0, P <0.001); LV relaxation decreased progressively (Ve_global', incm/s: 13.5 ± 2.8, 12.1 ± 3.0, 10.5 ± 2.2,P < 0.001) from Absent to Pre-Metabolic Syndrome to MetabolicSyndrome groups, respectively. Multiple variable analyses showedthat diastolic blood pressure, waist circumference, and triglyceridelevels were independent predictors of Ve after adjustment forLV mass. Conclusion Patients with metabolic syndrome have LV diastolicdysfunction independent of LV mass. These functional abnormalitiesmay partially explain the increased cardiovascular morbidityand mortality associated with metabolic syndrome.     

Acute effects of balloon valvuloplasty and pacing on left ventricular performance in children with moderate pulmonary valve stenosis, analysed by systolic and diastolic pressure--volume relationships

Right ventricular overload of volume and/or pressure type mayaffect left ventricular systolic and diastolic function. Thishas been shown in animal studies and has been suggested in non-invasivestudies in man. Altered geometry of the left ventricle, myocardialhypertrophy and changes in contractile state may be responsiblefor the change in function. Balloon valvuloplasty is an effectivetreatment for isolated valvular pulmonary stenosis in children,and results in an immediate decrease of right ventricular systolicpressure. Whether this results in immediate changes in leftventricular performance is unknown. Eight children (age 5·2to 13·9 years) with moderate pulmonary valve stenosisunderwent pulmonary balloon valvuloplasty under general anaesthesia.Left ventricular function measurements before and after valvuloplastywere performed using a combined micromanometer-conductance catheterto obtain end-systolic (ESPVR) and end-diastolic (EDPVR) pressure-volumerelationships employing inferior vena cava occlusion both atnormal and pacing-induced increased heart rates. Pulmonary valvuloplasty resulted in a decrease in peak systolicright ventricular pressure from 62·8±13·5to 34·4 ± 7·3 mmHg (P<0·001),without significant changes in left ventricular systolic andend-diastolic pressure, or in cardiac index. The ESPVR was fittedto a linear function to obtain the slope (E_es and the volumeintercept at 75 mmHg (V₇₅ The EDPVR was fitted to an exponentialfunction. At baseline, E_es was 1·68±0·99mmHg. ml^–1 and V₇₅ was 33·6 ± 21·8ml. Neither valvuloplasty nor pacing, which increased mean heartrate from 81 to 112 beats. min^–1 (P<0·001) resultedin significant changes of the parameters E_es, or V₇₅ The EDPVRwas not affected by valvuloplasty either, but pacing resultedin a change of its stiffness constant from 0·042 ±0·019 to 0·034 ± 0·018 mmHg . ml^–1(P<0·05) and pressure intercept from 0·97±0·51to 1·37±0·86 mmHg (P<0·05). Theeffect of pacing on left ventricular function before and aftervalvuloplasty was comparable. Neither balloon dilatation for moderate valvular pulmonary slenosis,nor pacing within the physiological range results in immediatechanges in left ventricular contractile performance in children.     

Dipyridamole stress thallium-201 perfusion abnormalities in patients with hypertrophic cardiomyopathy. Relationship to clinical presentation and outcome

Aims Thallium-201 perfusion abnormalities are common in patientswith hypertrophic cardiomyopathy and may be associated withan adverse prognosis in the young. The aim of this study wasto prospectively determine the relationship between thallium-201defects during dipyridamole stress to clinical presentationand outcome in a large consecutive series of patients with hypertrophiccardiomyopathy. Methods/Results Thallium-201 single photon computed tomography was performedin 216 patients with hypertrophic cardiomyopathy during dipyridamolestress (0·5mg.kg^–1). Fixed perfusion defects occurredin 25%, and reversible defects in 22%. A combination of defectswas present in 7%. Fixed defects were associated with: a historyof syncope (17 of 46 with, vs 36 of 170 without syncope, P=0·03);larger left ventricular end-diastolic (46·9±7·4mmvs 43·3±6·4mm; P=0·001) and end-systolicdimension (30·2±8·4mm vs 24·5±5·9mm,P<0·0001); increased left atrial diameter (46·1±8·1mmvs 40·5±7·7mm, P<0·0001); lowerfractional shortening (35·9±10·4% vs 43·8±8·6%,P<0·0001); and lower maximal exercise oxygen consumption(24·2±8·1ml.min^–1.kg^–1vs 29·4±8·8ml.min^–1.kg^–1,P<0·0003). Reversible defects did not correlate withsymptomatic status, but were associated with: larger left atrialdimensions (44·5±8·1mm vs 41·0±8·0mm;P=0·009) and greater maximal left ventricular wall thickness(24·0±7·0mm vs 20·6±7·0mm,P=0·003). The mean follow up time was 41±21 months,range 0·6–124. There was no association betweenany thallium-201 abnormality and disease related death in youngor adult patients. Conclusion The present study shows that fixed thallium-201 perfusion defectsdetected during dipyridamole stress in patients with hypertrophiccardiomyopathy are associated with syncope, larger left ventricularcavity dimensions and reduced exercise capacity. Although theevent rate was relatively small, there was no evidence for anassociation between thallium-201 defects and survival.     

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.