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Background: Coronavirus disease-19 (COVID-19) infection causes persistent health problems such as breathlessness, chest pain and fatigue, and therapies for the prevention and early treatment of post-COVID-19 syndromes are needed. Accordingly, we are investigating the effect of a resistance exercise intervention on exercise capacity and health status following COVID-19 infection.Methods: A two-arm randomised, controlled clinical trial including 220 adults with a diagnosis of COVID-19 in the preceding 6 months. Participants will be classified according to clinical presentation: Group A, not hospitalised due to COVID but persisting symptoms for at least 4 weeks leading to medical review; Group B, discharged after an admission for COVID and with persistent symptoms for at least 4 weeks; or Group C, convalescing in hospital after an admission for COVID. Participants will be randomised to usual care or usual care plus a personalised and pragmatic resistance exercise intervention for 12 weeks. The primary outcome is the incremental shuttle walks test (ISWT) 3 months after randomisation with secondary outcomes including spirometry, grip strength, short performance physical battery (SPPB), frailty status, contacts with healthcare professionals, hospitalisation and questionnaires assessing health-related quality of life, physical activity, fatigue and dyspnoea.Discussion: Ethical approval has been granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (REC) (reference: GN20CA537) and recruitment is ongoing. Trial findings will be disseminated through patient and public forums, scientific conferences and journals.Trial Registration: ClinicialTrials.gov NCT04900961 . Prospectively registered on 25 May 2021. [ABSTRACT FROM AUTHOR]

Background: Heart failure is heterogeneous in aetiology, pathophysiology, and presentation. Despite this diversity, clinical trials of patients hospitalized for HF deal with this problem as a single entity, which may be one reason for repeated failures. Methods: The first EuroHeart Failure Survey screened consecutive deaths and discharges of patients with suspected heart failure during 2000–2001. Patients were sorted into seven mutually exclusive hierarchical presentations: (1) with cardiac arrest/ventricular arrhythmia; (2) with acute coronary syndrome; (3) with rapid atrial fibrillation; (4) with acute breathlessness; (5) with other symptoms/signs such as peripheral oedema; (6) with stable symptoms; and (7) others in whom the contribution of HF to admission was not clear. Results: The 10,701 patients enrolled were classified into the above seven presentations as follows: 260 (2%), 560 (5%), 799 (8%), 2479 (24%), 1040 (10%), 703 (7%), and 4691 (45%) for which index-admission mortality was 26%, 20%, 10%, 8%, 6%, 6%, and 4%, respectively. Compared to those in group 7, the hazard ratios for death during the index admission were 4.9 (p ≤ 0.001), 4.0 (p < 0.001), 2.2 (p < 0.001), 2.1 (p < 0.001), 1.4 (p < 0.04) and 1.4 (p = 0.04), respectively. These differences were no longer statistically significant by 12 weeks. Conclusion: There is great diversity in the presentation of heart failure that is associated with very different short-term outcomes. Only a minority of hospitalizations associated with suspected heart failure are associated with acute breathlessness. This should be taken into account in the design of future clinical trials. [ABSTRACT FROM AUTHOR]

Summary: Objective: Cardiopulmonary exercise testing (CPET) is the ‘gold standard’ method of determining VO2peak. When CPET is unavailable, VO2peak may be estimated from treadmill or cycle ergometer workloads and expressed as estimated metabolic equivalents (METs). Cardiac rehabilitation (CR) programmes use estimated VO2peak (METs) to report changes in cardiorespiratory fitness (CRF). However, the accuracy of determining changes in VO2peak based on estimated functional capacity is not known. Methods: A total of 27 patients with coronary heart disease (88·9% male; age 59·5 ± 10·0 years, body mass index 29·6 ± 3·8 kg m−2) performed maximal CPET before and after an exercise‐based CR intervention. VO2peak was directly determined using ventilatory gas exchange data and was also estimated using the American College of Sports Medicine (ACSM) leg cycling equation. Agreement between changes in directly determined VO2peak and estimated VO2peak was evaluated using Bland–Altman limits of agreement (LoA) and intraclass correlation coefficients. Results: Directly determined VO2peak did not increase following CR (0·5 ml kg−1 min−1 (2·7%); P = 0·332). Estimated VO2peak increased significantly (0·4 METs; 1·4 ml kg−1 min−1; 6·7%; P = 0·006). The mean bias for estimated VO2peak versus directly determined VO2peak was 0·7 ml kg−1 min−1 (LoA −4·7 to 5·9 ml kg−1 min−1). Aerobic efficiency (ΔVO2/ΔWR slope) was significantly associated with estimated VO2peak measurement error. Conclusion: Change in estimated VO2peak derived from the ACSM leg cycling equation is not an accurate surrogate for directly determined changes in VO2peak. Our findings show poor agreement between estimates of VO2peak and directly determined VO2peak. Applying estimates of VO2peak to determine CRF change may over‐estimate the efficacy of CR and lead to a different interpretation of study findings. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether age-related increases in N-terminal pro-brain natriuretic peptide (NT-proBNP) represent a normal physiological process—possibly affecting the prognostic power—of NT-proBNP—or reflect age-related subclinical pathological changes. Objective: To determine the effect of age on the short-term prognostic value of NT-proBNP in patients with chronic heart failure (CHF). Design: Prospective observational study with inclusion and matching of consecutive patients aged >65 years (mean (SD) 73.1 (6.0) years) to patients <65 years (53.7 (8.6) years) with respect to NT-proBNP, New York Heart Association stage, sex and aetiology of CHF (final n = 443). Setting: University hospital outpatient departments in the UK and Germany. Patients: Chronic stable heart failure due to systolic left ventricular dysfunction. Intervention: None. Outcome measure: All-cause mortality. Results: In both age groups, NT-proBNP was a significant univariate predictor of mortality, and independent of age, sex and other established risk markers. The prognostic information given by NT-proBNP was comparable between the two groups, as reflected by the 1-year mortality of 9% in both groups. The prognostic accuracy of NT-proBNP as judged by the area under the receiver operating characteristics curve for the prediction of 1-year mortality was comparable for elderly and younger patients (0.67 vs 0.71; p = 0.09). Conclusion: NT-proBNP reflects disease severity in elderly and younger patients alike. In patients with chronic stable heart failure, the NT-proBNP value carries the same 1-year prognostic information regardless of the age of the patient. [ABSTRACT FROM PUBLISHER]

Background: Epidemiological studies suggest that "diastolic heart failure" )DHF) is common and has a prognosis similar to that of systolic heart failure (SHE). We wanted to assess whether patients with breathlessness who were being treated for UHF had objective evidence of cardiac impairment and exercise limitation. Methods: Consecutive patients with a clinical diagnosis of chronic heart failure completed a standardised 6- minute walk test )6-M\NT) and underwent an echocardiographic examination to determine the presence of major structural heart disease )MSHD). N-terminal pro- brain natriuretic peptide )NT-proBNP) was measured to determine degree of cardiac pathology. Results: 568 patients were identified with SHF (75.7% males) and 104 with DHF (54.7% males). They were compared with 400 healthy controls (matched with DHF group for age, sex and body mass index (BMI)). Controls (median )interquartile range); 43)20-62) pmol/l)) and DHF patients )27 )13-67) pmol/l) had significantly lower NT-proBNP levels compared to SHF patients (178 (82- 422) pmol/l). There was no difference in NT-proBNP levels between controls and DHF patients (p = 0.348). There was no correlation between BMI and NT-proBNP in either UHF )r2 = 0.03; p = 0.287) or SHF )r2 = 0.02; p = 0.346) patients. Both SHF and UHF patients reported similar degrees of breathlessness. 6-MWT distance )p = 0.973) was similar between SHE and DHF patients. UHF patients had a higher BMI (p<0.0001). Conclusion: Patients being treated for a clinical diagnosis of UHF have the same self-reported symptoms and 6- MVVT performance as patients with SHF, yet have normal NT-proBNP levels. Their perception of their symptoms is out of proportion to their evidence of cardiac pathology. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated gender differences in clinical characteristics, treatment and outcome among patients with heart failure, and to what extent these differences are due to age and differences in left ventricular (LV) function. Although gender differences are observed among heart failure patients, few studies have been adequately powered to investigate these differences. Methods: A total of 8914 (out of 10 701) patients (47% women) from the Euro Heart Survey on Heart Failure with confirmed diagnosis of heart failure were included in the analyses. Results: Women were older (74.7 vs 68.3 years, p,0.001), and less often had evidence of coronary artery disease (56% vs 66%, age-adjusted odds ratio (OR) 0.62; 95% CI 0.57 to 0.68). Women were more likely to have hypertension, diabetes, or valvular heart disease. Fewer women had an investigation of LV function (59% vs 74%, age-adjusted OR 0.67; 95% CI 0.61 to 0.74), and, among those investigated, fewer had moderate/severe left ventricular systolic dysfunction (44% vs 71%, age-adjusted OR 0.35; 95% CI 0.32 to 0.39). Drugs with a documented impact on survival, that is ACE-inhibitors and β-blockers, were given less often to women, even in the adjusted analysis (OR 0.72; 95% CI 0.61 to 0.86 and OR 0.76; 95% CI 0.65 to 0.89, respectively). 12-week mortality was similar for men and women. Conclusions: Fewer women had an assessment of LV function, but, when investigated, women had better ventricular function. Women were less often treated with evidence-based drugs, even after adjustment for age and important clinical characteristics. Clinicians need to be aware of deficiencies in the treatment of women with heart failure and measures should be taken to rectify them. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronisation therapy (CAT) improves symptoms and prognosis in patients with heart failure and cardiac dyssynchrony. Guidelines from the National Institute of Health and Clinical Excellence in the United Kingdom recommend CAT for patients with recent or persistent moderate or severe symptoms of heart failure. This analysis investigated whether the severity of symptoms was an important determinant of the prognostic benefits of CAT. Methods: In CARE-HF, patients with left ventricular ejection fraction ⩽35% and markers of cardiac dyssynchrony who were, in the investigators' opinion, in New York Heart Association INYHAI class lll/IV were randomly assigned to pharmacological treatment alone or with addition of CRT. This analysis investigated whether the severity of symptoms reported by patients, using Likert Scales from the EuroHeart Failure Questionnaire and self-assessed NYHA class, influenced prognosis and the response to CRT. Results: Of 813 patients, 175 121.5%) assessed themselves to be in NYHA class I or II. These patients also reported less severe symptoms and better quality of life than patients who assessed themselves to be in NYHA class Ill or IV. No statistical interaction was observed between the severity of symptoms assessed in several ways and the benefits of CRT on morbidity and mortality. Conclusions: The severity of symptoms was not an important determinant of the prognostic effects of CRT in patients with moderate or severe LVSD and markers of dyssynchrony in the CARE-HF study. This finding requires confirmation in an adequately powered prospective randomised controlled trial in patients with milder symptoms. [ABSTRACT FROM AUTHOR]

Objectives: To obtain national data on demographics, investigation, treatment and short-term outcome for patients admitted with acute heart failure. Design: Retrospective survey of emergency admissions with acute heart failure from October 2005 to March 2006. Setting: Acute NHS trusts in England, Wales and Northern Ireland. Main Outcome Measures: Patient demographics, referral source, admission characteristics, admission pathway, patient heart failure treatment on admission, length of stay, short-term mortality, discharge heart failure treatment, specialist follow-up and delayed discharge. Results: 176/177 (99%) acute trusts responded and 9387 records were surveyed. Patients mean age was 77 (SD 11) years, 50% were women and 56% had prior history of heart failure. On average, women were 5 years older than men (80 vs 75 years, p<0.001), were less likely to have had echocardiography (52% vs 60%, p<0.001), and if previously diagnosed with heart failure less likely to be treated with ACE inhibitors (58.3% vs 66.8%, p<0.001), beta-blockers (30.1% vs 35.5%, p = 0.033) or aldosterone antagonists (18.9% vs 22.5%, p<0.001) at admission. In-hospital mortality was 15%. Age-adjusted mortality was higher in men (16% vs 14%, p = 0.042). 75% of patients were admitted with moderate to severe symptoms (NYHA class III or IV). Women were less likely to be prescribed anti-failure medication, except diuretics, on discharge (ACE-I/AIIRA 66.5% vs 73.4%, beta-blocker 31.3% vs 37.5%, aldosterone antagonists 23.4% vs 30.1%, all p<0.001). Only 20% of patients had planned specialist heart failure follow-up, with <1% referred for rehabilitation or specialist palliative care. Conclusion: Many patients admitted to acute hospitals in England, Wales and Northern Ireland are not being managed fully in accordance with international evidence-based guidelines. In comparison with earlier UK studies, the use of echocardiography and ACE-I and beta-blockers has increased, and length of stay reduced. Only a minority of patients are seen, or followed up, by a specialist service. Women seem to be less well managed against recommended guidelines. Significant and sustained effort is required to address gender inequalities in the provision of heart failure care. [ABSTRACT FROM AUTHOR]

Objectives: To obtain national data on demographics, investigation, treatment and short-term outcome for patients admitted with acute heart failure. Design: Retrospective survey of emergency admissions with acute heart failure from October 2005 to March 2006. Setting: Acute NHS trusts in England, Wales and Northern Ireland. Main outcome measures: Patient demographics, referral source, admission characteristics, admission pathway, patient heart failure treatment on admission, length of stay, short-term mortality, discharge heart failure treatment, specialist follow-up and delayed discharge. Results: 176/177(99%) acute trusts responded and 9387 records were surveyed. Patients mean age was 77 (SD 11) years, 50% were women and 56% had prior history of heart failure. On average, women were 5 years older than men (80 vs 75 years, p<0.001), were less likely to have had echocardiography (52% vs 60%, p<0.001), and if previously diagnosed with heart failure less likely to be treated with ACE inhibitors (58.3% vs 66.8%, p<0.001), β-blockers (30.1% vs 35.5%, p = 0.033) or aldosterone antagonists (18.9% vs 22.5%, p<0.001) at admission. In-hospital mortality was 15%. Age-adjusted mortality was higher in men (16% vs 14%, p = 0.042). 75% of patients were admitted with moderate to severe symptoms (NYHA class III or IV). Women were less likely to be prescribed anti-failure medication, except diuretics, on discharge (ACE-I/AIIRA 66.5% vs 73.4%, β-blocker 31.3% vs 37.5%, aldosterone antagonists 23.4% vs 30.1%, all p<0.001). Only 20% of patients had planned specialist heart failure follow-up, with <1% referred for rehabilitation or specialist palliative care. Conclusion: Many patients admitted to acute hospitals in England, Wales and Northern Ireland are not being managed fully in accordance with international evidence-based guidelines. In comparison with earlier UK studies, the use of echocardiography and ACE-I and 3-blockers has increased, and length of stay reduced. Only a minority of patients are seen, or followed up, by a specialist service. Women seem to be less well managed against recommended guidelines. Significant and sustained effort is required to address gender inequalities in the provision of heart failure care. [ABSTRACT FROM AUTHOR]

Objective To examine the criterion validity of the Hospital Anxiety and Depression Scale (HADS) and the Geriatric Depression Scale 15-item (GDS-15) in a community sample of Chronic Heart Failure (CHF) out-patients. Methods Eighty-eight of 203 older adults with confirmed CHF responded to a postal survey and participated in a face-to-face interview. The GDS-15 and HADS were compared to diagnoses from the Structured Clinical Interview for DSM-IV (SCID-I), using a receiver operating characteristic (ROC) analysis and positive and negative predictive values, sensitivity and specificity for various cut-off points. Results For all depressive disorders, the area under the ROC curve for the GDS-15 was 0.883 and a cut-off of 5 gave a sensitivity of 0.818 and a specificity of 0.833. The area under the ROC curve for the HADS Depression (D) and Anxiety (A) were 0.889 and 0.941 respectively. At a cut-off of 7, the HADS-A gave a sensitivity of 0.938 and a specificity of 0.847. At a cut-off of 4, the HADS-D gave a sensitivity of 0.864 and a specificity of 0.788. Conclusions The GDS-15 and HADS are valid screening tools for detecting depression in aged CHF out-patients. However, use of the HADS requires reduced cut-points to ensure that patients with mood disorder are not missed in this population. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Angiotensin receptor blockers (ARB's) are an important class of antihypertensive agents and appear to have a role in the prevention and management of ischaemic stroke. We present a discussion of the data on ARB's in this important condition. [ABSTRACT FROM AUTHOR]

Objectives: 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.Methods: 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) (PSF(DD); n = 113 or 26% of referrals) and those without DD (PSF(N); n = 55 or 13% of referrals). The controls were divided into those with (C(DD); n = 32) and those without (C(N); n = 102) echocardiographic evidence of DD.Results: Patients with SHF had lower peak oxygen consumption (pVo(2)), steeper slope of minute ventilation (Ve) to carbon dioxide production, lower exercise time and shorter 6 min walk test than PSF patients and controls. PSF(DD) patients had lower pVo(2), exercise time and 6 min walk test than C(DD), although their echocardiograms were not different. Exercise capacity did not differ between PSF(DD) and PSF(N) patients. The slope relating Ve to symptoms (Borg/Ve slope) was less steep in those with SHF than in PSF(DD) (0.17 (0.04) v 0.20 (0.08), p < 0.05) and in PSF(N) (0.19 (0.10), p < 0.05), implying greater symptoms of breathlessness for a given level of Ve. Both PSF groups had a steeper slope than C(DD) (0.14 (0.09), p < 0.05 for both comparisons).Conclusions: Patients with PSF have exercise tolerance intermediate between that of patients with SHF and controls. Exercise tolerance is similar in PSF(DD) and PSF(N). Both groups have worse exercise tolerance than C(DD). PSF(DD) and PSF(N) patients seem to experience a greater awareness of Ve than C(DD) and patients with SHF. [ABSTRACT FROM AUTHOR]

Objectives: 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. Methods: 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 = 11 3 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. Results: Patients with SHF had lower peak oxygen consumption (pVo2), steeper slope of minute ventilation (VE) to carbon dioxide production, lower exercise time and shorter 6 mm walk test than PSF patients and controls. PSFDD patients had lower pVo2, exercise time and 6 mm walk test than CDD, although their echocardiograms were not different. Exercise capacity did not differ between PSFDD and PSFN patients. The slope relating VE to symptoms (Borg/VE 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 VE. Both PSF groups had a steeper slope than CDD (0.14 (0.09), p < 0.05 for both comparisons). Conclusions: 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 VE than CDD and patients with SHF. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective: To compare the effect of the dual endothelin A/B receptor antagonist enrasentan with enalapril on left ventricular (LV) remodelling. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective: To establish the prevalence of chronotropic incompetence in a cohort of patients with chronic heart failure (CHF) taking modern medications far heart failure, and whether this affected exercise capacity and predicted prognosis. Methods: 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. Results: %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 13 blockers than in those not taking 13 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. Conclusions: pVO2 is a powerful marker of prognosis for patients with CHF whether they are taking 13 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. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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 13 blocker initiation and dose up titration. Results: Within one year 157 patients died. 143 patients started 13 blockers resulting in 315 (88%) patients taking 13 blockers at one year; 38% were taking the target dose. 124 had evidence of airways obstruction at baseline, 100 (81%) of whom were taking 13 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. Conclusion: The majority of patients with heart failure and obstructive airways disease can safely tolerate low dose initiation and gradual up titration of β blockers. [ABSTRACT FROM AUTHOR]

Background. Treatment of angina recalcitrant to conventional pharmacological therapy and revascularization remains problematic. Safe, effective and affordable treatments with high patient acceptability are desirable. Enhanced external counterpulsation (EECP) may fulfil these criteria better than many other proposed interventions. Objective. To examine the immediate and long-term effect of EECP in treatment of chronic stable refractory angina. Design. Prospective observational study of consecutive patients treated with EECP and follow-up for 1 year. Setting. Teaching hospital. Main outcome measures. Canadian Cardiovascular Society (CCS) angina grading, weekly angina frequency and glyceryl trinitrate (GTN) use. Results. Sixty-one patients were treated with EECP and 58 completed a course of treatment. Further analysis is confined to those who completed EECP. About 52% of patients suffered from CCS III and IV angina prior to EECP. Immediately post-EECP, angina improved by at least one CCS class in 86% and by two classes in 59%. At 1-year follow-up, sustained improvement in CCS was observed in 78% of the patients. The median weekly angina frequency and GTN use were significantly reduced immediately after EECP [7 (4–14) vs. 1 (0–4) episodes per week and 7 (2–16) vs. 0 (0–2) times per week respectively, P < 0.0001; data in median (interquartile range)]. The reduction was sustained at 1-year follow-up. In 48 patients, their mean exercise time improved significantly after EECP [301 ± 130 s vs. 379 ± 147 s, P < 0.0001]. Major adverse treatment-related events were rare. Conclusion. This study shows that for patients who fail to respond to conventional measures, a high proportion gain symptomatic benefit from EECP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (election 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 (p&Vdot;o2) (r = 0.35, p <0.0001) than LVEF (r = 0.21, p <0.02). The Em/Am ratio was not correlated with p&Vdot;o2. 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. [ABSTRACT FROM AUTHOR]

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 we well balanced at baseline, with no significant intergroup differences. Over the study period, there was a significant reduction in end systolic volume index (ESV1) and end diastolic volume index (EDV1) 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. [ABSTRACT FROM AUTHOR]

To determine the cost to the NHS of prescribed low-dose aspirin. This was a population based observational cohort study. Patients from Tayside Scotland (17 244 new users of dispensed aspirin each with 10 matched comparators) were included. A pragmatic analysis totalled costs from the start to end of the study and compared these with a matched cohort of aspirin nonusers to estimate excess costs. Fastidious analyses were done of subjects with no prior history of upper gastrointestinal (UGI) or renal disease where the cost that occurred during aspirin exposure, the 30 days following aspirin exposure and subsequent nonexposure was calculated adjusting for risk factors in each period. Subjects took aspirin for only 1.18 of the 2.53 years follow-up (47% compliance). Aspirin use cost an additional £49.86 per year (pragmatic analysis) made up of £1.96 for aspirin tablets (4%), £5.49 for dispensing costs (11%), £24.60 for UGI complications (49%) and £17.81 for renal complications (36%). The costs for managing complications were substantially lower in the fastidious analysis (£2.66 for UGI complications and £2.92 for renal complications). Assuming that the antiplatelet trial meta-analysis is an accurate assessment of the benefits of aspirin, the costs of preventing one vascular event lay between £62 500 (primary prevention, pragmatic analysis) and £867 (secondary prevention, fastidious analysis). These costs may be underestimates due to the low compliance observed. Compliance with aspirin was poor. Serious adverse events were uncommon but despite this aspirin cost the NHS between 6 and 25 times the cost of aspirin tablets due to dispensing costs and the cost of managing adverse effects. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) is potentially an important new treatment for patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. There is growing evidence that CRT can improve symptoms although it is possible that similar benefits could be obtained by skilful manipulation of pharmacological therapy. There is also preliminary but inconclusive evidence to suggest that CRT alone or in synergy with an implant able cardiac defibrillator (lCD) may reduce morbidity and mortality. However, fashion is in danger of overtaking facts and it is important to ensure that benefits are not only statistically proven but clinically meaningful and cost-effective. Optimal timing of intervention and patient selection will be essential to ensure that treatment is deployed efficiently. If CRT with or without lCD becomes part of main-stream therapy for heart failure this will have far-reaching consequences for heart failure management. Implantation is a skilled and often time-consuming procedure. Long-term management of both CRT and lCD is likely to provide challenges in terms of lead technology, pacing thresholds and device management. Heart failure physicians will have to learn new skills and collaborate more closely with electrophysiologists. Such developments, in addition to the need for complex pharmacological interventions will accelerate the move away from general practice and towards specialist care for this most common of malignant diseases. If CRT does reduce mortality, it will graduate from an adjunctive therapy which could be used to an essential one that should be used as part of routine therapy for appropriate patients. Currently, CRT is a symptomatic therapy for patients with severe heart failure resistant to intensive pharmacological therapy delivered by a heart failure specialist. [ABSTRACT FROM AUTHOR]

A meta-analysis of the benefits of coronary artery bypass graft (CABG) surgery has been used as the basis of a model for comparing the costs and benefits of surgical and medical treatment of angina pectoris. In order to allow for the results of recent research, the economic model included the addition of aspirin and aspirin plus an HMG-CoA reductase inhibitor (statin) to medical management. The analysis indicates that in unselected patients the cost-effectiveness of CABG vs initial standard medical therapy over 5 years is towards the upper limit of what can be considered a cost-effective treatment both in terms of its effect on mortality (life-years gained) and morbidity (quality adjusted life-years). Addition of a statin to medical therapy reduced mortality and made coronary artery bypass graft surgery an expensive option in terms of improvement of quality of life. In patients with three-vessel disease or left ventricular dysfunction surgery appears fairly cost-effective in comparison with standard medical therapy but becomes relatively expensive when the benefits of aspirin or lipid-lowering therapy are added to medical treatment. [ABSTRACT FROM PUBLISHER]

Angina pectoris is a common symptom in patients over 50 years and is usually secondary to myocardial ischaemia resulting from coronary artery disease. The management of angina should be aimed at the maintenance or improvement of quality of life and delaying death. There are three strategies that may be adopted: medical, percutaneous transluminal coronary angioplasty and surgery. The majority of patients with angina can be controlled symptomatically most of the time by medical treatment alone. Any assessment of cost of treatment must take into account the cost of investigation, treatment, the morbidity associated with procedures or side effects of drugs, together with that of recurrent hospitalization, prolonged life and premature death. In addition, the duration of treatment has a major bearing on cost. Taking these factors into account, medical therapy is the least expensive short- and long-term treatment for angina pectoris. A medical approach to treatment also has considerable advantages over an interventional approach in terms of major morbidity. Only one of six surgical trials has demonstrated a survival benefit. [ABSTRACT FROM PUBLISHER]

The proportion of patients reported to die suddenly or from progressive circulatory failure is not consistent among studies of heart failure. Lack of an adequate or consistent classification of how patients die contributes to the current confusion over the mode of death in heart failure. Defining how patients with heart failure die could be important in developing strategies to reduce the continuing high mortality associated with this condition.We identified 27 studies that reported 50 or more deaths among patients with heart failure to ascertain how death was classified. Definitions of sudden death appeared heterogeneous and the majority of studies failed to publish or make reference to how circulatory failure was defined.A framework for the classification of the mode of death has been developed in which clear separation of the activity and place at the time of death, cause of death, mode of death, and events prior to death is made (ACME: Activity, Cause, Mode and Event). This mode of classifying death has been successfully piloted in two mortality studies; AIRE and NETWORK.Classifying mortality in this way will help identify pathways leading to death and hence suggest therapies and strategies to reduce mortality in patients with heart failure, a group of patients whose prognosis remains poor. [ABSTRACT FROM PUBLISHER]

There is a wealth of evidence that angiotensin converting enzyme (ACE) inhibitors improve symptoms, morbidity and mortality in patients with heart failure. In this context the use of ACE inhibitors could be considered a tool with which to assess the effect of trial design and methodology on the ability to detect improvement in symptoms and exercise performance.Thirty-five published, double-blind, randomized placebocontrolled trials, involving a total of 3411 patients, which compared the effect of ACE inhibitors and placebo on exercise capacity in patients with symptomatic chronic heart failure were identified. Studies were examined in relation to whether they used cross-over or parallel group study design, study size, use of treadmill vs bicycle exercise test, year of publication, patient entry criteria, duration of follow-up and the particular ACE inhibitor used.Exercise duration improved in 23 of the studies, while symptoms improved in 25 of the 33 studies which evaluated this. In the majority of the trials (27 of 33) there was concordance between the effect on symptoms and on exercise capacity. There were six trials which showed discrepant results. Study size, duration of follow-up and method of exercise testing used were found to be major factors affecting the outcome. Trials using treadmill exercise tests were more likely to be positive than those using bicycle ergometry. All nine trials with study size more than 50, follow-up of 3–6 months and using treadmill exercise tests showed improved exercise capacity as well as symptoms. These findings may be useful in designing future trials for evaluating treatment for heart failure. [ABSTRACT FROM PUBLISHER]

Marked neuro-endocrine activation in patients with heart failure indicates a worse prognosis and a greater prognostic benefit from the use of ACE inhibitors. However, although the incidence of heart failure rises rapidly with age, relatively little is known about activation of the renin-angiotensin and sympathetic nervous system in patients with heart failure over the age of 75 years. This study was undertaken to investigate plasma concentrations of neurohormonal variables in elderly patients referred to the cardiac clinic with a presumptive, but unconfirmed, diagnosis of heart failure, and to compare these values to plasma concentrations found in age-matched normal subjects. Fifty patients referred with a diagnosis of heart failure were studied. All were receiving a diuretic but not an ACE inhibitor. Patients with renal, haematological and valve disease were excluded Routine biochemistry and neuro-hormonal measurements were performed at their first visit, together with an electrocardiogram, chest X-ray and a full clinical examination by an experienced cardiologist. An echocardiogram and Doppler study was also performed and the diagnosis of heart failure either confirmed or refuted. Plasma concentrations of neuro-endocrine variables in healthy elderly subjects were similar to our normal laboratory range in younger subjects with the exception ofatrial natriuretic peptide (ANP) (40 ± 6 pg. ml, normal range <40) and noradrenaline (5.7±0.7 nmol. l), normal range <2.8). Impairment of left ventricular systolic function was confirmed in 38 of the 50 symptomatic patients (76%) and was associated with increases in plasma concentrations of active renin (58 ± 8 IU. mol P<0.001 compared to healthy elderly subjects), angiotensin II (23 ± 5pg. ml, P<0.008), noradrenaline (7.7±1.2 nmol. l, P<0.01) and atrial natriuretic peptide (121 ± 18 pg. ml, P<0.002). Plasma concentrations were similar in normal subjects and those receiving treatment for heart failure but in whom the diagnosis was not confirmed A weak relationship between plasma atrial natriuretic peptide (ANP) and left ventricular fractional shortening was demonstrated (r= −0.5, P<0.001). Using an upper limit of ANP in the healthy elderly subjects of 62 pmol. ml (mean+SD), plasma concentrations of ANP in the population with suspected heart failure had a sensitivity of 74% and specificity of 66% for the diagnosis of heart failure among elderly patients in the community or where access to echocardiography is limited. Left ventricular diastolic filling (assessed by Doppler) was abnormal in healthy elderly subjects and patients with heart failure, and appeared of limited value in the diagnosis of heart failure secondary to diastolic dysfunction. This study confirms that the renin-angiotensin system is activated in elderly patients with heart failure treated with diuretics. ANP may be helpful in diagnosing heart failure where it appears to have a complimentary role to echocardiography. [ABSTRACT FROM PUBLISHER]

Endothelin is a powerful vasoconstrictor that may be partly responsible for the increases in venous and arterial tone characteristic of heart failure. The release of endothelin from endothelial cells in culture is stimulated by angiotensin II. We investigated the relationship between plasma concentrations of immuno reactive endothelin-1 and angiotensin II in 25 patients with heart failure and eight with ischaemic heart disease but normal left ventricular function. Plasma concentrations of endothelin and angiotensin II were correlated (Spearman rank correlation coefficient of 0.72; P<0.0001) in patients with heart disease. Plasma concentrations of angiotensin II and endothelin were higher in those patients with heart failure. Angiotensin II was infused over a 3 h period in eight healthy volunteers. Infusion of angiotensin II increased plasma concentrations of angiotensin II to levels greater than those usually found in patients with severe heart failure but induced only a modest rise in plasma concentrations of immunoreactive endothelin-1 (0.77 ±0.16 to 1.03 ± 0.03 pmol. I, P<0.02). Increased plasma concentrations of angiotensin II and endothelin-1 both appear to reflect the presence and severity of heart failure. Although a significant correlation exists between plasma concentrations of angiotensin II and endothelin in patients with heart failure, the relationship may not be causal. [ABSTRACT FROM PUBLISHER]

Our understanding of the clinical course of heart failure and the mechanism by which ACE inhibitors reduce mortality and morbidity is being enhanced by recent results from large trials. The belief that heart failure constitutes a gradual progression of symptoms and signs leading eventually to death has been challenged by the finding that many patients die suddenly, before the onset of symptoms at rest. Indeed, many studies have shown that sudden death, with or without the progression of heart failure, is the most common mode of death. Studies suggest that ACE inhibitors reduce mortality in heart failure both by preventing or delaying the progression of heart failure or sudden death, and by reducing the incidence of myocardial infarction. ACE inhibitors may improve ventricular function by a variety of mechanisms, including effects on neuro-endocrine systems, haemodynamic effects, and direct actions on the myocardium. ACE inhibitors may also have a long-term effect on plaque growth or rupture, which may account for the observed reduction in the incidence of myocardial infarction. Although ACE inhibitors would be expected to lower the risk of arrlhythmias, through their ability to reduce pressure and volume overload, this effect has not been observed consistently in large- scale trials. One of the most important clinical benefits of ACE inhibition may prove to be the reduction in myocardial infarction. The use of an ACE inhibitor should be considered in all patients with significantly impaired systolic left ventricular function (in the absence of contra- indications), even those who are asymptomatic, although the precise level of ventricular dysfunction at which treatment should be initiated remains to be clarified. The ability of long-term ACE inhibitor treatment to reduce ischaemic events in patients with normal left ventricular function is currently being studied. The optimum dose remains to be determined, although beneficial results have been obtained with enalapril, 20 mg daily, captopril, 150 mg daily and ramipril 5 mg b.i.d. [ABSTRACT FROM PUBLISHER]

One hundred and seven patients with chronic heart failure (NYHA class II to IV) stabilized on digitalis and/or diuretics, recruited from 11 centres were randomized into a double-blind, placebo-controlled study to assess the effect of 12 weeks of cilazapril therapy on exercise tolerance and clinical status. Thirty-five patients were randomized to placebo and 72 to cilazapril at a starting dose of 1 mg daily; titration to cilazapril 2.5 mg at week 4 and 5 mg at week 8 (or matching placebo) was carried out in patients who did not improve clinically. Demographic characteristics, including exercise test duration increased from 402 s (±17 SEM) at baseline to 462 s (±19 SEM) at week 12 for the cilazapril group (+15%) and from 405 s (±23 SEM) at baseline to 408 s (±30 SEM) at week 12 in patients on placebo (+1%) (P < 0.001). In the placebo group, patients able to exercise for more than 6 min at baseline showed an increase in exercise duration at week 12 while those able to exercise for up to 6 min at baseline showed a decrease (P = ns). In contrast, cilazapril-treated patients showed an increase in exercise tolerance regardless of baseline exercise test duration; patients with the most impaired exercise tolerance at baseline showed a greater improvement than patients with mildly impaired baseline exercise tolerance (P < 0.05 vs placebo). NYHA class improved by at least one grade in 51% of the cilazapril group vs 32% in the placebo group (P = ns).At the end of the trial, 15% of the patients were non-responders on cilazapril vs 41% on placebo (P < 0.01). A similar incidence of drop-out due to adverse events was observed in both groups (8.6% on placebo vs 8.3% on cilazapril) although adverse events were reported by fewer patients on placebo (17%) than on cilazapril (43%). Nine patients were withdrawn from the study for adverse events (three on placebo and six on cilazapril) and two patients died during the study (one in each group). Thus, in patients with chronic heart failure stabilized on digitalis and/or diuretics, angiotensin converting enzyme inhibition by cilazapril once a day was effective in prolonging exercise 'est duration, improving NYHA classification, heart failure signs and symptoms and was well-tolerated. This effect was greater in patients with the most impaired exercise tolerance at baseline. [ABSTRACT FROM PUBLISHER]

Despite the successful therapeutic applications of angiotensin-converting enzyme (ACE) inhibitors to date, knowledge of how they work and guidelines for their use are still incomplete. On their role as monotherapy in congestive heart failure, we have scarce and conflicting data. Nor is there a clear answer to the question, when should an ACE inhibitor be started in a patient with heart failure? In patients with severe heart failure, the addition of an ACE inhibitor to a diuretic regimen has been shown to improve prognosis. In patients with mild heart failure, a benefit has not been demonstrated. In one preliminary report, monotherapy with the ACE inhibitor quinapril was shown to improve exercise time and functional class in patients with mildheart failure compared to placebo. [ABSTRACT FROM PUBLISHER]

Few studies exist on the interaction of diuretics and angiotensin-converting enzyme inhibitors in patients with chronic heart failure. Twelve subjects with heart failure were studied before and after their usual oral dose of frusemide in random order on consecutive days during fixed sodium, potassium and water intake. Patients then received 10 mg day of enalapril for 5 days and subsequently restudied before and after their usual dose of frusemide. Frusemide was not observed to have an effect on systemic or renal haemodynamics prior to enalapril, but urine volume and sodium content rose as expected. Treatment with enalapril, in the absence of frusemide, was associated with a fall in mean blood pressure from 89 ±5 mmHg to 85 ±4 mmHg (P < 0.02) and a rise in renal blood flow from 424 ±202 ml min to 494±225ml min (P<0.02), but cardiac output and glomerular filtration rate were again unchanged. Addition of frusemide to enalapril therapy resulted in a greater fall in mean blood pressure (87±5mmHg to 79±4 mmHg; P<001) and an increase in cardiac output (3.1 ± 11 lmin-1 to 3.6± 1.01 min; P<0.02). Renal blood flow increased further than after enalapril alone to 579 ±211 ml min but the glomerular filtration rate fell to 63±26 ml min (P<0.01) and the filtration fraction fell to 19±5% (P<0.001). Weight gain occurred and the diuretic response to frusemide was reduced during this early phase of enalapril therapy. [ABSTRACT FROM PUBLISHER]

In a group of 62 patients with chronic heart failure 29% developed ventricular tachycardia during exercise testing. The two-year survival of this group was only 22%, compared to 55%, in those not demonstrating ventricular tachycardia (P < 0.01).In a double-blind cross-over study against placebo, with three-month treatment periods, amiodarone, in a dose of 200 mg day−1, was found effectively to suppress ventricular arrhythmias during exercise and in the immediate post-exercise period. Exercise performance was not impaired.Amiodarone may be useful in preventing life-threatening arrhythmias in patients with heart failure. [ABSTRACT FROM PUBLISHER]

We compared the long-term effects of captopril and placebo on patients with heart failure in a double blind crossover fashion. Serum and total body elecrolytes were measured and the response to 6 week periods of treatment with captopril determined. During the placebo phase of the study, total body potassium was low at 92±14% of predicted normal (P<0.05) and total body sodium was high at 104+7% of predicted normal (P<0.05). Total body chlorine did not differ from predicted normal (99+12%). In those patients with active plasma renin concentrations above the normal range (greater than 50 μU ml) total body potassium was even more markedly deplete (85+13% of predicted normal). This group was also characterized by lower serum potassium and sodium concentrations and lower blood pressure. Total body potassium increased significantly on captopril, and the rise was greatest in those with the highest plasma renin concentrations during the placebo phase of the study. However, captopril had no significant effect on total body sodium and chlorine or weight indicating that no long-term natriuresis had occurred. [ABSTRACT FROM PUBLISHER]

—To compare outcome in patients with medically treated secundum atrial septal defect (ASD) first diagnosed after the age of 25 with the long-term outcome in a similar group of patients after surgical closure. —A historical, prospective, unrandomised study. —A tertiary referral centre. —All patients with ASD followed up since 1955 who fulfilled the entry criteria and had reached a current age of over 45 years—that is, 34 medical and 48 surgical patients with a mean follow up of 25 years. —Survival, symptoms, and complications. —There was no difference in survival or symptoms between the two groups and no difference in the incidence of new arrhythmias, stroke or other embolic phenomena, or cardiac failure. No patient in either group developed progressive pulmonary vascular disease. —Outcome in adults with ASD was not improved by surgical closure. Because progressive pulmonary vascular disease did not develop in any of these patients its prevention is not a reason for advising closure of ASD in adults. [ABSTRACT FROM PUBLISHER]