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Biomedical subjects

L B Tan

Publications and source records attributed to L B Tan.

At least 19 recordsLinked to original sources
PubMed2005

Complementary roles of simple variables, NYHA and N-BNP, in indicating aerobic capacity and severity of heart failure.

AIMS: The extent of exercise intolerance in patients with chronic heart failure (CHF) is dependent on and representative of the severity of heart failure. However, few primary care physicians have direct access to facilities for formal exercise testing. We have therefore explored whether information readily obtainable in the community can reliably predict the functional capacity of patients. METHODS AND RESULTS: Ninety-six subjects with a wide range of cardiac function (10 healthy controls and 86 CHF patients with NYHA classes I-IV, LVEF 36.9+/-15.2%) were recruited into the study and had resting plasma N-BNP and cardiopulmonary exercise testing to measure peak oxygen consumption (VO2). Significantly higher N-BNP levels were found in the CHF group (299.3 [704.8] fmol/ml, median [IQR]) compared with the healthy control group (7.2 [51.2] fmol/ml), p<0.0001. There were significant correlations between peak VO2 and N-BNP levels (R=0.64, P<0.001), peak VO2 and NYHA class (R=0.76, P=0.001), but no significant correlation was seen between peak VO2 and LVEF (R=0.0788, P=0.33). Multivariate analysis identified plasma N-BNP (P<0.0001) and NYHA class (P<0.0001) as significant independent predictors of peak VO2. Logistic modelling with NYHA class and log N-BNP to predict peak VO2<20 ml/kg/min showed that the area under the curve of receiver-operating-characteristic (ROC) curve was 0.906 (95% CI 0.844-0.968). A nomogram based on the data has been constructed to allow clinicians to estimate the likelihood of peak VO2 to be <20 ml/kg/min for given values of plasma N-BNP and NYHA class. CONCLUSIONS: By combining information from a simple objective blood test (N-BNP) and a simple scoring of functional status (NYHA), a clinician can deduce the aerobic exercise capacity and indirectly the extent of cardiac dysfunction of patients with CHF.

Adult↗
PubMed2004

From CONSENSUS to CHARM--how do ACEI and ARB produce clinical benefits in CHF?

Two decades of research from CONSENSUS to CHARM using modulators of the renin-angiotensin-aldosterone system (RAAS) in chronic heart failure (CHF) patients have shown convincing clinical benefits, but the majority of clinicians prescribing these drugs are still unclear about what mechanisms are responsible for the observed benefits. Of the candidate mechanisms hitherto proposed, there emerges a theme that best fits the spectrum of known factors from pathophysiology of heart failure to how the drugs enhance longevity of patients. This concept can be summarised as follows: after the onset of heart failure, neurohormones are activated resulting in raised levels of angiotensin, aldosterone and catecholamines, which are all known cardiotoxic agents. Cumulatively over time, they are responsible for accelerated cardiomyocyte attrition, manifesting as a faster reduction of cardiac pumping reserve, leading to worsening heart failure, more neurohormonal activation, thus propagating a vicious cycle spiralling towards an earlier fatality. The vicious cycle can be interrupted by dampening the excessive neurohormonal activities, thereby minimising cardiomyocyte losses and preserving cardiac functional reserve for longer. This culminates in maintenance of a reasonable quality of life and enhanced longevity. Such a mechanistic understanding would enable clinicians to have a better perspective on how to apply data from various clinical trials involving these drugs into clinical practice, to optimise and tailor therapy to the individual patient so that each patient can gain maximal benefits.

Angiotensin Receptor Antagonists↗
PubMed2004

The benefits of valsartan in the treatment of heart failure: results from Val-HeFT.

Angiotensin II receptor blockers (ARBs) are the most recent class of anti-hypertensive drug to enter clinical use for chronic heart failure (CHF). In the landmark Valsartan Heart Failure Trial (Val-HeFT), valsartan reduced the risk of the combined endpoint of all-cause mortality and morbidity by 13.2% over a 2-year follow-up. Although it significantly improved a pre-specified primary endpoint, it did not improve the endpoint of all-cause mortality. Valsartan administered to patients not receiving angiotensin-converting enzyme inhibitors (ACEI) at baseline reduced the endpoint of all-cause mortality by 33% and the combined endpoint of mortality and morbidity by 44%, compared with placebo. Based on these findings, valsartan became the first ARB to be approved by the US Food and Drug Administration for the treatment of New York Heart Association class II-IV HF in patients who are intolerant of ACEIs. This review provides a summary of the key Val-HeFT results and their implications in the treatment of CHF patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Does balloon mitral valvuloplasty improve cardiac function? A mechanistic investigation into impact on exercise capacity.

Procedural technical success of balloon mitral valvuloplasty (BMV) is indicated by an increase in valve area and a reduction in transvalvar gradient, but there are conflicting results regarding whether these indicators correlate with subsequent improvements in exercise capacity. We conducted a study to explore the effects of valvuloplasty on cardiac function to gain insight into the mechanisms responsible for the impact on exercise ability. Sixteen patients with mitral stenosis participated in the study and the five who did not proceed to valvuloplasty served as the control group. All patients performed maximal cardiopulmonary exercise tests before and 6 weeks after valvuloplasty (without valvuloplasty in controls). Central haemodynamics including cardiac output were measured non-invasively at rest and peak exercise. At baseline, the cardiopulmonary exercise test results were similar in the two groups. Following valvuloplasty, cardiac output did not alter at rest, but increased significantly at peak exercise (8.7+/-1.7 to 10.5+/-2.1 l min(-1), P<0.01), as did peak cardiac power output (1.88+/-0.55 to 2.28+/-0.74, P<0.05) and cardiac reserve (1.07+/-0.33 to 1.45+/-0.55 watts, P<0.05). Aerobic exercise capacity improved (13.9+/-4.2 to 16.4+/-4.3 ml kg(-1) min(-1), P<0.01) as did exercise duration (354+/-270 to 500+/-266 s, P<0.01). There were no significant changes in the controls. There was a significant correlation between the changes in peak VO(2) and changes in cardiac reserve (r=0.62, P<0.01) but not with changes in resting haemodynamics. These changes did not correlate with changes in peri-procedural mitral valve haemodynamics, despite increases in mitral valve area from 1.05+/-0.16 to 1.74+/-0.4 cm(2) (P<0.0001), accompanied by falls in the transvalvar gradient and pulmonary artery pressure (12.4+/-4.7 to 4.5+/-3 mmHg, and 26.8+/-8.4 to 17.4+/-5.2 mmHg, respectively, all P<0.0001). In conclusion, we found that successful mitral valvuloplasty in our patient cohort led to improved cardiac and physical functional capacity but not resting haemodynamics. Neither indicators of technical success nor resting haemodynamics were very reliable in predicting functional improvement.

Adult↗
PubMed2002

Central sleep apnoea syndrome in patients with chronic heart disease: a critical review of the current literature.

The prevalence, prognosis, clinical presentation, pathophysiology, diagnosis, and treatment of the central sleep apnoea syndrome (CSAS) are reviewed and its relationship with congestive heart failure (CHF) is discussed. Adequately powered trials are needed with survival and health status as end points to establish whether correction of sleep related breathing abnormalities improves the outcome in patients with CHF.

Heart Failure↗
PubMed2002

Assisted ventilation for heart failure patients with Cheyne-Stokes respiration.

Patients with chronic congestive cardiac failure (CCF) frequently suffer from central sleep apnoea syndrome (CSAS). Continuous positive airway pressure (CPAP) has been suggested as a treatment. The authors hypothesised that bilevel ventilation might be easier to initiate and superior to CPAP at correcting the sleep-related abnormality of breathing in patients with CCF. After excluding those with a history suggestive of obstructive sleep apnoea, 35 patients with CCF (left ventricular ejection fraction <35%) were screened with overnight oximetry and the diagnosis of CSAS was established with polysomnography in 18. Two 14-day cycles of CPAP (0.85 kPa (8.5 mbar)) or bilevel ventilation (0.85/0.3 kPa (8.5/3 mbar)) in random order, were compared in a crossover study. Sixteen patients (13 males), mean age 62.0+/-7.4 yrs completed the study. The pretreatment apnoea/hypopnoea index of 26.7+/-10.7 was significantly reduced by CPAP and bilevel ventilation to 7.7+/-5.6 and 6.5+/-6.6, respectively. The arousal index fell from 31.1+/-10.0 per hour of sleep to 15.7+/-5.4 and 16.4+/-6.9, respectively. Significant and equal improvements with CPAP and bilevel ventilation were found for sleep quality, daytime fatigue, circulation time and New York Heart Association class. The authors conclude that continuous positive airway pressure and bilevel ventilation equally and effectively improve Cheyne-Stokes respiration in patients with congestive cardiac failure.

Adolescent↗
PubMed2001

Left ventricular volume reduction without ventriculectomy.

Partial left ventriculectomy (the Batista procedure) to achieve left ventricular volume reduction (LVVR) has been advocated as an alternative to cardiac transplantation in patients with end-stage dilated left ventricles. Here, we describe a new technique of LVVR that uses realignment of the papillary muscles, thus avoiding ventriculectomy, and report preliminary results. Eight patients (all male, mean age 49.3 [range 38 to 70] years) underwent LVVR between October 1998 and March 2000 as an adjunct to surgical coronary revascularization. Five were assessed with echocardiography and cardiopulmonary exercise testing before and after (mean follow-up time 267 [range 94 to 416] days) the operation. LVVR significantly improved left ventricular end-diastolic volume (254 +/- 32 to 218 +/- 36 mL, p = 0.03), left ventricular ejection fraction (20.14% +/- 1.36% to 31.28% +/- 2.32%, p = 0.007), and exercise duration (from 394 +/- 88 to 611 +/- 79 seconds, p = 0.03). A nonsignificant improvement in maximal oxygen consumption was also observed. This technique of LVVR is relatively simple to perform and is accomplished through a small apical cardiotomy. Preliminary results show an encouraging functional improvement following surgery. Future controlled studies are required to assess this novel technique further.

Adult↗
PubMed2001

Disparate results of ACE inhibitor dosage on exercise capacity in heart failure: a reappraisal of vasodilator therapy and study design.

Despite manifest benefits of angiotensin converting enzyme (ACE) inhibitors on the prognosis of patients with heart failure, there is a lack of consistency in the results of trials investigating the effects of ACE inhibitors on exercise capacity. The inconsistencies cannot be readily explained by variations in effects on known neurohumoral or conventional haemodynamic factors. Drawing on insights from physiology of pump-load interactions, in a normal circulation there is an optimal extent of systemic vasodilation at which the delivery of hydraulic energy from the cardiac pump is maximal (the 'impedance matchpoint'). In heart failure, the vasoconstrictive effects shift the operating point towards mismatch at higher resistances, and optimal vasodilatory therapy would reshift the operating point to the matchpoint. Excessive dosage, however, would cause overvasodilatation leading to a reduction in cardiac power output and consequently compromising exercise ability. High levels of ACE inhibitors may not therefore improve exercise ability. Another potential reason for the observed inconsistencies is that the often used parallel-group study design (ideal for mortality studies) may not be suitable for investigating drug effects on exercise capacity because dropouts from such studies would introduce occult selection biases, thereby confounding treatment effects. In conclusion, this reappraisal of the conflicting observations reported on ACE inhibitor effects on exercise capacity has highlighted a proposition that there is an optimal dosage of ACE inhibitors which will most enhance exercise capacity, and this will require further well designed cross-over studies to elucidate.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

A method for investigating the mechanical properties of intracoronary stents using finite element numerical simulation.

The proliferation of stent designs poses difficult problems to clinicians, who have to learn the relative merits of all stents to ensure optimal selection for each lesion, and also to regulatory authorities who have the dilemma of preventing the inappropriate marketing of substandard stents while not denying patients the benefits of advanced technology. Of the major factors influencing long-term results, those of patency and restenosis are being actively studied whereas the mechanical characteristics of devices influencing the technical results of stenting remain under-investigated. Each different stent design has its own particular features. A robust method for the independent objective comparison of the mechanical performance of each design is required. To do this by experimental measurement alone may be prohibitively expensive. A less costly option is to combine computer analysis, employing the standard numerical technique of the finite element method (FEM), with targeted experimental measurements of the specific mechanical behaviour of stents. In this paper the FEM technique is used to investigate the structural behaviour of two different stent geometries: Freedom stent geometry and Palmaz-Schatz (P-S) stent geometry. The effects of altering the stent geometry, the stent wire diameter and contact with (and material properties of) a hard eccentric intravascular lesion (simulating a calcified plaque) on stent mechanical performance were investigated. Increasing the wire diameter and the arterial elastic modulus by 150% results in the need to increase the balloon pressure to expand the stent by 10-fold. Increasing the number of circumferential convolutions increases the pressure required to initiate radial expansion of mounted stents. An incompressible plaque impinging on the mid portion of a stent causes a gross distortion of the Freedom stent and an hour-glass deformity in the P-S stent. These findings are of relevance for future comparative studies of the mechanical performance of stents, in designing newer stents and also in clinical practice.

Finite Element Analysis↗
PubMed2001

Peak exercise cardiac power output; a direct indicator of cardiac function strongly predictive of prognosis in chronic heart failure.

OBJECTIVES: This study assessed the prognostic value of peak cardiac power output, measured non-invasively during maximal cardiopulmonary exercise testing, against other exercise-derived haemodynamic variables in patients with chronic congestive heart failure. METHOD AND RESULTS: Two hundred and nineteen unselected, consecutive patients with congestive heart failure (166 men, mean (+/-SD) age of 56+/-13 years) who underwent maximal symptom limited cardiopulmonary treadmill exercise testing with non-invasive estimation of cardiac output using carbon dioxide re-breathing techniques, were followed-up for a mean period of 4.64 (4.47--4.82, 95% CI) years. Cardiac power output was calculated from the product of cardiac output and mean arterial blood pressure. All cause mortality was 12.3% (27 deaths). Peak and resting cardiac power output, peak mean arterial blood pressure, peak and resting cardiac output and peak VO(2)were all predictive of outcome on univariate analyses. Peak cardiac power output, either entered continuously or categorically with a cut-off value of 1.96 watts, was the only independent predictor of mortality (P=0.0004 for values < or >1.96 watts and P=0.001 for continuous values) using multivariate analysis. A relative risk ratio of 5.08 (1.94-13.3, 95% CI) was obtained for a cardiac power output <1.96 watts. CONCLUSION: Peak cardiac power output is an independent predictor of mortality that can be measured non-invasively using cardiopulmonary exercise testing. It can give further prognostic power to a peak VO(2)in the assessment of patients with congestive heart failure.

Adult↗
PubMed2001

Randomized controlled trial of home-based exercise training to evaluate cardiac functional gains.

There is evidence that multiple benefits can be obtained through exercise training that leads to increases in peak oxygen consumption (V(O(2))). It is unclear whether significant improvements can also be achieved through unsupervised low-budget home-based training regimes, especially in terms of cardiac functional gains. A randomized cross-over trial was conducted to investigate the effects of a home-based unsupervised exercise training programme of moderate intensity on aerobic capacity, cardiac reserve and peak cardiac power output in healthy middle-aged volunteers. Nine subjects with no known cardiovascular diseases performed symptom-limited treadmill cardiopulmonary exercise tests after an 8-week period of exercise training, and results were compared with those obtained after a similar 'non-exercising' control period. Cardiac output was measured non-invasively during exercise tests using the CO(2)-rebreathing method. With exercise training, resting heart rate decreased significantly from 88.3+/-3.4 to 78.7+/-3.2 beats.min(-1) (P<0.05), heart rate at a submaximal workload (V(O(2))=1.5 litres.min(-1)) decreased from 125.5+/-2.4 to 115.5+/-1.6 beats.min(-1), and peak V(O(2)) increased by 9% from 2.62+/-0.19 to 2.85+/-0.18 litres.min(-1) (P<0.01). Baseline cardiac power output was 1.11+/-0.05 W, and this remained unchanged with training. Peak cardiac power output increased by 16% from 4.1+/-0.3 to 4.7+/-0.3 W (P<0.001), and cardiac reserve increased by 21% (P<0.01). A major contribution to these increases was from the 11% increase in stroke volume, from 100.1+/-5.3 to 111.2+/-6.2 ml (P<0.001). All subjects reported more positive perceptions of their health (P<0.05), fitness (P<0.01) and levels of activity (P<0.01) after the training period. These results show that motivated subjects undergoing low-budget unsupervised home-based exercise training of moderate intensity can derive benefit in terms of symptoms, aerobic capacity and cardiac functional reserve.

Analysis of Variance↗