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Biomedical subjects

Andrew L Clark

Publications and source records attributed to Andrew L Clark.

At least 19 recordsLinked to original sources
PubMed2007

Prevalence of ECG abnormalities in an international survey of patients with suspected or confirmed heart failure at death or discharge.

BACKGROUND: Most patients suspected of having heart failure (HF) will get a 12-lead electrocardiogram (ECG) but its utility for excluding HF or assisting in its management has rarely been investigated. METHODS: The EuroHeart Failure survey identified 11,327 patients hospitalised with a suspected diagnosis of HF from 115 hospitals in 24 countries. ECGs were obtained from 9315 patients, of whom 5934 had cardiac imaging tests. The utility of the ECG was assessed for excluding or diagnosing major structural heart disease (MSHD) or major left ventricular systolic dysfunction (MLVSD) and for therapeutic decision making. FINDINGS: MSHD was present in 70% and MLVSD in 54% of patients overall but in only 21% and 5%, respectively, if the ECG was entirely normal. However, <2% of patients had a normal ECG. No single ECG characteristic identified a probability <25% of MSHD or <20% of MLVSD. Patients with QRS width >or=120 ms or anterior pathological Q-waves had a probability >80% of MSHD and >70% of MLVSD. Diagnostic models suggested that electrocardiographic criteria alone were not accurate for the diagnosis or exclusion of important heart disease in this population. However, 2468 patients (42%) had an electrocardiographic finding that should be used to guide the choice of therapy. CONCLUSIONS: A normal ECG is rare in patients with suspected HF but has limited diagnostic value in this setting. The ECG has an important role in guiding therapy.

Adolescent↗
PubMed2006

Clinical trials update from the American Heart Association 2006: OAT, SALT 1 and 2, MAGIC, ABCD, PABA-CHF, IMPROVE-CHF, and percutaneous mitral annuloplasty.

This article provides information and a commentary on trials presented at the American Heart Association meeting held in November 2006, 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. The OAT study failed to show a benefit of PCI over optimal medical therapy in patients with persistent total occlusion of the infarct related artery following a myocardial infarction. In SALT 1 and 2, tolvaptan was found to correct hyponatraemia of various aetiologies; however, whether this has an impact on heart failure prognosis requires further evaluation. A placebo controlled study of myocardial implantation of skeletal myoblasts in patients with moderate to severe LVSD (MAGIC) showed equivocal/uncertain effects, long term follow-up data are awaited. The ABCD study which compared the ability of an invasive and a non-invasive test to identify patients at risk of arrhythmic events prior to ICD implantation, suggested that the two strategies were comparable, although the practical value of either test remains uncertain and the study had many major flaws. The PABA-CHF study hinted that pulmonary vein antrum isolation might be more effective than AV node ablation with bi-ventricular pacing for the treatment of patients with heart failure in atrial fibrillation. In IMPROVE-CHF, an NT-pro BNP guided treatment strategy was found to reduce the cost of managing patients with acute breathlessness.

American Hospital Association↗
PubMed2006

Effects of applying a standardised management algorithm for moderate to severe renal dysfunction in patients with chronic stable heart failure.

BACKGROUND: No specific guidelines exist on how to manage renal dysfunction (RD) in patients with chronic heart failure (CHF). AIMS: To identify the proportion of patients with moderate to severe RD and CHF who showed an improvement in their renal function in response to a systematic management algorithm. METHODS: Stable patients with CHF and RD (defined by a serum creatinine (SCr) of >130 micromol/l (>1.5 mg/dl)) were enrolled into a systematic management algorithm. The following changes were implemented: switching aspirin to clopidogrel, halving the dose of both diuretics and angiotensin converting enzyme (ACE) inhibitors and switching between bisoprolol and carvedilol. RESULTS: Two thirds of patients in whom diuretics were reduced, and one fifth of patients in whom ACE inhibitors were reduced, improved their SCr by >25.5 micromol/l (0.3 mg/dl). All these changes were more marked in the presence of bilateral renal artery stenosis. Compared to a reference group, in whom no changes were implemented, the treatment group showed an improvement in their mean SCr by 35 micromol/l (0.4 mg/dl), p<0.001. CONCLUSION: Manipulation of pharmacological therapy for patients with CHF and RD results in a substantial recovery of renal function in a minority of patients.

Aged↗
PubMed2006

Prognostic value of the VE/VCO2 slope calculated from different time intervals in patients with suspected heart failure.

BACKGROUND: Maximal exercises testing, whether involving cycling- or walking-based protocols, are often not well tolerated in patients with chronic heart failure (CHF). The peak oxygen consumption and the slope of the relation between ventilation (V(E)) and carbon dioxide production (V(CO(2))) are independent predictors of outcome and help risk stratification. The prognostic usefulness of submaximal exercise testing is not clear. The aim of the present study was to assess the prognostic value of the V(E)/V(CO(2)) slope when derived from data acquired from submaximal exercise. METHODS: 394 patients referred with breathlessness and suspected heart failure (74% male) (mean+/-S.D.) age 60+/-12 years; BMI 27+/-5 performed a CPET to determine peak V(O(2)) and the V(E)/V(CO(2)) slope. The V(E)/V(CO(2)) slope was calculated using least squares regression from data acquired from the first 25% of exercise (mean V(E)/V(CO(2)) slope+/-SD; 30.6+/-5.7), 50% (29.6+/-6.9), below the ventilatory compensation point (sub-VCP) (29.9+/-6.8), and all data points (full slope) (32.1+/-7.8). For each measure, patients were divided into quartiles and Kaplan-Meier curves were constructed to determine probability of death after 24 months. The prognostic value of the different classifications was assessed using the chi(2) statistic from the Mantel-Cox log-rank test. RESULTS: During a mean follow-up period of 41+/-19 months, 48 patients died. For the V(E)/V(CO(2)) slope, the log-rank statistic was greatest for the full slope (chi(2)=53.7; P=0.0001), followed by the sub-VCP (chi(2)=45.5; P=0.0001), 50% (chi(2)=41.9; P=0.0001), and 25% (chi(2)= 26.0; P=0.01). The pair-wise log-rank statistic between the fourth and third quartiles was also greatest using the full slope (chi(2)=25.4; P=0.001) followed in order by the sub-VCP (chi(2)=20.1; P=0.001), 50% (chi(2)=19.7; P=0.001), and 25% (chi(2)=14.2; P=0.05). Using the stratified slope measurements entered into a Cox regression analysis using a forward LR stepwise elimination procedure; only the full slope remained significant (P=0.0001). CONCLUSIONS: The V(E)/V(CO(2)) slope should be calculated from all data points to optimise prognostic sensitivity. Data acquired from the first 50% of exercise and below the VCP provide adequate prognostic surrogates in patients who may not be able to perform maximal exercise testing (i.e. in patients with a respiratory exchange ratio<1.10).

Aged↗
PubMed2006

Clinical trials update from the Heart Failure Society of America meeting: FIX-CHF-4, selective cardiac myosin activator and OPT-CHF.

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the Heart Failure Society of America meeting held in Seattle in September 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. Devices designed to improve cardiac contractility may have improved exercise tolerance and quality of life in the FIX-CHF-4 study; however, uncertainties in trial interpretation exist. The results of a study reporting the first administration of the selective myosin activator CK-1827452 to human volunteers, support the initiation of clinical trials in heart failure patients. In OPT-CHF, oxypurinol failed to show benefit compared to placebo for the treatment of heart failure, although a retrospective subgroup analysis suggests that it may be beneficial in patients with elevated serum uric acid levels.

Cardiotonic Agents↗
PubMed2006

Clinical trials update from the joint European Society and World Congress of Cardiology meeting: PEP-CHF, ACCLAIM and the HHH study.

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the joint European Society and World Congress of Cardiology meeting held in Barcelona in September 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. The PEP-CHF study suggests that perindopril improves symptoms and functional capacity and may reduce heart failure hospitalisations in patients with diastolic heart failure. Although immune modulation therapy failed to reduce the incidence of all-cause mortality and cardiovascular hospitalisations in the ACCLAIM study, the observed differences in outcome in some heart failure patients warrants further investigation. The HHH study failed to show a beneficial effect of telemonitoring over usual care in patients with heart failure but potentially important country interactions were observed.

Aged↗
PubMed2006

The diagnostic utility of N-terminal pro-B-type natriuretic peptide for the detection of major structural heart disease in patients with atrial fibrillation.

AIMS: To assess the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the diagnosis of major structural heart disease (MSHD) in patients with atrial fibrillation (AF) compared with those with sinus rhythm (SR) using receiver operator characteristic (ROC) analysis. NT-proBNP is elevated in MSHD and heart failure (HF). AF, a common finding in HF and MSHD, is also associated with raised plasma NT-proBNP. As a result, the utility of NT-proBNP for predicting MSHD may be reduced. METHODS AND RESULTS: One thousand four hundred and seventy-six patients underwent assessment at a single centre, performed without the knowledge of NT-proBNP levels. MSHD included left ventricular (LV) systolic and diastolic dysfunctions, left-sided valvular disease, right heart disease (including pulmonary hypertension) and severe LV hypertrophy. One hundred and fifty-five patients were excluded due to renal impairment, atrial flutter, or a pacemaker. Seven hundred and ninety-three patients were diagnosed with MSHD. Median NT-proBNP concentrations for patients with MSHD were 960 (IQR 359-2625) pg/mL and 2491 (1443-4368) pg/mL for SR (n = 591) and AF (n = 202), respectively (P < 0.001). Patients without MSHD had NT-proBNP levels of 179 (90-401) pg/mL and 1000 (659-1760) pg/mL for SR (n = 454) and AF (n = 74), respectively (P < 0.001). The area under the ROC curve for NT-proBNP to detect MSHD was 0.79 for SR (95% CI 0.77-0.82) and 0.78 for AF (95% CI 0.72-0.84). NT-proBNP cut-off levels necessary to achieve a 1 in 100 false negative rate were 27.5 (7.5-30.5) pg/ml and 524 (253-662) pg/ml for SR and AF, respectively. CONCLUSION: NT-proBNP performs as well in patients with SR as in those with AF. However, significantly higher cut-off levels are required for patients with AF to achieve similar levels of diagnostic specificity.

Aged↗
PubMed2006

New generation 3-dimensional echocardiography for left ventricular volumetric and functional measurements: comparison with cardiac magnetic resonance.

AIMS: Non-invasive assessment of left ventricular (LV) structure and function is important in the evaluation of cardiac patients. This study was designed to test the accuracy and reproducibility of new generation 3-dimensional echocardiography (3DE) in measuring volumetric and functional LV indices as compared with current "gold standard" of non-invasive cardiac imaging, cardiac magnetic resonance (CMR). METHODS AND RESULTS: Sixty-four subjects with good acoustic windows, including 40 cardiac patients with LV ejection fraction (EF)<45%, 14 patients with EF>45% and 10 normal volunteers underwent 3DE using a commercially available Philips Sonos 7500 scanner equipped with a matrix phase-array x4 xMATRIX transducer, and CMR on a 1.5 T Signa CV/i scanner (GE Medical Systems). Volumetric assessment was performed with analytical 4D-LV-Analysis software (TomTec) for 3DE and MRI-Mass software (Medis) for CMR. We found no significant differences in LV end-diastolic volume (EDV), end-systolic volume (ESV) and EF with excellent correlations between the indices measured using 3DE and CMR (r=0.97, r=0.98, and r=0.94, respectively). Bland-Altman analysis showed bias of 7 ml for EDV, 3 ml for ESV and -1% for EF with 3DE with corresponding limits of agreement (2SD) of 28 ml, 22 ml and 10%, respectively. Intraobserver and interobserver variabilities were for EDV: 3% and 4% (3DE) vs 2% and 2% (CMR), for ESV: 3% and 6% (3DE) vs 2% and 3% (CMR), and for EF: 4% and 4% (3DE) vs 2% and 4% (CMR), respectively. CONCLUSION: New generation 3DE provides accurate and reproducible quantification of LV volumetric and functional data in subjects with good acoustic windows as compared with CMR.

Adult↗
PubMed2006

Clinical trials update from the European Society of Cardiology heart failure meeting: TNT subgroup analysis, darbepoetin alfa, FERRIC-HF and KW-3902.

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the European Society of Cardiology heart failure meeting held in June 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. In a sub-group analysis of the TNT study, intensive treatment with high-dose atorvastatin significantly reduced hospitalisations for heart failure in patients with stable coronary heart disease, compared with low-dose atorvastatin; this benefit was most evident in patients with a history of heart failure at baseline. In a combined analysis of two studies of darbepoetin alfa, which included 475 patients, treatment increased and maintained haemoglobin levels and produced non-significant improvements in symptoms and morbidity in anaemic heart failure patients compared to placebo. In the FERRIC-HF study (n=35), intravenous iron sucrose therapy improved exercise capacity and symptom status in iron-deficient heart failure patients. In a combined analysis of two studies (n=186), the adenosine A(1) receptor antagonist KW-3902 showed diuretic properties and appeared to enhance response to loop diuretics in heart failure patients hospitalised with fluid overload.

Anemia↗
PubMed2006

Statin use and survival in patients with chronic heart failure--results from two observational studies with 5200 patients.

BACKGROUND: There is minimal evidence that HMG-CoA reductase inhibitors (statins) are beneficial in patients with chronic heart failure (CHF). Treatment with statins may lead to a lower mortality in CHF, independent of cholesterol levels, CHF etiology and clinical status. METHODS: In a first study, we included 3132 patients with CHF from the ELITE 2 study in whom information on body mass index (BMI) and statin use at baseline were available. In a second study, we pooled the databases of 5 tertiary referral centers with 2068 CHF patients. In this cohort 705 patients were on a statin (34%), 585 of 1202 (49%) patients with ischemic etiology, and 120 of 866 (14%) patients with non-ischemic etiology (established by coronary angiography). FINDINGS: Patients in ELITE 2 who received statin therapy at baseline (n=397, 13%) had lower mortality (hazard ratio [HR] 0.61, 95% CI 0.45-0.83; p=0.0007). In univariate analysis, increasing age, NYHA class, creatinine, and decreasing BMI, LVEF, and cholesterol, as well as lack of beta-blocker treatment and ischemic etiology (all p<0.002) related to higher mortality. In multivariable analysis, statin therapy related to lower mortality independently of all these variables (adjusted HR 0.66, 95% CI 0.47-0.93; p=0.017). In the second study CHF patients on statins had lower mortality (adjusted HR 0.58, 95% CI 0.44-0.77; p=0.0001). Both in patients with ischemic (p<0.0001) and non-ischemic etiology (p=0.028) statin treatment related to better survival. INTERPRETATION: In chronic heart failure, treatment with statins is related to lower mortality, independent of cholesterol levels, disease etiology and clinical status.

Aged↗
PubMed2006

Anemia, renal dysfunction, and their interaction in patients with chronic heart failure.

Anemia and renal dysfunction (RD) are frequent complications seen in chronic heart failure (HF). However, the prevalence and interaction of these co-morbidities in a representative population of outpatients with chronic HF is poorly described. In this study, it was sought to determine the association between RD and anemia in patients with HF enrolled in a community-based HF program. Nine hundred fifty-five patients with HF due to left ventricular systolic dysfunction were investigated for the prevalence of anemia and its cause and followed for a median of 531 days. Anemia was defined as hemoglobin < 12.0 g/dl in women and < 13.0 g/dl in men. RD was defined as a calculated glomerular filtration rate of < 60 ml/min. The prevalence of anemia was 32%. Fifty-three percent of patients with and 27% of those without anemia had > or = 1 test suggesting hematinic deficiency. The prevalence of RD was 54%. Forty-one percent of patients with and 22% of patients without RD had anemia, with similar proportions associated with iron deficiency in the presence or absence of RD. Anemia and RD independently predicted a worse outcome, and this effect was additive. In conclusion, in outpatients with chronic HF, anemia and RD are common and co-exist but confer independent prognostic information. A deficiency of conventional hematinic factors may cause about 1/3 of anemia in this clinical setting.

Aged↗
PubMed2006

Left ventricular morphology, global and longitudinal function in normal older individuals: a cardiac magnetic resonance study.

BACKGROUND: The heart transforms structurally and functionally with age but the nature and magnitude of reported changes appear inconsistent. This study was designed to assess left ventricular (LV) morphology, global and longitudinal function in healthy older men and women using cardiac magnetic resonance (CMR). METHODS: Ninety-five healthy subjects (age 62+/-16 years, range 22-91 years) underwent breath-hold cine CMR. LV end-diastolic volume (EDV), end-systolic volume (ESV), myocardial mass, ejection fraction (EF), mass-to-volume ratio, mean midventricular wall motion, thickness and thickening were calculated from short-axis data sets. Average mitral annular displacement was measured to assess longitudinal LV function. RESULTS: Subjects were divided according to age (< 65 and > or = 65 years) and sex. EDV and ESV indices (corrected for body surface area) decreased whilst EF increased with age. There was no difference in LV myocardial mass index between the age groups, but midventricular wall thickness was significantly higher in older people. Mass-to-volume ratio also increased with age. In contrast to EF, mitral annular displacement declined with age. Midventricular LV wall thickness, myocardial mass index and mass-to-volume ratio were higher in men than in women but there were no differences in measures of global and longitudinal LV systolic function. CONCLUSIONS: Due to smaller LV volumes but higher wall thickness, myocardial mass remains unchanged with age. We have found an age-related increase in EF and reduction in longitudinal LV function in apparently normal subjects. This must be borne in mind when assessing older patients with possible heart failure and normal LV systolic function. Men have higher myocardial mass than women.

Adult↗
PubMed2006

Micronutrients and their supplementation in chronic cardiac failure. An update beyond theoretical perspectives.

Physicians' use of micronutrients to improve symptoms or outcomes in chronic illness has until recently been guided by limited data on the actions of individual agents in vitro or in animal studies. However several recently published clinical trials have provided information about which groups of patients are likely to benefit from which combination of micronutrients. Patients with chronic cardiac failure (CCF), particularly elderly individuals, have several reasons to be deficient in micronutrients including reduced intake, impaired gastrointestinal absorption and increased losses on the background of increased utilisation due for example to increased oxidative stress. Studies of nutritional supplementation in CCF patients have usually concentrated on specific agents. However given that many micronutrients have synergistic influences upon metabolic processes this strategy might merely lead to a shifting of a limiting step. Rather, a strategy of increasing the availability of multiple agents at once might be more logical. The aim of this article is to briefly review the experimental rationale for each of the micronutrients of potential benefit in chronic heart failure and examine the current clinical trial evidence supporting their use.

Animals↗
PubMed2006

The effect of altering heart rate on ventricular function in patients with heart failure treated with beta-blockers.

BACKGROUND: Beta-blockers are effective for the treatment of heart failure, but their mechanism of action is unresolved. Heart rate reduction may be a central mechanism or a troublesome side effect. METHODS: A randomized, double-blind, parallel group study comparing chronic higher-rate (80 pulses per minute) with lower-rate (60 pulses per minute) pacing in pacemaker-dependent patients with symptomatic left ventricular (LV) systolic dysfunction, receiving beta-blockers. Gated radionuclide ventriculography (RNVG) was performed at baseline and after at least 9 months. The primary outcome was change in LV volumes, as a marker of beneficial reverse remodeling, from baseline to follow-up. RESULTS: Forty-nine patients were randomized. Mean age was 74 +/- 6 years and with LV ejection fraction of 26% +/- 9% at baseline. During 14 +/- 13 months of follow-up, 21 patients (43%) died and 25 (51%) completed the study protocol: 12 in the higher-rate and 13 in the lower-rate group. Mean LV end-diastolic (higher rate +20 +/- 104 mL vs lower rate -65 +/- 92 mL, P = .03) and systolic (higher rate +29 +/- 83 mL vs lower rate -60 +/- 74 mL, P = .006) volumes increased with higher-rate versus lower-rate pacing, whereas LV ejection fraction declined (higher rate -4.2% +/- 4.4% vs lower rate +2.2% +/- 5.4%, P = .002). CONCLUSION: Reversal of beta-blocker-induced bradycardia has deleterious effects on ventricular function, suggesting heart rate reduction is an important mediator of their effects. The prognosis of patients with pacemakers and heart failure is poor.

Adrenergic beta-Antagonists↗