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1.  Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks? 
Diabetologia  2013;56(7):1462-1470.
In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice.
PMCID: PMC3671104  PMID: 23613085
Cardiovascular disease; Double diabetes; HDL-cholesterol; Hepatic fat; Insulin resistance; Metabolic syndrome; Obesity; Review; Type 1 diabetes; Type 2 diabetes
2.  Unmasking the truth 
BMJ Case Reports  2011;2011:bcr0720103193.
In the emergency setting, shortness of breath is a frequent presenting complaint to physicians worldwide. The differential diagnosis is often broad and requires careful analysis of investigations to reach the correct diagnosis. The authors present a case of acute heart failure with a number of unusual presenting features that suggested an uncommon aetiology.
PMCID: PMC3027961  PMID: 22715233
3.  Excessive breathlessness in patients with diastolic heart failure 
Heart  2006;92(10):1425-1429.
To establish the prevalence of preserved left ventricular (LV) systolic function (PSF) in 435 consecutive symptomatic patients referred to a heart failure clinic and to examine their ventilatory response to exercise when compared with 134 control volunteers.
216 (50%) patients had systolic heart failure (SHF) (ejection fraction < 45%). 51 (11%) had an immediately apparent alternative causes of breathlessness and 168 (39%), with no obvious other cause of breathlessness, were divided into those with PSF and diastolic dysfunction (DD) (PSFDD; n  =  113 or 26% of referrals) and those without DD (PSFN; n  =  55 or 13% of referrals). The controls were divided into those with (CDD; n  =  32) and those without (CN; n  =  102) echocardiographic evidence of DD.
Patients with SHF had lower peak oxygen consumption (pV̇o2), steeper slope of minute ventilation (V̇e) to carbon dioxide production, lower exercise time and shorter 6 min walk test than PSF patients and controls. PSFDD patients had lower pV̇o2, exercise time and 6 min walk test than CDD, although their echocardiograms were not different. Exercise capacity did not differ between PSFDD and PSFN patients. The slope relating V̇e to symptoms (Borg/V̇e slope) was less steep in those with SHF than in PSFDD (0.17 (0.04) v 0.20 (0.08), p < 0.05) and in PSFN (0.19 (0.10), p < 0.05), implying greater symptoms of breathlessness for a given level of V̇e. Both PSF groups had a steeper slope than CDD (0.14 (0.09), p < 0.05 for both comparisons).
Patients with PSF have exercise tolerance intermediate between that of patients with SHF and controls. Exercise tolerance is similar in PSFDD and PSFN. Both groups have worse exercise tolerance than CDD. PSFDD and PSFN patients seem to experience a greater awareness of V̇e than CDD and patients with SHF.
PMCID: PMC1861064  PMID: 16621875
4.  Migrant men: a priority for HIV control in Pakistan? 
Sexually Transmitted Infections  2006;82(4):307-310.
To assess sexual risk behaviour and prevalence of treatable sexually transmitted infections (STI) in migrant male workers in Lahore, Pakistan.
Behavioural interviews were conducted on a representative sample of 590 migrant men aged 20–49 years. Biological samples were collected from a subsample of 190 and tested for chlamydia, gonorrhoea, and syphilis.
Over half (55%) of single men were sexually experienced and 36% of married men reported premarital sex. The median ages at first intercourse and first marriage were 21 years and 28 years, respectively. In the total sample (including virgins), 13% reported any female non‐marital partner in the past 12 months, 7% contact with a female sex worker, and 2% sex with a man. Only 10% reported using a condom during most recent contact with a sex worker. STI symptoms in the past 3 months were reported by 8% of men. Laboratory tests disclosed that STI prevalence was 3.2%.
If and when HIV infection spreads among sex workers in Lahore, the reported behaviour of migrant men suggests that they may act as a conduit for further transmission to the general population. Condom promotion focused on the sex trade is likely to be the most effective way of reducing this risk.
PMCID: PMC2564715  PMID: 16877580
Pakistan; migrants; sex workers; sexual behaviour; condoms; HIV
5.  Prognostic value of systolic mitral annular velocity measured with Doppler tissue imaging in patients with chronic heart failure caused by left ventricular systolic dysfunction 
Heart  2005;92(6):775-779.
To assess the prognostic value of various conventional and novel echocardiographic indices in patients with chronic heart failure (CHF) caused by left ventricular (LV) systolic dysfunction.
185 patients with a mean (SD) age of 67 (11) years with CHF and LV ejection fraction < 45% despite optimal pharmacological treatment were prospectively enrolled. The patients underwent two dimensional echocardiography with tissue harmonic imaging to assess global LV systolic function and obtain volumetric data. Transmitral flow was assessed with conventional pulse wave Doppler. Systolic (Sm), early, and late diastolic mitral annular velocities were measured with the use of colour coded Doppler tissue imaging.
During a median follow up of 32 months (range 24–38 months in survivors), 34 patients died and one underwent heart transplantation. Sm velocity (hazard ratio (HR) 0.648, 95% confidence interval (CI) 0.463 to 0.907, p  =  0.011), diastolic arterial pressure (HR 0.965, 95% CI 0.938 to 0.993, p  =  0.015), serum creatinine (HR 1.006, 95% CI 1.001 to 1.011, p  =  0.023), LV ejection fraction (HR 0.945, 95% CI 0.899 to 0.992, p  =  0.024), age (HR 1.035, 95% CI 1.000 to 1.071, p  =  0.052), LV end systolic volume index (HR 1.009, 95% CI 0.999 to 1.019, p  =  0.067), and restrictive pattern of transmitral flow (HR 0.543, 95% CI 0.278 to 1.061, p  =  0.074) predicted the outcome of death or transplantation on univariate analysis. On multivariate analysis, only Sm velocity (HR 0.648, 95% CI 0.460 to 0.912, p  =  0.013) and diastolic arterial pressure (HR 0.966, 95% CI 0.938 to 0.994, p  =  0.016) emerged as independent predictors of outcome.
In patients with CHF and LV systolic dysfunction despite optimal pharmacological treatment, the strongest independent echocardiographic predictor of prognosis was Sm velocity measured with quantitative colour coded Doppler tissue imaging.
PMCID: PMC1860660  PMID: 16251233
congestive heart failure; left ventricular dysfunction; diastole; Doppler echocardiography; prognosis
6.  Comparison of the dual receptor endothelin antagonist enrasentan with enalapril in asymptomatic left ventricular systolic dysfunction: a cardiovascular magnetic resonance study 
Heart  2005;92(6):798-803.
To compare the effect of the dual endothelin A/B receptor antagonist enrasentan with enalapril on left ventricular (LV) remodelling.
Multicentre, randomised, double blind, parallel group study of 72 asymptomatic patients with LV dysfunction. Patients received enrasentan (60–90 mg/day) or enalapril (10–20 mg/day). The primary end point was the change in LV end diastolic volume index (EDVI) after six months' treatment.
LV EDVI increased with enrasentan but decreased with enalapril (3.9 (1.8) v −3.4 (1.4) ml/m2, p  =  0.001). Enrasentan increased resting cardiac index compared with enalapril (0.11 (0.07) v −0.10 (0.07) l/m2, p  =  0.04), as well as LV mass index (0.67 (1.6) v −3.6 (1.6) g/m2, p  =  0.04). Other variables were comparable between groups. Enalapril lowered brain natriuretic peptide more than enrasentan (–19.3 (9.4) v –5.8 (6.9) pg/ml, p  =  0.005). Noradrenaline (norepinephrine) (p  =  0.02) increased more with enrasentan than with enalapril. Enrasentan was associated with more serious adverse events compared with enalapril (six (16.7%) patients v one (2.8%), p  =  0.02); the rate of progression of heart failure did not differ.
In asymptomatic patients with LV dysfunction, LV EDVI increased over six months with enrasentan compared with enalapril treatment, with adverse neurohormonal effects. This suggests that enrasentan at a dose of 60–90 mg/day over six months causes adverse ventricular remodelling despite an increase in the resting cardiac index.
PMCID: PMC1860639  PMID: 16339819
left ventricle; endothelin antagonist; remodelling; enrasentan; cardiovascular magnetic resonance
7.  Chronic heart failure, chronotropic incompetence, and the effects of β blockade 
Heart  2005;92(4):481-486.
To establish the prevalence of chronotropic incompetence in a cohort of patients with chronic heart failure (CHF) taking modern medications for heart failure, and whether this affected exercise capacity and predicted prognosis.
Heart rate response to exercise was examined in 237 patients with CHF in sinus rhythm, who were compared with 118 control volunteers. The percentage of maximum age predicted peak heart rate (%Max‐PPHR) and percentage heart rate reserve (%HRR) were calculated, with a cut off of < 80% as the definition of chronotropic incompetence for both. Patients were followed up for an average (SD) of 2.8 (9) years. Mortality was related to peak oxygen consumption (pVo2), and the presence or absence of chronotropic incompetence.
%Max‐PPHR < 80% identified 103 (43%) and %HRR < 80% identified 170 patients (72%) as having chronotropic incompetence. Chronotropic incompetence was more common in patients taking β blockers than in those not taking β blockers as assessed by both methods (80 (49%) v 23 (32%) by %Max‐PPHR and 123 (75%) v 47 (64%) by %HRR, respectively). Patients with chronotropic incompetence by either method had a lower pVo2 than those without. These differences remained significant for both patients taking and not taking a β blocker. %HRR, Max‐PPHR%, and HRR were related to New York Heart Association class and correlated with pVo2. There was no difference in the slopes relating heart rate to pVo2 between patients with and those without chronotropic incompetence (6.1 (1.7) v 5.1 (1.8), p  =  0.34). During an average 2.8 year follow up 40 patients (17%) died. In Cox proportional hazard models, pVo2 was the most powerful predictor of survival and neither measure of chronotropic incompetence independently predicted outcome.
pVo2 is a powerful marker of prognosis for patients with CHF whether they are taking β blockers or not. A low heart rate response to exercise in patients with CHF correlates with worse exercise tolerance but is unlikely to contribute to exercise impairment.
PMCID: PMC1860848  PMID: 16159968
chronic heart failure; heart rate; β blockers
8.  Effect of a community heart failure clinic on uptake of β blockers by patients with obstructive airways disease and heart failure 
Heart  2005;92(3):331-336.
To determine the pattern of β blocker prescribing over one year in a heart failure clinic with a structured approach towards initiation and dose titration and to give a real life perspective on β blocker use, compliance, and target dose achievement.
Data were retrospectively analysed on 513 consecutive patients regularly attending a community heart failure clinic over a year. Systolic dysfunction was determined from two dimensional echocardiography (left ventricular ejection fraction ⩽ 40%) and lung function was assessed by spirometry. All patients were considered for β blocker initiation and dose up titration.
Within one year 157 patients died. 143 patients started β blockers resulting in 315 (88%) patients taking β blockers at one year; 38% were taking the target dose. 124 had evidence of airways obstruction at baseline, 100 (81%) of whom were taking β blockers at one year. Forced expiratory volume in one second (1.1 v 1.5 l, p < 0.01) and forced vital capacity (2.3 v 2.5 l/min, p  =  0.2) were not reduced in patients with airways obstruction who received β blockers. Daily doses of β blockers at one year did not differ statistically between patients with obstructive and patients with non‐obstructive spirometry results. 12 patients discontinued β blockers and 14 required dose reduction due to side effects.
The majority of patients with heart failure and obstructive airways disease can safely tolerate low dose initiation and gradual up titration of β blockers.
PMCID: PMC1860814  PMID: 15951394
heart failure; β blockers; chronic obstructive pulmonary disease
9.  Relation between severity of left ventricular systolic dysfunction and repolarisation abnormalities on the surface ECG: a report from the Euro heart failure survey 
Heart  2006;92(2):255-256.
PMCID: PMC1860786  PMID: 16415196
QT interval; QRS duration; repolarisation; heart failure; electrocardiography; ECG
10.  Exercise training has greater effects on insulin sensitivity in daughters of patients with type 2 diabetes than in women with no family history of diabetes 
Diabetologia  2008;51(10):1912-1919.
Sedentary offspring of patients with type 2 diabetes are often more insulin-resistant than persons with no family history of diabetes, but when active or fit offspring of type 2 diabetic patients are compared with non-diabetic persons, differences in insulin resistance are less evident. This study aimed to determine the effects of an exercise training intervention on insulin sensitivity in both groups.
Women offspring (n = 34) of type 2 diabetic patients (offspring age 35.6 ± 7.0 years, BMI 28.1 ± 5.1 kg/m2) and 36 matched female controls (age 33.6 ± 6.1 years, BMI 27.3 ± 4.7 kg/m2) participated. Body composition, fitness and metabolic measurements were made at baseline and after a controlled 7 week exercise intervention.
At baseline, insulin sensitivity index (ISI) was 22% lower in offspring than controls (p < 0.05), despite similar body fat and maximal oxygen uptake \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\left( {\dot VO_{2\max } } \right)$$\end{document} values in the two groups. ISI increased by 23% (p < 0.05) in offspring following the exercise intervention, compared with 7% (NS) in the controls. Increases in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot VO_{2\max } $$\end{document} were similar in both groups (controls 12%, offspring 15%, p < 0.05 for both). Plasma leptin concentrations decreased significantly in the offspring (−24%, p < 0.01) but not in controls (0%, NS). Change in ISI correlated significantly with baseline ISI (r = −0.47, p < 0.0005) and change in leptin (r = −0.43, p < 0.0005). The latter relationship was not attenuated by adjustment for changes in body fat.
Offspring, but not controls, significantly increased ISI in response to an exercise intervention, indicating that insulin sensitivity is more highly modulated by physical activity in daughters of patients with type 2 diabetes than in women with no family history of the disease.
Trial registration: NCT00268541
Funding: British Heart Foundation (PG/03/145).
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-008-1097-6) contains supplementary material, which is available to authorised users.
PMCID: PMC2584356  PMID: 18663427
Diabetes family history; Exercise; Insulin resistance; Insulin sensitivity; Leptin; Offspring; Training; Women
11.  Multidisciplinary interventions in heart failure 
Heart  2005;91(7):849-850.
A National Service Framework for heart failure is urgently needed
PMCID: PMC1769010  PMID: 15958338
heart failure; multidisciplinary interventions; National Service Framework
12.  Early sexual debut among young men in rural South Africa: heightened vulnerability to sexual risk? 
Sexually Transmitted Infections  2005;81(3):259-261.
Methods: Analysis of sexual behaviour data for men 15–24 years (n = 314) from representative cross sectional household survey.
Results: 13.1% of 15–24 year old men experienced sexual debut before age 15. Men with sexual debut at less than age 15 were more likely to report risk behaviours at first sexual experience: no condom use (19%), a casual partner (26.8%), and not feeling they had been "ready and wanted to have sex" (19.5%). In multivariate analysis, early sexual debut was strongly associated with ⩾3 partners in the past 3 years (OR = 10.26, p<0.01).
Conclusions: Men who initiate sex before age 15 form a distinct risk group in this setting. Specific interventions are needed for young men in the preteen years, before sexual debut.
PMCID: PMC1744981  PMID: 15923298
13.  Epidemiology and management of heart failure and left ventricular systolic dysfunction in the aftermath of a myocardial infarction 
Heart  2005;91(Suppl 2):ii7-ii13.
Robust epidemiological data on the incidence of myocardial infarction (MI) are hard to find, but synthesis of data from a number of sources indicates that the average hospital in the UK should admit about two patients with a first MI and one recurrent MI per 1000 population per year. Possibly the most relevant data on the incidence, prevalence, and persistence of post-MI heart failure can be derived from the TRACE study. Most patients will develop heart failure or major left ventricular systolic dysfunction (LVSD) at some time after an MI, most commonly during the index admission. In up to 20% of cases this will be transient, but such patients still have a poor prognosis. There is likely to be around one patient discharged per thousand population per year with heart failure or major LVSD after an acute MI. It is important to organise care structures to ensure that patients with post-MI heart failure and LVSD are identified and managed appropriately.
PMCID: PMC1876349  PMID: 15831613
14.  Monitoring sexual behaviour in general populations: a synthesis of lessons of the past decade 
Sexually Transmitted Infections  2004;80(Suppl 2):ii1-ii7.
This supplement contains selected papers from a workshop on the measurement of sexual behaviour in the era of HIV/AIDS held at the London School of Hygiene and Tropical Medicine in September 2003. The focus was on low and middle income countries, where the majority of HIV infections occur. The motive for holding such a meeting is easy to discern. As the AIDS pandemic continues to spread and as prevention programmes are scaling up, the need to monitor trends in sexual risk behaviours becomes ever more pressing. Behavioural data are an essential complement to biological evidence of changes in HIV prevalence or incidence. Biological evidence, though indispensable, is by itself insufficient for policy and programme guidance. AIDS control programmes need to be based on monitoring of not only trends in infections but also of trends in those behaviours that underlie epidemic curtailment or further spread.
PMCID: PMC1765850  PMID: 15572634
15.  Exercise capacity and cardiac function assessed by tissue Doppler imaging in chronic heart failure 
Heart  2004;90(10):1144-1150.
Objective: To examine the relation between longitudinal left ventricular function assessed by tissue Doppler imaging (TDi) and exercise capacity in heart failure.
Subjects: 153 patients with chronic heart failure from left ventricular systolic dysfunction (ejection fraction < 45%) and 87 age and sex matched controls.
Methods: Echocardiography was used to measure conventional indices of left ventricular systolic function. TDi was used to assess left and right ventricular longitudinal function by measuring mitral and lateral tricuspid annular velocities during the cardiac cycle. Velocities measured at each point were the systolic peak (Sm) and the diastolic troughs (Em and Am), corresponding to passive and active (atrial) left ventricular filling. Each patient also underwent treadmill exercise testing with metabolic gas exchange measurements.
Results: Left and right ventricular TDi velocities were greater in controls than in patients. Left ventricular ejection fraction (LVEF) correlated with Sm (r  =  0.30, p  =  0.0005), but not with Em, Am, or the Em/Am ratio. There were no significant differences between New York Heart Association (NYHA) functional class for any of the TDi variables. Right ventricular indices were not related to exercise capacity. Systolic myocardial motion measured by TDi correlated more closely with peak oxygen consumption (pV̇o2) (r  =  0.35, p < 0.0001) than LVEF (r  =  0.21, p < 0.02). The Em/Am ratio was not correlated with pV̇o2. In multiple regression, Sm was the only left ventricular TDi variable to predict exercise capacity independently (p < 0.05).
Conclusions: Exercise capacity and symptoms are poorly related to conventional measures of cardiac function and more closely correlated with indices of longitudinal left ventricular function as assessed by TDi.
PMCID: PMC1768502  PMID: 15367509
chronic heart failure; breathlessness; echocardiography; tissue Doppler imaging
16.  The utility of a comprehensive cardiac magnetic resonance examination for the evaluation of patients with heart failure 
Heart  2004;90(10):1166.
PMCID: PMC1768469  PMID: 15367515
Images in cardiology
17.  Low grade inflammation is notably suppressed by conventional anti-inflammatory treatment: a randomised crossover trial 
Heart  2004;90(7):804-805.
PMCID: PMC1768325  PMID: 15201258
C reactive protein; cortisol; statin; steroid
18.  Effects of carvedilol on left ventricular remodelling in chronic stable heart failure: a cardiovascular magnetic resonance study 
Heart  2004;90(7):760-764.
Background: The ability of β blockers to improve left ventricular function has been demonstrated, but data on the effects on cardiac remodelling are limited.
Objective: To investigate, using cardiovascular magnetic resonance (CMR), the effects of carvedilol on left ventricular remodelling in patients with chronic stable heart failure and left ventricular systolic dysfunction caused by coronary artery disease.
Design: Randomised, double blind, placebo controlled study.
Setting: Chronic stable heart failure.
Patients and intervention: 34 patients with chronic stable heart failure and left ventricular systolic function taking part in the CHRISTMAS trial (double blind carvedilol v placebo) underwent CMR before randomisation and after six months of treatment.
Main outcome measure: Left ventricular remodelling at six months.
Results: The carvedilol and placebo groups were well balanced at baseline, with no significant intergroup differences. Over the study period, there was a significant reduction in end systolic volume index (ESVI) and end diastolic volume index (EDVI) between the carvedilol and the placebo group (carvedilol −9 v placebo +3 ml/m2, p  =  0.0004; carvedilol −8 v placebo 0 ml/m2, p  =  0.05). The ejection fraction increased significantly between the groups (carvedilol +3% v placebo −2%, p  =  0.003).
Conclusions: Treatment of chronic stable heart failure with carvedilol results in significant improvement in left ventricular volumes and function. These effects might contribute to the benefits of carvedilol on mortality and morbidity in patients with chronic heart failure.
PMCID: PMC1768304  PMID: 15201244
β blockers; remodelling; heart failure; magnetic resonance imaging
19.  The effects of α and β blockade on ventilatory responses to exercise in chronic heart failure 
Heart  2003;89(10):1169-1173.
Objective: To assess the influence of acute α and β blockade on ventilation and symptoms of breathlessness during exercise in patients with chronic heart failure and in controls.
Methods: 11 patients with chronic heart failure and 11 control subjects underwent repeated exercise testing with metabolic gas exchange after random, double blind administration of either an α blocker and placebo, a β blocker and a placebo, both an α blocker and a β blocker, or double placebo.
Results: Patients had a lower peak oxygen consumption (mean (SD) 20.7 (4.9) v 37.6 (9.6) ml/kg/min, p < 0.0001) and a steeper slope relating ventilation to carbon dioxide production (VE/V̇co2 slope) (26.5 (4.1) v 37.1 (8.2), p = 0.0011), than controls. Blood pressure was lower following α and β blockade (p < 0.05) and the gradients of the slopes relating heart rate to oxygen consumption following the β blocker were reduced (p < 0.05). Exercise time and peak ventilatory variables following β or α blockers were unchanged. Ventilation was reduced during submaximal exercise following the active medications. Combined α and β blockade produced the greatest difference (p < 0.005), but the α and β blockers alone also reduced ventilation (p < 0.05). There was no difference in perceived exertion during exercise with any of the treatments.
Conclusion: Acute sympathetic inhibition can reduce submaximal ventilation during exercise in patients with heart failure and control subjects, suggesting that autonomic nervous system activation has an important role in the abnormal ventilatory response to exercise in chronic heart failure.
PMCID: PMC1767894  PMID: 12975409
α receptors; β receptors; ventilatory response; chronic heart failure; exercise testing
20.  Pattern of ventilation during exercise in chronic heart failure 
Heart  2003;89(6):610-614.
Objective: To determine the pattern of the abnormal ventilatory response in heart failure and how it relates to symptoms by looking at tidal volume (Vt) and frequency (f) during exercise.
Methods: 45 patients with heart failure and 21 controls underwent maximal treadmill based exercise testing with metabolic gas exchange analysis. The relation of ventilation (V̇E) to Vt was plotted to look for an inflection point where Vt failed to increase further. The slope of the relation before this inflection point was documented. Time to the inflection point, Vt, and f at the inflection point were recorded. The relation of symptom scores to f and V̇E was also examined.
Results: Peak oxygen consumption (PV̇o2) (mean (SD)) was lower (19.7 (4.5) v 37.9 (8.6) ml/kg/min; p < 0001) and the ventilation to carbon dioxide production (V̇E/V̇co2) slope was steeper (40.0 (6.5) v 26.0 (1.6); p < 0.0001) in patients with heart failure than in the control group. The patients reached the inflection point of the V̇E/Vt slope sooner during exercise than the controls (271 (110) v 502 (196) seconds; p < 0.0001). Patients had a higher f and a smaller Vt at that point and throughout exercise until the peak where f was the same for patients and controls. Vt at the inflection point correlated with PV̇o2 (r = 0.67; p < 0.0001). Despite having an increased sensation of breathlessness for a given V̇E, patients were less symptomatic of f than controls.
Conclusions: Patients with heart failure breathe at a higher f throughout exercise, reaching an apparent maximal Vt earlier. The Vt at an inflection point on the V̇E/Vt slope predicts PV̇o2.
PMCID: PMC1767691  PMID: 12748213
chronic heart failure; ventilation; frequency; breathlessness
21.  Mode of death in heart failure: findings from the ATLAS trial 
Heart  2003;89(1):42-48.
Objective: To investigate markers that predict modes of death in patients with chronic heart failure.
Design: Randomised, double blind, three period, comparative, parallel group study (ATLAS, assessment of treatment with lisinopril and survival).
Patients: 3164 patients with mild, moderate, or severe chronic heart failure (New York Heart Association functional class II–IV).
Interventions: High dose (32.5 or 35 mg) or low dose (2.5 or 5 mg) lisinopril once daily for a median of 46 months.
Main outcome measures: All cause mortality, cardiovascular mortality, sudden death, and chronic heart failure death related to prognostic factors using competing risks analysis. Mode of death was classified by trialists and by an independent end point committee.
Results: Age, male sex, pre-existing ischaemic heart disease, increasing heart rate, creatinine concentration, and certain drugs taken at randomisation were markers of increased risk of all cause mortality and cardiovascular death. There were risk markers for sudden death that were different from the risk markers for death from chronic heart failure. Low systolic blood pressure at baseline, raised creatinine, reduced serum sodium or haemoglobin, and increased heart rate were associated with chronic heart failure death. Use of β blockers or antiarrhythmic agents (mainly amiodarone) was associated with a reduced risk of sudden death, whereas long acting nitrates and previous use of angiotensin converting enzyme inhibitors were markers for increased risk.
Conclusions: The use of competing risks analysis on the data from the ATLAS study has identified variables associated with certain modes of death in heart failure patients. This approach to analysing outcomes may make it possible to predict which patients might benefit most from particular therapeutic interventions.
PMCID: PMC1767481  PMID: 12482789
congestive heart failure; lisinopril; competing risks analysis; predictive factors
22.  Contemporary management of heart failure in clinical practice 
Heart  2002;88(Suppl 2):ii5-ii8.
PMCID: PMC1876266  PMID: 12213792
23.  Surveys on sexual health: recent developments and future directions 
Sexually Transmitted Infections  2001;77(4):238-241.
The increasingly widespread adoption of the term sexual health reflects a move away from the medicalisation of this specialty. The focus has shifted from clinical practice to lifestyle and behaviour; from clinician to client, and from treatment to prevention. This article discusses these themes, identifying their implications for sexual health research. Recent times have seen, for example, a growing number of studies combining biological and behavioural measures conducted by interdisciplinary teams able to combine biomedical measurements of morbidity with insights into the subjective interpretations of symptoms and consequences. Considerable progress has been made, too, in mounting community based studies, and much has been achieved in gaining compliance and refining sampling methods. Integrated sexual health services, encompassing more than contraceptive or prophylactic service provision, have provided the impetus to investigation of the costs and benefits of coordinated family planning and genitourinary medicine services. Despite its broader focus, there remain opportunities for sexual health research to expand its remit. Studies to date may have focused too narrowly on pathological, to the neglect of health enhancing, consequences of sexual behaviour.
Key Words: surveys; sexual health
PMCID: PMC1744341  PMID: 11463921
24.  Improving patient outcomes in heart failure: evidence and barriers 
Heart  2000;84(Suppl 1):i8-i10.
PMCID: PMC1766537  PMID: 10956311

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