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Andrew L Clark

Publications and source records attributed to Andrew L Clark.

At least 37 records · Page 2Linked to original sources
PubMed2006

Clinical trials update from the American Heart Association: REPAIR-AMI, ASTAMI, JELIS, MEGA, REVIVE-II, SURVIVE, and PROACTIVE.

This article provides information and a commentary on trials presented at the American Heart Association meeting held in November 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. In REPAIR-AMI an improvement in ejection fraction was observed in post-MI patients following infusion of bone marrow stem cells. However, the ASTAMI study showed no benefit of stem cell implantation in a similar patient cohort. The JELIS study reported a reduction in major coronary events in patients receiving statins plus fish oil compared to statins alone. MEGA showed that low dose statins in a low risk population reduce the incidence of major cardiovascular events. Two studies of levosimendan in acute heart failure gave conflicting results, in the REVIVE-II study levosimendan was reported to have a superior effect on the composite primary outcome compared to placebo, however, in SURVIVE despite a trend to early benefit with levosimendan, there was no difference in effect on long-term outcome versus dobutamine. The PROACTIVE study showed encouraging results for the use of pioglitazone in post-myocardial infarction patients with concomitant type 2 diabetes.

Clinical Trials as Topic↗
PubMed2006

Clinical trials update from the American College of Cardiology: Darbepoetin alfa, ASTEROID, UNIVERSE, paediatric carvedilol, UNLOAD and ICELAND.

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the American College of Cardiology 55th Annual Scientific Session held in March 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. Darbepoetin alfa increased haemoglobin levels in heart failure patients and improved some aspects of quality of life compared to placebo. In the ASTEROID study rosuvastatin significantly reduced LDL-cholesterol levels and induced regression of atherosclerosis in patients with CAD. Rosuvastatin also produced a significant reduction in LDL-cholesterol levels in heart failure patients in the UNIVERSE study, but had no effect on left ventricular remodelling compared to placebo. The paediatric carvedilol study failed to show a benefit of carvedilol in children with heart failure. Ultrafiltration produced a greater weight and fluid loss than intravenous diuretics in heart failure patients with volume overload in the UNLOAD study but did not exert a greater improvement in breathlessness; however, ultrafiltration did reduce readmission rates. The ICELAND MI study showed that CMR imaging was more sensitive than ECG or clinical criteria for detecting myocardial infarction.

Carbazoles↗
PubMed2005

Incidence of renal dysfunction over 6 months in patients with chronic heart failure due to left ventricular systolic dysfunction: contributing factors and relationship to prognosis.

AIMS: To determine the prevalence and incidence of renal dysfunction (RD) in patients with chronic heart failure (CHF), to identify contributory factors and predictors of worsening renal function (WRF), and to explore the relationship between RD and mortality. METHODS AND RESULTS: Prospective data on 1216 patients with CHF were analysed. The glomerular filtration rate (GFR) was used to determine renal function, and WRF was defined as an increase in serum creatinine of >26.5 micromol/L (>0.3 mg/dL). The prevalence of RD defined as a GFR of <60 mL/min was 57%. During 6 months, WRF occurred in 161 (13.0%) patients. Predictors of WRF were vascular disease, the use of thiazide diuretics, and a baseline urea >9 mmol/L. Two hundred and sixty-three (21.6%) patients died, and baseline RD and WRF both predicted a higher mortality (P<0.001), whereas an improvement in renal function over the first 6 months predicted a lower mortality (hazard ratio 0.8, 95% confidence interval 0.6-1.0). CONCLUSION: In ambulatory patients with CHF, RD is common, commonly deteriorates over a relatively short period of time, is unlikely to recover substantially, and augurs a poor prognosis.

Adult↗
PubMed2005

N-terminal brain natriuretic peptide as a screening tool for heart failure in the pacemaker population.

AIMS: Assessment of N-terminal brain natriuretic peptide (NT-BNP) as a screening tool for heart failure in patients with a permanent pacemaker. METHODS AND RESULTS: Consecutive patients undergoing a routine permanent pacemaker assessment were enrolled. Patients underwent medical history and examination, echocardiography and blood sampling for NT-BNP. Analysis was performed on 261 patients (132 DDD, 121 VVI, eight others), mean age 73+/-12 years, range 34-99 years. Seventy two subjects (27%) had heart failure as defined by left ventricular ejection fraction (LVEF) <or=40% and symptoms of heart failure (NYHA class II, III, or IV). Screening with NT-BNP gave a sensitivity of 73% and specificity of 72% for detecting heart failure in all patients [area under the curve (AUC) 0.76, P<0.001, 95% CI 0.69-0.83]. This increased in subjects with a DDD type pacemaker (sensitivity 80%, specificity 66%, AUC=0.8, CI 0.7-0.90) and reduced in subjects with a VVI type pacemaker (sensitivity 66%, specificity 61%, AUC 0.68 CI 0.57-0.78). CONCLUSION: Symptoms of heart failure are common in patients with pacemakers. Screening with NT-BNP is feasible and assists in the detection of important cardiac co-morbidity, particularly in patients with a DDD type pacemaker.

Adult↗
PubMed2005

Metabolic gas kinetics depend upon the level of exercise performed.

BACKGROUND: The kinetics of oxygen and carbon dioxide at the onset of and recovery from exercise are slowed in patients with chronic heart failure (CHF). The aim of the present study was to establish whether the kinetics of O2 are influenced by the work rate. METHODS: Thirteen CHF patients and 12 control subjects underwent bicycle-based peak exercise testing with metabolic gas exchange analysis. Each subject then exercised at 15%, 25% and 50% of the maximal workload achieved until reaching steady state. Time constants for onset (T(onset)) and offset (T(offset)) for O2 uptake and CO2 output were correlated to the workload and the percentage of peak V(O2) performed during the steady state tests. RESULTS: Patients had lower peak oxygen uptake (pV(O2)) and the relation between ventilation and carbon dioxide output was steeper in patients than controls. T(offset) for both oxygen (O2) and carbon dioxide (CO(2)) from peak exercise was significantly greater in the patients than the controls and correlated with peak V(O2) (r=0.56, p<0.005 and r=0.58, p<0.005). T(onset) and T(offset) for O2 were increased in patients for each of the steady state tests and peak V(O2) correlated with T for recovery of O2 (r=0.44; p<0.05 from 15%, r=0.35; p= or <0.05 from 25%, and r=0.54; p<0.01 from 50%). There was a correlation between the T(onset) (r=0.42; p<0.0005 for O2 and r=0.23; p<0.05 for CO2) and T(offset) (r=0.49; p<0.0001 for O2 and r=0.42; p<0.0005 for CO2) and oxygen uptake as a percentage of peak exercise. CONCLUSIONS: This study demonstrates that the time constants of onset and offset for oxygen are dependent upon the degree of exertion performed relative to the individual's peak capacity.

Blood Gas Analysis↗
PubMed2005

The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure.

AIMS: Chronic heart failure (CHF) is a common and leading cause of death in industrialized countries. The potential benefits of micronutrient supplementation in CHF are extensive. Therefore, we examined the influence of long-term multiple micronutrient supplementation on left ventricular (LV) function, levels of pro-inflammatory cytokines, and quality-of-life (QoL) in elderly patients with CHF. METHODS AND RESULTS: Thirty CHF patients [age 75.4 (0.7), mean (SEM), LV ejection fraction (LVEF) < or =35%] were randomized to receive capsules containing a combination of high-dose micronutrients (calcium, magnesium, zinc, copper, selenium, vitamin A, thiamine, riboflavin, vitamin B(6), folate, vitamin B(12), vitamin C, vitamin E, vitamin D, and Coenzyme Q10) or placebo for 9 months in a double-blind fashion. All subjects were on stable optimal medical therapy for at least 3 months before enrolment. At randomization and at study end, tumour necrosis factor-alpha and its soluble receptors TNFR-1 and TNFR-2 were measured and six-minute walk test and QoL were assessed. Cardiac magnetic resonance scanning was performed to evaluate cardiac dimensions and LVEF. Two patients died during follow-up. The remaining patients (14 randomized to placebo and 14 to micronutrients) were well matched for LV function, symptoms, and exercise capacity. At the end of the follow-up period, LV volumes were reduced in the intervention group with no change in the placebo group [-13.1 (17.1)% vs. +3.8 (10.0)%; P<0.05]. LVEF increased by 5.3+/-1.4% in the intervention group and was unchanged in the placebo group (P<0.05). Patients taking micronutrients also had a significant improvement in QoL score between enrolment and study end [+9.5 (1.6)%; P<0.05], whereas those taking placebo had a slight deterioration [-1.1 (0.8)%; P=0.12]. Six-minute walk test and inflammatory cytokine levels remained unchanged in both groups. CONCLUSION: Long-term multiple micronutrient supplementation can improve LV volumes and LVEF and QoL scores in elderly patients with heart failure due to LV systolic dysfunction.

Aged↗
PubMed2005

The effect of ventricular pacing on measurements of left ventricular function: a comparison between echocardiographic methods and with radionuclide ventriculography.

AIMS: Different methods exist for measuring left ventricular function echocardiographically; each may be error prone due to the abnormal pattern of ventricular activation during pacing. METHODS AND RESULTS: Echocardiography was undertaken on 307 patients with permanent pacemakers; a subset of 57 underwent radionuclide ventriculography. Intrinsic and paced beats were analysed for left ventricular function by: Simpson's bi-plane, Teicholz M-mode, wall-motion scoring and 'eyeball' assessment. Agreement between techniques and with radionuclide ventriculography were compared according to intrinsic or paced beats. Echocardiographic measures of ejection fraction give mean values 5% higher than radionuclide ventriculography (Simpson's 30+/-9%, vs. Teicholz 30+/-13% vs. radionuclide ventriculography 25+/-9%, p=0.03). Agreement between Simpson's, Teicholz and radionuclide ventriculography by Bland-Altman analysis showed poor agreement (Simpson's vs. Teicholz range (4xSD)=57%, Simpson's vs. radionuclide ventriculography=36%, Teicholz vs. radionuclide ventriculography=46%, p=0.02), the level of agreement deteriorates with ventricular pacing (Simpson's vs. Teicholz range=61%, Simpson's vs. radionuclide ventriculography=34%, Teicholz vs. radionuclide ventriculography=47%, p=0.02). The correlation between wall motion analysis and radionuclide ventriculography is moderately poor (all subjects r=0.58, ventricular pacing r=0.52, not pacing r=0.66). CONCLUSION: Echocardiography and radionuclide ventriculography are the only non-invasive techniques to assess left ventricular function in the paced population. Results are poorly interchangeable and the accuracy of any comparison dependent on the underlying rhythm.

Echocardiography↗
PubMed2005

Atherosclerotic renovascular disease in chronic heart failure: should we intervene?

Renal artery stenosis (RAS) is most commonly caused by atherosclerosis, which is also the most common cause of chronic heart failure (CHF). One-third of patients with CHF are reported to have significant renovascular disease. The presence of RAS confers a worse outcome in studies of hypertension and coronary disease, though data are lacking for patients with CHF. As the kidney is intricately involved in the fluid retention that occurs in CHF, an adverse effect of RAS on outcome would be expected. Presentations of RAS in CHF include flash pulmonary oedema, hypertension, worsening of CHF, and worsening renal function. RAS commonly progresses and may cause worsening of renal function in patients with CHF and previously stable renal function. A variety of investigations that can safely and accurately identify RAS in CHF are available, although none is recommended in current guidelines for the management of CHF. Treatment for RAS, whether for hypertension, for renal dysfunction, or for pulmonary oedema, is at the discretion of the physician due to the lack of adequate randomized controlled trials demonstrating the efficacy and safety of intervention. As it is not clear how RAS should be managed in CHF, screening cannot be advocated. Currently, a multicentre randomized outcome trial, which includes a cohort of patients with RAS and CHF, is in progress to provide answers in this area of uncertainty.

Atherosclerosis↗
PubMed2005

The reproducibility and sensitivity of the 6-min walk test in elderly patients with chronic heart failure.

AIMS: The 6-min walk test (6-MWT) is used to estimate functional capacity. However, in elderly patients with chronic heart failure (CHF): (i) 1 year reproducibility of the 6-MWT; (ii) sensitivity of the 6-MWT to self-perceived changes in symptoms of heart failure; and (iii) implications for patient numbers required for studies using the 6-MWT as an endpoint have not been described. METHODS AND RESULTS: One thousand and seventy-seven patients with CHF, aged>60, with NYHA Class > or =II were recruited. Heart failure symptom assessment was determined using a questionnaire related to aspects of physical function, and patients performed a baseline 6-MWT, with follow-up 1 year later. Seventy-four patients with unchanged symptoms had an unchanged 6-MWT distance, with an overall intraclass correlation coefficient of 0.80 (95% CI=0.69-0.87). Four hundred and twenty-three patients reported an improvement in symptoms during follow-up. There was a negative correlation (r=-0.55; P=0.0001) between Delta symptoms and Delta 6-MWT (i.e. a reduced 6-MWT distance is associated with reduced symptom severity at follow-up). Five hundred and sixteen patients reported worsening symptoms of heart failure, a moderate inverse correlation (r=-0.53; P=0.0001) was displayed between Delta symptoms and Delta 6-MWT. For all patients, irrespective of symptom status, a high inverse correlation (r=-0.75; P=0.0001) was evident. On the basis of the data for patients with unchanged symptoms, it is calculated that to detect an increase in 6-MWT of 50 m, with 90% power, a study size of approximately 120 is required. CONCLUSION: In elderly patients with CHF, the 6-MWT shows satisfactory agreement when repeated 1 year later. Change in 6-MWT distance is sensitive to change in self-perceived symptoms of heart failure.

Aged↗
PubMed2005

Six minute corridor walk test as an outcome measure for the assessment of treatment in randomized, blinded intervention trials of chronic heart failure: a systematic review.

AIMS: The 6 min walk test (6MWT) is commonly used in clinical trials to assess treatments for heart failure, but its ability to distinguish between effective and ineffective treatments is questionable. The aim of this study is to investigate, using a systematic literature review, the utility of the 6MWT as a measure of the effectiveness of treatment in randomized controlled trials of heart failure. METHODS AND RESULTS: A literature search was performed using Medline, EMBASE, CINAHL, and Biological abstracts for randomized controlled trials that measured 6MWT between 1988 and 31 May 2004. A significant increase in 6MWT distance was observed in only 9 of 47 randomized controlled trials of pharmacological therapy; 2 of 6 trials of ACE-inhibitors; 3 of 17 trials of beta-blockers; 1 of 4 trials of digoxin; one trial of ibopamine; one trial of l-arginine; one trial of beriberine; and one trial showed superiority of captopril over flosequinan. A significant increase in 6MWT was observed in four out of six placebo-controlled trials of cardiac resynchronization. Smaller pharmacological trials with fewer centres were more likely to be positive; six out of nine positive pharmacological trials had four or less participating centres, raising the possibility of publication bias. Pharmacological trials including patients with more severe heart failure were more likely to show a significant improvement with therapy than trials of milder heart failure. Five out of seven pharmacological trials that reported an improvement in symptoms also reported an improvement in 6MWT distance. Of 30 pharmacological trials, 29 that reported no improvement in symptoms also reported no improvement in 6MWT. Using mean values in these trials, the age of patients appeared a more important determinant of 6MWT distance than New York Heart Association classification. CONCLUSION: The 6MWT has not yet been proven to be a robust test for the identification of effective pharmacological interventions although it appears useful for the assessment of cardiac resynchronization therapy. The results of the 6MWT were concordant with changes in symptoms, suggesting that it may be used as supportive evidence for symptom benefit. The test may be of greater value in patients with more advanced heart failure, where it may function as a maximal exercise test.

Cardiotonic Agents↗
PubMed2005

Home-based exercise training modulates pro-oxidant substrates in patients with chronic heart failure.

BACKGROUND: In chronic heart failure, oxidative stress is thought to lead to endothelial dysfunction. In this study, we assessed the effect of home-based exercise training on variables of the NO and purine pathways. METHODS AND RESULTS: Eighteen patients and nine controls were randomly assigned in cross-over design to 8 weeks of exercise training (5 days/week, submaximal bicycle ergometer training, 30 min/day; calisthenics 9 min/day) and 8 weeks of sedentary lifestyle. Hypoxanthine, xanthine, l-arginine, asymmetric dimethylarginine (ADMA), symmetric DMA (SDMA) and nitrite were measured. In patients, exercise training led to an increase in peak VO(2) (p<0.003). At baseline hypoxanthine-a pro-oxidant substrate and marker of hypoxia-was higher in patients than in controls (24.6+/-4.3 vs. 11.9+/-4.2 micromol/l; p<0.05). After training there was a reduction in hypoxanthine (p<0.01). Nitrite levels were lower in patients (416+/-31 micromol/l) than in healthy controls (583+/-35 micromol/l, p<0.001). Although nitrite levels were highest after exercise, the changes did not reach statistical significance (p=n.s.). l-Arginine, ADMA, and SDMA levels were not different between groups and were not altered by exercise training. CONCLUSIONS: Chronic heart failure is associated with increased levels of hypoxanthine and decreased levels of nitrite. This imbalance can be beneficially modulated by chronic home-based exercise training.

Adult↗
PubMed2005

Exercise training in chronic heart failure: effects on pro-inflammatory markers.

BACKGROUND: Acute bouts of exercise have been shown to induce inflammatory cytokine activation and peripheral hypoxia in patients with chronic heart failure (CHF). In this study, we set out to investigate the impact of chronic exercise training on pro-inflammatory cytokines and markers of endothelial damage. METHODS AND RESULTS: We measured tumor necrosis factor alpha (TNFalpha), its soluble TNF-receptors 1 and 2, interleukin 6 (IL-6), soluble e-selectin, soluble intracellular adhesion molecule-1 (sICAM) and sCD14 in 18 patients with CHF and 9 age-matched controls in a randomized cross-over study of 8 weeks of exercise training (5 days/week, submaximal bicycle ergometer training, 30 min/day; calisthenics 9 min/day) versus 8 weeks of rest. At baseline, patients had a lower peak Vo(2) (p=0.009) and a trend for higher levels of e-selectin (p=0.08) and sCD14 (p=0.06), in addition to significantly elevated levels of sICAM (p=0.02), TNFalpha (p=0.02) and TNF-R2 (p=0.002); TNF-R1 and IL-6 were not elevated. Although exercise training was effective and led to an increase in peak Vo(2) in CHF (p<0.003), there was no activation of any of the above variables observed, neither in patients nor controls. CONCLUSIONS: Chronic heart failure is associated with increased levels of TNFalpha and markers of endothelial damage. Whereas acute bouts of exercise have been reported to lead to an increase in pro-inflammatory cytokines and markers of endothelial damage, these effects are not seen when exercise is performed chronically.

Adult↗
PubMed2005

Longitudinal myocardial dysfunction in healthy older subjects as a manifestation of cardiac ageing.

BACKGROUND: Abnormalities of longitudinal left ventricular (LV) contraction and relaxation may be early markers of cardiac disease. This study was designed to assess the relationship between long-axis LV function and age in healthy subjects. METHODS: 118 healthy individuals aged 57 +/-19 years (range 20-90 years) with no evidence of cardiovascular disease under-went echocardiography with Doppler examination of transmitral flow. To assess longitudinal LV function, systolic (S(m)), early diastolic (E(m)) and late diastolic (A(m)) mitral annular velocities were measured using colour-coded tissue Doppler imaging. RESULTS: The left atrium was enlarged (P<0.001) in subjects >/=60 years of age compared to those <60 years, but there were no differences in LV volumetric indices and ejection fraction. Peak E velocity was lower (P<0.001) and peak A velocity of transmitral flow was higher in older subjects (P<0.001) with a higher E/A ratio (P<0.001) and longer isovolumic relaxation time (P= 0.001) indicative of impaired ventricular relaxation. S m and E m mitral annular velocities decreased (P<0.001) and A m velocity increased (P=0.002) in the older group. E m velocity and E m /A m ratio showed a strong negative correlation with age (r= -0.80, P<0.001 and r=-0.78, P<0.001, respectively). CONCLUSIONS: Global LV systolic function is preserved but the velocity of long-axis systolic shortening is depressed in older individuals, indicating selective impairment of the longitudinal component of systolic contraction. The decline in the velocity of early diastolic long-axis LV lengthening and the changes in the pattern of transmitral flow suggest impaired ventricular relaxation. These measures of cardiac function may be a useful index of normal cardiac ageing.

Adult↗
PubMed2005

Beta-blockers and inspiratory pulmonary function in chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) patients complain of breathlessness and fatigue. Respiratory muscle function is impaired in CHF patients and may contribute to their symptoms. Beta-blockers cause fatigue but have become part of the standard management of CHF. We explored the relation between respiratory muscle power in CHF and the effects of long-term beta-blockade. METHODS AND RESULTS: A total of 52 CHF patients and 25 control subjects underwent echocardiography, peak exercise testing with metabolic gas exchange analysis, and measurement of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak inspiratory flow (PIF), and forced inspiratory volume in 1 second (FIV1). Of the patients, 35 started beta-blocker therapy and were tested again at 1 year. Patients had lower peak oxygen consumption (pV(O2) (19.3 [4.5] versus 37.3 [8.4] mL/kg/min, P < .0001), exercise time (414 [134] versus 817 [193] seconds, P < .0001), and anaerobic threshold (13.8 [3.8] versus 27.2 [8.2] mL/kg/min, P < .0001). Patients also had a steeper relationship between ventilation (V(E)) and carbon dioxide (CO2 ) (V(E)/V(CO2)) (40.0 [6.8] versus 26.4 [2.0], P < .0001); lower FEV1, FVC, and FIV1 (89 [15] versus 111 [24]% expected, P < .0001, 80 [20] versus 94 [21]% expected, P < .001 and 2.5 [1.6] versus 3.0 (0.9) L, P < .02); and there was a correlation between pV(O2) and FIV1 (r = 0.24, P < .05) for the patients. The slope relating symptoms of breathlessness (Borg score) to ventilation (Borg/V(E) slope) also correlated with FIV1 (r = 0.36, P < .02). Beta-blocker therapy improved echocardiographic variables, but not pV(O2). There was no change in PIF or FIV1. There was a significant reduction in FEV 1 after beta-blocker treatment (P < .01). CONCLUSION: Inspiratory flows are impaired in patients with chronic heart failure and correlate with the degree of functional impairment. This may be due to a combination of respiratory muscle weakness and reduced lung compliance. The reduction in inspiratory capacity is not influenced by long-term beta-blockade.

Adrenergic beta-Antagonists↗