Doppler haemodynamic assessment of clinically and echocardiographically normal mitral and aortic Allcarbon valve prostheses

Doppler echocardiographic characteristics of normally functioningAllcarbon prostheses were studied in 149 consecutive patientswith 157 valves in the mitral (n=73) and aortic (n=84) positionswhose function was considered normal by clinical and echocardiographicevaluation. In the mitral position, the mean gradient and theeffective mitral orifice area were not significantly differentin either the 25-mm or the 31-mm size valves (from 5±1to 4±1 mmHg and from 2.2±0.6 to 2.8±0.9cm², respectively; P=ns for both). Conversely, peak gradientwas significantly and inversely correlated to actual orificearea (r=–0.70; P<0.0006), decreasing from 15±3mmHg in the 25-mm size valve to 9±1 mmHg in the 31-mmsize. In the aortic position, the mean gradient was 29±8 mmHgin the 19-mm size valve; it decreased to 8±2 mmHg inthe 29-mm size. Effective prosthetic aortic valve area, calculatedusing the continuity equation, ranged between 0.9±0.1cm² for the 19-mm size valve to 4.1±0.7 cm² for the 29-mmsize. By analysis of variance, effective prosthetic aortic valvearea differentiated various valve sizes (F=25.3; P<0.0001)better than peak (F=5.34; P=0.012) or mean (F=4.34; P=0.0052)gradients alone, and it correlated better with actual orificearea (r=0.89, r=–0.70 and r=–0.65, respectively).This study provides the normal range for Doppler haemodynamiccharacteristics of the various sizes of the Allcarbon valvein the mitral and aortic positions so that prosthetic malfunctioncan be identified.     

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.     

Determinants of exercise capacity in patients with coronary artery disease and mild to moderate systolic dysfunction: Role of heart rate and diastolic filling abnormalities

BACKGROUND: To test the hypothesis that diastolic filling abnormalitiesare an important cause of exercise limitation in some patientswith coronary artery disease we assessed the factors limitingexercise capacity in a group of patients with coronary arterydisease in whom exercise limitation was greater than expectedfrom the degree of resting left ventricular systolic dysfunction. METHODS AND RESULTS: We assessed the relationship between exercise capacity (maximaloxygen consumption) during erect cycle ergometry, heart rate,radionuclide indi ces of left ventricular systolic function(ejection fraction) and diastolic filling (peak filling rate,and time to peak filling) during semi-erect cycle ergometryin 20 patients (15 male, five female) who were aged 42–72years (mean 61 years) and had angiographically proven coronaryartery disease and evidence of reversible myocardial ischaemiaon thallium scintigraphy. All patients exhibited marked exerciselimitation (maximal oxygen consumption 8.7–22.4 ml. min^–1.kg^–1— mean 15.9 ml. kg^–1. min^–1, whichwas 611 ± 16% of age and gender predicted maxi mum) dueto breathlessness or fatigue rather than angina, in spite ofa mean ejection fraction for the group of 465% (range 30–67%).We also compared the diastolic filling characteristics of thesepatients during exercise with 10 healthy controls (age 38–66,mean 58 years; eight male, two female). Comparing diastolicfilling characteristics, peak filling rate was higher and timeto peak filling shorter both at rest and peak exercise in controlsthan patients (peak filling rate 3.1± 0.5 vs 2.2±0.9 EDV. s^–1 P =0.01 at rest and 8.3± 0.8 vs 5.2±1.9 EDV. s^–1 , P< 0.0000l on exercise; time to peakfilling 115.2± 29.8 vs 228.9± 71.7 ms, p< 0.0001.atrest and 52.8± 16.2 vs 139.6± 4.48 ms, P<0.0000lon exercise respectively). On univariate analysis in the patientsstudied, maximal oxygen consumption was correlated with peakheart rate (r=0.45 P=0.04), peak exercise time to peak filling(r=– 0.85 P< 0.0001 peak exercise peak filling rate(r = 0.58, P=0.019), and the relative increase in cardiac outputi.e. cardiac output peak/cardiac output rest (r=0.58, P=0.008).There was no correlation between maximal oxygen consumptionand resting indices of diastolic filling (peak filling rateand time to peak filling) or with resting or peak exercise ejectionfraction. On multiple regression analysis, only peak exercisetime to peak filling was significantly related to maximal oxygenconsumption. CONCLUSION: We have observed a strong correlation between exercise capacityand indices of exercise left ventricular diastolic filling,and have confirmed previous studies showing a poor correlationwith resting and exercise indices of systolic function and restingdiastolic filling, in patients with coronary artery disease.     

Prognostic significance of silent myocardial ischaemia during maximal exercise testing after a first acute myocardial infarction

Clinical, exercise, and angiographic variables, and long-termfollow-up were compared in patients, who, during maximal Bruceexercise testing after a first acute myocardial infarction (AMI),had positive responses to exercise testing (n = 116, 38% of303) with (n % 23, group I) or without (n = 93, group II) angina.Group I patients more often (52 vs 19%, P < 0.001) had ahistory of pre-infarction angina. Group II had a greater proportion(75 vs 52%, P < 0.05) of inferior wall AMI, whereas groupI had a greater proportion (30 vs 19%, P < 0.01) of non-Qwave AMI. Total exercise duration was significantly (P <0.01) longer in group II (7.6 ± 3.2 vs 5.5 ± 3.1min). Maximal exercise heart rate (144 ± 22 vs 133 ±21, beats . min^–1 P < 0.05 was also higher in groupII. A greater proportion of group II patients (37 vs 9%, P <0.05) had single-vessel disease, whereas multivessel diseasewas more common (91 vs 63% P < 0.03) in group I. Left ventricularfunction was similar in both groups. During follow-up (48 ±22 months) the incidence of cardiac death (group I, 3.3%, groupII, 4.8%), of recurrent infarction (group I, 4.8%, group II3.3%), and of revascularization procedures (group I, 28.5%,group II, 19.8%) were similar in both groups. Although asymptomaticexercise-induced ischaemia was associated with better exerciseperformance and less extensive coronary disease than symptomaticischaemia, it had the same long-term prognostic implications.     

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

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

Measurement of effective aortic valve area using three-dimensional echocardiography in children undergoing aortic balloon valvuloplasty for aortic stenosis

Aims: Pressure gradient is used for timing of balloon aortic valvuloplasty for aortic stenosis (AS) in children, but does not correlate well with outcome and is limited if ventricular function is poor. In adults, effective orifice area (EOA) is used to assess AS severity, but EOA by continuity equation or 2D echo is unreliable in children. Three‐dimensional echocardiography (3DE) may reliably assess EOA but has not been studied in children. We assessed measurement of aortic valve EOA by 3DE in children with AS before and after balloon aortic valvuloplasty and compared results with change in aortic valve gradient. Methods: 3DE was performed at time of catheterization before and after balloon aortic valvuloplasty. Using 3DE multiplanar review mode, valve annulus diameter, area, and EOA were measured and compared with change in aortic gradient and degree of aortic insufficiency. Results: Twenty‐four 3DE studies in 12 children (mean age 4.4 ± 5.0 years) were analyzed. EOA was measurable in all. Catheter peak gradient decreased from 45 ± 10 to 26 ± 17 mmHg (P = 0.0018). 3DE EOA increased after balloon aortic valvuloplasty (0.59 ± 0.52 cm² vs 0.80 ± 0.70 cm²; P = 0.03), without change in valve diameter. EOA change correlated with change in peak (r = 0.77; P = 0.005) and mean (r = 0.60; P = 0.03) aortic valve gradient post balloon aortic valvuloplasty. Conclusion: 3DE facilitates EOA measurement in pediatric AS and correlates with change in aortic valve gradient after balloon valvuloplasty. (Echocardiography 2012;29:484‐491)     

Effects of antianginal therapy with a calcium antagonist and nitrates on dobutamine--atropine stress echocardiography: Comparison with exercise electrocardiography

BACKGROUND: Anti-ischaemic therapy with nitrates and/or calcium channelblockers profoundly affects the results of pharmacological stressechocardiography with coronary vasodilators but the influenceon catecholamine stress testing remains unsettled. AIMS: The present study aimed to assess the effects of non-beta-blockerantianginal therapy on dobutamine (up to 40 µg.kg^–1.min^–1)-atropine(up to 1 mg) stress echocardiography and to evaluate whetherdrug-induced changes in the dobutamine-atropine stress echocardiographyresponse may predict variations in exercise tolerance. METHODS: Twenty six patients with angiographically assessed coronaryartery disease (seven patients with single-, 10 with double-,and nine with triple-vessel disease) performed a dobutamine-atropinestress echocardiography and an exercise electrocardiographytest in random order both off and on antianginal drugs (nitratesand calcium antagonists). In dobutamine-atropine stress echocardiography,we evaluated: dobutamine time (i.e. the time from initiationof the dobutamine infusion to obvious dyssynergy), wall motionscore index (in a 16-segment model of the left ventricle, eachsegment ranging from 1=normal, to 4=dyskinetic), and rate-pressureproduct at peak stress. RESULTS: Dobutamine-atropine stress echocardiography positivity occurredin 26 out of 26 patients off and in 23 patients on therapy (100vs 88%, P=ns). Atropine coadministration was needed to evokeecho positivity in no patient off and in five out of 26 on therapy(0 vs 19%, P<0·01). The achieved rate-pressure productduring dobutamine-atropine stress echocardiography was comparableon and off therapy (17±4 vs 19±5x10³ mmHgxheartrate. min^–1, Pns). Therapy induced an increase in dobutaminetime (on=16±3 vs off=13±3 min, P<0·01)and a decrease in peak wall motion score index (on=1·3±0·2vs off=1·5±0·3, P<0·01). Thetherapy-induced changes in exercise time during the exerciseelectrocardiography test were not significantly correlated todobutamine-atropine stress echocardiography variations in eitherdobutamine time (r=0·07, P=ns), or peak rate-pressureproduct (r=0·24, P=ns), or peak wall motion score index(r=0·02, P=ns). CONCLUSION: (1) non-beta-blocker antianginal therapy only modestly reducesdobutamine-atropine stress echocardiography sensitivity, althoughatropine coadministration is more often required to reach stressecho positivity under therapy; (2) therapy reduces the severityof dobutamine-atropine stress echocardiography ischaemia stratifiedin the time and space domain, but these changes are only poorlycorrelated to variations in exercise tolerance.     

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.     

Dyspnoea and exercise intolerance during cardiopulmonary exercise testing in patients with univentricular heart: The effects of chronic hypoxaemia and Fontan procedure

BACKGROUND: Patients with univentricular hearts have decreased exercisetolerance and may demonstrate exertional dyspnoea. It is notknown if chronic hypoxaemia exacerbates exercise intoleranceand contributes to symptomatic limitation. The extent to whichsurgical correction of a right-to-left shunt by a Fontan-typeprocedure can increase exercise tolerance by reducing arterialdeoxygenation is not well documented. The cardiopulmonary exerciseresponses and the symptomatic status in two groups of univentricularpatients, those who are cyanotic and those who are acyanoticwith Fontan-type circulation, were compared. METHODS AND FINDINGS: Cardiopulmonary exercise testing was performed in 10 univentricularpatients with rest or stress-induced cyanosis (age 30·5±2·3[SE] years; 5 men) who had palliative or no surgery and eightpatients (age 29·4±1·5 years; 4 men) withFontan-type circulation. Peak oxygen consumption was comparablein both groups of univentricular patients (21·7±2·5vs 21·0±1·9 ml. kg^–1 . min^–1,P=0·85) but was less than an age-matched group of 10healthy subjects (34·7±1·9 ml. kg^–1. min^–1, P<0·001 for both). Arterial oxygensaturation was 90·6% at rest in the cyanotic patientscompared with 95·1% in the Fontan patients (P<0·001)and at peak exercise, 66·2% compared with 90·5%(P<0·001). Using a modified Borg scale (0–10),the symptoms of dyspnoea and fatigue were also assessed duringexercise in the patient groups. The Borg scores for dyspnoeain the cyanotic and the corrected univentricular patients were,respectively, as follows: Stage 1: 0·5 vs 1·7;P=0·04; Stage 2: 1·8 vs 2·3, P=0·5;Stage 3: 3·0 vs 3·5, P=0·7; Peak Exercise:4·9 vs 4·8, P=0·9. In addition, the Borgscores for fatigue were: Stage 1: 0·4 vs 1·6,P=0·08; Stage 2: 2·0 vs 2·2, P=0·9;Stage 3: 3·0 vs 4·3, P=0·5; Peak Exercise:4·9 vs 5·4, P=0·5. The major limiting symptomat peak exercise was dyspnoea in four cyanotic patients comparedwith one in the Fontan group (Chi-square 0·982, P>0·10).The arterial oxygen desaturation at peak exercise in the cyanoticpatients limited by dyspnoea was not different from those limitedby fatigue (67·5±10·1% vs 66·7±13·7%,P=0·92). Exercise tolerance was also not related to thearterial oxygen saturation at peak exercise (r=0·47,P=0·17) in these patients. CONCLUSION: Despite correction with Fontan-type surgery, the exercise toleranceand symptoms of these univentricular patients remained similarto those who were cyanosed. Cyanotic patients have adjustedto chronic hypoxaemia and it does not appear to determine theexercise tolerance or the genesis of dyspnoea in these patients.Further randomized prospective studies are required to investigatethe long-term benefits of Fontan-type procedures in these patientson exercise tolerance, symptoms and prognosis.     

Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine

OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocytegrowth and contractility in vitro. This study was designed toinvestigate the effect of exogenous IGF-II on regional myocardialfun ction at the area of infarct in the pig. METHODS: Myocardial infarction was induced in 12 female anoesthetizedpigs by affigel blue beads, embolizing microvessels of the leftanterior descending coronary artery distribution. In the experimentalgroup (n=6), IGF-II (0.12 µg. kg^–1 in two animalsand 0.6 µg. kg^–1 in four) was incorporated intothe beads and delivered by them to the infarct area. Myocardialfunction was followed echocardiographically, and the excisedheart was analysed immunohistochemically and histopathologically. RESULTS: Myocardial function in injured zones, inversely related to anechocardiographic segmental wall motion score (mean ±SEM), was similar between the two groups at baseline, but at4 weeks post-infarction was significantly (P=0.008) reducedin the control group (0.58± 0.38 vs 3.42 ± 0.84),in contrast to nearly baseline values in the experimental group(0.58 ± 0.33 vs 1.17 ± 0.42, P=0.41). Cardiacperformance in injured segments was sign better after myocardialinjury in the experimental group (P=0.04). Tissue samples fromboth groups (4 weeks post-infarction), stained with haematoxylinand eosin demonstrated pen-infarct myocyte hypertrophy, correspondingto regions selectively stained by an antibody for CD56, whichhighlights growing cardiac myocytes. By image analysis semi-quantification,staining for CD56 was significantly (P=0.04) higher in the peri-infarctregion of the experimental group, as compared with controls(106.5 ± 2.8 vs 92 ± 4.4 gray level units). Microvesselsstained for von-Willebrand factor were similar in nwnber inboth groups (P=0.8), as were mesenchymal cells stained for vimentin(P=0.7). CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area amelioratesregional cardiac function in the pig, perhaps by inducing peri-infarctmyocyte growth.     

Doppler echocardiography in the evaluation of tricuspid stenosis

Seventeen patients (12 with native and five with prosthetictricuspid valves) with tricuspid stenosis were studied by Dopplerechocardiography followed by cardiac catheterization within24 h. The mean tricuspid diastolic pressure gradient was calculatedusing the modified Bernoulli equation. Tricuspid valve area(TVA) was calculated by the pressure half-time method (TVA =190 divided by pressure half-time). Data from Doppler echocardiographyand cardiac catheterization were compared. The Doppler-derivedtricuspid mean diastolic gradient was 1.9–9.9 mmHg (average5.3±2.5 mmHg), which correlated moderately well withthe catheterization-determined mean diastolic gradient of 2–17mmHg(average 7.3 ±4.0 mmHg), R = 0.74, standard error ofthe estimate (SEE) 1.70 mmHg, Y=0.45 x+2.00,P<0.001. TheDoppler-derived TVA was 0.56–1.58 cm² (average 1.06±0.32cm²), which correlated well with the catheterization-determinedTVA of 0.4–2.2cm² (average 1.06±0.46 cm²), R=0.81,SEE=0.20cm², Y=0.56 x+0.46, P<0.001. Of 12 patients undergoingright ventricular angiography, the angiographic and Dopplergrades of tricuspid regurgitation matched exactly in six anddiffered by one grade in the remaining six. This study demonstratedthat Doppler echocardiography compares very well to cardiaccatheterization in the quantification of tricuspid stenosisand in the assessment of concomitant tricuspid regurgitation.     

Skeletal muscle function at low work level as a model for daily activities in patients with chronic heart failure

AIM: Metabolic exercise abnormalities have been reported in chronicheart failure patients. This study sought to evaluate whetherthese abnormalities affected daily activity. METHODS AND RESULTS: In 16 patients with moderate-to-severe chronic heart failureand in eight controls we measured femoral flow (thermodilution)and metabolism (glucose, lactate, free fatty acids, blood gasvalues) at rest and during a constant load of 20 W, which maymimic a daily activity. At rest, chronic heart failure patientshad a leg flow similar to controls, but showed a higher legoxygen consumption (4·6±0· vs 2·6±0·4ml. min^–1; P>0·05), a higher arteriovenous oxygendifference (7·2±0·5 vs 5·4±0·7ml . d1^–1; P>0·05), and a lower femoral veinpH (7·37±5·–03 vs 7·42±0·01;P=0·01). At 20 W, chronic heart failure patients hada leg flow similar to controls, but showed increased lactaterelease (from resting 11·7±33 to 142+125 µg. min^–1 P>0·0001 vs controls, from resting 5·7±15·4to 50±149 µg . min^–1 ns), higher arterialconcentration of free fatty acids (781±69 vs 481±85µmol . 1^–1; P>0·01), lower femoral veinHCO₃ (24·1+2·6 vs 26·3±1·7mmol .1^–1;P>0·05) and base excess (–2·3+2·3vs –0·24±1·7 mmol . 1^–1 P=0·01 CONCLUSION: In chronic heart failure patients, the important cellular metabolicalterations already present at rest partially affect daily activities,owing to a further decrease in the efficiency of muscle metabolicprocesses, and may preclude tolerance of heavier activities.Such alterations appear, at least in part, independent of peripheralhaemodynamic responses to exercise.     

Non-rheumatic annular mitral stenosis: prevalence and characteristics

Aims: To define the prevalence and characteristics of non-rheumaticannular mitral stenosis (AMS) in a general population as comparedwith rheumatic mitral stenosis (RMS). Methods and results: Clinical and echocardiographical variables were assessed in70 patients with mitral stenosis. AMS and RMS patients wereage- and gender-matched for the comparison of echocardiographicvariables. Thirteen patients (18.5%) had AMS. Arterial hypertensionand hypercholesterolemia were more prevalent in AMS (77 vs.36% and 75 vs. 27%, respectively, P < 0.05). Mitral annuluscalcification severity score (2.2 vs. 1.3, P < 0.05) andleft ventricular mass (276 ± 73 vs. 209 ± 57 g,P < 0.05) were significantly higher in AMS. Mitral valvearea (MVA) was higher and mean gradient was lower (2.25 ±0.6 vs.1.9 ± 0.6 cm², 4 ± 1.2 vs. 5.6 ±3.5 mmHg, P = ns) in AMS. Pressure half-time (PHT) MVA and planimetryMVA had a better correlation in RMS than in AMS patients (r= 0.98 vs. 0.71, P < 0.05). Conclusion: AMS is more frequent than that is assumed and is associatedwith risk factors for coronary artery disease. AMS is generallymild and PHT may be less accurate for MVA calculation than inRMS.     

Mechanisms of the warm-up phenomenon

The warm-up phenomenon, described in patients with coronaryartery disease, refers to the improved performance followinga first exercise test. The aim of this study was to investigatethe causes of the warm-up phenomenon. Fifteen patients with coronary artery disease and positive exercisetest were enrolled. Patients were off treatment throughout thestudy. They underwent two consecutive treadmill exercise testsaccording to the Bruce protocol, with a recovery period of 10min to re-establish baseline conditions. A third exercise testwas then performed 2 h later. Before the onset of ischaemia,the rate-pressure product for a similar degree of workload wassimilar during the first and second exercise test, while itwas lower during the third test (P<0·05). Time to1·5 mm ST-segment depression during the second and thirdexercise test was greater than during the first test (454 ±133 and 410 ± 161 vs 354 ± 127 s, P<0·01,respectively). Similarly, the time to anginal pain onset wasincreased during the second and third exercise tests, comparedto the first test (356 ± 208 and 310 ± 203 vs257 ± 204s, P<0·0l, respectively). In contrast,rate-pressure product at 1·5 mm ST-segment depressionduring the second test was higher than that during the firsttest (232±47 vs 210±39 beats. min^–1. mmHg.10², P<0·0l), while in the third test it was similarto that during the first (209 ± 43 beats. min^–1.mmHg. 10², P=ns). The warm-up phenomenon observed a few minutes after exerciseis characterized by an increase of both time to ischaemia andischaemic threshold; this adaptation to ischaemia may be dueto an improvement of myocardial perfusion or to preconditioning.Conversely, the warm-up phenomenon observed a few hours afterrepeated exercise is characterized by an increase of time toischaemia but not of ischaemic threshold and is caused by aslower increase of cardiac workload. Thus, the mechanisms ofthe warm-up phenomenon may be different, time dependent andrelated to previous training.     

Skeletal muscle lactate accumulation and creatine phosphate depletion during heavy exercise in congestive heart failure: Cause of limited exercise capacity?

OBJECTIVE: To study the mechanisms of limited exercise capacity and skeletalmuscle energy production in male patients with congestive heartfailure. DESIGN: Muscle biopsy study. PATIENTS: Skeletal muscle metabolic response to maximal bicycle exercisewas studied in 10 patients with chronic congestive heart failure(ejection fraction 0·22±0·05; peak oxygenconsumption, Vo₂ 15·1±4·9 ml. min^–1.kg^–1) and in nine healthy subjects (peak Vo₂ 33·5±6·7ml. min^–1. kg^–1). Activities of skeletal muscleenzymes were measured from the vastus lateralis muscle of 48patients (ejection fraction 0·24±0·06,peak Vo₂ 17·4±5·4 ml. min^–1. kg^–1)and 36 healthy subjects (peak Vo₂ 38·3±8·4ml. min^–1. kg^–1). RESULTS: Although blood lactate levels were lower in patients than inhealthy subjects (2·2±0·3 vs 5·2±0·6mmol. 1^–1; P<0·001) at peak exercise (96±11W for patients and 273±14 W for controls), skeletal musclelactate was similarly elevated (25·6±3·2vs 22·7±2·7 mmol.kg^–1) and creatinephosphate was equally depressed (P<0·02) to low levels(7·0±1·9 vs 6·7±0·9mmol.kg^–1). The muscle ATP decreased by 21% (P<0·05)and 8% (P<0·01) in the patients and controls, respectively.Activities of rate limiting enzymes of the citric acid cycle(alpha-ketoglutarate dehydrogenase) and oxidation of free fattyacids (carnitine palmitoyltransferase II) were 48% and 21% lowerthan in controls, but the mean phosphofructokinase activitywas unchanged in congestive heart failure. CONCLUSIONS: It seems that the main limiting factor of exercise performanceduring heavy exercise is the same in congestive heart failureand healthy subjects, a high rate of skeletal muscle lactateaccumulation and high-energy phosphate depletion. In congestiveheart failure, the low activity of aerobic enzymes is likelyto impair energy production and lead to lactate acidosis atlow workloads.     

The influence of muscle mass, strength, fatigability and blood flow on exercise capacity in cachectic and non-cachectic patients with chronic heart failure

BACKGROUND: The influence of age, skeletal muscle function and peripheralblood flow on exercise capacity in chronic heart failure patientsis controversial, possibly due to variations in skeletal muscleatrophy. METHODS AND RESULTS: To assess predictors of exercise capacity in patients with clinicalcardiac cachexia, we studied 16 cachectic and 39 non-cachecticmale chronic heart failure patients of similar age and ejectionfraction. All cachectic patients were wasted (% ideal body weight:81 1·9 vs 105·2±2·1, P<0·mean±SEM) and had documented weight loss (5–30kg). Peak oxygen consumption (14·9±1·4vs 16·3±0·6 ml.kg^–1, min ^–1,resting, and peak blood flow (plethysmography) and 20 min fatigability(% baseline strength) were all similar between the two groups.Quadriceps strength, muscle size (all P<0·0001), strengthper unit muscle (right: P<0·05; left: P<0·0·01)and 5 min fatigability (P<0·05) were all lower incachectic patients. In non-cachectic patients, age (R=0·48and quadriceps strength (R=0·43, all P<0·01)predicted peak oxygen consumption. Only in cachectic patientsdid peak blood flow predict peak oxygen consumption significantly(R=0·72, P0·005), whereas age and strength didnot. Similar findings were confirmed using other previouslypublished definitions of cardiac cachexia. CONCLUSION: The predictors of exercise capacity change with the developmentof cardiac cachexia from age and strength to peak blood flow.This shift may be caused by additional endocrine or catabolicabnormalities active in end stage heart failure.     

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.     

Left ventricular filling pattern in {beta}-thalassaemia major -- a Doppler echocardiographic study

The pattern of left ventricular filling was assessed by Dopplerechocardiography in 38 adult ß-thalassaemia majorpatients; 28 with normal (age 25.2±5.3 years) and 10with abnormal (age 24.5±8.8 years) left ventricular systolicfunction. The findings were compared with those obtained from38 age and sex matched normal individuals. In patients with normal left ventricular systolic function,peak flow velocity in early diastole was higher than in thecontrols (94±16 vs 79±12 cm. s^–1 P <0.001).The peak flow velocity in late diastole was also greater (60±18vs 46±9cm. s^–1 P <0.001) but the ratio betweenthe early and late (atrial) peaks was approximately the samein both groups (1.74±0.72 vs 1.70±0.30 There wasno difference in deceleration time and rate between the twogroups (152±32 vs 151±21 ms and 504±93vs 508±115 cm. s^–2 respectively). None of the patientshad atrial predominant left ventricular inflow pattern. In patients with congestive heart failure the peak flow velocityin early diastole was greater than in the controls (96±10vs 79±2 cm. s^–1 P < 0.001) while in late diastoleit was smaller (39±6 vs 44±2 cm. s^–1 P <0.05).The ratio between the early and late peaks was greater in thepatients than in the controls (2.5±0.35 vs 1.8±0.08,P <0.001). The deceleration time and rate were not significantlydifferent in the two groups (153±33 vs 152±17msand 617±219 vs 550±56 cm. s^–2 respectively),until the end stage of congestive heart failure. Thus, leftventricular filling pattern in ß-thalassaemia majorpatients with normal left ventricular systolic function, issimilar to that seen in conditions of an increased preload.Patterns compatible with abnormally prolonged relaxation orrestriction do not appear.     

Platelet aggregability to platelet activating factor at rest and after exercise in patients with coronary artery disease

The platelet response to the aggregatory effect of platelet-activatingfactor (PAF) in relation to blood PAF levels, serum PAF-acetylhydrolase(PAF-AH) activity and to their lipidoemic profile, was studiedin 44 patients with coronary artery disease undergoing exercisetests. The PAF EC₅₀ values in 21 patients with positive exercisetest results were found to be significantly decreased at restcompared with 21 normal subjects (126±3•9 nM and24•9±11•7 nM respectively) (P<0•0001).Moreover, the maximal percentage of aggregation to 50 nM PAFwas found to be significantly increased (20•0±4•3%vs 13•5±3•6% respectively) (P<0•0001).By contrast, the PAF EC₅₀ values and the maximal percentageof aggregation in 23 patients with negative exercise test resultswere not statistically significantly different from the controlgroup (25•2±11•4 nM and 14•1±4•7%,respectively). At the end of exercise, the PAF EC₅₀ values and the maximalpercentage of aggregation did not change in any group, and therewere no significant differences in the whole-blood PAF levelseither at rest or at the end of exercise. In patients with positiveexercise test results, the PAF-AH activity at rest was significantlyhigher compared with the control group (37•2±8•0nmol. ml^–1. min^–1 vs 32•4±4•3 nmol.ml^–1. min^–1), (P<0•03), whereas the enzymeactivity did not differ in patients with negative exercise testresults compared to controls (33•6±6•1 nmol.ml^–1. min^–1). There was no change in PAF-AH activity during exercise in anygroup. The enzyme activity was positively correlated to theserum total and low density lipoprotein (LDL) cholesterol levelsin the control group and in patients with negative exercisetest results, whereas no correlation was found between PAF-AHactivity and total or LDL cholesterol levels in patients withpositive exercise test results. Our results suggest that platelethyper-reactivity to PAF may play a pathophysiological role inmyocardial ischaemia observed during exercise in coronary arterydisease patients.     

Effect of altered loading conditions during haemodialysis on left ventricular filling pattern

Changes in the circulating volume associated with haemodialysisresult in modification of left ventricular loading conditions.To determine the influence of haemodialysis on Doppler indicesof left ventricular filling, 12 patients (mean age 40.8 ±2.7(SEM) years) with renal insufficiency but without overt heartdisease were studied by Doppler-echocardiography immediatelybefore and after haemodialysis. Haemodialysis resulted in adecrease in body weight from 68.0±3.8 kg to 65.0 ±3.7kg (P< 0.01). Heart rate and blood pressure did not changesignificantly during haemodialysis. Left ventricular diastolicdimension (M-mode) decreased from 53.5±1.1 mm to 49.5±1.9mm (P < 0.05), whereas the shortening fraction did not change.Haemodialysis elicited marked changes in the early diastolicrapid filling wave (E wave) recorded by pulsed Doppler at thelevel of the mitral annulus. Peak velocity of the early rapidfilling phase (peak E) decreased significantly from 95.3 ±8.2 cm .s^–1 to 63.0 ±5.7cm .s^–1 (P< 0.001)and mid-diastolic deceleration of transmitral velocity decreasedfrom 437.3 ±54.2 cm . s^–2 to 239.7 ±54.4cm . s^–2 (P<0.01). The peak filling velocity duringatrial contraction (peak A) did not change (79.7 ±6.3cm .s^–1 vs 74.1±4.7 cm.s^–1;P=NS). The ratiopeak E/peak A decreasedfrom 1.19±0.06 to 0.85 ±0.04 (P < 0.01) during haemodialysis. The results providefurther evidence for the pronounced preload-dependence of Dopplerindices of left ventricular diastolic function.