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.     

Comparison of two methods of determining renal perfusion with and without captopril pretreatment in groups of patients with left ventricular dysfunction

Methods of effective renal plasma flow measurement by ¹²⁵I-orthoiodohippurateelimination and para-aminohippurate clearance were comparedwith and without captopril pretreatment in 10 chronic heartfailure patients and in 20 patients after transmural myocardialinfarction. In the chronic heart failure group measurements of effectiverenal plasma flow by the two techniques were strongly correlated(r=0·92, P<0·00001), as was the captopril-mediatedchange in effective renal plasma flow by the two methods (r=0·85,P=0·002). However, in absolute terms para-aminohippurateclearance significantly exceeded ¹²⁵I-orthoiodohippurate clearanceby a mean (± SD) of 24·8 ± 43·7ml. min^–1 (P<0·05) so that only using the formertechnique was a signifincant in renal perfusion observed inresponse to converting enzyme inhibition. In the post-myocardial infarction group, correlations betweenthe two methods were variable and much poorer than in the chronicheart failure group (r=0·54, P=0·01 and r=0·74,P=0·002 on consecutive days). Furthermore, captoprilmediatedincrements in effective renal plasma flow by the two techniqueswere unrelated (r= – 0·19, P=0·59). In thisgroup ¹²⁵I-orthoiodohippurate elimination significantly exceededpara-aminohippurate clearance (P<0·05). This reversedassociation and the weaker relationships between methods inpost-infarction as compared to chronic heart failure patientsmay be related to interference by thrombolytic or aspirin treatments.     

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.     

Uric acid in chronic heart failure: a marker of chronic inflammation

Background Chronic heart failure is associated with hyperuricaemia andelevations in circulating markers of inflammation. Activationof xanthine oxidase, through free radical release, causes leukocyteand endothelial cell activation. Associations could thereforebe expected between serum uric acid level, as a marker of increasedxanthine oxidase activity, and markers of inflammation. We haveexplored these associations in patients with chronic heart failure,taking into account the hyperuricaemic effects of diuretic therapyand insulin resistance. Methods and Results Circulating uric acid and markers of inflammation were measuredin 39 male patients with chronic heart failure and 16 healthycontrols. All patients underwent a metabolic assessment, whichprovided a measure of insulin sensitivity (intravenous glucosetolerance tests and minimal modelling analysis). Compared tocontrols, patients with chronic heart failure had significantlyhigher levels of circulating uric acid, interleukin-6, solubletumour necrosis factor receptor (sTNFR)-1, soluble intercellularadhesion molecule-1 (ICAM-1, allP<0·001), E-selectinand sTNFR2 (bothP<0·05). In patients with chronicheart failure, serum uric acid concentrations correlated withcirculating levels of sTNFR1 (r=0·74), interleukin-6(r=0·66), sTNFR2 (r=0·63), TNF(r=0·60)(allP<0·001), and ICAM-1 (r=0·41,P<0·01).In stepwise regression analyses, serum uric acid emerged asthe strongest predictor of ICAM-1, interleukin-6, TNF, sTNFR1and sTNFR2, independent of diuretic dose, age, body mass index,alcohol intake, serum creatinine, plasma insulin and glucose,and insulin sensitivity. Conclusions Serum uric acid is strongly related to circulating markers ofinflammation in patients with chronic heart failure. This isconsistent with a role for increased xanthine oxidase activityin the inflammatory response in patients with chronic heartfailure.     

A randomized controlled trial of inspiratory muscle training in stable chronic heart failure

Aims To assess whether a domiciliary programme of specific inspiratorymuscle training in stable chronic heart failure results in improvementsin exercise tolerance or quality of life. Methods and results We conducted a randomized controlled trialof 8 weeks of inspiratory muscle training in 18 patients withstable chronic heart failure, using the Threshold^\Rtrainer.Patients were randomized either to a training group inspiringfor 30min daily at 30% of maximum inspiratory mouth pressure,or to a control group of ‘sham’ training at 15%of maximum inspiratory mouth pressure. Sixteen of the 18 patientscompleted the study. Maximum inspiratory mouth pressure improvedsignificantly in the training group compared with controls,by a mean (SD) of 25·4 (11·2) cmH₂O (P=0·04).There were, however, no significant improvements in treadmillexercise time, corridor walk test time or quality of life scoresin the trained group compared with controls. Conclusion Despite achieving a significant increase in inspiratorymuscle strength, this trial of simple domiciliary inspiratorymuscle training using threshold loading at 30% of maximum inspiratorymouth pressure did not result in significant improvements inexercise tolerance or quality of life in patients with chronicheart failure.     

Long-term outcome of patients with incomplete vs complete revascularization after multivessel PTCA: A report from the NHLBI PTCA Registry

Background Incomplete revascularization is frequently the goalas well as the final outcome in patients with multivessel coronarydisease undergoing PTCA. However, the long-term impact of incompleterevascularization is not known and this common PTCA strategydeserves further scrutiny. Methods and results Complete revascularization was achievedin 132 of 757 patients with multivessel disease in the 1985–86NHLBI PTCA Registry. Compared to patients in whom complete revascularizationwas achieved, patients with incomplete revascularization wereolder (P<0·05), more likely to be females (P<0·05)and to have recent myocardial infarction (P<0·05),unstable angina (P<0·001), and urgent or emergentPTCA (P<0·001). Early death, Q wave myocardial infarctionand CABG rates were higher in patients with incomplete thanin those with complete revascularization [significantly different(P<0·05) only for emergency and elective CABG]. At9 years, nearly twice as many patients with incomplete revascularizationexperienced recurrent angina (19% vs 10% for patients with completerevascularization,P<0·05). Patients with completerevascularization were more likely to undergo repeat PTCA thanthose with incomplete revascularization (40% vs 30%,P<0·05).Patients with incomplete revascularization were more likelyto undergo CABG than patients with complete revascularization(32% vs 14%,P<0·001; adjusted risk 2·56, 95%CI 1·60, 4·10). Among patients with incompleterevascularization, those in whom PTCA was intended but not attemptedhad the highest early event rates and late CABG rates. Finally,the adjusted risk of dying, having a Q wave myocardial infarction,recurrent angina or repeat PTCA was not different at 9-yearfollow-up among patients with and without complete revascularization. Conclusions Complete revascularization achieved by PTCA reduceslate occurrence of CABG, but not adjusted rates of death, Qwave myocardial infarction, recurrent angina, and repeat PTCAin patients with multivessel coronary disease. These data tendto support the PTCA strategy of incomplete revascularizationin patients with multivessel disease when complete revascularizationis not feasible or not planned before the procedure.     

Eligibility for reperfusion therapy and outcome in elderly patients with acute myocardial infarction

Reperfusion therapy by thrombolysis or angioplasty was consideredin 260 unselected patients consecutively admitted within 6 hof the onset of Q wave myocardial infarction. Rates of reperfusionand in-hospital mortality were compared in 206 patients <70years and 54 patients 70 years. Early reperfusion was obtainedin 864% of the patients under 70 years and in 72·2% ofthose over 70 (P<0·01). Thrombolysis was more frequentlyused in the younger group (66·0% vs 31·5%, P<10^–5and primary angioplasty in the older (44·4% vs 29·6%,P<0·05). Overall in-hospital mortality was higherin the older group (22·2% vs 4·4 P<10^–5After successful reperfusion, mortality was 12·8% inthe patients over 70 and 3·9% in those under 70. Afterfailed or unproven reperfusion, mortality was 46·7% inthe patients over 70 and 7·1% in those under 70. Reperfusiontherapy is feasible in the majority of patients over 70 years,but failure to attempt or to achieve reperfusion is associatedwith a poor outcome. Although not controlled, this study providesan incentive for attempting early reperfusion therapy as oftenas possible in the elderly with acute myocardial infarction.     

Effects of captopril on ventricular arrhythmias in the early and late phase of suspected acute myocardial infarction: Randomized, placebo-controlled substudy of ISIS-4

The antiarrhythmic effect of oral captopril was studied duringthe early (day 3) and late (day 14) phase of acute myocardialinfarction among 304 patients in a randomized placebo-controlledsubstudy of ISIS-4. Ventricular arrhythmias (ventricular ectopic beats per hour)occurred significantly less frequently among captopril-allocatedpatients than among those allocated placebo at day 3 (logarithmicscale: 0·48 ± 0·8 captopril vs 0·84± 1·3 placebo; P<0·003) and at day 14(0·51 ± 1·0 vs 0·77 ± 1·3;P<0·05). The number of patients with frequent ventriculararrhythmias (more than 10 ventricular ectopic beats per hour)was also significantly lower among those allocated captoprilat day 3 (7·3% vs 14·4% P<0·05) andat day 14 (7·3% vs 14·8%; P<0·05). These results support the hypothesis that the activation ofthe renin-angiotensin-aldosterone and sympathetic system mayunderlie heart rhythm disturbances in acute myocardial infarction,and that early use of converting enzyme inhibitor therapy mayameliorate these disturbances. (Eur Heart J 1996; 17: 1506–1510)     

Improvement in lower limb vasodilatory reserve and exercise capacity in patients with chronic heart failure due to valvular heart disease

AIMS: Reduced skeletal muscle blood flow during exercise is an importantfactor contributing to exercise intolerance in patients withchronic heart failure. Reactive hyperaemic blood flow is themaximum flow response necessary to protect tissue against ischaemiaand hypoperfusion. We examined the vasodilatory response ofthe lower limb to ascertain whether response was increased withthe improvement in exercise capacity observed after intracardiacsurgery in patients with chronic heart failure due to valvularheart disease. METHODS AND RESULTS: Calf blood flow in 23 patients was measured by venous occlusionplethysmography at rest and after a 5 min period of femoralocclusion. Immediately after this evaluation, peak oxygen uptakeand anaerobic threshold were assessed by a symptom-limited cardiopulmonaryexercise test using a bicycle ergometer. Both baseline calfblood flow and peak calf blood flow during reactive hyperaemiawere significantly increased after surgery (baseline calf bloodflow; from 2·6±0·2 to 3·8±0·4ml.min^–1 per 100 ml calf volume, P<0·05: peakcalf blood flow; from 17·5±1·3 to 25·4±2·6ml.min^–1 per 100 ml calf volume, P<0.01). There wasa significant correlation between changes in peak calf bloodflow and improvement in exercise capacity (peak oxygen uptake;r=0·42, P<0·05; anaerobic threshold; r=0·68,P<0·0010). CONCLUSION: These results indicate that exercise tolerance is improved withincreased lower limb vasodilatory capacity after recovery fromchronic heart failure.     

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.     

KNEE PAIN AND DISABILITY IN THE COMMUNITY

In order to investigate the strength of any relationship betweenknee pain and disability, a postal questionnaire was sent to2102 men and women aged over 55 registered at a general practicein Bristol. A response rate of 80·6% was achieved atsecond reminder. Knee pain was common particularly in women(27·6% overall). Disability was also more frequentlyreported in women (P<0·05) and rose with increasingage. Respondents with knee pain had significantly more disabilityrelating to upper as well as lower limb activities (P<0·05). KEY WORDS: Knee osteoarthritis, Disability, HAQ ^*Now Senior Registrar in Rheumatology, St Thomas' Hospital,Lambeth Palace Road, London SE1 7EH.     

Hyperleptinaemia in chronic heart failure: Relationships with insulin

Background Leptin, a product of theobgene, is known to increaseenergy expenditure. Given that chronic heart failure is a hypercatabolicstate, we sought to determine whether congestive heart failureinvolves elevations in plasma leptin levels. Since leptin secretionis up-regulated by insulin, we also explored whether in congestiveheart failure, a hyperinsulinaemic state, plasma leptin levelsrelate to plasma insulin levels. Methods Male patients with weight-stable congestive heart failure(n=25, aged 55·5±2·0, mean±SEM,body mass index=27·4±0·8, radionuclideleft ventricular ejection fraction=29·3±3·0%)and 18 controls, matched for age, sex and body fat (dual energyX-ray absorp-tiometry), underwent measurement of fasting plasmaleptin (radioimmunoassay) and insulin levels. Results Compared to controls, patients with congestive heartfailure had higher plasma leptin [8·12 (–1·12,+1·31)vs 4·48 (–0·61,+0·70) ng.ml^–1,mean±asymmetrical SEM,P=0·003], 41·5% higherplasma leptin per percent body fat mass (P<0·001),and higher fasting insulin levels [67·8 (–11·1,+13·3)vs 32·9 (–5·7,+6·9) pmol.l^–1,P=0·010].In the congestive heart failure group, plasma leptin correlatedwith total body fat (r=0·66) and fasting insulin (r=0·68)(bothP<0·001). In multivariate regression analysesof the congestive heart failure group, fasting insulin (standardizedcoefficient=0·41,P=0·011) emerged as a predictorof plasma leptin levels, independent of total body fat (standardizedcoefficient=0·73,P=0·002, R²=0·66,P<0·001). Conclusions Plasma leptin levels are raised in patients withcongestive heart failure. The observation of a positive relationshipbetween plasma leptin and insulin concentrations suggests thatthe insulin–leptin axis may be related to the increasedenergy expenditure observed in patients with congestive heartfailure.     

Effects of surgical versus medical treatment of long-term prognosis in angina at rest: an observational non-randomized study of 400 patients

The effect of surgical versus medical treatment on long-termprognosis in angina at rest was assessed using the Cox regressionmodel for survival analysis in 400 patients complaining of recurrentepisodes of resting chest pain associated with transient repolarizationchanges. The surgical group included 185 patients, and the medicalgroup 215. Surgically treated patients more frequently had two-and three-vessel disease, while single-vessel disease prevailedin medically treated patients (P<0·01). No differencebetween the two groups was found in mean values of left ventricularend diastolic pressure and ejection fraction. Three variableswere identified as independent predictors of prognosis in allpatients: left ventricular end-diastolic pressure (P < 0·001),age > 45 years (P < 0·05), and number of diseasedvessels (P < 0·05). Treatment modality did not resultin different long-term survival in the entire population. However,patients with three-vessel disease had a better outcome withsurgical than with medical therapy (P < 0·05). Although our conclusions must be tempered by consideration ofthe limitations of non-randomized studies, these results showthat surgical treatment may improve survival in patients withangina at rest and three-vessel disease.     

Impact of restenosis 10 years after coronary angioplasty

Aims The aim of the study was to compare the 10-year follow-up resultsof patients with or without restenosis following single-vesselpercutaneous transluminal coronary angioplasty (PTCA). Methods and Results A total of 313 patients with successful PTCA (20% reductionin luminal diameter narrowingwithout acute complications) anda control angiography 6 months after PTCA were included in thestudy. Events during the follow-up period were defined as death,myocardial infarction, bypass surgery, or repeat PTCA. Statisticalevaluation was performed by the Fisher test, logistic regression,and life-table analysis. Restenosis (loss of >50% of the initialgain and diameter stenosis of <50%) was found in 87 (28%)patients. During follow-up, 11 patients (5%) without restenosis(group A) and 11 (13%) patients with restenosis (group B) died(P<0·05). In group A, 17 (8%) patients and in groupB, 11 (13%) patients suffered myocardial infarction (ns); 17group A (8%) patients and 25 (29%) group B patients had bypasssurgery (P<0·0001), and 34 (15%) group A patientsand 55 (63%) group B patients underwent repeat PTCA (P<0·0001).Logistic regression analysis identified restenosis as an independentrisk factor that increases the risk of death 2·8-fold(P=0·02), bypass surgery 5·6-fold (P<0·0001),and repeat PTCA 10-fold (P<0·0001). Conclusion: We conclude that patients with restenosis had a poorer long-termoutcome than patients without restenosis. Although most patientswith restenosis underwent repeat PTCA, the survival rate withoutany serious adverse events was only 59%, compared with 83% inpatients without restenosis (P<0·0001).     

Serum lipids and thyrotropin in women with coronary artery disease

Abnormalities of thyroid function are associated with changesin lipid concentrations and in the incidence of ischaemic heartdisease. Whether lipid concentration and thyroid function arerelated when thyroid function is normal in ischaemic heart diseaseis uncertain. This study was undertaken to investigate the relationshipbetween thyroid function, serum lipids and ischaemic heart diseasein euthyroid women. Forty-six euthyroid patients were studied. Patients with diseasesknown to affect lipid levels or receiving drugs known to alterlipid or thyroid metabolism were excluded Twenty-three had ischaemicheart disease (IHD) and were matched with 23 controls. Correlationswere found between thyrotropin (TSH) and cholesterol (P=0·05)low density lipoprotein (LDL) (P=0·09) and triglyceride(P=0·009 in the IHD group but not between any serum lipidsand TSH in the control group. Analysis of covariance showeda statistically significant difference between groups of theassociation between cholesterol and TSH (P<0·05 (slope)P<0·001 (means)), LDL and TSH (P<0·005 (means))and between triglyceride and TSH (P<0·05 (means)).This study suggests that TSH within the normal range is havinga statistically significant effect on lipid levels in womenwith ischaemic heart disease.     

Exercise tolerance in patients with mitral stenosis before and after acute percutaneous mitral valvuloplasty: Role of lung diffusing capacity limitation?

The aim of this study was to specify in patients with tightmitral stenosis whether lung diffusing capacity could play arole in their exercise intolerance. A similar study was recentlycarried out in patients with moderate chronic heart failure. Ten patients with tight mitral stenosis were studied beforeand 6 months after successful percutaneous transvenous balloonvalvuloplasty and compared to six control subjects. Measurementsof diffusing capacity, evaluated by the lung transfer factor(TLCO) and by the transfer coefficient (TLCO/VA), obtained atrest and during early recovery after cardiopulmonary exercisetesting were performed. Cardiac output was determined non-invasively,both at rest and during exercise, using the carbon dioxide exponentialrebreathing technique. Prior to valvuloplasty, TLCO and TLCO/VA were not differentat rest between the two groups. During exercise, patients differedfrom control subjects, with lower oxygen uptake (P<0·00l)and lower cardiac output at peak exercise (P<000l). Thesevalues at peak exercise were significantly correlated (p=0·02;r=0·75). Moreover, patients differed from control subjectsat early recovery after peak exercise with an absence of increasein TLCO (P<0·05). Six months after valvuloplasty, a decrease of both TLCO (P<Oand TLCO/VA (P<0 was observed at rest. During exercise, comparisonof patients demonstrated a significant increase of both peakexercise oxygen uptake (SLVO P<0·0l) and cardiac output(P<0·00l). At early recovery after peak exercise therewas a significant increase in TLCO (P<O05) and TLCO/VA (P<0·01),such that a TLCO and a TLCO/VA appeared (P<0·05) identicalto that observed in control subjects. Moreover, SLVO₂ was significantlycorrelated in patients with Q+TLCO/VA (p=0·02; r=0·72). In conclusion, this study suggests a role, at least partial,of lung diffusing capacity in exercise intolerance in patientswith tight mitral stenosis and in the improvement of their aerobicexercise capacity demonstrated after successful percutaneousballoon valvuloplasty.     

Sympathetic predominance of cardiac autonomic regulation in patients with left free wall accessory pathway and orthodromic atrioventricular reentrant tachycardia

AIMS: The aim of this study was to compare cardiac autonomic regulationin patients with a history of paroxysmal supraventricular tachyarrhythmias,such as atrioventricular nodal reentrant tachycardia and atrioventricularreentrant tachycardia, and healthy controls. METHODS AND RESULTS: Seventeen patients with paroxysmal atrioventricular nodal reentranttachycardia (atrioventricular nodal reentrant tachycardia group),14 patients with overt preexcitation and paroxysmal atrioventricularreentrant tachycardia caused by a left free wall accessory pathway(atrioventricular reentrant tachycardia group) and 14 healthycontrol subjects, were studied. The patients and the controlswere age and gender matched. Cardiac autonomic regulation wasassessed by means of frequency domain analysis of heart ratevariability at rest, during head-up tilt, active standing, treadmillexercise and after exercise. The high frequency component (0·15–0·5 Hz)of heart rate variability tended to be lower and the low frequencycomponent (0·04–0·15 Hz) tended to be higheramong the atrioventricular reentrant tachycardia patients thanin atrioventricular nodal reentrant tachycardia patients andcontrols. The difference reached statistical significance atrest (P<0·05) and during standing (P<0·05atrioventricular reentrant tachycardia vs atrioventricular nodalreentrant tachycardia and P<0·01 atrioventricularreentrant tachycardia vs controls). Accordingly, the low-to-highfrequency ratio — the marker of cardiac sympathetic regulation— was higher in atrioventricular reentrant tachycardiapatients than in atrioventricular nodal reentrant tachycardiapatients (P<0·05 at rest and during standing) andcontrols (P<0·01 during standing). CONCLUSION: The cardiac autonomic status in atrioventricular reentrant tachycardiapatients was suggestive of a higher sympathetic tone than inatrioventricular nodal reentrant tachycardia patients or healthycontrols. This may be related to inhomogeneous ventricular activationin the presence of antegrade conduction via the accessory atrioventricularpathway.     

Factors of importance to Doppler indices of left ventricular filling in 50-year-old healthy subjects

Age is an important determinant of Doppler indices of left ventriculardiastolic filling in normal subjects. To define reference valuesand factors of importance to Doppler indices of left ventricularfilling in subjects of similar age, 58 men and 76 women aged50 years underwent Doppler echocardiography. All those takingpart in the study were healthy. When gender was analysed ina multivariate model it showed a significant independent correlationwith the peak velocity of early diastolic filling (E wave) (P<0·00l)and the early to atrial peak velocity (E/A) ratio (P<0·0l).The peak E wave velocity was 0·75±0·11m . s^–1 vs 0·66±0·10 m . s^–1(P<0·0O1) and the E/A ratio was 1·24±0·25vs 1·14±0·20 (P<0·05) in womenand men, respectively. In multivariate analyses, heart rate,diastolic blood pressure and body mass index correlated independentlywith the E/A ratio in women (P<0·00l for all), whereasin men, heart rate, diastolic blood pressure, body mass indexand left ventricular diameter correlated independently withthe E/A ratio (P<0·00l for all). Doppler measurementsof left ventricular filling in 50-year-old healthy subjectsshowed a wide variation and were significantly associated withheart rate, diastolic blood pressure, body mass index and gender.     

Growth hormone and heart performance: A novel mechanism of cardiac wall stress regulation in humans

OBJECTIVES: This study was designed to assess systolic wall stress and ventricularfunction in patients with deranged growth hormone secretion,in an attempt to elucidate the mechanisms of growth hormoneinteraction with heart performance. DESIGN: A case-control study. SUBJECTS: Thirty patients with active acromegaly, free of diabetes mellitusand coronary artery disease, and 25 subjects with congenitalgrowth hormone deficiency were studied. Twelve growth hormone-deficientsubjects were reevaluated after 12 months of recombinant humangrowth hormone therapy. Two groups of 30 normal subjects eachwere used as controls for the acromegalic and growth hormone-deficientpatients, respectively. RESULTS: In the acromegalics, end-systolic wall stress was reduced (–20%;P<0·01) due to ventricular wall thickening (+26%;P<0·001), whereas cardiac output was significantlyincreased (+20%; P<0·01). The velocity of fibre shorteningwas unchanged. In growth hormone-deficient subjects, end-systolicwall stress was markedly increased (+38%; P<0·001)due to a significant reduction of ventricular wall thickness(–28%; P<0·001), whereas cardiac output wassignificantly decreased (–44%; P<0·001) Replacementtherapy with recombinant human growth hormone produced a partialcorrection of wall thickness and stress. Consequently, systolicperformance and cardiac output improved significantly. CONCLUSION: This study demonstrates that growth hormone plays a role inthe control of cardiac wall stress and performance through amechanism mediated by the effect of growth hormone on myocardialtissue growth. The data may have therapeutic implications incardiac diseases that lead to heart failure.     

Determinants and significance of declining blood pressure in old age. A prospective birth cohort study

Aims To investigate the changes in blood pressure and their causesin an elderly population. Methods Orthostatic blood pressure measurements were performed in randomlyin four birth cohorts (years 65–, 75–, 80–and 85, n=773) at 5-year intervals. Results Both systolic and diastolic blood pressures decreased in bothgenders and all age groups. The falls in blood pressure relatedclosely to initial blood pressure values and to the thicknessof the left ventricular posterior wall of the heart. The changesin supine (r=0·118,P=0·007) and standing systolicblood pressure (r=0·123,P=0·005), as well as supine(r=0·148,P<0·001) and standing diastolic bloodpressure (r=0·186,P<0·001) correlated withchanges in body weight. Changes in supine diastolic blood pressurealso related to changes in serum cholesterol (r=0·207,P=0·002)and triglycerides (r=0·160,P=0·016). Changes insupine and standing systolic and standing diastolic blood pressuresalso related to changes in dehydroepiandrosterone sulphate (r=0·161,P<0·05;r=0·205,P<0·01; r=0·140,P<0·05,respectively). Changes in blood pressure also correlated withself-estimated poor health after 5 years (r for supine systolicblood pressure=–0·133,P<0·001, for standingsystolic blood pressure=–0·135,P<0·001,for supine diastolic blood pressure=–0·111,P<0·002).Patients who were institutionalized during the follow-up orwho had severely impaired performance capacity after 5 years,displayed the most marked decline in blood pressure. Decliningsystolic blood pressure was also related to impaired survivalprognosis. According to the logistic regression analyses thebaseline blood pressure, antihypertensive drugs and changesin dehydroepiandrosterone sulphate and cholesterol explainedover 30% of the changes in blood pressure. In the logistic models,declining blood pressure was associated with baseline bloodpressure, antihypertensive treatment, poor health after 5 years,and decreasing cholesterol and triglycerides. Conclusion Decline in blood pressure in old age is associated with deterioratinghealth and is only partly explained by the use of antihypertensivedrugs.