Dipyridamole echocardiography evaluation of acute inferior myocardial infarction with concomitant anterior ST segment depression

The significance of anterior ST segment depression in inferioracute myocardial infarction (AMI) remains controversial. Theaim of this study was to relate precordial ST segment depressionto the topography of residual myocardial ischaemia, with myocardialmapping of the asynergic area and coronary anatomy. Twenty-fivepatients with first inferior AMI (15 patients with anteriorST segment depression: group A and 10 patients without anteriorST segment shift: group B), all underwent: (1) electrocardiographicevaluation on admission to the Coronary Care Unit and at 24h intervals thereafter; (2) 2D-echocardiographic study within3 h of CCU admission: (3) dipyridamole echocardiographic test(DET) (doses of dipyridamole up to 0.84 mg.kg^–1 i.v. over10 min) 4 days after AMI; (4) coronary arteriography within14 days from AMI. To assess regional left ventricular wall motion,a 16 segment model was used and a wall motion score index (WMSI)was derived. The results of DET were correlated to the anatomyof the infarct-related vessel. Compared to group B, group Apatients showed a significantly greater maximal ST segment elevationin inferior limb leads (lead III: 3.9±1.9 mm vs 2.2±1.1mm, P<0.05; aVF: 3.5±13 mm vs 1.7±0.8 mm, P<0.001).Group A patients showed greater WMSI (1.35±0.22 vs 117±0.12,P<0.05), with more frequent postero-lateral wall involvement(72% vs 20%, P<0.05). No patient of either group showed asynergyof the anterior, anterolateral or anteroseptal segments. Nodifferences in the distribution of coronary artery disease wereobserved. Left anterior descending coronary artery disease waspresent in only three patients (20%) in group A and in one patientin group B. DET was positive in eight patients (53%) in groupA and in three (30%) in group B (P = statistically not significant).In all patients DET induced new wall motion abnormalities locatedin the territory of the infarct-related artery. None of thepatients developed new wall motion abnormalities remote fromthe infarct zone or adjacent to the infarct zone, but locatedin different vascular regions. In conclusion, anterior ST segmentdepression in inferior A MI appears to indicate a more extensivearea of asynergy, with frequent involvement of the posterolateralwall. The topography of DET-induced residual myocardial ischaemiadoes not support the hypothesis of concomitant anterior ischaemia.     

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

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

Coronary vasodilation without myocardial erection: Simultaneous haemodynamic, echocardiographic and arteriographic findings during adenosine and dipyridamole infusion

AIM: The aim of this study was to evaluate simultaneously echocardiographic,haemodynamic and angiographic changes that occur during adenosineand dipyridamole infusion, in patients with one-vessel coronaryartery stenosis. This would assess whether deterioration inleft ventricular haemodynamics during vasodilator agent infusionis influenced by vasodilation per se, or the development ofmyocardial ischaemia. METHODS AND RESULTS: We performed adenosine (140 µg.kg^–1.min^–1over 4 min) and dipyridamole (up to 0·84 mg.kg^–1over 10 min) stress echocardiography tests, together with angiographicand haemodynamic assessment, in 26 patients undergoing electivecoronary angioplasty. In 12 of 26 patients, adenosine and dipyridamoletests were repeated 24 h after angioplasty. The criterion forechocardiography test positivity was the appearance of a newtransient regional wall motion abnormality. Coronary angiogramswere analysed with quantitative coronary arteriography. Adenosineand dipyridamole induced regional dysfunction in 18/26 (69%)and 14/26 (54%) patients before angioplasty, respectively (P=ns).In the echocardiography-positive patients, the percent diameterstenosis was significantly (P<0·05) tighter stenosisthan in the echocardiography-negative patients (adenosine, 66·6±8·3%vs 58·0±8·9%; dipyridamole, 69·2±7·1%vs 57·±7·6%). During both tests, left ventricularend-diastolic pressure significantly increased (P<0·05)in echocardiography-positive patients (adenosine, 9·8±2·7mmHg to 13·5±4·1 mmHg; dipyridamole, 10·1±2·8mmHg to 14·1±4·3 mmHg), but not in echocardiography-negativepatients. In the patients who had undergone successful angioplasty(reduction to <50% diameter stenosis), both adenosine anddipyridamole confirmed the arteriographic success of the procedure(echocardiography negative in all patients). In this group ofpatients, no significant change was observed in left ventricularend-diastolic pressure during adenosine or dipyridamole infusion. CONCLUSIONS: Intravenous infusion of either adenosine or dipyridamole wasaccompanied by an obvious increase in left ventricular end-diastolicpressure only in patients with induced wall motion abnormalities.Coronary vasodilation per se has no significant effect on leftventricular end-diastolic pressure when no ischaemia is induced,disproving any clinically significant ‘erectile’and adverse effects of coronary vasodilation per se.     

Mechanisms of adenosine-induced epicardial coronary artery dilatation

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

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.     

Safety of dobutamine stress echocardiography: A 24 h Holter monitoring study

BACKGROUND: Dobutamine-atropine stress echocardiography is an efficientmethod in the evaluation of patients with coronary artery disease.However, because high-dose dobutamine is potentially arrhythmogenic,the safety of this stress modality has been questioned. METHODS: We performed a 24 h Holter monitoring, before and immediatelyafter this test, in 73 consecutive patients (60 men and 13 women),mean age 60 ± 12 years. Twentyeight patients had hada recent myocardial infarction, 25 had stable chronic angina,10 chronic ischaemic cardiomyopathy and 10 idiopathic dilatedcardiomyopathy. Dobutamine was progressively increased (5–40µg . kg^–1. min^–1) and atropine was injectedin 30 patients. Arrhythmias and ST-segment deviation beforeand after the stress test were evaluated. RESULTS: The mean peak dobutamine dose was 32 ± 11 µg .kg^–1. min^–1. The heart rate at rest and at peakdose was, respectively, 69 ± 16 and 110 ± 28 beats.min^–1. Side effects during the injection of dobutaminewere mainly ventricular (n=14) or atrial (n=4) premature contractions.Three patients had non-sustained ventricular tachycardia andfive had hypotension during the test. No sustained episode ofsupraventricular or ventricular tachycardia was observed duringthe study. Nonsustained supraventricular and ventricular tachycardiaswere detected in 8 and 21 patients before and in 11 and 16 patientsafter dobutamine stress echocardiography (P=ns). AsymptomaticST-segment deviation was observed in two patients before andfour after dobutamine stress echocardiography. An increase intotal ischaemic time (20 vs 102 mn) was observed after the test,but only five patients had ST modifications. A separate analysisof patients with and without beta-blocker did not alter theseresults. In addition, when the occurrence of significant arrhythmiaswas stratified according to a left ventricular ejection fractionthreshold of 45%, we observed no difference in frequency andseverity of cardiac arrhythmias. CONCLUSION: This study demonstrates that dobutamine stress echocardiographydoes not significantly increase arrhythmia during the following24 h. Further studies are required to evaluate the influenceof the test on ST-segment modification during the same period.     

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.     

High-dose dipyridamole echocardiography test in coronary artery disease after heart transplantation

In order to evaluate the usefulness of high-dose dipyridamoleechocardiography test (DET) for the detection of coronary arterydisease (CAD) after heart transplant and for the assessmentof prognosis, 80 heart transplant patients underwent this testwithin 48 h of tile scheduled yearly coronary angiography. Coronary angiography showed normal coronary arteries in 55 patientsand CAD in 25, eight of whom had >50% luminal narrowing.Segmental hypokinesis on baseline echocardiography was presentin 27 patients, 19 of whom had CAD (sensitivity = 76%; specificity= 85%). DET was negative in all the patients with normal coronaryarteries (specificity 100%). Out of 25 patients with CAD, eighthad a positive DET and 17 a negative DET (sensitivity 32%),but DET was positive in seven of the eight patients with coronaryartery stenosis >50% (sensitivity 87%). During follow-up(9.8±4.5 months) seven cardiac events occurred in sevenpatients, all with CAD and wall motion hypokinesis (six on baselineechocardiogram and four after dipyridamole infusion). In our experience, DET does not seem adequate for the screeningof post-transplant CAD, but useful in identifying patients withsevere lesions (>50%). Wall motion abnormalities on baselineechocardiogram or after dipyridamole infusion might identifypatients who require closer surveillance. A longer experienceis needed to confirm these results.     

The influence of intravenous magnesium sulphate on the occurrence of atrial fibrillation after coronary artery by-pass operation

To examine the influence of (Mg) on hypomagnesaemia and atrialfibrillation (AF) following coronary artery by-pass surgery,140 consecutive patients were randomized to receive 70 mmolof magnesium sulphate intravenously (n = 69) or placebo (n =71). Serum magnesium concentrations fell to 0.77 ± 0.10mmol. l^–1 in the control group but rose to 1.09 ±0.17 mmol. l^–1 in the Mg group (P <0.001). The incidenceof AF was 29% in the Mg group and 26% in the placebo group (NS).The AF patients were older, more of them had had prior AF episodes,their sinus rates (SR) were slower (78 ± 10 vs 86 ±12 beats. Min^–1; P <0.01) and serum Mg concentrationshigher (0.89 ± 0.21 vs 0.11 mmol. ^l–1; P <0.05)The incidence of AF was 43% in the highest quartile of serumMg and 23% among the rest (P = 0.056). In patients experiencingAF during the first three post-operative days, serum Mg concentrationswere higher and SR slower on each day compared with non-AF patients.SR increased post-operatively less with high Mg levels (P =0.044). In the Mg group, serum Mg and SR were the only independentpredictors of AF. In conclusion, the incidence of post-operativeAF is not decreased with magnesium. High Mg levels are likelyto provoke AF probably by mechanisms that modify SR.     

Vasodilator reserve in collateral-dependent myocardium as measured by positron emission tomography

Myocardial blood flow can be accurately quantitated in patientsusing positron emission tomography and oxygen-15 labelled water.The purpose of this study was to determine the vasodilator reservein myocardium completely perfused by intramyocardial collateralblood flow. We hypothesized that altered relative flow reservein such regions would correlate with the degree of ischaemiaobserved in these patients during exercise. The technique involves the inhalation of the positron emittingtracer C¹⁵O₂ which is converted to freely diffusible H₂¹⁵O bythe lung. With rapid dynamic scanning, arterial and regionalmyocardial tissue concentrations can be obtained and time activitycurves generated. With a two-compartment kinetic model, myocardialblood flow can be accurately quantitated over a wide range ofblood flows. Five patients with stable exertional angina andnormal ventricular function studies and who had an occludedmajor epicardial artery which completely opacified via intramyocardialcollateral blood flow were studied. Myocardial blood flow (MBF)was measured both at rest and following an infusion of intravenousdipyridamole (0.56 mg. kg^–1) and the results were comparedwith measurements obtained from a group of eight normal volunteers.During resting conditions, MBF in the control group was 0.86±0.10ml.g^–1. min^–1 and in the patient group was 0.99±0.10ml. g^–1. min^–1 in normally perfused myocardium (ns)and 0.86±0.14 ml. g^–1. min^–1 in collateral-dependentmyocardium (ns). Following dipyridamole, MBF increased to 3.58±0.89ml. g^–1. min^–1 in the control group and to 2.97±0.94ml. g^–1. min^–1 in the normal regions of the patients(ns). In the collateralized regions of the patients, the increasewas less than that observed in the control group (1.66±1.02,P <0.005). Absolute coronary flow reserve (ACFR) (dipyridamoleMBF/resting MBF) in the control group was 4.1±0.8 andin the patient group was 3.1±1.1 (ns) in normal regionsand 1.9± 1.0 (P <0.001) in collateralized regions.Relative coronary flow reserve, the ratio of ACFR in collateralizedvs that of normally perfused myocardium was determined in eachpatient and correlated well with total exercise time (r = 0.98;P <0.01) and peak double product (r = 0.85; P = 0.06) observedduring a symptom-limited modified Bruce treadmill test. These studies support the hypothesis that vasodilator reservein the distribution of non-infarcted collateral-dependent myocardiumis abnormal compared with normally perfused myocardium. Thedegree of altered flow reserve correlates well with the degreeof ischaemia during symptom-limited exercise, and may explainwhy these patients experience angina at high work loads.