Exercise capacity in chronic heart failure is related to the aetiology of heart disease

Objective—To assess whether the underlying aetiology of chronic heart failure is a predictor of exercise performance.
Setting—Tertiary referral centre for cardiology.
Patients and outcome measures—Retrospective study of maximum exercise testing with metabolic gas exchange measurements in 212 patients with chronic heart failure who had undergone coronary angiography. Echocardiography and radionucleide ventriculography were used to determine indices of left ventricular function, and coronary arteriography was used to determine whether the cause of chronic heart failure was ischaemic heart disease (n = 122) or dilated cardiomyopathy (n = 90).
Results—The cardiomyopathy group was younger (mean (SD) age 58.45 (11.66) years v 61.49 (7.42); p = 0.02) but there was no difference between the groups in ejection fraction or fractional shortening. Peak oxygen consumption (O₂) was higher in the dilated group, while the slope relating carbon dioxide production and ventilation (E/CO₂ slope) was the same in both groups. Both groups achieved similar respiratory exchange ratios at peak exercise, suggesting that there was near maximum exertion. There was a relation between peak O₂ and age (peak O₂ = 33.9 − 0.267*age; r = 0.36; p < 0.001). After correcting for age, the peak achieved O₂ was still greater in the cardiomyopathy group than in the ischaemic group (p < 0.002).
Conclusions—Exercise performance for a given level of cardiac dysfunction appears to vary with the aetiology of heart failure. Thus the two diagnostic categories should be considered separately in relation to abnormalities of exercise physiology. The difference may in part account for the worse prognosis in ischaemic patients.

Keywords: exercise performance;  heart failure;  ischaemic heart disease;  dilated cardiomyopathy     

Physiological cardiac reserve: development of a non-invasive method and first estimates in man

Objective—To investigate whether physiological cardiac reserve can be measured in man without invasive procedures and whether it is a major determinant of exercise capacity.
Design—Development of method of measurement and an observational study.
Setting—A regional cardiothoracic centre.
Subjects—70 subjects with a wide range of cardiac function, from heart failure patients to athletes.
Methods—Subjects underwent treadmill, symptom limited cardiopulmonary exercise tests to measure aerobic exercise capacity (represented by O₂max) and cardiac reserve. Cardiac output was measured non-invasively using the CO₂ rebreathing technique.
Results—Cardiac power output (CPO_max) at peak exercise was found to be significantly related to aerobic capacity: CPO_max (W) = 0.35 + 1.5O₂max (l/min), r = 0.87, p < 0.001. It also correlated well with exercise duration (r = 0.62, p < 0.001), suggesting that cardiac reserve is a major determinant of exercise capacity. In the study, cardiac reserve ranged from 0.27 to 5.65 W, indicating a 20-fold difference between the most impaired cardiac function and that of the fittest subject.
Conclusions—A non-invasive method of estimating physiological cardiac reserve was developed. The reserve was found to be a major determinant of exercise capacity in a population of normal subjects and patients with heart disease. This method may thus be used to provide a clearer definition of the extent of cardiac impairment in patients with heart failure.

Keywords: cardiac reserve;  cardiac power output;  oxygen consumption;  congestive heart failure     

Acute and chronic effects of surgical thromboendarterectomy on exercise capacity and ventilatory efficiency in patients with chronic thromboembolic pulmonary hypertension

OBJECTIVE—To assess acute and chronic effects of surgical thromboendarterectomy on exercise capacity and ventilatory efficiency in patients with chronic thromboembolic pulmonary hypertension (CTEPH).
DESIGN—Cardiopulmonary exercise testing was performed in 20 patients with CTEPH before thromboendarterectomy (baseline), one month after (early phase), and four months after (late phase). Peak oxygen uptake (peak O₂) and the ventilatory response to carbon dioxide production (E-CO₂ slope) were measured for assessment of exercise capacity and ventilatory efficiency. Right heart catheterisation was performed in all patients before and one month after surgery.
RESULTS—Baseline peak O₂ decreased and E-CO₂ slope increased along with the increase in pulmonary vascular resistance in patients with CTEPH. After thromboendarterectomy, the E-CO₂ slope decreased greatly from baseline to the early phase (mean (SD), 50 (9) to 37 (7), p < 0.05) and reached a steady level thereafter. In contrast, a continued increase in peak O₂ was noted from the early to the late phase (16.9 (4.1) to 21.1 (5.0) ml/kg/min, p < 0.05). The decrease in the E-CO₂ slope from baseline to the early phase, but not the increase in peak O₂, correlated strongly with the decrease in pulmonary vascular resistance after surgery (r = 0.75, p < 0.01).
CONCLUSIONS—Thromboendarterectomy may cause an immediate improvement in ventilatory efficiency, possibly through its beneficial haemodynamic effects. In contrast, exercise capacity may continue to improve towards the late phase, reflecting peripheral adaptation to exercise.


Keywords: thromboendarterectomy; exercise capacity; pulmonary thromboembolism; pulmonary hypertension     

Oxygen uptake kinetics during low level exercise in patients with heart failure: relation to neurohormones, peak oxygen consumption, and clinical findings

Objective—To investigate whether oxygen uptake (O₂) kinetics during low intensity exercise are related to clinical signs, symptoms, and neurohumoral activation independently of peak oxygen consumption in chronic heart failure.
Design—Comparison of O₂ kinetics with peak O₂, neurohormones, and clinical signs of chronic heart failure.
Setting—Tertiary care centre.
Patients—48 patients with mild to moderate chronic heart failure.
Interventions—Treadmill exercise testing with "breath by breath" gas exchange monitoring. Measurement of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and noradrenaline. Assessment of clinical findings by questionnaire.
Main outcome measures—O₂ kinetics were defined as O₂ deficit (time [rest to steady state] × ΔO₂ − ∑O₂ [rest to steady state]; normalised to body weight) and mean response time of oxygen consumption (MRT; O₂ deficit/ΔO₂).
Results—O₂ kinetics were weakly to moderately correlated to the peak O₂ (O₂ deficit, r = −0.37, p < 0.05; MRT, r = −0.49, p < 0.001). Natriuretic peptides were more closely correlated with MRT (ANF, r = 0.58; BNP, r = 0.53, p < 0.001) than with O₂ deficit (ANF, r = 0.48, p = 0.001; BNP, r = 0.37, p < 0.01) or peak O₂ (ANF, r = −0.40; BNP, r = −0.31, p < 0.05). Noradrenaline was correlated with MRT (r = 0.33, p < 0.05) and O₂ deficit (r = 0.39, p < 0.01) but not with peak O₂ (r = −0.20, NS). Symptoms of chronic heart failure were correlated with all indices of oxygen consumption (MRT, r = 0.47, p < 0.01; O₂ deficit, r = 0.39, p < 0.01; peak O₂, r = −0.48, p < 0.01). Multivariate analysis showed that the correlation of O₂ kinetics with neurohormones and symptoms of chronic heart failure was independent of peak O₂ and other variables.
Conclusions—Oxygen kinetics during low intensity exercise may provide additional information over peak O₂ in patients with chronic heart failure, given the better correlation with neurohormones which represent an index of homeostasis of the cardiovascular system.

Keywords: oxygen consumption; low intensity exercise; heart failure; neurohormones     

Cardiopulmonary responses to exercise in patients with hypertrophic cardiomyopathy

Objective—To examine the submaximal and maximal indices of the exercise response of patients with hypertrophic cardiomyopathy.
Design and setting—Prospective examination of cardiopulmonary responses to ramp exercise test of a consecutive group of patients with hypertrophic cardiomyopathy attending a cardiomyopathy outpatient clinic.
Methods—50 patients aged 12 to 76 years (mean (SD) 35 (14)) with diagnosis of hypertrophic cardiomyopathy performed incremental cycle ergometry; 22 sedentary volunteers (seven female, 15 male) aged 14 to 58 years (mean (SD) 31 (12)) served as controls. Respiratory gas was continuously sampled from the mouthpiece, and its concentration profile phase aligned to the respired air flow signals. Following analogue to digital conversion, gas exchange variables were computed breath by breath and the data were averaged every 30 seconds for graphic display. A 12 lead ECG was monitored continuously and recorded every three minutes during the exercise.
Results—Both the peak oxygen uptake attained on the test (O₂ peak) and anaerobic threshold were reduced in patients with hypertrophic cardiomyopathy compared with the control group (p < 0.0001). In 29 patients (59%) the O₂ peak was less than 60% and only two patients achieved a peak above 80% of their predicted values. The anaerobic threshold was below 60% of the predicted value in 31 patients and above 80% in only three patients. The slope of oxygen uptake/work rate relation (ΔO₂/ΔWR) was decreased in 16 patients (32%). The maximum oxygen pulse (O₂/HR) was reduced as a percentage of the predicted value, and became flat at high work rates in 32 patients. There was a significant correlation between anaerobic threshold and O₂ peak (p < 0.0001), work efficiency (p < 0.0001), and maximum oxygen pulse (p < 0.0001). The slope of change in ventilation against change in carbon dioxide output (ΔE/ΔCO₂) for the subanaerobic threshold range was increased in 36 patients (72%) and was inversely correlated with anaerobic threshold (p < 0.0002).
Conclusions—There were severe abnormalities in maximal and submaximal indices of pulmonary gas exchange in a cohort of hypertrophic cardiomyopathy patients attending a referral cardiovascular clinic. The pattern of the abnormalities suggests that a reduced stroke volume response, ventilation/perfusion mismatch, and abnormal peripheral oxygen utilisation are the possible mechanisms of exercise intolerance.

Keywords: exercise tolerance;  work efficiency;  oxygen pulse;  hypertrophic cardiomyopathy     

Age dependent efficacy of implantable cardioverter-defibrillator treatment: observations in 450 patients over an 11 year period

Objective—To determine whether implantable cardioverter-defibrillator (ICD) treatment is beneficial in elderly patients with life threatening ventricular tachyarrhythmias.
Design—Since January 1984, ICDs were implanted in 450 patients to evaluate surgical risk, complications and mean survival in relation to patient age; 81 patients (18%) were  50 years at the time of ICD implant, 254 patients (56%) were between 51 and 64 years, and the remaining 115 (26%) were  65 years. Epicardial lead systems were implanted in 209 patients (46%), while transvenous lead systems were implanted in 241 (54%).
Results—13 patients (3%) died perioperatively, more often after epicardial (11 of 209 patients, 5%) than after transvenous ICD implantation (one of 241 patients, < 1%) (p < 0.05). During a mean (SD) follow up of 28 (24) months (range < 1 to 114 months), 90 patients (20%) died. Of these, nine (2%) died from sudden arrhythmic death; five (1%) died suddenly, probably as a result of non-arrhythmic causes; 55 (12%) died from other cardiac causes (congestive heart failure, myocardial infarction); and 21 (5%) died from non-cardiac causes. The three, five, and seven year survival for arrhythmic mortality was 95% in patients  50 years compared with a three year survival of 93% and a five and seven year survival of 91% in patients of 51 to 64 years, and a three, five, and seven year survival of 99% in patients  65 years. 362 patients (80%) received ICD discharges (21 (43) shocks per patient), with a similar incidence among all three patient groups ( 50 years, 80%; 51 to 64 years, 81%; 65 years, 79%). The time interval between ICD implant and the first ICD treatment was shorter in patients  65 years (8 (8) months) than in patients between 51 and 64 years (11 (14) months) or  50 years (11 (11) months) (p < 0.05). Survival time following first appropriate shock was 30 (24) months in patients  50 years, 30 (26) months in patients of 51 to 64 years, and 19 (20) months in patients  65 years.
Conclusions—Elderly patients benefit from ICD treatment, and survive for a considerable time after the first treatment. Therefore, elderly patients should be considered candidates for ICD implantation if life threatening ventricular tachyarrhythmias are present.

Keywords: cardioverter-defibrillator;  heart failure;  sudden death;  ICD discharges;  elderly patients     

Effect of time from onset to coming under care on fatality of patients with acute myocardial infarction: effect of resuscitation and thrombolytic treatment

Objective—To examine the relation between time from onset of symptoms and coming under ambulance and hospital care on fatality in patients with evolving acute myocardial infarction, and on the proportions who survive because of resuscitation and thrombolytic treatment.
Design—Prospective community and hospital study over two years. Delay was measured from the onset of symptoms to arrival at hospital, and from the onset to coming under care from ambulance personnel.
Setting—Four general hospitals serving three United Kingdom health districts.
Patients—2213 patients under 75 years of age, 111 of whom had been successfully resuscitated from out of hospital cardiac arrest.
Interventions—Resuscitation from cardiac arrest; thrombolytic treatment.
Main outcome measures—30 day fatality and lives saved by the two forms of treatment.
Results—Times from symptom onset to coming under hospital care and to starting thrombolytic treatment (given to 53% of patients) were  1 hour in 15% and 2% of patients respectively,  2 hours in 54% and 25%, and  4 hours in 67% and 55%. Overall, 30 day fatality was 138/1000 patients treated; 64/1000 (95% confidence interval 54 to 74) survived because of treatment, and 80% of this salvage was attributable to resuscitation. Delay was an important factor: 107/1000 (60 to 144) lives were saved for those coming under care within 1 hour compared with 21/1000 (5 to 37) for those who delayed for more than 12 hours. Further analysis including the 111 patients with out of hospital arrest showed that 34% of those coming to hospital by ambulance came under ambulance care within 1 hour; for this subset, 30 day fatality was 173/1000, and 136 (109 to 163) lives were saved by treatment.
Conclusions—Results of treatment are strongly related to delay in coming under care. Reduction in delay can reduce mortality from acute myocardial infarction.

Keywords: acute myocardial infarction;  fatality;  resuscitation;  thrombolytic treatment     

Predictors of loss of atrioventricular synchrony in single lead VDD pacing

Objective—To evaluate maintenance of proper VDD function, defined as persistence of sinus rhythm with atrial synchronous ventricular pacing, and to define factors predicting failure of the VDD mode in patients with atrioventricular (AV) block and normal sinus function.
Design—Observational study in 86 consecutive patients (mean (SD) age 74 (12) years; 38 women, 48 men) with single lead VDD pacing systems (Intermedics Unity, n = 66, Medtronic Thera VDD, n = 20), implanted for high degree AV block with documented normal sinus node. Pacemaker function was assessed by event counters, telemetric measurements, and Holter recordings. Demographic, radiological, and pacing variables were correlated with loss of proper VDD function.
Results—During a mean (SD) follow up of 10 (10) months (range 1-37), sinus rhythm and atrial triggered ventricular pacing were maintained in 70 of 86 patients (81%). Atrial undersensing was observed in nine patients, lead migration in two, atrial fibrillation in three, and symptomatic sinus bradycardia in two. Univariate predictors of loss of proper VDD function were: low position of the atrial dipole relative to the carina ( 6 cm; p < 0.01) during fluoroscopy; and maximum programmable atrial sensitivity of the pacemaker (p = 0.03). In a multivariate analysis, only dipole position remained predictive of outcome (p < 0.02). Not predictive were sex, age, symptoms before pacemaker implantation, cardiothoracic ratio or dilatation of individual heart chambers on chest x ray, side of device implant, and P wave amplitude at implant.
Conclusions—To maintain proper VDD function in the long term, a low anatomical dipole position relative to the carina should be avoided. Electrical guidance of dipole positioning does not seem to influence long term outcome.

Keywords: VDD pacing;  atrioventricular synchrony;  arrhythmias     

Changes in pulmonary artery size before and after total cavopulmonary connection

Objective—To assess changes in size of the central pulmonary arteries following a total cavopulmonary connection (TCPC).
Design—A retrospective analysis of the angiographic diameters of the central pulmonary arteries, expressed as z scores, in infancy before the TCPC and 3.5 (0.9) years (mean (SD)) later. Analysis of the relation between the pulmonary arteriolar resistance and the z scores at follow up.
Setting—Tertiary referral centre.
Patients—32 patients who had TCPC from February 1990 to July 1993.
Results—The patients were divided into two groups (n = 16) depending on their preoperative flow ratio: group I, Qp/Qs  1; group II, Qp/Qs > 1. At the initial study in infancy the mean z scores in group I were −6.0 for the right pulmonary artery (RPA) and −9.6 for the left pulmonary artery (LPA); in group II the respective values were −2.7 and −3.0. Before the TCPC the values increased to 0.5 (RPA) and −0.5 (LPA) in group I, and to 8.8 (RPA) and 8.2 (LPA) in group II. At follow up the z scores decreased to −2.4 (RPA) and −4.9 (LPA) in group I, and to 2.2 (RPA) and −0.7 (LPA) in group II. The changes in pulmonary artery diameters were significant for both groups (p < 0.02). Following the TCPC, no significant difference in pulmonary arteriolar resistance index was found between patients with relatively small pulmonary arteries (z score RPA+LPA  0) and those with relatively large pulmonary arteries (z score RPA+LPA > 0).
Conclusions—Creation of a TCPC results in a significant reduction in size of the central pulmonary arteries. At a mean interval of 3.5 years following the TCPC, however, there was no significant difference in pulmonary arteriolar resistance index between patients with smaller and larger central pulmonary arteries.

Keywords: total cavopulmonary connection;  congenital heart disease;  pulmonary artery size;  pulmonary arteriolar resistance     

Delayed improvement of autonomic nervous abnormality after the Maze procedure: time and frequency domain analysis of heart rate variability using 24 hour Holter monitoring

Objective—To analyse heart rate variability in patients with atrial fibrillation after the Maze procedure, to investigate whether the procedure damages the cardiac autonomic fibres supplying the sinus node.
Design and patients—Time and frequency domain analyses of RR variability were performed using 24 hour Holter monitoring one month after surgery in 12 patients with atrial fibrillation who underwent the Maze procedure (Maze group) and in seven patients who underwent cardiac surgery without the Maze procedure (control group). Mean RR intervals (mRR) and the standard deviation of successive RR intervals (SDRR) were determined by time domain analysis, and high frequency (HF), low frequency (LF), and total power (TP) spectral components of RR variability were calculated by frequency domain analysis. Holter monitoring was also performed at six and 12 months after cardiac surgery in the Maze group.
Results—Circadian variation (mean (SD)) in mRR (daytime to night time difference: 119 (60) v 302 (143) ms), SDRR (daytime: 8.4 (3.3) v 37.0 (12.0) ms), TP (daytime: 46.7 (16.0) v 171.8 (30.4) ms), HF (daytime: 19.6 (9.9) v 36.7 (7.1) ms²), and LF/HF (daytime: 0.31 (0.07) v 1.18 (0.46)) was decreased in the Maze group at one month compared with the control group (p < 0.01), but showed improvement at six and 12 months (p < 0.05).
Conclusions—Surgery combined with the Maze procedure markedly suppressed the circadian variation of heart rate over a 24 hour period within one month after surgery, mainly because of damage to the innervation of the sinus node. However, at six and 12 months there was restoration of circadian variation, probably as the result of reinnervation of the sinus node.

Keywords: autonomic nervous system;  heart rate variability;  Maze procedure     

Long term intravenous prostaglandin (epoprostenol or iloprost) for treatment of severe pulmonary hypertension

Objective—To investigate the relation between the severity of pulmonary hypertension and the outcome of medical treatment.
Methods—98 patients with primary pulmonary hypertension—nine (6%) with systemic disease and pulmonary hypertension and 39 (27%) with thromboembolic pulmonary hypertension—received medical treatment and were followed between 1982 and 1995. They were given long term intravenous prostaglandin treatment (either epoprostenol (n = 61) or iloprost (n = 13)) or conventional treatment with oral anticoagulants (n = 24) with or without calcium channel blockers. Event-free survival was measured to death or transplant surgery, or pulmonary thromboendarterectomy.
Results—Prognosis (hazard ratio) was affected by: New York Heart Association grade, 1.52 (95% confidence interval 1.11 to 2.09); mixed venous oxygen saturation (SvO₂%), 0.97 (0.95 to 0.98); cardiac index, 0.72 (0.49 to 1.06); mean right atrial pressure, 1.04 (1.01 to 1.07); and pulmonary vascular resistance, 1.02 (1.00 to 1.04). The median event-free survival time of patients with SvO₂ < 60% was 239 days (0 to 502) on conventional treatment (n = 22) and 585 days (300 to 870) on prostaglandin treatment (n = 42). No difference was seen in patients with SvO₂  60% between conventional treatment and prostaglandin treatment, survival being 1275 days (732 to 1818; (n = 48)) and 986 days (541 to 1431; n = 30)), respectively. Capacity for pulmonary vasodilatation did not predict outcome of treatment.
Conclusions—Continuous intravenous prostaglandins were more effective than anticoagulants, with or without calcium channel blockers, in prolonging survival in patients with right heart failure. In these patients a capacity to vasodilate did not predict outcome from medical treatment.

Keywords: prostacyclin;  iloprost;  pulmonary hypertension;  event-free survival     

Assessment of atrial septal defect morphology by transthoracic three dimensional echocardiography using standard grey scale and Doppler myocardial imaging techniques: comparison with magnetic resonance imaging and intraoperative findings

Objective—To determine whether transthoracic three dimensional echocardiography is an accurate non-invasive technique for defining the morphology of atrial septal defects (ASD).
Methods—In 34 patients with secundum ASD, mean (SD) age 20 (17) years (14 male, 20 female), the measurements obtained from three dimensional echocardiography were compared to those obtained from magnetic resonance imaging (MRI) or surgery. Three dimensional images were constructed to simulate the ASD view as seen by a surgeon. Measured variables were: maximum and minimum vertical and horizontal ASD dimension, and distances to inferior and superior vena cava, coronary sinus, and tricuspid valve. In each patient two ultrasound techniques were used to acquire three dimensional data: standard grey scale imaging (GSI) and Doppler myocardial imaging (DMI).
Results—Good correlation was found in maximum ASD dimension (both horizontal and vertical) between three dimensional echocardiography and both MRI (GSI r = 0.96, SEE = 0.05 cm; DMI r = 0.97, SEE = 0.04 cm) and surgery (GSI r = 0.92, SEE = 0.06 cm; DMI r = 0.95, SEE = 0.06 cm). The systematic error was similar for both three dimensional techniques when compared to both MRI (GSI = 0.40 cm (27%); DMI = 0.38 cm (25%)) and surgery (GSI = 0.50 cm (29%); DMI = 0.37 cm (22%)). A significant difference was found in both horizontal and vertical ASD dimension changes during the cardiac cycle. This change was inversely correlated with age. These findings were consistent for both DMI and GSI technique. In children (age  17 years), the feasibility of detecting structures and undertaking measurements was similar for both echo techniques. However, in adult ASD patients (age  18 years) this feasibility was higher for DMI than for GSI.
Conclusions—Transthoracic three dimensional imaging using both GSI and DMI accurately displayed the varying morphology, dimensions, and spatial relations of ASD. However, DMI was a more effective technique than GSI in describing ASD morphology in adults.

Keywords: atrial septal defect;  morphology;  three dimensional echocardiography;  magnetic resonance imaging     

Cost effective management programme for heart failure reduces hospitalisation

Objective—To study the effects of a management programme on hospitalisation and health care costs one year after admission for heart failure.
Design—Prospective, randomised trial.
Setting—University hospital with a primary catchment area of 250 000 inhabitants.
Patients—190 patients (aged 65-84 years, 52.3% men) hospitalised because of heart failure.
Intervention—Two types of patient management were compared. The intervention group received education on heart failure and self management, with follow up at an easy access, nurse directed outpatient clinic for one year after discharge. The control group was managed according to routine clinical practice.
Main outcome measures—Time to readmission, days in hospital, and health care costs during one year.
Results—The one year survival rate was 71.8% (n = 79) in the control group and 70.0% (n = 56) in the intervention group (NS). The mean time to readmission was longer in the intervention group than in the control group (141 (87) v 106 (101); p < 0.05) and number of days in hospital tended to be fewer (4.2 (7.8) v 8.2 (14.3); p = 0.07). There was a trend towards a mean annual reduction in health care costs per patient of US$1300 (US$1 = SEK 7.76) in the intervention group compared with costs in the controls (US$3594 v 2294; p = 0.07).
Conclusions—A management programme for patients with heart failure discharged after hospitalisation reduces health care costs and the need for readmission.

Keywords: heart failure;  hospitalisation;  management;  health care costs;  nurse led clinics     

Distribution of fast heart rate episodes during paroxysmal atrial fibrillation

Objective—To investigate the defibrillator waiting time (time between the recognition of atrial fibrillation and the actual shock) by studying paroxysmal atrial fibrillation episodes with RR intervals shorter than a certain limit (that is, episodes during which defibrillation should not be attempted).
Methods—Long term 24 hour Holter recordings from a digoxin v placebo crossover study in patients with paroxysmal atrial fibrillation were analysed. In all, 23 recordings with atrial fibrillation episodes of at least 1000 ventricular cycles and with < 20% Holter artefacts or noise were used (11 recorded on placebo and 12 on digoxin). For each recording, the mean ("mean waiting time") and maximum ("maximum waiting time") duration of continuous sections of atrial fibrillation episodes with all RR intervals shorter than a certain threshold were evaluated, ranging the threshold from 400 to 1000 ms in 10 ms steps. For each threshold, the mean and maximum waiting times were compared between recordings on placebo and on digoxin.
Results—Both the mean and maximum waiting times increased exponentially with increasing threshold. Practically acceptable mean waiting times less than one minute were observed with thresholds below 600 ms. There were no significant differences in mean waiting times and maximum waiting times between recordings on placebo and digoxin, and only a trend towards shorter waiting times on digoxin.
Conclusions—Introduction of a minimum RR interval threshold required to deliver atrial defibrillation leads to practically acceptable delays between atrial fibrillation recognition and the actual shock. These delays are not prolonged by digoxin treatment.

Keywords: atrial defibrillator;  shock delivery;  ventricular proarrhythmia;  digoxin     

Prognostic value of non-sustained ventricular tachycardia and the potential role of amiodarone treatment in hypertrophic cardiomyopathy: assessment in an unselected non-referral based patient population

Background—Amiodarone has been reported to reduce the likelihood of sudden death in patients with hypertrophic cardiomyopathy (HCM). However, data regarding the clinical course in HCM have traditionally come from selected referral populations biased toward assessment of high risk patients.
Aims—To evaluate antiarrhythmic treatment for sudden death in an HCM population not subject to tertiary referral bias, closely resembling the true disease state present in the community.
Methods—Cardiovascular mortality was assessed in relation to the occurrence of non-sustained ventricular tachycardia (NSVT) on 24 or 48 hour ambulatory Holter recording, a finding previously regarded as a marker for sudden death, particularly when the arrhythmia was frequent, repetitive or prolonged. 167 consecutive patients were analysed by multiple Holter ECG recordings (mean (SD) 157 (129) hours) and followed for a mean of 10 (5) years. Only patients with multiple repetitive NSVT were treated with amiodarone, and in relatively low doses (220 (44) mg/day).
Results—Nine HCM related deaths occurred: 8 were the consequence of congestive heart failure, but only 1 was sudden and unexpected. Three groups of patients were segregated based on their NSVT profile: group 1 (n = 39), multiple ( 2 runs) and repetitive bursts (on 2 Holters) of NSVT, or prolonged runs of ventricular tachycardia, included 4 deaths due to heart failure; group 2 (n = 38), isolated infrequent bursts of NSVT, included 1 sudden death; group 3 (n = 90), without NSVT, included 4 heart failure deaths. Kaplan-Meier survival analysis showed no significant differences in survival between the three groups throughout follow up.
Conclusions—In an unselected patient population with HCM, isolated, non-repetitive bursts of NSVT were not associated with adverse prognosis and so this arrhythmia does not appear to justify chronic antiarrhythmic treatment. Amiodarone, administered in relatively low doses, did not carry an independent and additive risk for cardiac mortality. Amiodarone may have contributed to the absence of sudden cardiac death in patients believed to be at higher risk because of multiple repetitive NSVT.

Keywords: hypertrophic cardiomyopathy; ventricular tachycardia; amiodarone     

Adenosine induced transient cardiac standstill in catheter interventional procedures for congenital heart disease

Objective—To describe the use of intravenous adenosine to create transient cardiac standstill during balloon dilatation procedures for congenital heart defects.
Setting—A tertiary paediatric cardiac centre.
Design and patients—This was a prospective pilot study. Thirteen patients born with congenital heart disease and who had stenotic lesions requiring relief were considered for the technique. All were suitable for balloon dilatation. Their ages ranged from 2 months to 30 years, mean (SD) 9.9 (9.8) years. The dose of adenosine varied from 0.125 mg/kg to 0.555 mg/kg, mean 0.33 (0.127).
Results—Two patients only developed sinus bradycardia in response to adenosine, which may have been related to the technique of administration. The other 11 experienced a period of asystole, which ranged from 2.4 to 10.8 seconds, mean 4.99 (2.27), and a total atrioventricular block period of 5.0 to 21.2 seconds, mean 9.47 (4.64). The interval between adenosine injection and the onset of asystole varied from 2.4 to 15.8 seconds, mean 8.05 (3.6), depending on cannula size, site of administration, and cardiac output. The peak gradient across the stenotic lesions fell from 52.3 (23.7) to 17.8 (11.9) mm Hg (p < 0.001). Apart from one short episode of atrial fibrillation there were no complications.
Conclusions—Intravenous adenosine is a safe and effective agent for creating transient cardiac standstill during balloon dilatation procedures for congenital heart disease. This achieves stability which is likely to improve results and reduce complications. It may have applications in other fields of cardiac intervention where an immobile heart is desirable during the critical phase of a procedure.

Keywords: adenosine;  asystole;  balloon dilatation;  congenital heart disease     

Direct current cardioversion does not cause cardiac damage: evidence from cardiac troponin T estimation

Aim—To determine whether elective direct current (dc) cardioversion of atrial fibrillation/flutter causes myocardial damage.
Methods and results—Cardiac troponin T and creatine kinase were estimated 20-28 hours after dc cardioversion in 51 patients who received dc shocks for elective cardioversion of chronic atrial fibrillation/flutter. Although creatine kinase was raised in 44 patients, cardiac troponin T was undetectable in all patients.
Conclusion—Cardiac damage does not occur as a result of cardioversion.

Keywords: cardioversion;  troponin T;  creatine kinase;  atrial fibrillation     

Estimation of cardiac reserve by peak power: validation and initial application of a simplified index

OBJECTIVES—To validate a simplified estimate of peak power (SPP) against true (invasively measured) peak instantaneous power (TPP), to assess the feasibility of measuring SPP during exercise and to correlate this with functional capacity.
DESIGN—Development of a simplified method of measurement and observational study.
SETTING—Tertiary referral centre for cardiothoracic disease.
SUBJECTS—For validation of SPP with TPP, seven normal dogs and four dogs with dilated cardiomyopathy were studied. To assess feasibility and clinical significance in humans, 40 subjects were studied (26 patients; 14 normal controls).
METHODS—In the animal validation study, TPP was derived from ascending aortic pressure and flow probe, and from Doppler measurements of flow. SPP, calculated using the different flow measures, was compared with peak instantaneous power under different loading conditions. For the assessment in humans, SPP was measured at rest and during maximum exercise. Peak aortic flow was measured with transthoracic continuous wave Doppler, and systolic and diastolic blood pressures were derived from brachial sphygmomanometry. The difference between exercise and rest simplified peak power (Δ SPP) was compared with maximum oxygen uptake (O₂max), measured from expired gas analysis.
RESULTS—SPP estimates using peak flow measures correlated well with true peak instantaneous power (r = 0.89 to 0.97), despite marked changes in systemic pressure and flow induced by manipulation of loading conditions. In the human study, O₂max correlated with Δ SPP (r = 0.78) better than Δ ejection fraction (r = 0.18) and Δ rate-pressure product (r = 0.59).
CONCLUSIONS—The simple product of mean arterial pressure and peak aortic flow (simplified peak power, SPP) correlates with peak instantaneous power over a range of loading conditions in dogs. In humans, it can be estimated during exercise echocardiography, and correlates with maximum oxygen uptake better than ejection fraction or rate-pressure product.


Keywords: stress echocardiography; oxygen consumption; left ventricular function; cardiac power output     

Combination treatment with trimetazidine and diltiazem in stable angina pectoris

Objective—To assess antianginal efficacy and possible adverse haemodynamic effects of combination treatment with trimetazidine and diltiazem in patients with stable angina.
Design—Double blind, randomised, placebo controlled trial of four weeks duration.
Setting—Outpatient department of two Indian hospitals.
Subjects—64 male patients with stable angina, uncontrolled on diltiazem alone.
Interventions—Diltiazem 180 mg and trimetazidine 60 mg, or diltiazem 180 mg and placebo daily.
Main outcome measure—Change in exercise time to 1 mm ST segment depression.
Results—33 patients (55%) had no exercise induced angina at 3 mm ST segment depression at inclusion in the study (silent ischaemia). Intention to treat analysis showed that of 32 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was: for anginal attacks, 28 (87.5) v 15 (46.9), p < 0.001; for exercise time to 1 mm ST segment depression, 21 (65.6) v 9 (28.1), p < 0.003; for exercise time to angina, 12 (37.5) v 5 (15.6), p < 0.05; and for maximum work at peak exercise, 17 (53.1) v 8 (25), p < 0.02. Compared to placebo, there was net improvement with trimetazidine in mean anginal attacks of 4.8/week (95% confidence interval (CI) 7.5 to 2.1; p < 0.002); in mean exercise times at 1 mm ST segment depression of 94.2 seconds (95% CI 182.8 to 5.6; p < 0.05), and at onset of angina of 113.1 seconds (95% CI 181.6 to 44.6; p < 0.02); and in mean maximum work at peak exercise of 1.4 metabolic equivalents (95% CI 2.4 to 0.3; p < 0.05).
Conclusions—Patients with stable angina uncontrolled with diltiazem had a clinically important improvement after combination treatment with trimetazidine, without adverse haemodynamic events or increased side effects.

Keywords: trimetazidine;  diltiazem;  blood pressure;  stable angina;  treatment     

Autonomic modulation of the atrial cycle length by the head up tilt test: non-invasive evaluation in patients with chronic atrial fibrillation

Objective—To determine the effects of upright posture compared with supine position on the dominant atrial cycle length (DACL) in patients with chronic atrial fibrillation.
Design—The power/frequency spectrum of QRST suppressed lead V1 ECG was studied in 14 patients in the supine position and during the head up tilt table test. The DACL changes were compared with changes in heart rate and blood pressure.
Results—Compared with the supine position, the upright position reduced the DACL from 160 to 150 ms (p < 0.01). The DACL was increased after returning to the supine position from the upright position, from 147 to 154 ms (p < 0.01). Heart rate increased from 91 beats/min in the supine position to 106 in the upright position (p < 0.01). There was a decrease in heart rate from 109 beats/min in the upright position to 93 after returning to the supine position (p < 0.01). No significant changes were seen in systolic or diastolic blood pressure. There were indications of an inverse relation between DACL and heart rate when comparing the supine position before and after tilt with the upright position (p < 0.001).
Conclusions—The sympathetic stimulation and vagal withdrawal induced by rising to upright body position are associated with a decrease in DACL during chronic atrial fibrillation. Thus a reflex increase in sympathetic discharge after induction of atrial fibrillation could favour the persistence of the arrhythmia.

Keywords: atrial fibrillation;  autonomic nervous system;  atrial cycle length;  heart rate