Does dobutamine prevent the rise in left ventricular filling pressures observed during exercise after heart transplantation?

The purpose of the study was to evaluate whether infusion ofa beta-adrenergic agonist, prior to and during exercise, couldcompensate for reduced sympathetic stimulation and correct deficientacceleration of left ventricular relaxation, so preventing arise in left ventricular filling pressures during exercise aftercardiac transplantation. Abnormal left ventricular relaxationkinetics can contribute to exercise-induced diastolic dysfunctionof the cardiac allograft. This was demonstrated in transplantrecipients whose acceleration of left ventricular relaxationduring exercise was almost negligible recently and whose elevationof left ventricular end-diastolic pressure was high. Decreasedadrenergic tone due to denervation could be involved in deficientleft ventricular lusitropic response to exercise, because accelerationof left ventricular relaxation during exercise depends on adequatesympathetic stimulation. Serial supine bicycle exercise was performed at an identicalworkload in eight transplant recipients while in the controlstate and during continuous infusion of dobutamine, titratedbefore exercise to achieve a heart rate matching the heart rateat peak exercise in the control state. During control exercise,heart rate rose from 87 ± 8 to 104 ± 12 beats.min^–1 (P<0.05), left ventricular end-diastolic pressurefrom 14 ± 5 to 20 ± 4 mmHg (P<0.05), left ventriculardP/dt_max from 1374 ± 172 to 1854 ± 278 mmHg. s^–1(P<0.05), and cardiac output from 5.8 ± 0.9 to 8.5± 1.11. min^–1 P<0.05). There was a small butsignificant decrease of the time constant of left ventricularpressure decay (T) from 42 ± 6 to 38 ± 6 ms (P<0.05).During dobutamine infusion, exercise resulted in a further increasein heart rate from 108± 11 to 122 ± 17 mmHg (P<0.05),in cardiac output from 7.4 ± 0.9 to 10.3 ± 2.5l. min^–1 (P<0.05), and in left ventricular dP/dt_maxfrom2181 ± 220 to 2620 ± 214 mmHg. s^–1 (P<0.05).These values were higher than the measurements obtained at theend of the control exercise run (P<0.05). T failed to change(29 ± 4 vs 27 ± 5 mmHg, P>0.05) and left ventricularend-diastolic pressure increased from 5 ± 3 to 11 ±5 mmHg (P<0.05) but remained lower than at the end of thecontrol exercise run (11 ± 5 vs 20 ± 4 mmHg, P<0.05). Compensation for reduced sympathetic stimulation by administrationof dobutamine improves exercise haemodynamics in cardiac transplantrecipients, but cannot prevent the exercise-induced rise inleft ventricular end-diastolic pressure and correct deficientacceleration of left ventricular relaxation. Abnormal exercisehaemodynamics after heart transplantation are therefore onlypartly related to deficient sympathetic stimulation.     

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).     

Dipyridamole slows the rate of isovolumic pressure fall in patients with normal coronary arteries

Dipyridamole is currently used for thallium imaging and stressechocardiography. The coronary and haemodynamic effects of dipyridamoleare well documented while its effects on left ventricular relaxationremain to be determined. The aim of the present study was toevaluate the effects of dipyridamole on left ventricular relaxationrate in healthy subjects. High fidelity pressure recordingswere obtained at fixed atrial pacing (89 ±2 beats. min^–1)in 10 subjects with normal left ventricular angiography andcoronary arteriograms. Left ventricular pressure was recordedat rest and 5 min after a 4 min infusion of dipyridamole (0.14mg. kg^–1. min^–1). Dipyridamole infusion decreasedleft ventricular systolic pressure (P<0.01) and time to leftventricular systolic pressure (P<0.01)r with no changes inend-diastolic pressure or peak rate of pressure rise. The peakrate of isovolumic pressure fall decreased (from 1957 ±105 to 1488 ± 100 mmHg. s^–1, Y<0.01) and thetime constant of isovolumic relaxation increased (from 37 ±2to 44±3 ms, P<0.02). In conclusion, our study indicatesthat acute administration of clinically relevant doses of dipyridamoledisplays deleterious effects on heart relaxation in healthyhumans.     

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.     

Range of normal values for left and right ventricular ejection fraction at rest and during exercise assessed by radionuclide angiocardiography

In order to reach a world-wide consensus on the normal rangeof left (LV) and right ventricular (RV) ejection fraction (EF)at rest and during exercise, pooled data of 1200 normal subjectsfrom 28 leading centres in the field of nuclear cardiology (68%of those contacted) was analysed. Weighted mean normal valuesfor LVEF at rest were 62.3±6.1% (1SD) with a lower limitof normal of 50% and for RVEF 52.3±6.2% (N=365) witha lower limit of normal of 40%. During exercise, LVEF increasedin 475 subjects by +8.0 EF% (range 3–15%), a normal increasebeing accepted to be 5% over a normal resting value for bothLVEF and RVEF. Subgroup analysis of results at rest revealedno significant differences regarding selection of normal subjects(based on normal catheterization findings vs. normal volunteerswith low probability of disease), age or sex. During exercise,however, significantly larger increases in LVEF measurementswere noted for men versus women (P<0.01), for normal volunteersversus subjects selected as ‘normals’ based on anormal coronary angiogram (P<0.001) and for younger versusolder subjects (P<0.001). Data on reproducibility and variabilityshowed that radionuclide angiocardiography can be consideredto be a reliable method today. No consensus was found for measurementsof regional LV function or wall motion mainly because of differencesin methodology used. These normal values may serve as generalguidelines for future applications of these techniques but factorswhich may influence the normal range as defined and discussedin this study should be recognized.     

Influence of nifedipine on left ventricular dysfunction at rest and during exercise

In order to determine the acute hemodynamic effect of nifedipineat rest and during a standardized supine bicycle exercise test(3 min, 50 W), 14 patients with left ventricular dysfunctionwere studied before and 60 min after taking 30 mg nifedipinesublingually. At rest (R) and during exercise (E), nifedipine produced a significantincrease in left ventricular systolic performance in terms ofstroke volume index (R: 33±6 to 38±4 ml/m², P<0.005;E: 32±5 to 37±6 ml/m², P<0.005) and cardiacindex (R: 2.9±0.4 to 3.6±0.5 l/min/m², P<0.001;E: 4.1±0.7 to 4.9±0.9 l/min/m², P<0.001) dueto a marked reduction in systemic vascular resistance (R: 1517±246to 1129±247 dynes s cm^–5, P<0.001; E: 1170±176to 908±129 dynes s cm^–5, P< 0.01). Pulmonary artery pressures did not change at rest, but droppedsignificantly during exercise, probably due to a shift in theleft ventricular pressure-volume relationship. The findingsof this study indicate that acute hemodynamic improvement canbe achieved by the sublingual use of nifedipine both at restand during exercise in patients with left ventricular dysfunction.Because the hemodynamic response in individual subjects mayvary, careful clinical observation or hemodynamic control isrecommended.     

Corrected QT-interval during one year follow-up after an acute myocardial infarction

One hundred and one unselected patients less than 66 years ofage who had had a myocardial infarction were investigated withexercise ECG and technetium resting left ventricular ejectionfraction (LVEF) within one month of the myocardial infarction(MI), and at 6 months and 12 months. QTc was measured at rest (QTc^rest) and at maximal exercise (QTc^work).In patients with QTc^work < QTc^rest LVEF was found to be lower(mean 0.42) and QTc^rest longer (mean 0.467 s) than in patientswith QTc^work QTc^rest. In this latter group LVEF was 0.50 (meanvalue) (P<0.001) and QTc^rest 0.426 s (mean value) (P<0.001). A negative correlation was found between LVEF and QTc^rest, r= –0.35, P < 0.001. A negative correlation was alsofound between QTc^work-QTc^rest (i.e. the change in QTc duringmaximal exercise) and QTc^rest, r = –0.69, P<0.001. In patients with QTc^rest > 0.480 s at the first investigation,the one-year mortality was 50%, compared with 9% in patientswith QTc^rest < 0.480s (P = 0.0002). It is concluded that in post-MI patients, QTc^rest reflects thecondition of the left ventricular myocardium, a prolonged QTcrestbeing found with impaired myocardial function.     

Improvement in left ventricular dysfunction after aortic reimplantation in 11 consecutive paediatric patients with anomalous origin of the left coronary artery from the pulmonary artery: Early results of a serial echocardiographic follow-up

To study the potential for recovery of left ventricular functionin patients with anomalous origin of the left coronary arteryfrom the pulmonary artery (ALCAPA) after aortic reimplantation,serial two-dimensional echocardiographic examinations were performedbefore and up to 9 months after operation in 11 consecutivepaediatric patients (group 1: six infants; group 2: five childrenabove the age of 1 year). End-diastolic volume (EDV), end-systolicvolume (ESV), stroke volume (SV), ejection fraction (EF), myocardialvolume (MV), ratio of myocardial volume!end-diastolic volume(MVI), and regional wall motion of the left ventricle (LV) werestudied. Pre-operativety, mean LVEDV was 339% of normal in group 1 and289% in group 2 (P<0.001); mean LVMV was about twice thenormal value in both groups (P<0.001); LVMVI was 0–79± 0–23 in group 1 and 0–83 ± 0–3in group 2; LVEF was 28 ± 10% in group 1 and 46 ±18% in group 2; regional wall motion was normal in two group2 patients, the other showed uniform reduction in segmentalshortening fraction. Postoperatively, mean LVEDV tended to become normal after 2weeks in group 1 and after 3 months in group 2. In both groupsmean LVEF reached the normal range after 3 months; LVMV as wellas LVMVI normalized after 9 months. Three months after the operation,all infants had a nearly normal pattern of regional wall motion,while in three group 2 children a residual reduced shorteningfraction could be observed in anterior or lateral segments. The study shows that (1) aortic reimplantation in patients withALCAPA results in progressive improvement left ventricular functioneven in patients with severely damaged myocardium. (2) For aquick and complete recovery of global and regional left ventricularfunction, the operation should be undertaken early in infancy.(3) Left ventricular dysfunction is probably associated with‘hibernating myocardium’, which may ‘wakeup’ after surgical repair.     

The effects of early captopril treatment on left ventricular volumes and function in patients with and without depressed global ejection fraction after acute myocardial infarction

To determine the effects of captopril on left ventricular volumesand function in patients with and without depressed ventricularfunction following acute myocardial infarction (AMI) we studied78 patients with a first Q wave AMI and no clinical evidenceof heart failure. All patients underwent radionuclide ventriculography(RVG) on the 4th day after admission and were then randomlyassigned to receive conventional treatment alone (36 patients,control group) or with the addition of oral captopril, 25 mgthree times daily (42 patients, captopril group). RVG was repeatedone month after the baseline examination. After one month theleft ventricular ejection fraction (LVEF) significantly increasedin the captopril group (from 43.2±1.3 to 50.9±1.6%,P<0.001) and remained relatively unchanged in the controlgroup (from 47±1.3 to 49.2±1.7%, P=ns). In thecaptopril group the subgroup of patients with a baseline LVEF<45% demonstrated a significant decrease in end-systolicvolume index (ESVI) (from 53.3 ±3.2 to 42.4±2.8ml.m^–2,P<0.002) and a highly significant improvement in LVEF (from36.3±1.3 to 49.6±1.8%, P<0.00005). In the controlgroup, LVEF also increased in those in whom it was <45% (from38±1.4 to 42±2.4%, P<0.01), but the increasewas less than that in the captopril group (P<0.01), mainlydue to an increase in end-diastolic volume index (EDVI) (from78.2±4.6 to 84.6±12.3 ml.m^–2, P=ns). Inboth the captopril and control subgroups of patients with abaseline LVEF 45% there was no significant change in LVEF (from50.1±0.8 to 52.1±2.6% and 53.4±1.5 to 54.2±2.1%respectively), but there was a trend for both left ventricularvolumes to increase (EDVI: from 81.4±4.7 to 91.1±9.9ml.m^–2and 76±5.7 to 90.3±9.2 ml.m^–2; ESVI: from40.6±2.6 to 45.2 ±3.4 ml.m^–2 and 32.1±2.6to 40.1 ±3.8 ml.m^–2 respectively, all P=ns). In conclusion, our study confirmed the beneficial effect ofcaptopril on left ventricular size and function in patientswith depressed global LVEF after AMI, but there was no evidenceof a similar effect in patients with preserved global LVEF,at least during the first month of treatment.     

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.     

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.     

Haemodynamic effects of intravenous diltiazem at rest and exercise in patients with coronary artery disease

The acute effects of intravenous diltiazem on exercise performancewere studied in 10 patients with coronary artery disease. Haemodynamicmeasurements were made at rest and during exercise before andafter 0-5 mgkg^–1 of diltiazem. Diltiazem prolonged theduration of exercise (+2.85 min, P>0.001) and delayed theonset of ischaemic ST depression or angina in all patients.The highest tolerated heart rate and pressure rate product wereincreased in all but one patient after diltiazem. At rest diltiazem decreased mean arterial pressure (–10.8%,P>0.005), systemic vascular resistance (SVR) (-11.8%, P>005)and left ventricular stroke work index (SWI) (–14.1%,P>0.005). During exercise under diltiazem therapy, at the level achievedbefore the drug, the pulmonary capillary wedge pressure (-30%,P>0005) and the SVR (–13.6%, P>0.02) were lowered,the SWI (+13%, P>0.01) was increased: at the end of exerciseonly the SVR (14%, P>0.05) was reduced. Two patients experiencedangina on lying down and one had orthostatic hypotension afterexercise with diltiazem. This study indicates that intravenousdiltiazem is a potentially useful agent for the treatment ofangina by reducing myocardial oxygen demand at rest and by improvingleft ventricular performances on exercise.     

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.     

Acute haemodynamic effects of diltiazem in patients with recent Q-wave myocardial infarction

The effects of diltiazem on left ventricular systolic and diastolicfunction were studied in 14 patients with a recent (12–20days) Q-wave myocardial infarction. Left ventriculography withsimultaneous recording of high-fidelity left ventricular pressurewas performed in control conditions, and after i.v. administrationof diltiazem (0.2 mg kg^–1 as a bolus followed by constantinfusion of 0.005 mg kg^–1 min^–1 lasting 8–10min). After the administration of the drug, left ventricularsystolic pressure decreased by 12.7% and mean circumferentialwall stress by 14% (both P<0.01); the heart rate did notchange; the ejection fraction increased by 9.6% (P<0.05)and maximum dp/dt/P by 11% (P<0.01). Quantitative segmentalwall motion analysis showed that the beneficial effects of diltiazemon global left ventricular systolic function were associatedwith an increase in contraction in hypokinetic regions, wherethey were supplied by normal or diseased coronary vessels (bothP<0.01). Left ventricular and-diastolic pressure decreasedby 23.6% (P<0.05) and minimal diastolic pressure by 38% (P<0.05).Passive diastolic properties of the left ventricular chamberremained unaltered but isovolumic relaxation markedly improved:the T constant decreased 26% (P<0.01). Thus, in patientswith a recent Q-wave myocardial infarction, the i.v. administrationof diltiazem unloads the left ventricular chamber without showingdepressant effects on myocardial contractility     

Heterogeneity of left ventricular regional wall thickening following dobutamine infusion in normal human subjects: A quantitative two-dimensional echocardiographic study

Background: Pathophysiological data and pragmatic clinical experiencewith stress echocardiography suggest that inotropic stimulationwith simultaneous changes in heart rate and loading conditionscan affect the function of various myocardial regions asymmetrically,inducing heterogeneity in wall motion and thickening, possiblymimicking ‘ischaemic’ regional hypokinesis or lackof hyperkinesis during stress. Objectives: To describe, in a quantitative fashion, the physiologicalcontractile response of different left ventricular regions followingdobutamine infusion. Methods: Two hundred and twenty-three in-hospital patients undergoingdobutamine stress echocardiography and coronary angiographywere initially considered. Of these 223 patients, 18 had angiographicallynormal coronary arteries, normal resting function, negativeergonovine and exercise stress tests, and negative dobutaminestress echo-cardiograms; of the 18, only in 11 patients (sixfemales, age=56 ± 10 years) was it possible to obtainquantitative measurements of the middle segments of the inferior,anterior, lateral, and septa! walls. Two-dimensional echocardio-graphicmeasurements of wall thickness were obtained at the end-diastolic(onset of Q wave) and end-systolic phases, both at baseline(rest) and at the peak of the dobutamine infusion (40 fig. min^–1.kg^–1plus atropine). Results: Dobutamine increased heart rate (rest-69 ±9vs dobutamine=138 ± 13 beats. min^–1; P<0.01),whereas systolic blood pressure did not change significantly(rest-136 ± 75 vs dobutamine.150 ± 25 mmHg, P=ns).During stress, % systolic thickening decreased in the inferiorwall (rest = 73 ± 24 vs dobutamine ± 50 ±9%; P<0.01), whereas it tended to increase to a variableextent in the other regions, i.e. septal (rest=46± 17vs dobutamine=68 ± 13%, P<0.01), anterior (rest 62± 19 vs dobutamine=69 ± 11%, P=ns), and lateralwall (rest=48± 16 vs dobu-tamine=61 ± 18%, P=ns).The decrease in % systolic thickening of the inferior wall wasinversely correlated with the increase in end-diastolic wallthickness (r=– 0.75; P<0.01), but neither with heartrate (r=0.15; P=ns) nor with systolic blood pressure changes(r=0.05; P=ns). Conclusions: Heterogeneity of left ventricular wall thickeningcan be induced or magnified by dobutamine infusion even in subjectswithout coronary artery disease, with the inferior wall showinga lack of hyperkinesis, up to relative hypokinesis, in comparisonwith other myocardial regions. Caution in aggressive dobutaminestress echocardiography reading, especially in the inferiorwall, might be warranted.     

Reversal of ischaemic systolic and diastolic left ventricular dysfunction by successful coronary angioplasty in patients with non-Q wave anterior myocardial infarction

The effect of PTCA on global and regional left ventricular systolicfunction, isovolumic relaxation, chamber and muscle stiffnesswere studied in 30 patients with angina pectoris, previous non-Qwave anterior myocardial infarction (AMI) and significant stenosisof the left anterior descending coronary artery (LAD). In 11of the 30 patients the condition was stable, but it was unstablein 19. Left ventricular angiograms were obtained before and4. 85± 3.67 months after PTCA. The RAO was in the 30^°projection, with the silhouette of the left ventricle slicedinto 90 regions; changes in left ventricular volume, pressureand anterior wall thickness during the full cardiac cycle, togetherwith dpldt were demonstrated. After PTCA, global ejection fractionincreased from 68. 77 ± 5.96% to 76.57 ±3.18%,P<0.001. Impaired contractility was found in 29190 (32.2%)regions before PTCA and in 5190 (5.6%) after PTCA, P<0.001.The time constant of the isovolumic pressure fall decreasedafter PTCA (52.56 ± 17. 40 ms vs 39. 61 ± 11.26ms, P<0.01). Elastic chamber stiffness coefficient decreased(0.022 ± 0.003 vs 0.008 ± 0.004, P<0001) andpeak rate of left ventricular filling increased (319.0 ±107.9 ml. min^–1 vs 396.8 ±201.4 ml. min^–1,P<0.05) after PTCA. The muscle stiffness coefficient waswithin normal values before and did not change after PTCA. Thestudy findings show that in patients with persistent anginapectoris after non-Q wave AMI, complex systolic and diastolicischaemic dysfunction occurs. This dysfunction can be reversedafter successful PTCA of LAD.     

Plasma neuro-endocrine activity in very elderly subjects and patients with and without heart failure

Marked neuro-endocrine activation in patients with heart failureindicates a worse prognosis and a greater prognostic benefitfrom the use of ACE inhibitors. However, although the incidenceof heart failure rises rapidly with age, relatively little isknown about activation of the renin-angiotensin and sympatheticnervous system in patients with heart failure over the age of75 years. This study was undertaken to investigate plasma concentrationsof neurohormonal variables in elderly patients referred to thecardiac clinic with a presumptive, but unconfirmed, diagnosisof heart failure, and to compare these values to plasma concentrationsfound in age-matched normal subjects. Fifty patients referred with a diagnosis of heart failure werestudied. All were receiving a diuretic but not an ACE inhibitor.Patients with renal, haematological and valve disease were excludedRoutine biochemistry and neuro-hormonal measurements were performedat their first visit, together with an electrocardiogram, chestX-ray and a full clinical examination by an experienced cardiologist.An echocardiogram and Doppler study was also performed and thediagnosis of heart failure either confirmed or refuted. Plasma concentrations of neuro-endocrine variables in healthyelderly subjects were similar to our normal laboratory rangein younger subjects with the exception ofatrial natriureticpeptide (ANP) (40 ± 6 pg. ml^–1, normal range <40)and noradrenaline (5.7±0.7 nmol. l^–1), normal range<2.8). Impairment of left ventricular systolic function wasconfirmed in 38 of the 50 symptomatic patients (76%) and wasassociated with increases in plasma concentrations of activerenin (58 ± 8 IU. mol^–1 P<0.001 compared tohealthy elderly subjects), angiotensin II (23 ± 5pg.ml^–1, P<0.008), noradrenaline (7.7±1.2 nmol.l^–1, P<0.01) and atrial natriuretic peptide (121 ±18 pg. ml^–1, P<0.002). Plasma concentrations were similar in normal subjects and thosereceiving treatment for heart failure but in whom the diagnosiswas not confirmed A weak relationship between plasma atrialnatriuretic peptide (ANP) and left ventricular fractional shorteningwas demonstrated (r= –0.5, P<0.001). Using an upperlimit of ANP in the healthy elderly subjects of 62 pmol. ml^–1(mean+SD), plasma concentrations of ANP in the population withsuspected heart failure had a sensitivity of 74% and specificityof 66% for the diagnosis of heart failure among elderly patientsin the community or where access to echocardiography is limited.Left ventricular diastolic filling (assessed by Doppler) wasabnormal in healthy elderly subjects and patients with heartfailure, and appeared of limited value in the diagnosis of heartfailure secondary to diastolic dysfunction. This study confirms that the renin-angiotensin system is activatedin elderly patients with heart failure treated with diuretics.ANP may be helpful in diagnosing heart failure where it appearsto have a complimentary role to echocardiography.     

Platelet activation in angina at rest. Evidence by paired measurement of plasma beta-thromboglobulin and platelet factor 4

Indexes of in vivo platelet activation, beta-thromboglobulinand platelet factor 4 were measured in triplicate in plasmafrom venous blood of 69 patients with proven ischaemic heartdisease (IHD), discarding samples with a ratio of the plasmaconcentrations of the two proteins <2.6, in order to ruleout sampling artifacts. Compared with 60 control volunteers,differences were not significant [for beta-thromboglobulin controls(ng ml^–1, mean±SD) 27.8–8.6, ischaemic patients32.3±17.1; for platelet factor 4 controls 4.3±1.4,ischaemic patients 5.9±5.7]. However, when patients werestratified according to disease activity (Group I—;patientswithout spontaneous ischaemic episodes at rest during 4 daysof continuous electrocardiographic monitoring; Group II—patientswith <l ischaemic episode/day; Group III—patients with>l episode/day), these indexes were increased in ‘active’patients (for beta-thromboglobulin, in Group II—32.4±10.5ng ml^–1, P<0.05 vs. Group I; in Group III—42.6±14.6ng ml^–1, P<0.01 vs. Group I, P<0.05 vs. control.Platelet factor 4 was increased only in Group III—8.9±7.2ngml^–1, P<0.05 vs. control). Beta-thromboglobulin andplatelet factor 4 were 25.0±6.7 ng ml^–1 and 4.9±4.8ng ml^–1, respectively, in Group I (P=NS vs. control).A relationship with the number of spontaenous ischaemic episodesat rest was confirmed by linear regression analysis (in GroupIII patients for beta-thromboglobulin: r=0.76, P<0.01, andfor platelet factor 4 r=0.62, P<0.01). Levles were not elevatedin patients with pervious myocardial infarction without ischaemiaat rest and/or patients with stable angina, and were not influencedby the occurrence of a positive exercise stress test. Coronaryangiograms of ischaemic patients were analyzed to assess theextent and severity of atherosclerotic involvement; for bothextent and severity, involvement was similar in the three groups.These data support the hypothesis of the occurrence of plateletactivation in patients with spontaneous angina at rest, butnot in other subsets of IHD patients, and establish the possibilityof detecting in vivo platelet activation in IHD by means ofsuch circulating markers.     

Relationship between ventilatory threshold and onset of ischaemia in ECG during stress testing

The study was carried out to determine the relationship betweenventilatory threshold and the onset of ischaemia, as shown onthe ECG (horizontal and/or descending ST depression of 0.05mV, on average). Twenty-seven male patients (aged 58 ±7 years) with angiographically documented coronary artery disease(CAD) were assessed by cardiopul-monary exercise testing withoutmedication. Oxygen uptake (VO₂), heart rate (HR), rate-pressure-product(RPP) and blood lactate were measured and/or calculated every30 s during exercise. In addition, 10 patients, comparable withthe above group, were examined to find out the acute effectsof isosorbide dinitrate (ISDN) at ventilatory threshold in relationto ischaemic threshold. The first cardiopulmonary exercise testwas carried out without medication, the second 1 h later with5 mg ISDN, taken sublingually 30 min before the test. RESULTS: (x SD): (1) The mean ventilatory threshold preceded the ischaemicthreshold in relation to exercise capacity (48 ±14 vs55±20 watts; P<0.05), VO₂. kg^–1 (10.0 ±2.2vs 12.0 ±2.9 ml. kg^–1. min; P<0.05), HR (93± 15 vs 100 ± 16. min ^–1; P<0.01), RPP(15095 ± 4424 vs 17166 ± 5245; P<0.01) andblood lactate (1.28 ± 0.53 vs 1.44 ±0.60 mmol.l^–1; P<0.05). (2) This relationship was observed moreoften in the subgroup of patients with angina during cardiopulmonaryexercise testing or with myocardial infarction or with three-vesseldisease than in patients without angina or infarction or withone- and two-vessel disease. (3) ISDN improved the ischaemicthreshold from 55 ±26 watts (without medication) to 81±32 watts (P<0.01) but not the ventilatory threshold(56 ±23 vs 59 ±21 watts, ns). CONCLUSION: The ventilatory threshold seems to precede the ischaemic thresholdbecause of impaired aerobic capacity of the leg muscles, causedby deconditioning on account of the disease. However, ischaemia-inducedleft ventricular dysfunction did not seem to have a direct influenceon ventilatory threshold as ISDN improved the ischaemic threshold,but not the ventilatory threshold.     

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.