Haemodynamic findings in experimental right ventricular ischaemia after right coronary arterial ligation

Acute ischaemia limited to the free wall of the right ventriclewas produced by right coronary arterial ligation (RCAL) in 20dogs. Contrast M-mode and cross-sectional echocardiography wasperformed in 7 cases to investigate the presence of tricuspidinsufficiency. The haemodynamic findings obtained with an openpericardium at 15 to 30 min showed increases in right (l.20.5to 2.70.7 mmHg, P0.01) andleft (5.0 0.8 to 6.60.9 mmHg, P005)ventricular end-diastolic pressures, and decreases in heartrate (1394.9 to 1195.1 bpm, P0.01), cardiac index (1066.6 to817.3 ml min^–1 kg^–1, P001), stroke index (79 6 to72 8 ml x 100 beat^–1 kg^–1, P0.02), right (23.8l.5to 19.41.5 mmHg, P0.01) and left (1097.2 to 958.2 mmHg, P005)ventricular systolic pressures and right ventricular strokework index (18.32.4 to 11.41.8 g m kg^–1, P0.01). In 6of 15 cases the 'y' descent became deeper than the 'x' descentin right atrial pressure (RAP). Tricuspid insufficiency gradeI–II/IV was present in 3 of 7 cases, 2 of them with a'y'>'x' in RAP. Right ventricular mechanical alternans, probablysecondary to a decrease in contractility, appeared in 10 of20 cases after RCAL. Closure of the pericardium exaggeratedthe haemodynamic alterations and a dip-plateau appeared in 2cases on the right ventricular pressure curve. We conclude thatsignificant aemodynamic alterations in right ventricular functionare produced by RCAL in dogs, and they are exaggerated afterclosing the pericardium.     

Evaluation and prognostic significance of left ventricular diastolic function assessed by Doppler echocardiography in the early phase of a first acute myocardial infarction

AIM: To study the prognostic significance of left ventricular diastolicfunction evaluated by transmitral and pulmonary venous flowvelocities obtained in the early phase of a first acute myocardialinfarction in relation to later development of congestive heartfailure. METHODS: Pulsed Doppler echocardiography of transmitral and pulmonaryvenous flow was assessed in 65 consecutive patients with a firstmyocardial infarction within 1 h of arrival in the coronarycare unit. RESULTS: A univariate regression analysis identified age, left ventricularejection fraction 45%, mitral E deceleration time 130 ms, E/Aratio >1·5, peak pulmonary venous atrial flow velocity30 cm . s^–1 and a difference between mitral and pulmonaryvenous atrial flow duration >0 ms as variables significantlyrelated to the development of congestive heart failure. However,in a multivariate analysis only mitral E deceleration time 130ms and age were significant independent variables related tothe development of congestive heart failure during the firstweek following a first acute myocardial infarction. CONCLUSION: Assessment of left ventricular diastolic function complementsmeasurements of systolic function in the evaluation of cardiacfunction, and mitral deceleration 130 ms best identifies patientsat risk of development of congestive heart failure followingacute myocardial infarction.     

Early administration of captopril and nitroglycerin in combination after acute myocardial infarction: an invasive haemodynamic study

The combination of captopril and nitroglycerin early after acutemyocardial infarction (AMI) could lead to a dangerous decreasein blood pressure coronary perfusion. To evaluate the safetyaspects and haemodynamic effects of this combination, we studied36 first ‘Q wave’ thrombolysed anterior wall AMIpatients during the 24 h following the onset of symptoms. Afterwards, thrombolysis patients received a continuous infusionof nitroglycerin and were submitted to pulmonary artery catheterization.Those patients with mean arterial pressure (MAP) 70 mmHg, cardiacindex 2.21. min^–1.m^–2, and wedge pressure 10 mmHgwere included and randomized to receive 6.25 mg of captoprilevery 6 h on the first day and 12.5 mg qid on the second f MAP 70mmHg (group 1). A second group (group 2) received a placebo.Haemodynamic parameters were determined after 1, 6 and thenevery 6 h up to 48 h after basal measurements. Significant differenceswere observed only for the MAP and the rate-pressure product(reduction in group 1 values, P <0.05). However, MAP wasmaintained within acceptable limits. Our data support the factthat the combination of captopril and nitroglycerin in the earlyhours of a non-complicated anterior wall AMI is safe, and couldguarantee its use in large clinical trials to determine theeffects on left ventricle remodelling and survival after AMI.     

Submaximal early exercise test compared to clinical findings for evaluation of short- and long-term prognosis after the first myocardial infarction

Clinical and ergometric data were derived from 1098 consecutiveexercise tests in patients with a first acute myocardial infarctionbetween 1974–1983. In 1992 a follow-up was performed inorder to analyse the importance of a submaximal early exercisetest, in combination with clinical data, for the predictionof short- and long-term prognosis of cardiovascular death. The relative value of 20 clinical variables, including medicalhistory, markers of infarction size, medication etc., and 28variables at exercise test were studied. Univariate, multivariateand survival analysis, for estimation of prognosis and independentprediction of cardiovascular death was used. Independent clinical risk factors for cardiovascular death were(1) Within 1 year: relative heart volume (ml.m^–2 bodysurface area) on chest X-ray. (2) Long-term mortality: maximumheart rate and relative heart volume, diabetes, age and digitalismedication. Independent exercise risk factors were: (1) Within1 year: heart rate, ventricular arrhythmia and ST depression 1 mm before exercise, diastolic blood pressure at maximum exerciseand target heart rate. (2) Long-term mortality: angina pectorisand/or ST depression 1 mm at maximum exercise. In subgroupsof patients with clinical risk factors, mortality risk increasedif there were signs of angina pectoris and/or ST depression 1 mm during exercise. The risk increased 100% in diabetics,91% with age >70 years, 58% with relative heart volume 500ml.m^–2 body surface area, 42% with heart rate 100 atadmission, and 34% with digitalis medication. No increase wasfound in the subgroup of patients without clinical risk factors. Thus, submaximal early exercise stress testing provides importantinformation for short- and long-term prognosis in patients afterthe first acute myocardial infarction compared to clinical evaluationalone.     

Determination of left ventricular wall thickness and muscle mass by intravenous digital subtractionangiocardiography: validation of the method

Left ventricular (LV) wall thickness and muscle mass are importantmeasures of LV hypertrophy. In 24 patients LV end-diastolicwall thickness and muscle mass were determined (two observers)by digital subtraction angiocardiography (DSA) and conventionalLV angiocardiography (LVA). Wall thickness was determined overthe anterolateral wall of the left ventricle according to thetechnique of Rackley (method 1) or by planimetry (method 2).Seventeen patients were studied at rest and seven during dynamicexercise. Wall thickness correlated well between LVA and DSA;the best correlations were obtained by a combined subtractionmode using either method 1 or 2 (method 1, r0–80; method2,r0. 75). The standard error of estimate of the mean (SEE) wasslightly lower for method 2 ( 10%) than for method 1 ( 13%).DSA significantly overestimated wall thickness by 5–7%with method 1 and underestimated by 12–14% with method2. Muscle mass correlated well between LVA and DSA; the SEEwas 15% for method 1 and 12% for method 2. Overestimation ofmuscle mass by DSA was 7–11% with method 1 and underestimationwas 13–15% with method 2.It is concluded that LV wallthickness can be determined accurately by DSA with an SEE rangingbetween 10 and 13%. Determination of LV muscle mass is slightlyless accurate and the SEE is slightly larger ranging between13 to 17%. With method 1, wall thickness and muscle mass wereover estimated and with method 2 underestimated.     

Biplane transoesophageal echocardiography, transthoracic Doppler, and magnetic resonance imaging in the assesment of coarctation of the aorta

This study compared flow-sensitive magnetic resonance imagingwith biplane transoesophageal echocardiography in combinationwith continuous wave Doppler from the suprasternal notch inpatients with native coarctation or after surgical repair. Twenty patients (mean age 33 years, range 17–60) wereinvestigated, of whom 15 had undergone surgery at mean age 13years, range 5.43. Peak and mean flow in the ascending and descendingaorta as well as coarctation peak velocity were determined withthe magnetic resonance imaging phase contrast technique. Coarctationpeak velocity was also measured by Doppler from the jugulum.Magnetic resonance imaging axial sections as well as biplanetransoesophageal echocardiography were used to measure the smallestdiameter of the constricted segment. Sixteen healthy volunteers,mean age 36 years, range 22.63, provided reference values formagnetic resonance imaging determined volume of flow in theaorta. Peak flow in the descending aorta was 9.2 ±3.71.min ^{– 1} (reference 130 ± 2.5, P<0.01) and meanflow 3.1 ±0.9 I. min^{– 1} (reference 3.4 ±0.8,P>0.05). The ratio of descending-to-ascending peak flow was0.54 ±0.17 (reference 0.69 ± 0.10, P<0.01)and mean flow 0.68 ± 0.15 (reference 0.69 ± 0.08,P>0.05). The coarctation velocity was slightly higher withDoppler than with magnetic resonance imaging (+ 0.24 ±0.44 m. s^{– 1}, 95% confidence interval +0.45 to + 0.02m.s^{– 1}, P= 0.05). The coarctation diameter was slightlylarger with magnetic resonance imaging than with transoesophagealechocardiography (1.4 ±3.5 mm, 95% confidence interval+ 3.1 to – 0.3 mm, P= 0.11). Both methods are suitable for the assessment and follow-up ofcoarctation of the aorta Flow assessment with magnetic resonanceimaging provides a hitherto unavailable measure with which toassess the severity of obstruction.     

Lipoprotein(a) as a risk predictor for cardiac mortality in patients with acute coronary syndromes

Aims Raised lipoprotein(a) concentrations are considered to be arisk factor for atherothrombotic diseases. We examined whetherbaseline concentrations were a risk factor for an adverse outcomein patients admitted with acute coronary syndromes. Methods and Results Five hundred and nineteen patients admitted with suspected acutecoronary syndromes were studied and followed prospectively fora median of 3 years. The prognostic significance of a baselinelipoprotein(a) concentration of 30mg.dl^–1or lower forsubsequent cardiac death was assessed in patients with myocardialinfarction (266) and unstable angina (197) and compared withother variables in regression models. In patients with myocardialinfarction, a baseline lipoprotein(a) concentration of 30mg.dl^–1wasassociated with a 62% increase in subsequent cardiac death comparedto the lower concentration group (29·8% vs 18·6%,Log rankP=0·04). In a multivariate regression model abaseline lipoprotein(a) concentration of 30mg.dl^–1retainedits significance as an independent predictor of cardiac death(P=0·037). In patients with unstable angina, baselineconcentrations of 7·9mg.dl^–1were found to be significantpredictors of cardiac death in univariate (P=0·021) andmultivariate (P=0·035) regression models. Conclusion Baseline lipoprotein(a) concentrations in patients admittedwith acute coronary syndromes are associated with an increasedrisk of cardiac death. For patients with myocardial infarctiona concentration of 30mg.dl^–1appears appropriate as a riskdiscriminator; for patients admitted with unstable angina, however,much lower concentrations of lipoprotein(a) appear to be prognosticallyimportant.     

Detection of acute myocardial infarction by a new, sensitive and rabid method for determination of creatine kinase B-subunit activity

An immunoinhibition method for the assay of creatine kinase(CK) isoenzymes by continuous monitoring of the ATP formationin the CK reaction by a purified firefly luciferase reagenthas been developed. The sensitivity of the firefly assay ofATP makes it possible to assay CK-B subunit activity (CK-B)in serum down to 1 U/l. In healthy individuals CK-B varied between 2 and 12, mean 3U/l. A wide range of CK-B activity was observed after acutemyocardial infarction (AMI), intramuscular injection and surgerywith overlapping between these different categories. Thereforethe maximal change in CK-B activity (CK-B) was studied in 98patients admitted to a coronary care unit. In all 57 patientswithout a subsequent diagnosis of AMI according to conventionalcriteria CK-B was < 5 U/l. In all 41 patients with AMI CK-Bwas 5 U/l. In all healthy individuals CK-B was < 2 U/l.CK-B 5 U/l was found after i.m. injection and different kindsof surgery in three out of 60 patients. Thus, the present method for determination of CK activity hasbeen shown to possess high precision in low activities, to beas rapid as conventional methods and to be simple enough tobe used in a routine laboratory. With these properties the methodshould be suited for early diagnosis and early exclusion ofeven very small AMIs.     

Age-related mortality, clinical heart failure, and ventricular fibrillation in 4259 Danish patients after acute myocardial infarction

AIMS: To evaluate the prognosis of patients 80 years old, we analyseda large, community-based population with acute myocardial infarctionwho received intensive observation and similar pharmacotherapyregardless of age. METHODS AND RESULTS: In a 12-year period, before the introduction of thrombolysis,4259 consecutive patients hospitalized with acute myocardialinfarction from the same hospital in Denmark were prospectivelyregistered. Their complications and mortality in hospital, and1 and 5 years after discharge were analysed retrospectively.Overall, in-hospital mortality was 11% for patients less than<50 years old, 22% for patients 60–69 years old and43% for patients 80 years old. Two thirds of patients 80 yearsold had heart failure, and cardiogenic shock was twice as commonin this age group than in patients 60–69 years. Heart failure was a strong independent risk, factor for post-dischargemortality, particularly in the oldest age groups. Four out ofeight patients 80 years survived one year if discharged aliveafter experiencing in-hospital ventricular fibrillation. CONCLUSION: The life-saving potential of preventing or treating heart failureseems considerable even in the oldest patient groups. Patients80 years old who survive in-hospital ventricular fibrillationhave an acceptable prognosis 1 year post-discharge.     

Lack of correlation between haemodynamic and cardiopulmonary exercise capacity improvement after catheter-balloon mitral valvuloplasty

The long-term effects of percutaneous transvenous mitral commissurotomyon exercise capacity and ventilation were investigated to determinewhether a dissociation between haemodynamic improvement andexercise capacity increase occurs in patients with mitral stenosis.Eighteen patients aged 45 ± 12.3 years (mean ±SD) with symptomatic mitral stenosis performed a symptom-limitedbicycle exercise test while respiratory gases were measuredbefore and 6 months after percutaneous transvenous mitral commissurotomy.The mitral valve area increased from 1.07 ±0.22 to 1.98±0.67 cm². P<0.0001 and the mean mitral gradient decreasedfrom 12.9 ±4.5 to 5.3±4.8mmHg, P<0.001, withouta significant increase in cardiac output index (from 2.64 ±0.55 to 2.77 ± 0.56 l. min_{– 1}. m_{– 2}, P= ns).This haemodynamic improvement was still present at the 6-monthfollow-up catheterization. Mean exercise workload and peak oxygenuptake increased 6 months after percutaneous transvenous mitralcommissurotomy from 88.3 ± 28.1 to 97.8 ± 25.1watts, P= 0.01, and from 18.1 ± 5.3 to 19.9 ±4.8 ml. kg_{– 1}.min_{– 1}, P<0.05. Total ventilation,ventilatory equivalents and oxygen pulse at the end of the exercisetest remained unchanged Correlations between peak oxygen orexercise capacity improvement and mitral valve area increasewere poor (r= 0.27, P= ns, r= 0.24, P=ns). This clear dissociationbetween haemodynamic improvement and improvements in minor exercisecapacity after percutaneous transvenous mitral commissurotomysuggests that peripheral alterations persist. Future studiesin which patients are trained after valvuloplasty may be helpful.     

Autonomic balance in patients with angina and a normal coronary angiogram

The pathophysiology of angina pectoris in patients with a normalcoronary angiogram is not clear. Furthermore, the pathophysiologicalimpact of ST changes in syndrome X is controversial. The purposeof this study was to investigate cardiac autonomic function,by measuring 24 h heart rate variability, in patients with andwithout electrocardiographic evidence of ischaemia during exercise. Thirty-two patients with angina pectoris, a normal coronaryangiogram, echocardiogram, hyperventilation test and gastro-oesophagealinvestigation were studied. Fourteen healthy subjects servedas controls. Fifteen patients had significant ST segment depressionduring stress testing, whereas 17 had no electrocardiographicsigns of ischaemia. Heart rate variability was calculated as(1) mean RR= mean of all normal RR intervals, (2) the differencein mean RR level between when awake and when asleep (mean RRwake-sleep)—a tentative index of sympathetic activation,(3) the standard deviation (SD)—a broad band measure ofautonomic balance, and (4) a percentage of successive RR intervaldifferences 6% (pNN6%)—an index of vagal modulation. Thecoronary vascular resistance was measured at rest and duringpacing. Mean RR and autonomic indexes did not differ between patientswith a positive exercise test and controls (831/884 m 24 h SD125/134 m pNN6% 6.715.4%, respectively). Patients with a normalexercise test had shorter mean RR (758 ms vs 844 m P<0.05)and significantly reduced 24-h SD (103 ms vs 134 m P<0.05)than controls, whereas values for vagal index (6.5% vs 5.4%)did not differ from healthy controls. Mean RR wake-sleep alsotended to be lower in patients with a normal exercise test (–125 ms vs – 173 ms) compared to controls (P<0.1). Patientswith a positive exercise test had a significantly attenuatedreduction in coronary vascular resistance during pacing in comparisonto patients with a normal exercise test (–0.131–0.26mmHg x min. ml^{– 1}; P<0.05). The findings suggest the occurrence of general elevated sympatheticactivation in angina patients with a normal exercise test. Patientswith a positive exercise test exhibited no signs of autonomicdysfunction although these patients had altered coronary vascularresistance indicating microvascular angina. This supports thesuggestion that patients with a normal exercise test constitutean independent pathophysiological entity.     

Hypersensitivity reactions to streptokinase in patients with high pre-treatment antistreptokinase antibody and neutralisation titres

After streptokinase or antistreplase administration, raisedantibody levels can persist for many years, but it is unclearif these antibodies can cause allergic reactions following streptokinasere-administration for myocardial re-infarction. Pre-treatmentantistreptokinase antibody (AB) and neutralisation litres (NT)were measured in 189 consecutive patients (57 received streptokinaseor anistreplase). Seven patients had previous exposure to streptokinaseor anistreplase; they had high mean (SEM) antibody litres of1:801 (332) and neutralisation litres of 3.3 (1.7) million units.The 182 patients without previous thrombolysis had mean (SD)antibody titres of 1:25 (3) and neutralisation litres of 0.14(0.08) million units; nine patients (4.95%), however, had raisedantibody litres of 1:160 and neutralisation litres of 0.3million units. Of the 15 patients with antibody litres of 1:160,three received streptokinase or anistreplase. Hypersensitivityreactions occurred in all three patients — neutralisationlitres 0.48, 1.5 and 1.1 million units respectively. Two becameseverely hypotensive with systolic pressures of 70 mmHg; onedeveloped a serum sickness-like reaction. Importantly, noneof the 54 patients with antibody titres of < 1:160 who receivedstreptokinase or antistreplase reacted adversely to the thrombolyticagents (² with Yates 's correction = 38.71 , P<0.01). Highantibody titres are associated with hypersensitivity reactionsto streptokinase. This has important implications in reinfarctionthrombolysis. In patients whose antistreptokinase antibody titresare likely to be raised the avoidance of streptokinase-relatedthrombolytic agents should be considered.     

Inferior ST segment depression as a useful marker for identifying proximal left anterior descending artery occlusion during acute anterior myocardial infarction

To determine whether or not ST segment deviation on admissionelectrocardiograms can identify patients with anterior acutgemyocardial infarction due to proximal left anterior descendingartery occlusion, the magnitude and location of ST segment elevationor depression were compared between patients with proximal leftanterior descending artery occlusion (group A, n=47) and thosewith distal left anterior descending artery occlusion (groupB, n =59). ST segment depression in each of the inferior leadswas significantly greater in group A than in group B. The incidenceof ST segment depression 1 mm in each of the inferior leads(II; 81% vs 27%, III; 85% vs 54%, aVF; 87% vs 47%, P<0·01)was significantly higher in group A than in group B. In addition,the incidence of ST segment depression 1 mm in all of the inferiorleads was significantly greater in group A than in group B (77%vs 22%, P<0·01). In group A, maximal ST segment elevationwas more frequent in lead V alone (43% vs 14%, P<0·01).Group A had greater ST segment elevation in lead a VL than groupB, and the incidence of ST segment elevation 1 mm in lead aVL was significantly higher in group A than in group B (66%vs 47%, P<0·05). ST segment depression 1 mm in allof the inferior leads was most valuable for identifying groupA patients (77% sensitivity and 78% specificity). In contrast,the maximal ST segment elevation in lead V₂ alone or ST segmentelevation 1 mm in lead a VL had a low diagnostic value (43%sensitivity and 86% specificity, 66% sensitivity and 53% specificity,respectively). In conclusion, this study indicates that analysisof ST segment deviation in the inferior leads is useful foridentifying patients with acute anterior myocardial infarctiondue to proximal left anterior descending occlusion.     

Right and left ventricular ejection fraction and left ventricular volume changes at rest and during exercise in normal subjects

The effect of exercise upon right and left ventricular ejectionfractions (RVEF and LVEF) as well as the changes upon left ventricularend-diastolic and end-systolic volume indices (LVEDVI and LVESVI)were investigated. Twenty-two normal subjects were studied atrest and during upright submaximal exercise. RVEF was determinedusing a first-pass method. LVEF was measured using multiplegated blood pool imaging. During the exercise test ECGs remained normal. HR and BP increasedsignificantly (P<0.01). RVEF increased from 44%±4(mean±SD) to 60%±6 (P<0.001). LVEF increasedfrom 62%±6 to 76±5 (P<0.001). A wider scatterwas observed in RVEF than in LVEF. There was a 14% increasein LVEDV-index and a 14% decrease in LVESV-index (P<0.001).A multiple regression analysis with RVEF as the dependent variableand HR, systolic BP, LVEF, LVEDV-index and LVESV-index as independentvariables showed a significant correlation between RVEF andLVEF and systolic BP (P<0.05). Our data provide insight intothe mechanisms by which the pump performance is increased innormal subjects. The central mechanisms observed are the Starlingeffect and an increase in contractility of the myocardium. Thisis connected in the general circulation to an increase in afterload,indicating a redistribution of blood from the vascular bedsto the muscles and to the heart.     

Antihypertensive treatment with felodipine but not with a diuretic reduces episodes of myocardial ischaemia in elderly patients with hypertension

Episodes of transient myocardial ischaemia can frequently beobserved in hypertensive patients. To assess the effects ofantihypertensive treatment with the calcium antagonist felodipineor the diuretic combination hydrochlorothiazidel triamtereneon episodes of ischaemic-type ST-segment depression (ST-D),simultaneous ambulatory electrocardio-graphic and blood pressure(BP) monitoring was performed in 42 elderly hypertensives withoutmanifest coronary artery disease. All patients (mean age 79± 6 years, office BP 160/95 mmHg) were evaluated offany antihypertensive or anti-ischaemic therapy and after 3 monthstreatment with either felodipine or the diuretic (randomized,double-blind study) for episodes of significant ST-D (0.1 mV,duration 1 min, interval 1 min). The reduction in office BPand daytime ambulatory BP was similar for both agents, as wasa significant reduction in the heart rate x systolic BP product(DP) over 24 h (felodipine: 12 441 ±2076 vs 11 643 ±1953 mmHg. min^–1; P=0.048; diuretic: 12 366 ± 2782vs 11 062 ± 2012 mmHg. min^–1; P=0.003). While felodipinesignificantly decreased the total number of ST-D (from 40 tosix episodes; P=0.03), the total number of ST-D remained unchangedwith the diuretic (non-significant increase from 31 to 45 episodes;P=0.24). The same trend was observed for the number of patientswith ST-D. The ischaemic threshold, defined as DP at the onsetof the episodes of ST-D, increased with felodipine (12 171 ±340vs 13 770 ± 138 mmHg. min^–1) and decreased withthe diuretic (16 210 ±312 vs 14 092 ± 319 mmHg.min^–1). In conclusion, antihypertensive treatment withfelodipine reduces blood pressure and episodes of transientmyocardial ischaemia in elderly hypertensive patients, whilehydrochlorothiazidel triamterene increases these episodes despitea similar BP reduction. Felodipine may influence structuraland functional factors at the coronary micro circulation level.These mechanisms improve coronary blood flow and increase theischaemic threshold.     

Increased mortality in men with ST segment depression during 24 h ambulatory long-term ECG recording: Results from prospective population study 'Men born in 1914', from Malmo Sweden

‘Men born in 1914’, from Malmö, Sweden, isa cohort study of the morbidity and mortality of cardiovasculardiseases among 68-year-old men in an urban population. Ambulatorylong-term ECG recording was part of the health examination thatthese men were invited to undergo in 1982. Five hundred attended(80.5%) of the 621 invited. Ninety-eight of the 394 men in whomthe ECG recording was technically satisfactory had at leastone episode with horizontal or down sloping ST segment depression0.1 mV. The median total duration of ST segment depression was135 min. 90% of these episodes were not preceeded by any increasein heart rate. In only eight of the 47 men who reported an occurrenceof chest symptoms during the recording period did ST segmentdepression and chest symptoms occur simultaneously. 43 monthsafter the health examination, 33 (8.4%) men had died. The mortalityin men without ST segment depression and without any historyof coronary heart disease was 6.5%. The incidence of fatal andnon-fatal myocardial infarction in men without ST depression0.l mV and without a history of IHD was 2.3%. Men with ST depression0.1 mV in comparison with this group had a 4.4 times greaterrelative risk. The risk in men with both ST segment depression0.1 mV and history of coronary heart disease was 16.0 timesgreater. This study shows that asymptomatic ST segment depressionis a frequent finding in elderly men. The occurrence of asymptomaticST segment depression is associated with an increased cardiovascularmortality. This increased mortality is independent of a historycompatible with angina pectoris or previous myocardial infarction.     

Diagnostic criteria for congenital long QT syndrome in the era of molecular genetics: do we need a scoring system?

Aims Previously published diagnostic systems, based on ECG analysisand clinical parameters (Schwartz criteria and Keating criteria),have been used to estimate the probability of inherited longQT syndrome (LQTS). Nowadays, a certain diagnosis can oftenbe made by DNA testing. We aimed to establish the predictivepower of the Schwartz and Keating criteria, using DNA testingas a reference, and to determine the best diagnostic strategy. Methods and results We studied 513 relatives (aged >10 years)of 77 consecutive LQTS probands with a known disease-causingmutation. The Schwartz criteria identified ‘high probabilityof LQTS’ (score 4) in 41 of 208 mutation carriers, yielding19% sensitivity and 99% specificity. The Keating criteria had36% sensitivity and 99% specificity. Alternatively, by analysingQTc duration alone, we found that 430 ms is the optimalcut-off value to distinguish carriers (430 ms) from non-carriers(<430 ms), yielding 72% sensitivity and 86% specificity(area under the curve 0.788). Conclusion The existing clinical criteria have good specificityin identifying mutation carriers. However, their sensitivityis too low for clinical use. Analysis of QTc duration aloneis more useful to screen for LQTS carriership (QTc 430 ms)as its sensitivity is far superior, although its specificityremains acceptable. In genotyped families, genetic testing isthe preferred diagnostic test.     

Nocturnal angina in patients with fixed coronary stenosis. Increased coronary vasoconstrictive sensitivity with independence of pacing ischaemic threshold

Atrial pacing and ergonovine tests were performed in 18 consecutivepatients with unstable angina at rest and significant coronaryartery stenosis ( 90% in one vessel in 16 patients). 13 ofthem also had exertional angina. 14 patients presented at leastone positive response (1.0 mm ST-segment shift) to pacing, witha heart rate (144±11 vs 75±13 beats min^–1,P<0.001) and double product (195±26 vs 108±32x 10^–2 P<0.001) significantly higher than during anginaat rest. In the ten patients who presented nocturnal angina,the incidence of positive response to pacing and the pacingischaemic threshold, tested on three different days, were similarto those seen in the remaining patients. In contrast, the ergonovinetest was positive in all patients with nocturnal angina (100%),who required a low dose (0.28±0.2 mg), but it was positivein only four (50%) of those without nocturnal angina, who neededa higher dose (0.55±0.12 mg, P<0.005). Therefore, in patients with severe coronary stenosis and exertionalangina, spontaneous episodes, including nocturnal angina, arenot related to increases in heart rate. The increased coronaryvasoconstrictive sensitivity found in these patients, particularlythose with nocturnal angina, was not dependent on the statusof the coronary reserve, which strongly suggests that changesin coronary tone, focal or diffuse, are involved in the mechanismsof these ischaemic events.     

Left ventricular hypertrophy and myocardial ischaemia in hypertension: The THAMES Study

A multicentre epidemiological study to detect the prevalenceof myocardial ischaemia in hypertensive left ventricular hypertrophy(LVH) was performed in 188 asymptomatic male hypertensives (131treated). The mean age was 55 (range 40–82) years withblood pressure (BP) 160/100 mmHg or a systolic BP 180 mmHg.The participants were screened with echocardiography, and leftventricular hypertrophy (LVH), defined as LV mass index (LVMI) 130 g . m^–2, was found in 127 (68%), of whom 95 wereon antihypertensive treatment. Patients with LVH underwent amaximal bicycle ergometer exercise test and significant ST depression,indicating possible stress-induced ischaemia was found in 29men (23%). These subjects were subjected to exercise thallium-201scintigraphy, which was normal in 14 but showed reversible perfusiondefects in 15. Thus, a high prevalence of LVH (70%) was detected in male hypertensivesselected only on age and BP. In addition, although chest painon exertion excluded patients from entry, a substantial portionhad signs of ischaemia (23% on exercise ECG alone, and in 52%confirmed by thallium scan). The prevalence of these risk factorsshould be considered when evaluating hyper tensive patients.     

Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis

Aims Polymorphisms in the RANTES (G-403A), monocyte chemoattractantprotein-1 (MCP-1; A-2518G), stromal cell-derived factor-1ß(SDF-1ß; G801A), and C–C chemokine receptor-5(CCR5; 32) genes have been associated with functional effects.These chemokines have been implicated in leucocyte recruitmentto arterial lesions. In a case-control study, we explored relationsbetween these polymorphisms and coronary artery disease (CAD),with respect to angiographic abnormalities and acute coronarysyndromes (ACS). Methods and Results The LUdwigshafen Risk and Cardiovascularhealth (LURIC) cohort was genotyped by RFLP-PCR. Based on coronaryangiography, individuals were sub-divided into CAD cases and controls . RANTES-403 genotype frequencies were significantly different in cases and controls, as were A allele carrier frequencies (36.01% vs. 30.19%, OR=1.30 [95%-CI=1.06–1.60], ). By multivariate analysis, RANTES A-403 retained significantassociation with CAD . RANTES A-403 was associated with increased ACS prevalence (OR=1.36 [95%-CI=1.08–1.71],). MCP-1 G-2518, SDF-1ß A801, and CCR5 32 were not associated with CAD. Conclusions RANTES A-403 was associated with CAD independentlyfrom conventional risk factors and CRP or fibrinogen as inflammatorybiomarkers. The association was enhanced in smokers and ACS,conditions where platelet activation and inflammation predominate.RANTES A-403 may increase genetic susceptibility to CAD.