Assessment of accuracy of the Doppler pressure half-time method in the estimation of the mitral valve area immediately after balloon mitral valvuloplasty

AIM: The reliability of Doppler echocardiography in determining themitral valve area after balloon mitral valvuloplasty has beenquestioned, as discrepancies were noted between measurementsobtained by the pressure half-time method and those derivedhaemodynamically, immediately following completion of the procedure.Recent investigations, however, have indicated that these discrepanciesmay be attributable to the over-estimation of the mitral valvearea by haemodynamic measurements, caused by the presence ofthe iatrogenic atrial septal defect complicating transseptalcatheterization. The aim of the present study was to furthertest this hypothesis. METHODS AND RESULTS: Measurements of the mitral valve area by the Doppler pressurehalf-time method and the Gorlin formula were obtained and comparedin 238 consecutive patients before and immediately after retrogradenon-transseptal balloon mitral valvuloplasty, which does notinvolve puncture and/or dilatation of the inter-atrial septum.No significant difference was found between Doppler- and Gorlin-derivedmeasurements, neither before (1·04±0·23vs 1·03±0·23cm², P=ns) nor immediatelyafter (2·14±0·47 vs 2·12±0·49cm², P=ns) valvuloplasty. Linear regression analysis demonstrateda high degree of correlation between Doppler and Gorlin measurementsbefore (r=0·778) and after (r=0·886) the procedure.Good agreement was confirmed by the Bland—Altman method. CONCLUSION: Doppler echocardiography yields accurate measurements of themitral valve area immediately after retrograde non-transseptalballoon mitral valvuloplasty. This finding supports the hypothesisthat the creation of an iatrogenic atrial septal defect duringtransseptal catheterization may contribute to the poor agreementbetween Doppler and Gorlin data after balloon mitral valvuloplasty.     

Balloon mitral valvotomy: comparison between antegrade Inoue and retrograde non-transseptal techniques

AIMS: The results of percutaneous mitral valvotomy performed by theantegrade transseptal method using the Inoue balloon (n=1000;group 1) and by the retrograde non-transseptal technique usinga polyethylene balloon (n=100; group 2) were compared in a retrospective,non-randomized study. METHODS AND RESULTS: Both the groups were similar with respect to baseline characteristics.The success rate was 95% in group 1 and 93% in group 2. Therewas a significant increase in mitral valve area estimated byGorlin's equation (Group 1: from 0·8 ± 0·5to 2·1 ± 0·8 cm²; Group 2: from 0·8± 0·3 to 1·9 ± 0·8 cm², bothP<0·001) and by Doppler echocardiography using thepressure half-time method (Group 1: from 0·9 ±0·4 to 2·2 ± 0·6 cm²; Group 2: from0·9 ± 0·3 to 2·0 ± 0·7cm², both P<0·001). However, the calculated immediatepost-valvotomy mitral valve area was larger with the Inoue technique(2·1 ± 0·8 vs 1·9 ± 0·8cm²; P<0·02). Results were considered optimal whenthe mitral valve area increased to 1·5 cm², the percentageincrease was 50, and mitral regurgitation was 2/4. Out of thetotal successful procedures, optimal results were obtained in95% patients in Group 1 and 94% in Group 2. Incidence of significantmitral regurgitation (grade 3/4) was similar in two groups (Group1: 4% vs Group 2: 5%, P=ns). A significant left to right atrialshunt (Qp/Qs 1·5:1) in 2·5% and tamponade in2% of cases occurred exclusively with the Inoue technique, whileconduction disturbances, such as transient (<24 h) left bundlebranch block (28%) and complete heart block (2%) were notedwith the retrograde technique (Group 2). Local complicationswere significantly higher in Group 2 (3% vs 0·5%, P<0·01).The procedure time with the Inoue technique was shorter thanwith the retrograde (Group 1: 15 ± 8, range 10 to 35min; Group 2: 22 ± 14, range 15 to 45 min, P=0·05).Echocardiographic follow-up at 1 year showed no significantdifference in mitral valve area between the two groups (Group1 (n=300): 1·8 ± 0·8 vs Group 2 (n=60):1·9 ± 0·9 cm²; P=0·3). CONCLUSION: Balloon mitral valvotomy using the Inoue balloon and the retrogradenon-transseptal technique results in significant immediate haemodynamicand symptomatic improvement. The Inoue technique achieved alarger immediate post-valvotomy mitral valve area, but the differencewas not apparent at 1 year follow-up. Incidence of significantmitral regurgitation was similar with both the techniques; however,local complications occurred more frequently with the retrogradetechnique. Both techniques may complement each other in technicallydifficult cases.     

Effects of percutaneous balloon mitral valvuloplasty and exercise training on the kinetics of recovery oxygen consumption after exercise in patients with mitral stenosis

Aims Kinetics of recovery oxygen consumption after exercise playsan important role in determining exer-cise capacity. This studywas performed to assess the kinetics of recovery oxygen consumptionin mitral stenosis and evaluate the effects of percutaneousballoon mitral valvuloplasty and exercise training on the kinetics. Methods and Results Thirty patients with mitral stenosis (valve area 1·0cm²)and same sized age- and size-matched healthy volunteers wereincluded for this study. All subjects performed maximal uprightgraded bicycle exercise. Thirty consecutive patients who underwentsuccessful percutaneous balloon mitral valvuloplasty (valvearea 1·5cm²and mitral regurgitation grade 2), were randomizedto an exercise training group or non-training group. The exercisegroup performed daily exercise training for 3 months. Half-recoverytime of peak oxygen consumption was significantly delayed inmitral stenosis as compared to normal subjects (120±42svs 59±5,P<0·01). Peak oxygen consumption (ml.min^–1.kg^–1)was significantly increased in both the training (16·8±4·9to 25·3±6·9) and non-training groups (16·3±5·1to 19·6±6·0) 3 months after percutaneousballoon mitral valvuloplasty. Half-recovery time of peak oxygenconsumption was significantly shortened in the training group(124±39 to 76±13,P<0·01), but not inthe non-training group (114±46 to 109±44s,P=0·12)at 3 months follow-up. The degrees of symptomatic improvementafter percutaneous balloon mitral valvuloplasty were more closelycorrelated with the changes of the half-recovery time of peakoxygen consumption than those of peak oxygen consumption. Conclusion Kinetics of recovery oxygen consumption was markedly delayedin mitral stenosis, which was improved after exercise trainingbut not after percutaneous balloon mitral valvuloplasty alone.These results suggest that adjunctive exercise training maybe useful for improvement of recovery kinetics and subjectivesymptoms after percutaneous balloon mitral valvuloplasty.     

Physical training improves exercise capacity in patients with mitral stenosis after balloon valvuloplasty

BACKGROUND: Haemodynamic measurements taken at rest and during exerciseshowed that percutaneous transvenous mitral commissurotomy resultsin both acute and long-term improvement. However, the time lagbefore there is an increase in exercise and in peak oxygen uptakeappears to be delayed and irregular. PATIENTS AND METHODS: To assess the potential of physical training to restore betterphysical capacity after percutaneous transvenous mitral commissurotomy,26 patients with mitral stenosis were studied after the procedure.The group was split into two. Thirteen underwent a 3-month rehabilitationprogramme, and the other 13, who did not, acted as controls. RESULTS: The mitral valve orifice area increased similarly, from 1·;12±017to 1·88 ±0·28 cm² in the training groupand from 1·04±0·16 to 1·88±0·19cm² in the control group. Cardiopulmonary parameters were similarbefore percutaneous transvenous mitral commissurotomy (peako₂: 19·9±2·4 vs 18·9±4·5ml. min^–1. kg^–1; peak workload: 94·6±29·3vs 96·1±25 watts; o₂ at anaerobic threshold: 17±3·4vs 16·1±5·2 ml. .min^–1. kg^–1;all P=ns). Three months later the results were higher in thetraining group (peak o₂: 26·6±4·7 vs 21·6±3·8ml. min^–1. kg^–1, P=0·001; peak workload:125·4±26·6 vs 108·5±23 watts,p=0·03; o₂ at anaerobic threshold: 19·6±5·8vs 15·8±2·9 ml. min^–1. kg^–1;P=0·02). CONCLUSION: These results indicate that patients should take up exerciseafter successful percutaneous transvenous mitral commissurotomyfor better functional improvement.     

Early results after mitral valvuloplasty for pure mitral regurgitation

In this study we present the results of 105 consecutive patientswith pure mitral regurgitation who underwent surgical treatment.In all patients mitral regurgitation was associated with mitralvalve prolapse: 54 patients underwent mitral valvuloplasty and51 patients mitral valve replacement. Clinical assessment and echocardiography were used as follow-upcriteria at one year after surgery. After mitral valvuloplasty,NYH A decreased from 2.7±0.8 to 1.1±0.7 (P<0.01)and workload capacity increased from 65±28% to 96±25%(P<0.001); left endsystolic atrial dimension and enddiastolicdimension decreased from 6.2±0.8 to 4.8±1.2 cm(P<0.001) and from 7.2±1.3 to 5.9±0.8 cm (P<0.01);ventricular contraction fraction did not change significantly. After mitral valve replacement, clinical and echocardiographicimprovement was significant but less remarkable than after valvuloplasty;ventricular contraction fraction fell from 39±7% to 29±8%in contrast to patients undergoing mitral valvuloplasty in whomno significant change occurred. Complications were rare in both groups though only a minorityof patients undergoing mitral valvuloplasty received anticoagulants.We conclude that mitral valvuloplasty in patients with puremitral regurgitation associated with mitral valve prolapse givesexcellent results, particularly regarding left ventricular functionwhen compared with the patients after mitral valve replacement.     

Early results after mitral valvuloplasty for pure mitral regurgitation

In this study we present the results of 105 consecutive patientswith pure mitral regurgitation who underwent surgical treatment.In all patients mitral regurgitation was associated with mitralvalve prolapse: 54 patients underwent mitral valvuloplasty and51 patients mitral valve replacement. Clinical assessment and echocardiography were used as follow-upcriteria at one year after surgery. After mitral valvuloplasty,NYH A decreased from 2.7±0.8 to 1.1±0.7 (P<0.01)and workload capacity increased from 65±28% to 96±25%(P<0.001); left endsystolic atrial dimension and enddiastolicdimension decreased from 6.2±0.8 to 4.8±1.2 cm(P<0.001) and from 7.2±1.3 to 5.9±0.8 cm (P<0.01);ventricular contraction fraction did not change significantly. After mitral valve replacement, clinical and echocardiographicimprovement was significant but less remarkable than after valvuloplasty;ventricular contraction fraction fell from 39±7% to 29±8%in contrast to patients undergoing mitral valvuloplasty in whomno significant change occurred. Complications were rare in both groups though only a minorityof patients undergoing mitral valvuloplasty received anticoagulants.We conclude that mitral valvuloplasty in patients with puremitral regurgitation associated with mitral valve prolapse givesexcellent results, particularly regarding left ventricular functionwhen compared with the patients after mitral valve replacement.     

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

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

Validation of continuous-wave Doppler measurements of mitral valve gradients during exercise -- a simultaneous Doppler-catheter study

In patients with mitral stenosis, continuous-wave Doppler measurementsof the maximal transmitral inflow velocity can be convertedinto transvalvular pressure gradients using the modified Bernoulliequation. Because of close correlations between Doppler- andcatheter-measured gradients this method has become a valuabletool in non-invasive evaluation of mitral stenosis at rest.However, in some patients, exercise studies are necessary todetermine the haemodynamic significance of the valve stenosis.The accuracy of continuous-wave Doppler in this setting hasnot yet been validated. Thus, in 20 selected patients with pure or predominant mitralstenosis, continuous-wave Doppler echo-cardiography was performedduring left- and right-heart catheterization. At rest and duringsubmaximal bicycle exercise, Doppler and pressure measurementswere simultaneously performed. The Doppler gradient was calculatedaccording to the modified Bernoulli equation while the meanmanometric gradient was determined from the simultaneous pulmonarywedge and left ventricular pressure curves. Exercise caused a significant increase of cardiac output (4·8+1·3 to 5·7±1·31 min^–1) andheart rate (59·7±12·0 to 95·3±14·3beats minmin^–1). The mean Doppler gradient increased from6·8 ± 2·1 to 12·2 ± 3·2mmHg. The manometric gradient showed a comparable increase of9·5 ± 2·4 to 17·2 ± 3·7mmHg, respectively. Correlation between Doppler and manometric data was close (y= 0·79x – 0·67,r = 0·90, SEE= 0·97mmHg) at rest and still good during exercise (y = 0·71x– 0·10, r = 0·82, SEE= 1·97 mmHg). Thus, in some patients with borderline resting gradients andvalve areas, exercise Doppler might allow further identificationof the haemodynamic severity of mitral stenosis.     

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.     

Peak oxygen uptake during exercise in mitral stenosis with sinus rhythm or atrial fibrillation: lack of correlation with valve area: A study in 70 patients

Although the haemodynamic response during submaximal supineexercise in mitral stenosis has been well described, the determinantsof peak oxygen uptake during maximal upright exercise are poorlycharacterized and may differ in sinus rhythm and atrial fibrillation.Seventy patients with isolated mitral stenosis underwent Doppler-echocardiographyand bicycle exercise with respiratory gas analysis. Forty-twopatients were in sinus rhythm (Group I) and 28 in atrial fibrillation(Group II). Peak oxygen uptake it was 21·3±5·6ml. min^–1 kg^–1 in group I and 18·1 ±5·1 ml min^–1 kg^–1 in group II (P<0·05).There was no significant correlation between indices of exercisetolerance (exercise duration, ventilatory threshold, peak oxygenuptake, indexed peak oxygen uptake, peak oxygen pulse) and valvearea or gradient in either group. Indexed peak oxygen uptakewas not correlated to oxygen pulse but was linearly related(r=0·43) to heart rate ( heart rate =peak heart rate=restheart rate) in Group I but not in Group II. Thus, in patientswith mitral stenosis, no correlation was found between the mitralvalve area or the gradient at rest and maximal upright exercisetolerance, suggesting that peripheral adaptation and, in sinusrhythm, chronotropic reserve, are important compensatory mechanisms.     

Blood volume and right heart haemodynamics in abrupt hypotension following sublingual isosorbide dinitrate in acute myocardial infarction

Arterial blood pressure and heart rate were measured in 43 patientswith acute myocardial infarction and a systolic blood pressure120 mmHg during sublingual administration of 5 mg of isosorbidedinitrate. In 25 of them right heart haemodynamics were alsomeasured. Severe (25%) hypotension developed in 12 patients(Group 1, systolic blood pressure 158 ± 28 to 78 ±17 mmHg, mean ± SD) but not in the remaining 31 (Group2) and was accompanied by a fall in heart rate (82 ±20 to 70 ± 22beats min^-1, P<0.05), in cardiac output(4.3 ± 0.3 to 3.2 ± 0.4l mm^-1, P<0.02, n =5) and in systemic vascular resistances (2326 ± 463 to1532 ± 442 dynes sec^-1 cm^-5, P<0.02) not present inGroup 2. The reduction in right (Group 1,8 ± 3 to 3 ±1, vs. Group 2,10 ± 3 to 6± 3 mmHg, V <0.005)and in left ventricular filling pressures (Group 1,15 ±4 to 8 ± 2, vs. Group 2,18 ± 6 to 13 ±5 mmHg, P<0.001) was more remarkable in Group 1. In thisgroup there was also a high incidence of anterior infarction(9/12, 75%). Blood volume measured in 30 patients was lowerin Group 1 but differences were not significant. A second doseof 5 mg of isosorbide dinitrate 36–48 h later producedneither symptomatic hypotension (Group 1, 147 ± 29 to129 ± 24 mmHg) nor a fall in cardiac output in any patient,whereas changes infilling pressures were comparable to thoseof the first dose. Thus, severe isosorbide dinitrate-induced hypotension in myocardialinfarction is limited to the acute phase and seems more prevalentin anterior infarction but can not be clearly predicted fromresting haemodynamic or blood volume measurements, at leastin non-hypotensive patients. Moreover, it appears to be causedby an excessive ventricular emptying due to a striking venousand arterial vasodilation, probably during a stage of a particularlydepressed ventricular compliance.     

Vascular and systemic diseases: Use of transthoracic Doppler echocardiography combined with clinical and electrocardiographic data to predict acute pulmonary embolism

Transthoracic echocardiography and continuous wave Doppler wereprospectively performed in 132 out-patients with suspicion ofpulmonary embolism, and who had no previous history of severecardiac or pulmonary disease. Bedside echocardiography determineddiagnosis other than pulmonary embolism in 55 patients. Furtherstudy was completed in 70 patients; pulmonary embolism was foundin 31 and excluded in 39. Significant differences were foundas regards right ventricular diameter (27±8 vs 22±5mm, P<0·001), left ventricular diameter (41±9vs 49±7 mm, P<0·001), right over left ventriculardiameter ratio (0·67±0·23 vs 0·43±0·15,P<0·0001), tricuspid regurgitant flow peak velocity(2·9±0·4 vs 2·4±0·7m. s^–1P<0·0001), and abnormal septum motion(12 vs 4, P<0·01). Multivariate analysis of echocardiographicdata included a tricuspid regurgitant flow peak velocity greaterthan 2·5 m . s^–1 and a right over left ventriculardiameter ratio greater than 0·5 in a logistic model (sensitivity93%, specificity 81%). The combination of echocardiographicand non-echocardiographic data included the two previous echocardiographicvariables, together with signs of deep vein thrombosis, a deepS wave in lead D1, and a Q wave in lead D3 on the electrocardiogramin a logistic model (sensitivity 96%, specificity 83%). It canbe concluded that emergency echocardiography, alone or combinedwith clinical examination and electrocardiogram, satisfactorilypredicts acute pulmonary embolism.     

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

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

Volume loading in predominant right ventricular infarction: bedside haemodynamics using rapid response thermistors

Intravenous fluid loading is commonly used for the treatmentof low cardiac output (CO) syndrome complicating severe rightventricular infarction (RVMI). We prospectively evaluated theeffectiveness of this method in 11 consecutive patients (age66 ± 14 years) with severe R VMI, using a newer thermodilutionmethod with rapid response thermistors. Volume loading was performeduntil pulmonary wedge pressure (PWP) reached 18 to 24 mmHg.Right atrial pressure (RAP), pressures of the right ventricle(RV) and pulmonary artery (PA), PWP, RV volumes, RV ejectionfraction (RVEF), stroke volume (SV), CO, pulmonary vascularresistance (PVR) and RAP/PWP ratio were measured before andafter volume loading. RAP rose from 12 ± 4 to 19 ±5 mmHg (P<0.0001) and its tracing showed a non-compliantpattern in all patients. RV end-diastolic pressure rose from13 ± 4 to 20 ± 5 mmHg (P<0.0001) and PWP from14 ± 3 to 20 ± 6 mmHg (P<0.0001). Mean PA pressurerose from 20 ± 3 to reach 25 ± 6 mmHg (P<0.001),while PVR did not change significantly (117± 39 vs 101± 49 dyn. s. cm^{– 5}, P ns). RAP/PWP ratio rose from0. 85 ± 0.14 to 1.05 ± 0.07 (P<0.01). The end-diastolicRV volume increased from 95 ± 26 to 113± 24ml.m^{– 2} (P<0.001); however, RV end-systolic volume increasedfrom 65 ± 28 to 83 ± 29 ml. m^{– 2} (P<0.01),thus SV did not change significantly (30± 6 vs 30±8ml. beat^{– 1}m^{– 2}, P ns). RVEF decreased from 32±11 to 28± 11% (P<0.001). CO did not improve significantly(2. 3 ± 0.42 vs 2.4± 0.62 l. min^{– 1}. m^–2, P ns) neither did the clinical status. In conclusion, volumeloading per se is not sufficient to improve CO in patients withsevere R VMI, despite the fact that it increases R V preloadLeft ventricular preload does not increase, but PWP rises becauseof the limiting role of the pericardium.     

Left ventricular function after total correction of tetralogy of Fallot

Conflicting data are available concerning left ventricular (LV)function in patients after total correction of tetralogy ofFallot (TOF). The response to afterload stress determined bymethoxamine challenge and the peak systolic blood pressure-end-systolicvolume relationship were evaluated echocardiographically in20 postoperative TOF patients (age range 9 to 15 years, mean12±2). All patients were without significant residualshunts or pulmonary stenosis. Results were compared with thosein 10 control subjects (age range 9 to 15 years, mean 11±2).The TOF group had higher mean end- diastolic (76·9±14·4vs 66·2±7·2 ml. m P<0·05) andmean end-systolic (36·7±8 vs 29·6±3·9ml. m^–2 P<0·05 volumes than controls. Strokevolume index (SVI) and LV ejection fraction were similar inthe two groups. In normal subjects, mnethoxamine caused a decreasein SVI in seven Out of 10 patients and a mild increase in three;the mean value of SVI at rest was not significantly differentfrom the mean value at peak pressor effect (36·5±4·4vs 35·9±4·0 ml. m^–2, P=NS). In theTOF group, methoxamine induceda reduction in SVI in all patients,the mean value of SVl at peak pressor effect was significantlylower than the mean value at rest (31·3±5·4vs 40·2±6·9 ml. m^–2 P<0·001).Ejection fraction decreased in both groups with the afterloadchallenge, but in the TOF patients the reduction was significantlyhigher than in the normal subjects (from 53±4 to 38±5%vs from 55±3 to 49±3%, P<0·001). Peaksystolic blood pressure-end- systolic volume relationships wereconstructed. The slope (m) of the relationship was significantlylower in the TOF group than in the control subjects (2·85±0·77vs 6·21+0·58, p<0·001);in the TOE groupm was below the 95% confidence limit in all studied patients.There was a significant correlation between aortic oxygen saturationpreoperatively and the slope of the peak systolic pressure-end-systolicvolume relation. Thus, LV function after successful total correctionof TOFmay be abnormal, with larger than normal LV size and decreasedcontractile function.     

Influence of haemodynamics and myocardial ischaemia on Doppler transmitral flow in patients undergoing dobutamine echocardiography

To examine whether pulsed Doppler left ventricular filling indicescan reliably detect myocardial ischaemia in patients with coronaryartery disease undergoing dobutamine stress echocardiographywe studied three groups matched for age and global indices ofleft ventricular function. Group 1 patients (n=10) had normalcoronary arteries whereas those in Groups 2 (n=12) and 3 (n=15)had significant coronary disease (70% diameter stenosis) atangiography. After stopping cardiouctive treatment, patientsunderwent incremental dobutamine stress (5, 10, 15 and 20 µg.kg^–1. min^–1) during pulsed Doppler interrogationof diastolic filling with simultaneous heart rate and bloodpressure measurements. Only Group 3 patients developed myocardialischaemia using electrocardiographic and cross sectional echocardiographiccriteria, subset 3A (n=4) comprised those with inducible mitralregurgitation on colour Doppler. Electrocardiographic R-R intervaldecreased (–311 ± 123 ms, P<0·001) andmean blood pressure altered (5±17 mmHg, P=ns) uniformlyacross groups. The respective changes in peak early velocity,peak atrial velocity and their ratio for Groups 1 (0·08± 0·09 m. s^–1, 0·26 ± 0·18m.s^–1 and – 0·32 ± 0·36), 2(0·07 ± 0·07 m.s^–1 0·18±0·15m.s^–1 and –0·13±0·21) and 3(0·09±0·12 m.s^–1, 0·20±0·13m.s^–1 and –0·17±0·21) weresimilar (all P=ns between groups). Corresponding data for subset3A (0·23 ± 0·04 m.s^–1 0·20± 0·10 m.s^–1and 0·00 ± 0·16)revealed a significantly greater increase in peak early velocityand normalized velocity ratio in these patients. Overall, changesin peak early (r= –0·47, P<0·01) andatrial velocity (r–0·65, P<0·001) andtheir ratio (r=0·35, P<0·05) correlated withreduction in R-R interval but not alterations in blood pressure.In conclusion, tachycardia during dobutamine stress masks theeffects of myocardial ischaemia on Doppler diastolic indicesalthough a minority of patients with inducible mitral regurgitationmanifest a relatively distinct filling profile.     

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.     

Dromotropic effects of oral theophylline in patients with atrial fibrillation and a slow ventricular response

Theophylline increases sinus rate, but as yet its use has notbeen investigated in patients with chronic atrio ventricularconduction disturbances. Resting electrocardiogram, 24-h Holterrecording and treadmill test were performed in 17 patients withchronic atrialfibrillation and a slow ventricular response notrelated to drugs (age: 75±8 years). Then slow-releasetheophylline was administered (700mg daily) and after 5 daysthese investigations were repeated with the same methods. Theophyllineincreased mean resting heart rate (51±6 versus 67±13beats.min^–1, P<0·01 mean 24-h heart rate (51±6versus 68±14 beats.min^–1, P<0·01 andminimal 24-h heart rate (32±6 versus 42±11 beats.min^–1,P<0·01 Cardiac pauses >2·5 s were presentin 13 patients during control recording; after theophyllinethey disappeared in 11 and markedly decreased in the remainingtwo. The longest R-R interval decreased in all patients (3218±943versus 2121±518ms, P<0·01). The daily numberof wide QRS complexes increased in 16 out of 17 patients (428±752versus 1146±1464 ms, P<0·01). Exercise heartrate, evaluated at the end offirsi andsecondstage, was higherafter theophylline than during control test (P<0·01). These data suggest that oral theophylline can represent a validtherapy in most patients with atrialfibrillation and a slowventricular response.     

Acute antiischaemic properties of high dosages of intravenous diltiazem in humans in relation to its coronary and systemic haemodynamic effects

The antiischaemic properties of intravenous diltiazem in recommendedtherapeutic doses are disputed. In 17 patients with coronaryartery disease the systemic and coronary haemodynamic effectsof diltiazem were assessed during a high-dose infusion (0.4mg kg^-1 per 5 min. followed by 0.4 mg kg^-1 per 10 min). In addition,its potential antiischaemic properties were investigated duringidentical pacing stress tests. 30 minutes before (P₁) and immediatelyafter diltiazem administration (P₂). Diltiazem reduced leftventricular systolic pressure from 133±5 to 116±5mmHg (P<0.005, ±SEM). persisting until after P₂. Itdecreased systemic and coronary resistance by 32% (P<0.001)and 29% (P<0.005), respectively, with a sustained increasein cardiac output from 5.9±0.4 to 7.3±0.61 min^-1(P<0.01), but a brief 20% rise in coronary flow (P<0.05),after the bolus infusion only. Heart rate, contractility, leftventricular filling pressure and myocardial O₂ consumption remainedunchanged. Despite high plasma levels (673±81 µgl^–1)diltiazem was well tolerated. During identical maximal pacingrates diltiazem considerably reduced myocardial O₂ demand (doubleproduct: 16.3±0.8 (P₂) vs 21.1±1.1 (P₁), P<0.005),due to an 18% decrease in left ventricular systolic pressure,resulting in diminished coronary flow and myocardial O₂ consumptionduring P₂ (14% and 15%, respectively, P<0.05 vs P₁). Diltiazemalso significantly reduced pacing-induced ischaemia, indicatedby normalization of myocardial lactate extraction (1±8%(P₂) vs –41±12% (P₁), P<0.05), and left ventricularfilling pressure (13±2 (P₂ vs 27±3 mmHg (P₁),P<0.01). less ST-segment depression (0.12±0.01 (P₂)vs 0.24±0.02 mV (P₁), P<0.01) and improved contractility(V_max 59±5 (P₂) vs 48±3 s^-1 (P₁), P<0.05).Angina was absent or less in 15 patients during pacing afterdiltiazem. Thus, diltiazem, in high dosages, induces continuingsystemic but short lasting coronary vasodilation, improves pumpfunction without negative chronotropic and inotropic effectsand has pronounced antiischaemic properties, predominantly dueto diminished myocardial O₂ demand.     

Prolonged proliferative response of smooth muscle cells after experimental intravascular stenting

The purpose of this experimental in vivo study was to determinethe time course of smooth muscle cell proliferation early andlate after intravascular stenting compared to conventional balloonangioplasty in normal vessels. A balloon expandable 2·0 mm tantalum Strecker stent wasplaced in the right carotid artery of 33 male New Zealand Whiterabbits after they had been fed a 0·5% cholesterol dietfor 28 days. In addition, balloon angioplasty was performedin 27 of the animals; 19 contralateral vessels served as controlswithout treatment. The vessels were excised at 7, 14, 28, 42or 90 days after treatment. During the final 18 h before therabbits were killed, bromodeoxyuridine (BrdU) was applied andproliferating cells were detected by using a monoclonal antibodyagainst BrdU. In histological cross sections the proportionof cells undergoing DNA synthesis was determined. Analysis wasperformed separately in the intimal and medial layers. Additionally,the area adjacent to the stent wire was compared with the intermediatearea. Smooth muscle cells were identified by alpha-actin staining.Intimal wall thickness increased from 23 ± 28,µm(control group without intervention) to 323 ± 84µmwithin 42 days after slenting (P<0·01), and to 81± 82µm at day 42 after balloon angioplasty (P<005).However, between 42 and 90 days following stent implantationa significant (P<0·05) decrease in neointimal thicknesswas observed (90 days: 215 ± 15 µm). A significantincrease in intimal cells undergoing DNA synthesis was foundat day 7 (16·2 ±3·7%, P<0·001),day 14 (7·5 ± 1·2%, P<0·001),day 28 (4·1 ± 1·8%, P<0·001)and day 42 (2 ± 0·3%, P<0·01) afterstenting as compared to the control group (0·3 ±0·4%). Regional determination of proliferating cellsin the area of the stent showed a significantly increased proliférationof smooth muscle cells (1·5 ± 0·5%, P<0·01)even 90 days after stent implantation. In contrast, after balloontreatment the proliferative activity was significantly increasedat day 7 (13·4 ± 5·0%, P<0·0001),day 14 (2·2 ± 1·7%, P<0·0001)and day 28 (1·0 ± 0·4%, P<0·01)only. Compared to conventional balloon angioplasty, the proliferativeresponse after intravascular stenting is increased and prolonged.Despite a decrease of intimal wall thickness between 42 and90 days following stent implantation, the cellular proliferationin the area adjacent to the stent was still increased at 3 monthsafter stenling.