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.     

Contractile state is the major determinant of functional outcome in patients with left ventricular dysfunction treated with enalapril

Large-scale drug trials have focused primarily on mortalityand morbidity and less on the functional state of the myocardium.A model was developed to assess myocardial contractile statein patients with left ventricular (LV) dysfunction and to addressthe questions of differences in function between patients withand without overt heart failure, effects of enalapril, and bestpredictors of functional outcome. Pressure-angiographic data were obtained from 16 patients withovert heart failure and 47 without heart failure. Repeat studieswere conducted in 41 patients following 1 year's treatment withenalapril or placebo. Left ventricular silhouettes were dividedinto 18 segments to estimate regional ejection fraction, wallstress and myocardial damage (% myocardial damage). Contractilestate was assessed and ranked by ejection rate-preload-afterloadrelationships and by a score method based on 10 myocardial andventricular function parameters. End-diastolic and end-systolicvolumes (EDV, ESV) were significantly greater (P<0·001),ejection fraction (EF) lower (P<0·009), % myocardialdamage greater (P<0·008) and contractile state moredepressed in patients with overt heart failure. Changes in EDV and ESV (placebo vs enalapril) were significant(EDV, P<0·003; ESV, P<0·014). Directionalshifts in the diastolic pressure-volume relationships with enalaprilor placebo depended primarily on the basal contractile stateand diastolic volume range. The best single predictors of post-treatmentEF were the score index (a surrogate parameter for the contractilestate) and ESV. Added benefits of enalapril include the preventionof further dilatation in patients with less depressed contractilestate and delay in the onset of heart failure. Asymptomaticpatients with LV dysfunction should also be considered for angiotensinconverting enzyme (ACE) inhibitor therapy.     

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.     

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.     

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.     

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.     

Assessment of coronary artery stenosis during PTCA by measurement of the trans-stenotic pressure gradient: Comparison with quantitative coronary angiography

A fibreoptic pressure sensor mounted on an 0 018 inch guidewire(Pressure Guide®, RadiMedical Systems, Uppsala, Sweden)was used to measure the trans-stenotic pressure gradient in20 patients admitted for percutaneous transluminal coronaryangioplasty (PTCA) of a single, discrete stenosis. Pressuremeasurements were made both at rest and during maximal vasodilatationinduced by intracoronary injection of papaverine. From the ratioof distal coronary pressure divided by the proximal pressure,the relative coronary flow reserve was calculated. The aim ofthe study was to compare the different pressure-derived parametersby correlating them to stenosis geometry estimated by quantitativecoronary angiography. There was a moderate correlation betweenbaseline pressure gradient and percent area stenosi r= 0.64,P<0.001 and minimal cross-sectional area; r= 0.45, P<0005.A higher correlation was found between hyperaemic pressure gradientand area stenosis (r= 080, P<0001) and minimal cross-sectionalareas, respectively (r= 0.55, P<0 005). The best correlationwas found between relative coronary flow reserve and area stenosis(r= 0.86, P<0.001) and minimal cross-sectional area (r= 0.70,P<0001). In conclusion, pressure measurement using a pressure guidewireis useful as a complement to angiography in evaluation of coronarystenoses during PTCA. Pressures should be measured during maximalvasodilatation. Relative coronary flow reserve calculated fromthe pressure measurements provides additional information aboutthe fraction of normal maximal flow possible in the presenceof a stenosis.     

Reassessment of the relation between QRS forces of the orthogonal electrocardiogram and left ventricular ejection fraction

Previous studies have demonstrated the existence of a strongpositive correlation between the amplitude of QRS forces ofthe orthogonal electrocardiogram and the angiographically determinedleft ventricular ejection fraction. In a large group of patientsevaluated for chest pain, we examined the relationship betweenthe arithmetic summation of R_x+R_y+Q_z (R) the maximal and meanspatial QRS vectors and the ejection fraction (EF). In a totalof 252 patients, there was a statistically significant correlationbetween R and EF but a low correlation coefficient value (r:0.22, P<0.001). This relationship was essentially due tothe group of patients with coronary artery disease and myocardialinfarction (r: 0.24, P<0.015) whereas there was no correlationin the group of normal subjects or in patients with coronaryartery disease without myocardial infarction. In the group withmyocardial infarction, a significant correlation between R andEF existed only in patients with anterior myocardial infarction(r: 0.41, P<0.025). In conclusion, both ejection fractionand amplitude of QRS forces decrease in coronary artery diseaseespecially when an anterior myocardial infarction is present.However, despite the positive association between these angiographicand electrocardiographic indices, the low value of the correlationcoefficient indicates that it is not possible to predict ejectionfraction from the value of R in individual patients.     

Rapid diminution of calcium in the myocardium by transfer to pericardial solutions: Myocardial dialysis

A new method is described for the controlled and specific depletionof calcium from the vascularly perfused heart of experimentalanimals by means of dialysis, using a pericardial solution. A 30–40ml isotonic phosphate buffer pH7.3 with a low Ca²⁺ and high Mg²⁺ concentration (0.2 and 2.7mM respectively) wasinserted into the pericardial cavity of anaesthetized dogs andkept therefor 10 or 60 min. The calcium content of the subendocardialand subepicardial halves of the left ventricular wall was similarlydecreased to about 70% (P<0.01) within 10 min and to 62%(P<0.001) at 60 min, compared to that of hearts dialysedfor60 min in a standard solution ofCa²⁺ 1.2 mM and Mg²⁺ 1 mM.Calcium content of the myocardium dialysed with low Co²⁺ anda standard Mg²⁺ solution decreased to only 75% (P<0.01)at 60 min. Similar changes of calcium were measured in otherparts of the heart. An increase in Co²⁺ concentration in the pericardial solutionwas observed at the same time as a decrease in calcium in themyocardium. The increase in Ca²⁺ reached about 0.7 mM at 60min, but decreased slightly, and finally, fell to 85% of pre-dialysisvalues at 60 min. It is concluded that this method of myocardial dialysis is effectivein reducing myocardial calcium and is influenced by the durationof dialysis and the Mg²⁺ content of dialysate.     

Protective effect of beta-blockade on dipyridamole-induced myocardial ischaemia: Role of heart rate

This study was designed to investigate the effect of heart ratechanges on dipyridamole echocardiographic tests in patientswith coronary artery disease treated with propranolol. We prospectively studied 12 patients (8 men and 4 women; meanage 56.5 ± 8.7 years) selected by: (a) angiographic evidenceof significant coronary artery disease; (b) adequate echocardiographicwindow; (c) positive dipyridamole echocardiography test resultsin baseline conditions (step I); (d) test reproducibility inthe absence of treatment; (e) negative dipyridamole echocardiographytest results after 7 days of treatment with propranolol (120mg. day^–1) in twice divided doses daily (step II). In all patients treated with propranolol, dipyridamole echocardiographictesting was repeated 24 h after the last negative test. In thesepatients, transoesophageal atrial pacing was performed at peakdipyridamole infusion to increase heart rate to values similarto those observed at baseline (step III). At baseline, heartrate and rate-pressure product were significantly lower in patientstreated with propranolol (–20.3% and –22.5% in groupII, P<0–001 vs step I; –24.3% and –26.4%in group III, P<0.05 vs step I), but the different treatmentsdid not produce significant differences in systolic and diastolicblood pressure. At peak dipyridamole infusion, heart rate andrate-pressure product increased with either placebo or propranololtreatments with respect to baseline, while remaining significantlylower with propranolol as compared to placebo ( –29.6%and –29.5% in step II, P<0001). During treatment withpropranolol plus transoesophageal pacing to maintain heart rateat values attained with placebo, the rate-pressure product didnot change significantly with respect to placebo, nor did systolicblood pressure. Transoesophageal atrial pacing performed duringpropranolol treatment to restore heart rate to baseline valuesdid not affect the dipyridamole echocardiographic test in eightpatients (group I), and induced transient wall abnormalitiesin four patients (group II) (P=ns). Our data suggest that the anti-ischaemic effect of propranololin man is not correlated only to reduction of heart rate.     

Nitroglycerin and afterload: effects of aortic compliance and capacity of the Windkessel

The effect of nitroglycerin (NTG) is mainly a reduction in preloadand afterload. The decrease in afterload may be caused by afall of total systemic resistance (TSR) or by an increase ofarterial compliance (AC). The effects of NTG on TSR and AC weretested in 10 patients given 1.6 mg NTG sublingually. The capacityof the whole Windkessel (C) was calculated as C=/TSR ( = timeconstant of the diastolic aortic pressure decay). The diameterof the descending thoracic aorta was measured from an aortogram.Aortic stiffness SAO) was calculated SAO = P/D. Since mean aorticpressure decreased by 6% after NTG without any change in cardiacindex or heart rate, there had to be a primary reduction ofafterload as measured from mean systolic resistance (–9%).This reduction of afterload could not be related to a decreasein TSR and SAO, C, however increased by an average of 27%. These data indicate that NTG decreases the muscular tone ofpostaortic muscular vessels and, hence, increases the Windkesselcapacity, while aortic compliance does not change.     

Differences in restenosis propensity of devices for transluminal coronary intervention: A quantitative angiographic comparison of balloon angioplasty, directional atherectomy, stent implantation and excimer laser angioplasty

With the increasing clinical application of new devices forpercutaneous coronary revascularization, maximization of theacute angiographic result has become widely recognized as akey factor in maintained clinical and angiographic success.What is unclear, however, is whether the specific mode of actionof different devices might exert an additional independent effecton late luminal renarrowing. The purpose of this study was toinvestigate such a difference in the degree of provocation ofluminal renarrowing (or ‘restenosis propensity’)by different devices, among 3660 patients, who had 4342 lesionssuccessfully treated by balloon angioplasty (n=3797), directionalcoronary atherectomy (n= 200), Palmaz-Schatz stent implantation(n= 229) or excimer laser coronary angioplasty (n= 116) andwho also underwent quantitative angiographic analysis pre- andpost-intervention and at 6-month follow-up. To allow valid comparisonsbetween the groups, because of significant differences in coronaryvessel size (balloon angioplasty=2.62±0.55 mm, directionalcoronary atherectomy= 3.28±0.62 mm, excimer laser coronaryangioplasty= 2.51±0.47 mm, Palmaz-Schatz=3.01±0.44mm;P<0.0001), the comparative measurements of interest selectedwere the ‘relative loss’ in luminal diameter (RLoss=losslvessel size) to denote the restenosis process, and the‘relative lumen at follow-up’ (RLfup=minimal luminaldiameter at follow uplvessel size) to represent the angiographicoutcome. For consistency, lesion severity pre-intervention was representedby the ‘relative lumen pre’ (RLpre=minimal luminaldiameter prelvessel size) and the luminal increase at interventionwas measured as ‘relative gain’ (relative gain=gainl vessel size). Differences in restenosis propensity betweendevices was evaluated by univariate and multivariate analysis.Multivariate models were constructed to determine relative lossand relative lumen at follow-up, taking account of relativelumen pre-intervention, lesion location, relative gain, vesselsize and the device used. In addition, model-estimated relativeloss and relative lumen at follow-up at given relative lumenpre-intervention relative gain and vessel size, were comparedamong the four groups. Significant differences were detectedamong the groups both with respect to these estimates, as wellas in the degree of influence of progressively increasing relativegain, on the extent of renarrowing (relative loss) and angiographicoutcome (relative lumen at follow-up), particularly at higherlevels of luminal increase (relative gain). Specifically, lesionstreated by balloon angioplasty or Palmaz-Schatz stent implantation(the predominantly ‘dilating’ interventions) wereassociated with more favourable angiographic profiles than directionalatherectomy or excimer laser (the mainly ‘debulking’interventions). Significant effects of lesion severity and location,as well as the well known influence of luminal increase on bothluminal renarrowing and late angiographic outcome were alsonoted. These findings indicate that propensity to restenosis afterapparently successful intervention is influenced not only bythe degree of luminal enlargement achieved at intervention,but by the device used to achieve it. In view of the clinicalimplications of such findings, further evaluation in largerrandomized patient populations is warranted.     

Doppler echocardiography in adults with isolated ventricular septal defect

Doppler echocardiography and cardiac catheterization were undertakenin 70 consecutive patients, 31-68 years of age (mean 39), whohad isolated congenital ventricular septal defects (VSD), 28of whom had been operated upon. In 50 patients with invasivelyproven VSD, 37 had a correct Doppler diagnosis of VSD (group1) and in 13 a false negative result was obtained (group 2);i.e. a sensitivity of 74%. No false positive Doppler diagnosiswas made in the 20 patients without evidence of shunt. Leftto right ventricular systolic pressure difference (P) rangedbetween 55 and 142 mm Hg, with a mean value of 103 mm Hg ingroup 1 and 99 mm Hg in group 2. There was good correlationbetween P obtained by continuous wave Dopier and catheterisationin 17 group 1 patients with moderate and large shunts (r=0.81,P<0.001). There was no correlation in the remaining 20 patientsin group 1 with small shunts (r=0.20, P>0.l). Doppler echocardiography in the adult with isolated VSD hasgood sensitivity and excellent specificity. Doppler predictionof P is reasonably correct in patients with moderate and largeshunts, but of no value in patients with small shunts.     

lschaemic heart disease: The QRS score: a promising new exercise score for detecting coronary artery disease based on exercise-induced changes of Q-, R- and S-waves: a relationship with myocardial ischaemia

BACKGROUND: Recently, a new exercise test criterion diagnosing coronaryartery disease was proposed, based on a composite of changesin Q-, R- and S-waves: the QRS score. We compared this new criterionwith conventional ST-segment depression and other compositionsof Q-, R and S-wave changes in patients and normals and relatedthe QRS score to reversible thallium-201 scintigraphic defectsand ST-segment depression as markers for ischaemia. The influenceof beta-blockade on the QRS score was also studied. METHODS: The study population consisted of 155 persons with 53 normals(group I) and 102 patients with documented coronary artery disease(group II). Another 20 patients (group III) with proven coronaryartery disease and a positive exercise test by ST-segment criteriawere studied for the influence of beta-blockade on the QRS score.A symptom-limited exercise protocol according to the modifiedBruce protocol was used. For the QRS score, Q-, R- and S-waveamplitudes which could be recovered immediately were subtractedfrom pretest values: Q, R, S respectively. The score was calculatedby the formula: (R – Q –S)AVF+(R –Q–S)V5. RESULTS: Using a cut-off point of >5 as normal, the QRS score resultedin a sensitivity of 88·2%, a specificity of 84·8%and a predictive accuracy of 87·1%. For ST-segment depressionthese values were 54·9% 83% and 64·5% respectively(P<0·00l compared to the QRS score.) Predictive accuraciesof changes in Q-, R- and S-waves in leads AVF and VS separately,combinations of changes and combining the two leads, resulted—withthe exception of solitary S-wave changes—in predictiveaccuracies higher than those of ST-segment depression, but allwere lower than the QRS score. We found a significant correlationbetween the QRS score, the summed ST-segment depres sion (P<0004)and the extent of reversible thallium-201 defects (P<0·004Applying Bayes' theorem, the combination of an abnormal QRSscore and ST-segment depression resulted in the highest post-testrisk for coronary artery disease and a normal QRS score withoutST-segment depression in the lowest post-test risk. The QRSscore and the maximal ST-segment depression changed significantlyunder the influence of beta-blockade (P<0·02 and P<0·001respectively). CONCLUSION: Our data suggest that an abnormal QRS score reflects myocardialischaemia. Furthermore, for the interpretation of the exercisetest, the combined analysis of ST-segments and the QRS scoreis of value for the prediction of the presence or absence ofcoronary artery disease and its follow-up.     

Volume loading in patients with ischemic right ventricular dysfunction

Volume loading tests with dextran 40 were performed on 36 patientsundergoing hemodynamic monitoring and diagnosed as acute myocardialinfarction with ischemic right ventricular dysfunction. Thisdiagnosis was made when right atrial pressure was higher thanJO mm Hg and greater than, equal to or not more than 5 mm Hgless than pulmonary capillary pressure in basal conditions (24patients), or after dextran administration (12 patients). The patients were divided into two groups according to basalcardiac index: group A: 16 patients with cardiac index 2.2 l/min/m²and group B: 20 patients with cardiac index <2.2l/min/m².In group B, the right atrial and pulmonary capillary pressuresassociated with the higher cardiac index were 15.6 ±4.2 and 16.8 ± 3.3 mm Hg respectively. Ventricular functioncurves were plotted comparing variations in right atrial andpulmonary capillary pressures with cardiac index and right andleft ventricular net work index. The response to volume loadingwas variable in both groups. Patient mortality in group B was related to basal left ventricularnet work index (P<0.05), to a cardiac .index lower than 2.2l/min/m²after dextran administration (V < 0.02) and to the followingventricular function curves slopes A cardiac index/, right atrialpressure (P <0.05), A cardiac index/, pulmonary capillarypressure (P<0.05) and A left ventricular net work index/pulmonary capillary pressure (P<0.05). This indicates thatmortality is dependent on global cardiac function and more preciselyon left ventricular function. Volume loading is useful to demonstrate the presence of ischemicright ventricular dysfunction, to assess right ventricular function,to find the optimal values of ventricular filling pressure inpatients with low output, and to determine the prognosis.     

T-CELL RECEPTOR GAMMA-DELTA POSITIVE LYMPHOCYTES IN SYNOVIAL MEMBRANE

The distribution of T-lymphocytes expressing CD3 and T-cellreceptor gamma-delta (T/) has been examined by immunocytochemistryin the synovial membrane of eight patients with inflammatoryarthritis (six rheumatoid arthritis, two spondyloarthritis)and eight with non-inflammatory arthritis (four osteoarthritis,four post-traumatic arthritis). T/ cells were present in eightout of eight inflammatory arthritis synovial membranes, butin only one out of eight noninflammatory membranes (P<0.005).The mean T/ percentage (of total T-cells) in inflammatory arthritiswas 14% (range 7–25%). T/ cells were found mainly in thetransitional area of the synovial membrane with a scattereddistribution as single cells or couplets. No relation was foundbetween the presence and percentage of T/ cells and diseaseduration or steroid treatment. KEY WORDS: Rheumatoid arthritis, Inflammatory arthritis, Degenerative joint disease, Synovium, Lymphocytes     

Combined tumour necrosis factor-alpha and tumour necrosis factor receptor genotypes could predict rheumatoid arthritis patients' response to anti-TNF-alpha therapy and explain controversies of studies based on a single polymorphism

SIR, Tumour necrosis factor- (TNF-) blocker therapies are widelyused in the treatment of chronic inflammatory diseases. However,patients show large heterogeneity in their response to anti-TNF-therapy. The genotypic background of TNF- and TNF receptor (TNFR)genes could account for patients’ resistance to TNF- blockers[1, 2]. HLA-DR haplotypes have been related with rheumatoidarthritis (RA) susceptibility, severity and course [3], butTNF and TNFR polymorphisms seem to have independent predictivevalue of patients’ response to anti-TNF- therapy [2, 4,5     

Costs of atrial fibrillation in five European countries: results from the Euro Heart Survey on atrial fibrillation

Aims: To estimate costs of admission and costs incurred on an annualbasis by patients with atrial fibrillation (AF) in Greece, Italy,Poland, Spain, and the Netherlands. Methods and results: The Euro Heart Survey on AF enrolled 5333 patients with AF in35 European countries in 2003 and 2004. This was a bottom-upcost study conducted for the five largest contributors in termsof patients enrolled. Quantities of resource use during theenrolment admission and during 1-year follow-up were inferredfrom survey data and multiplied by national unit costs in orderto estimate per patient costs associated with AF for each country.Mean costs of inpatient admission of an AF patient were estimatedat 1363, 5252, 2322, 6360, and 6445 and mean costs incurredon an annual basis at 1507, 3225, 1010, 2315, and 2328 in Greece,Italy, Poland, Spain, and the Netherlands, respectively. Inpatientcare and interventional procedures were identified as the maindrivers of costs, accounting for more than 70% of total annualcosts in all five countries. Conclusion: Estimates of the economic burden posed by AF are critical inlight of the increasing importance of AF as a public healthproblem.     

Signalling, inflammation and arthritis: NF-kappaB and its relevance to arthritis and inflammation

In the synovial cells of patients with RA, activation of thenuclear factor-B (NF-B) pathway results in the transactivationof a multitude of responsive genes that contribute to the inflammatoryphenotype, including TNF- from macrophages, matrix metalloproteinasesfrom synovial fibroblasts and chemokines that recruit immunecells to the inflamed pannus. This is largely a consequenceof activation of the ‘canonical’ NF-B pathway thatinvolves heterodimers of p50/p65. Whilst much information onthe role of NF-B in inflammation has been gleaned from geneticdeficiency of the respective genes in mice, important differencesexist in the signalling networks between human and murine immunecells and immortalized cell lines. Despite these differencesat the molecular level, the importance of NF-B in inflammationis undisputed and inhibition of the pathway is widely believedto have great potential as a therapeutic target in RA. Commercialeffort has gone into developing inhibitors of NF-B activation.However, inhibition of the NF-B activation can result in anexacerbation of inflammation if TNF- production by macrophagesis not controlled. It will be important that such inhibitorsare carefully monitored before their long-term use in chronicinflammatory conditions such as RA. KEY WORDS: NF-B, Signalling pathways, Review Submitted 13 July 2007; revised version accepted 4 October 2007.