Showing papers in "European Heart Journal in 1996"

Association of Chlamydia pneumoniae and acute coronary heart disease events in non-insulin dependent diabetic and non-diabetic subjects in Finland

Abstract: Objective It has been suggested that Chlamydia pneumoniae , a Gram-negative intracellular bacterium, is a risk factor for both myocardial infarction and chronic coronary heart disease. Previous studies have been done predominantly in non-diabetic subjects and thus the effect of diabetes on the association between C. pneumontae antibodies and coronary heart disease has not been analysed. The aim of our study was to investigate the association between prior chlamydial infection and the risk of serious coronary heart disease events (myocardial infarction or coronary death) in a 7-year prospective study of cohorts of diabetic and non-diabetic subjects in two areas of Finland. Results It was found that the prevalence of elevated chlamydial antibodies at baseline was higher in non-diabetic subjects who had serious coronary heart disease events during the follow-up than in subjects without coronary heart disease events (32 vs 15%, relative risk 2·56, P=0·013) in East Finland. In non-diabetic subjects living in West Finland we did not find this association. The association between the C pneumoniae antibodies and coronary heart disease events did not markedly change after controlling for other risk factors for coronary heart disease (OR 2·44, P=0·055) in non-diabetic subjects living in eastern Finland. In diabetic patients we did not find any association between chlamydial antibodies and coronary heart disease events. Conclusion We found an association between C. pneumoniae antibodies and coronary heart disease events in non-diabetics living in eastern Finland. This association remained strong even after controlling for the other risk factors for coronary heart disease. In diabetic patients with high risk for coronary heart disease, C. pneumnoniae was not a risk factor for coronary heart disease.(Eur Heart J 1996; 17: 682–688)

Serum C-reactive protein concentration in acute myocardial infarction and its relationship to mortality during 24 months of follow-up in patients under thrombolytic treatment

Abstract: Objectives We studied the relationship between serum C-reactive protein and mortality in acute myocardial infarction. Background Early recanalization of an infarct-related coronary artery is considered to be an essential prerequisite for reducing mortality by thrombolytic treatment in acute myocardial infarction. It also reduces the inflammatory reaction caused by acute myocardial infarction and is measurable by determination of serum C-reactive protein concentrations. We therefore studied the prognostic value of determining serum C-reactive protein in acute myocardial infarction. Methods We measured serum C-reactive protein concentrations daily for 6 days and creatine kinase, as well as its MB isoenzyme concentrations twice a day, for 3 days after a myocardial infarct, in 188 consecutive patients selected for thrombolytic therapy and treated in the same University Hospital Coronary Care Unit. The highest serum concentrations were related to total mortality as well as to the causes of death 3, 3–6, 6–12 and 12–24 months after the onset of the myocardial infarction. Results The highest serum concentrations of serum C-reactive protein were observed 2 to 4 days after the onset of myocardial infarction. The mean value of the highest serum concentration of C-reactive protein in patients who survived the whole 24-month study period was 65 mg. l−1 with the 95% confidence intervals for the mean ranging from 58 to 71. The corresponding values in those who died within 3, 3–6, 6–12 and 12–24 months were 166 (139–194), 136 (88–184), 85 (52–119) and 74 (38–111) mg.l−1 respectively. The values in those who died within 3 and 3–6 months of the infarction differed statistically significantly from the values in those who survived the whole period ( P <0.001 and P <0.05, respectively). In patients who died due to congestive heart failure the mean highest serum C-reactive protein concentration was 226 (189–265) mg . l−1 In those who suffered sudden cardiac death and those who died from a new myocardial infarction or non-cardiac causes, the respective values were 167 (138–196), 64 (38–89) and 48 (10–86) mg. l−1. The values in those who died due to congestive heart failure and those suffering sudden cardiac death differed statistically significantly ( P <0.001) from the values of those who survived or died due to other causes. The highest serum concentrations of creatine kinase or its MB isoenzyme were not associated with mortality in this study. Conclusions High serum C-reactive protein concentrations in acute myocardial infarction patients treated with thrombolytic drugs predict increased mortality up to 6 months following the infarction. Accordingly, reduction of inflammatory reaction by successful thrombolytic treat ment may make an important contribution to the survival benefit of thrombolytic treatment of acute myocardial infarction.

Effects of insulin treatment on cause-specific one-year mortality and morbidity in diabetic patients with acute myocardial infarction

Abstract: Diabetic patients with acute myocardial infarction have a poor prognosis, which has been attributed to a higher incidence of congestive heart failure and fatal reinfarction. This study reports on the one-year morbidity and mortality in a randomized study with the aim of testing whether insulin-glucose infusion initiated as soon as possible after onset of myocardial infarction and followed by long-term subcutaneous insulin treatment may have a beneficial effect on outcome in diabetic patients. In all, 306 patients were recruited to the insulin-treated group, while 314 patients served as controls. The overall mortality after one year was 19% in the insulin group compared to 26% among controls (P < 0.05). The treatment effect was most pronounced in patients without prior insulin medication and at low cardiovascular risk. In this stratum the in-hospital mortality was reduced by 58% (P < 0.05) and the one-year mortality by 52% (P < 0.02). The most frequent cause of death in all patients was congestive heart failure (66%), but cardiovascular mortality (congestive heart failure, fatal reinfarction, sudden death and stroke) tended to be decreased in insulin-treated patients. However, this difference did not reach the level of statistical significance. The number of reinfarctions was 53 (28% fatal) in the insulin group compared to 55 (45% fatal) in the control group. The two groups did not differ as regards need for hospital care or coronary revascularization during the year of follow-up. In summary, left ventricular failure and fatal reinfarctions contribute to increased mortality in diabetic patients following acute myocardial infarction. Intensive insulin treatment lowered this mortality during one year of follow-up.

Total Ischaemic Burden European Trial (TIBET). Effects of ischaemia and treatment with atenolol, nifedipine SR and their combination on outcome in patients with chronic stable angina. The TIBET Study Group.

Abstract: Objectives To study the relationship between presence or absence of ischaemic events on Holter monitoring and occurrence of a hard or hard+soft endpoint. Design A randomized double-blind parallel group study of atenolol, nifedipine and their combination, with ambulatory monitoring off-treatment and after 6 weeks of randomized treatment and prospective follow-up of 2 years on average. Setting Europe. Subjects 682 men and women with a diagnosis of chronic stable angina and who were not being considered for surgery. Main outcome Hard endpoints were cardiac death, nonfatal myocardial infarction and unstable angina; soft endpoints were coronary artery bypass surgery, coronary angioplasty and treatment failure. Results The study showed no evidence of an association between the presence, frequency or total duration of ischaemic events on Holter monitoring, either on or off treatment, and the main outcome measures. There was a non-significant trend to a lower rate of hard endpoints in the group receiving combination therapy. Compliance, as measured by withdrawal from trial medication, was clearly poorest in the nifedipine group with similar with drawal rates in the atenolol and combination therapy groups. Conclusion The recording of ischaemic events in 48 h Holter monitoring failed to predict hard or hard+soft endpoints in patients with chronic stable angina.

Mode of death in chronic heart failure A request and proposition for more accurate classification

Abstract: 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. (Eur Heart J 1996; 17: 1390-1403)

Effects of metoprolol vs verapamil in patients with stable angina pectoris

Abstract: Patients The study included 809 patients under 70 years of age with stable angina pectoris. The mean age of the patients was 59 ± 7 years and 31% were women. Exclusion criteria were myocardial infarction within the previous 3 years and contraindications to beta-blockers and calcium antagonists. The patients were followed between 6 and 75 months (median 3-4 years and a total of 2887 patient years).

Effects of metoprolol vs verapamil in patients with stable angina pectoris. The Angina Prognosis Study in Stockholm (APSIS)

Abstract: Objective To study long-term treatment effects of metoprolol or verapamil on combined cardiovascular end points and psychological variables in patients with stable angina pectoris. Design Randomized, double-blind, double-dummy trial. Patients The study included 809 patients under 70 years of age with stable angina pectoris. The mean age of the patients was 59 +/- 7 years and 31% were women. Exclusion criteria were myocardial infarction within the previous 3 years and contraindications to beta-blockers and calcium antagonists. The patients were followed between 6 and 75 months (median 3.4 years and a total of 2887 patient years). Intervention The patients were treated with either metoprolol (Seloken ZOC 200 mg o.d.) or verapamil (Isoptin Retard 240 b.i.d.). Acetylsalicylic acid, ACE inhibitors, lipid lowering drugs and long acting nitrates were allowed in the study. End points Death, non-fatal cardiovascular events including acute myocardial infarction, incapacitating or unstable angina, cerebrovascular or peripheral vascular events. Psychological variables reflecting quality of life i.e. psychosomatic symptoms, sleep disturbances and an evaluation of overall life satisfaction. Results Combined cardiovascular events did not differ and occurred in 30.8% and 29.3% of metoprolol and verapamil treated patients respectively. Total mortality in metoprolol and verapamil treated patients was 5.4 and 6.2%, respectively. Cardiovascular mortality was 4.7% in both groups. Non-fatal cardiovascular events occurred in 26.1 and 24.3% of metoprolol and verapamil-treated patients, respectively. Psychosomatic symptoms and sleep disturbances were significantly improved in both treatment groups. The magnitudes of change were small and did not differ between treatments. Life satisfaction did not change on either drug. Withdrawals due to side effects occurred in 11.1 and 14.6% respectively. Conclusion This long term study indicates that both drugs are well tolerated and that no difference was shown on the effect on mortality, cardiovascular end points and measures of quality of life.

The association between cardiac events and myocardial ischaemia following thrombolysis in acute myocardial infarction and the impact of carvedilol

Abstract: The majority of post-myocardi al infarction studies with /^-blocking drugs involved earlier generations. Newer drugs of this family with additional vasodilating and free-radical suppression properties, such as carvedilol, are now available which may improve the prognosis still further. This double-blind, randomized, placebo-controlled, parallel group study was designed to assess the extent of myocardial ischaemia in clinically stable patients 6 weeks after acute myocardial infarction and thrombolysis, and to determine the influence of carvedilol on ischaemic events during the subsequent 6 months. One hundred and one patients who remained event free at 6 weeks post myocardial infarction underwent rest and exercise thallium-201 (Tl-201) imaging. Reversible ischaemia was detected in 70 of the patients and there were 13 events in this group compared to one event in the 31 patients without ischaemia (P=007). Four of the 56 patients on carvedilol and 10 of the 45 on placebo had adverse cardiac events (/>=004). In patients with reversible ischaemia carvedilol was more effective in reducing these events than was placebo (P=003). These studies demonstrate that reversible myocardial ischaemia detected by Tl-201 imaging is present in a large proportion of clinically stable patients following thrombolysis. In these patients, there is an increased cardiac event rate which is significantly reduced by carvedilol.

Diastolic dysfunction and natriuretic peptides in systolic heart failure. Higher ANP and BNP levels are associated with the restrictive filling pattern

Abstract: Background Left ventricular diastolic dysfunction is common in patients with systolic heart failure andthe restrictive type of filling pattern appears to be associated with increased cardiac mortality. Both atrial and brain (or ventricular) natriuretic peptides are also proven markers of the severity of heart failure. The aim of this study was to determine in a large cohort of patientswith systolic heart failure whether diastolic abnormalities, and in particular the restrictive filling pattern of transmitral flow velocity, correlate with plasma atrial and brain natriuretic peptide levels. Methods Sixty-eight consecutive patients with symptomatic systolic heart failure (ejection fraction <0.5) underwent two-dimensional Doppler echocardiography of left ventricular systolic and diastolic function, together with measurement of atrial and brain natriuretic peptides. Results The restrictive filling pattern was present in 62%, the abnormal relaxation pattern in 31% and only 7% were normal. Atrial and brain natriuretic peptide (ANP/BNP)levels were significantly higher in the restrictive compared to the abnormal relaxation group (ANP: 202.2±31.7 vs 102.5 ± 22.1 pg. ml−1, P =0.0l2; BNP: 277.8 ± 27.7 vs 162.4±21.9 pg. ml−1, P =0.002). In addition, a restrictive filling pattern was associated with lower ejection fractions ( P =0.026), higher pulmonary artery systolic pressure ( P <0.001), larger left atrial size ( P =0.044), and were more likely to be in New York Heart Association class III or IV than those with an abnormal relaxation pattern ( P =0.007). Both atrial and brain natriuretic peptides correlated inversely with ejection fraction ( P <0.001), fractional shortening ( P <0.001), and positively with pulmonary artery pressure ( P =0.004 and 0.001 respectively). There were no significant correlations between single diastolic parameters and atrial or brain natriuretic peptide levels for the total patient group except between mitral peak A wave velocity and brain natriuretic peptides (r= − 0.3, P =0.01). For those with abnormal relaxation pattern mitral, valve E-wave deceleration time correlated significantly with both atrial and brain natriuretic peptide levels ( P <0.01). Conclusions This study confirms that the restrictive filling pattern of transmitral flow velocity is a marker of more severe heart failure, as indicated by its association with higher atrial and brain natriuretic peptide levels, lower ejection fraction and higher pulmonary artery pressure. Thus, this easily obtained Doppler-derived marker of diastolic dysfunction is useful for identifying those patients with more severe heart failure.

Cardiac adrenergic receptor effects of carvedilol

Abstract: Carvedilol is an adrenoceptor antagonist which modulates the activity not only of beta 1 and beta 2 but also of alpha 1 adrenergic receptors present on the cell surface membrane of the human cardiac myocyte. In the heart, carvedilol has approximately 7 times higher potency for beta 1 and beta 2 adrenoceptors, but in the doses 50-100 mg . day-1 used in clinical practice, it is essentially non-selective. In human myocardial preparations and in cultured heart cells, carvedilol has no intrinsic sympathomimetic activity but is able to identify high affinity agonist-binding receptors whose pharmacological signature is reduction in binding by incubation with guanine nucleotides (guanine nucleotide-modulatable binding). This property is more prominent for the human beta 2 than for the beta 1 adrenoceptor. The property of gaunine nucleotide-modulatable binding for carvedilol and structurally related bucindolol correlates with their ability to directly down-regulate beta 1-like receptors present in cultured chick myocytes, and with a lack of reversal of down-regulation of cardiac beta-receptors in patients with heart failure. Carvedilol does not exhibit high levels of inverse agonist activity, which may contribute to its good tolerability in subjects with heart failure. These data indicate that carvedilol produces a high degree of adrenergic receptor blockade in the failing human heart, and does not re-sensitize the beta-receptor pathway to stimulation by adrenergic agonists.

Cost-effectiveness of cholesterol lowering Results from the Scandinavian Simvastatin Survival Study (4S)

Abstract: An analysis of the cost-effectiveness of simvastatin was conducted, based on the Scandinavian Simvastatin Survival Study (4S). The total cost of hospitalization in the placebo group was 5·28 million Swedish kronor (SEK) (£5·l5 million), compared with SEK 36·0 million (£3·51 million) in the simvastatin group. This amounts to a 32% reduction, or a saving of SEK 16·8 million (£1·6 million) or SEK 7560 (£738) per patient. The net cost per patient for the duration of the study (5·4 years) was SEK 13 540 (£1324). Simvastatin treatment saved an estimated 0·377 undiscounted life years (0·240 life years discounted at 5% per annum). The cost of simvastatin therapy per discounted life-year saved was therefore SEK 56 400 (£5502) Sensitivity analysis, examining the effect of different life expectancies, costs of initiation and monitoring of simvastatin therapy, and discount rates, showed the results to be stable. Conclusion The cost per life-year saved of simvastatin in the treatment of post-myocardial infarction and angina patients, as determined from 4S data, is well within the range normally considered cost-effective.

Coronary artery spasm in patients with normal or near normal coronary arteries. Long-term follow-up of 277 patients.

Abstract: Most studies on the natural course of coronary artery spasm in patients with normal or nearly normal coronary arteries are based on medium-term follow-up in small populations. The present series includes 277 successive patients with a median follow-up of 89 months (range: 1 to 198 months). There were 206 men and 71 women whose mean age was 53.6 +/- 9.3 years. They were all assessed with coronary arteriography which revealed no stenoses greater than 50%. Spasm was confirmed during the coronary arteriography in 157 patients (56.7%), by a positive provocation test following the arteriography in 113 patients (40.8%), and by an electrocardiogram which showed Prinzmetal's variant angina in seven patients (2.5%). The majority of patients, 264 (95.3%) were treated with calcium channel blockers. At the end of this study: 35 patients (12.6%) were lost to follow-up; 20 patients (7.2% died) including 10 (3.6%) from cardiac causes; 18 patients (6.5%) experienced myocardial infarction in 11 of whom repeat coronary arteriography consistently demonstrated one or more significant stenoses (greater than 70%); 109 patients (39%) had persistent angina, in 52 of whom the severity (more than one episode per month) warranted repeat coronary arteriography which detected significant stenosis in 19 cases; 95 patients (34.3%) were asymptomatic. Multivariate statistical analyses showed that only predictors of major coronary events (death, myocardial infarction or angina requiring repeat coronary arteriography) were systemic hypertension or the finding of minor parietal irregularities on the initial coronary arteriogram. Conclusion. Despite treatment with calcium channel blockers, persistent or recurrent episodes of angina are frequently observed whereas complications such as myocardial infarction or death are rare.

Serious cardiovascular side effects of large doses of anabolic steroids in weight lifters

Abstract: Pathological cardiovascular manifestations are reported in four male patients, who had taken massive amounts of anabolic steroids while undergoing many years of strength training. One patient was referred because of ventricular fibrillation during exercise, one because of clinically manifest heart failure, and one because of arterial thrombus in his lower left leg. The fourth patient was persuaded to attend for a check-up because of a long history of massive use of anabolic steroids. All four patients had cardiac hypertrophy. Two of the patients had symptoms and signs of heart failure, and one of these two had a massive thrombosis in both right and left ventricles of his heart. After cessation of the use of anabolic steroids in the other patient with heart failure, left ventricular wall thickness reduced quickly from 12 to 10-5 mm, and fractional shortening increased from 14% to 27%. Endomyocardial biopsy revealed increased fibrosis in the myocardium in two of the three cases. HDL-cholesterol was 0-58mmol.l~' and 0-35 mmol . 1 ~ ' in the two patients still using multiple anabolic steroids at the time of investigation . The cardiovascular findings described in the present paper should warn all physicians and athletes about the possible serious acute and long-term side effects of the massive use of anabolic steroids. (Eur Heart J 1996; 17: 1576-1583)

Patient non-compliance with drug regimens: measurement, clinical correlates, economic impact.

Abstract: Poor compliance with rationally prescribed drug regimens attenuates benefits of treatment, making compliance a key link between process and outcome in ambulatory care. Compliance is defined as "the extent of correspondence between the patient's actual dosing history and the prescribed regimen'. Electronic monitoring methods reveal that > 30% of patients omit many prescribed doses, irrespective of disease, prognosis, or symptoms. Some drugs are better able than others to maintain therapeutic action during the more common lapses in dosing. These are called "forgiving' drugs; their duration of action is more than twice the prescribed interval between doses, allowing action to continue when one or more doses are missed. Forgiveness has limits, so long lapses in dosing will nullify action of any drug, with economic consequences that depend on the clinical consequences of lapsed action, or, with some drugs, rebound effects. These practical points have only come to light with the use of electronic monitoring of compliance, which avoids the biases created by tablet counts and other methods that make it easy for patients to censor evidence for omitted doses. All else being equal, the most forgiving drug in its class will be associated with the best outcomes, for it will be least impacted by prevalent poor and partial compliance.

Fibrinogen, viscosity and the 10-year incidence of ischaemic heart disease.

Abstract: Aims To use the ten year follow-up of the Caerphilly and Speedwell studies to assess the contributions of fibrinogen and viscosity to the prediction of risk of ischaemic heart disease Methods and Results Caerphilly and Speedwell are prospective studies based on representative samples of middleaged males Ischaemic heart disease morbidity and mortality were defined using hospital notes, repeat electrocardiographs and death certificates There were 603 incident events among the 4860 men Age-adjusted relative odds of ischaemic heart disease increased to 3 3 and 3-4 in the 20% of men with the highest levels of fibrinogen and viscosity, respectively After standardizing for the major cardiovascular risk factors, these relative odds were 2-2 (95% confidence interval I-6 to 31) for fibrinogen and 2-3 (95% confidence interval 1-7 to 3-2) for viscosity When fibrinogen and viscosity were entered jointly, both remained significant (/><0-01) predictors Incidence of ischaemic heart disease increased with increasing fibrinogen at every level of viscosity, and vice versa Interactions with lipids were also examined There was no support for the suggestion that risk is independent of cholesterol level when fibrinogen is low Conclusions Fibrinogen and viscosity are powerful, long term and independent predictors of the risk of ischaemic heart disease

Physical responses to different modes of interval exercise in patients with chronic heart failure—application to exercise training

Abstract: Method In exercise training with chronic heart failure patients, working muscles should be stressed with high intensity stimuli without causing cardiac overstraining. This is possible using interval method exercise. In this study, three interval exercise modes with different ratios of work/recovery phases (30/60 s, 15/60 s and 10/60 s) and different work rates were compared during cycle ergometer exercise in heart failure patients. Work rate for the three interval modes was 50% (30/60 s), 70% (15/60 s) and 80% (10/60 s) of the maximum achieved during a steep ramp test (increments of 25 w/l0s) corresponding to 71, 98 and 111 watts on average. Metabolic and cardiac responses to the three interval exercises were then examined including catecholamine levels and perceived exertion. Parameters measured during interval exercise were compared with an intensity level of 75% peak VO2, determined during an ordinary ramp exercise test (increments of l2·5 W. min−1). Results ( x ¯ ± SEM ) (1) In all three interval modes, VO2, ventilation and lactate did not increase significantly during the course of exercise. Mean values during the last work phase were between 754 ± 30 and 803 ± 46 ml. min−1 for VO2, between 26 ± 3 and 28 ± 11. min−1 for ventilation and between 1·24 ±0·14 and l·29 ± 0·10 mmol.1−1 for lactate. (2) In mode 10/60 s, heart rate and systolic blood pressure increased significantly (82 ± 4←85 ± 4 beats. min−1; 124 ± 5←134 ± 5 mmHg; P <0·05 each), while in mode 15/60 s catecholamines increased significantly (norepinephrine 0·804 ± 0·089←1·135 ± 0·094 nmol. 1−1; P <0·008; epinephrine 0·136 ± 0·012← 0 193 ± 0·019 nmol. 1−1; P <0·005). (3) In all three modes, rating of leg fatigue and dyspnoea increased significantly during exercise but remained within the range of values considered ‘very light to fairly light’ on the Borg scale. (4) Compared to an intensity level of 75% peak VO2, work rate durrng interval work phases was between 143 and 221%, while cardiac stress (rate-pressure product) was significantly lower (83–88%). Conclusion All three interval modes resulted in physical response in an acceptable range of values, and thus can be recommended.

High intensity knee extensor training, in patients with chronic heart failure Major skeletal muscle improvement

Abstract: Skeletal muscle adaptations to high intensity knee extensor strength and/or endurance training in patients with chronic heart failure were investigated. Eleven patients with chronic heart failure were randomized into two groups and exercised the m. quadriceps femoris 3 days/week for 8 weeks. After training, the maximal exercise intensity tolerated on the ergometer cycle was raised from 99 (32) to 114 (40) watts (W, P <0·05) for all 11 patients. Peak dynamic knee extensor work rate showed the greatest increase after endurance training (40%, P <0·01). Maximal dynamic and isometric strength were elevated by 40–45% ( P <0·05) after strength training. The cross-sectional area of m. quadriceps femoris was increased in the strength-trained legs (9%, P <0·05), and the capillary per fibre ratio of m. vastus lateralis was raised by 47 and 58% in the endurance-trained legs ( P <0·05). The oxidative enzyme activity in m. vastus lateralis was significantly raised above 50% after endurance training, whereas glycolytic enzyme activity was unaltered. The peripheral skeletal musculature in patients with chronic heart failure adapts fairly quickly to high intensity knee extensor training. This results in a marked rise in local, and a small rise in total work capacity, indicating maintained plasticity of skeletal muscle in chronic heart failure patients.

Female sex is associated with increased mortality and morbidity early, but not late, after coronary artery bypass grafting

Abstract: Objective To describe mortality and morbidity during a period of 2 years after coronary artery bypass grafting in relation to gender. Design Prospective follow-up study. Setting Two regional cardiothoracic centres which performed all the coronary artery bypass operations in western Sweden at the time. Sub|ects A total of 2129 (1727 (81%) men and 402 (19%) women) consecutive patients undergoing coronary artery bypass surgery between June 1988 and June 1991 without concomitant procedures. Results Females were older and more frequently had a history of hypertension, diabetes mellitus, congestive heart failure, renal dysfunction and obesity. In a multivariate analysis, taking account of age, history of cardiovascula r diseases and renal dysfunction, female sex appeared as a significant independent predictor of mortality during the 30 days after coronary artery bypass grafting (/><0-05), but not thereafter. Various postoperative complications including neurological deficit, hydro- and pneumo-thorax, perioperative myocardial damage and the need for assist devices and prolonged reperfusion were more common in females than males. Conclusion Females run an increased risk of early death and the development of postoperative complications after coronary artery bypass surgery as compared with males. Late mortality does not appear to be influenced by gender and the long-term benefit of the coronary artery bypass graft operation is similar in men and women. (Eur Heart J 1996; 17: 1426-1431)

Value of intracoronary ultrasound and Doppler in the differentiation of angiographically normal coronary arteries: a prospective study in patients with angina pectoris

Abstract: Background A substantial proportion of patients undergoing heart catheterization for suspected coronary artery disease have normal angiograms. Coronary morphology and blood flow velocity can be assessed very accurately with intracoronary ultrasound and Doppler. The purpose of this study was to use both methods to classify further patients with suspected coronary artery disease but with coronary angiograms adjudged normal at the time. Methods and results In forty-four patients with suspected coronary artery disease and normal coronary angiograms, intracoronary ultrasound and intracoronary Doppler were performed in the left anterior descending and left main coronary arteries. Coronary flow reserve was obtained by calculating the ratio of the maximal coronary flow mean velocity after the intracoronary administration of 10 mg papaverine to the coronary flow mean velocity at rest. Of 44 patients, 16 (36%) (group I) were found to have normal coronary morphology by intracoronary ultrasound and normal (>30) coronary flow reserve (5-3 ± 1-8). In seven patients (16%) (group II) there were normal intracoronary ultrasonic findings but a reduced coronary flow reserve (21 ±0-4). Plaque formation was found in a total of 21 (48%) of the 44 patients; mean plaque sizes were 3-6 ± 1-6 mm2 for those in group III (normal coronary flow reserve) and 50 ± 2-3 mm2 for those in group IV (reduced coronary flow reserve). Vessel area in both of these groups (16-3 ±80 mm2 and 19-2 ± 61 mm2) was significantly larger than that of group I (14-6 ± 5-7 mm2, /><001). Plaque calcification was found in 25% of those in group III and 44% of those in group IV. Thus, only 36% of the patients with normal angiograms were true normal, 48% exhibited early stage of coronary atherosclerosis, and the other 16% might be considered as syndrome X. Conclusion Intracoronary ultrasound and Doppler can be used to differentiate further heart disease in patients with normal coronary angiograms. Only a minority were true normal. Early signs of atheroscleros is cannot be detected by coronary angiography. This may have important therapeutic and prognostic implications. (Eur Heart J 1996; 17: 880-889)

The Total Ischaemic Burden European Trial (TIBET) Effects of atenolol, nifedipine SR and their combination on the exercise test and the total ischaemic burden in 608 patients with stable angina

Abstract: OBJECTIVES: To determine the effects of atenolol, nifedipine and their combination on exercise parameters and ambulatory ischaemic activity in patients with mild chronic stable angina. SETTING: Multicentre, multinational study involving 608 patients from 69 centres in nine countries. DESIGN: Placebo washout followed by double-blind parallel-group study comparing atenolol 50 mg bd, nifedipine SR 20 mg bd, and their combination. Patients underwent maximal exercise testing using either a bicycle (n = 289) or treadmill (n = 319) and 48 h of ambulatory ST segment monitoring outside the hospital environment at the end of the placebo washout period and after 6 weeks of active therapy. RESULTS: Both medications alone and in combination caused significant improvements in exercise parameters and significant reductions in ischaemic activity during daily activities, when compared with placebo. There were, however, no significant differences between groups, for any of the measured ischaemic parameters although combination therapy resulted in a greater fall in resting systolic and diastolic blood pressure than either treatment alone. CONCLUSIONS: In the management of mild chronic stable angina there appears to be little advantage gained from using combination therapy for ischaemia reduction.

The diagnoses of patients admitted with acute chest pain but without myocardial infarction

Abstract: Objective The purpose of this study was to describe the frequencies of various diagnoses in patients admitted with acute chest pain, but without acute myocardial infarction, and to evaluate a non-invasive screening programme for these patients. Patients A total of 204 consecutive non-acute myocardial infarction patients were included. Fifty-six had a definite diagnosis within 48 h, whereas 148 patients underwent an examination programme including pulmonary scintigraphy, echocardiography, exercise electrocardiography, myocardial scintigraphy, Holter monitoring, hyperventilation test, oesophago-gastro-duodenoscopy, 3 h monitoring of oesophageal pH, oesophageal manometry, Bernstein test, physical examination of the chest wall and thoracic spine, bronchial histamine provocation test and ultrasonic examination of the abdomen. Results According to predefined criteria, 186 patients (91%) had at least one diagnosis, 144 had one, whereas 39 had two, and three patients had three diagnoses. In 18 patients no diagnosis was obtained. The diagnoses belonged mainly to three groups: (1) ischaemic heart disease (n=64); (2) gastro-oesophageal diseases (n=85); (3) chest-wall syndromes (n=58). Less frequent diagnoses included pulmonary embolism, pleuritis/pneumonia, lung cancer. aortic stenosis, aortic aneurysm and herpes zoster. Conclusions The high risk subset of a non-acute myocardial infarction population can be identified by means of a clinical evaluation and non-invasive cardiac examinations. Among the remainder, pulmonary embolism, gastro-oesophageal diseases and chest-wall syndromes should be paid special attention. A careful physical examination of the chest wall and an upper endoscopy seems to be the most cost-beneficial examination to employ in this subset.

An increase in sudden unexpected cardiac deaths among young Swedish orienteers during 1979–1992

Abstract: Background Sixteen cases of sudden unexpected cardiac death, 15 males and one female, are known to have occurred among young Swedish orienteers from 1979 to 1992, of which seven cases occurred between 1989 and 1992. This is considered to be indicative of an increased death rate. Results Histopathological evaluation showed myocarditis in a higher than expected proportion of cases. In one such case, which we studied before the sudden unexpected death occurred, the victim had suffered a Chlamydia pneumoniae infection verified by serology, and a nucleotide sequence was found in the heart and lung by means of the polymerase chain reaction (PCR) that hybndized with a probe specific for that organism. Male Swedish orienteers do not, however, seem to have an increased rate of exposure to this agent. No further sudden unexpected deaths among young orienteers have occurred over the past 3·5 years. At the beginning of that period, attempts were made to modify training habits and attitudes.

Short and long term effects of exercise training on the tonic autonomic modulation of heart rate variability after myocardial infarction.

Abstract: We studied the effects of cardiac rehabilitation on the sympathovagal control of heart rate variability in 30 patients after a first, uncomplicated myocardial infarction. Twenty-two patients completed 8 weeks of endurance training (trained), while eight decided not to engage in the rehabilitation programme for logistical reasons, and were taken as untrained controls. Age, site of infarction, ejection fraction, ventricular diameter and stress test duration were similar in the two groups at baseline. Heart rate variability was evaluated 4 weeks after infarction before starting rehabilitation, and repeated 8 weeks and one year later in both trained and untrained patients. Measures of heart rate variability, obtained from both time- and frequencydomain analysis of a 15min ECG recording in resting conditions, were as follows: mean RR interval and its standard deviation (RRSD), the mean square successive differences (MSSD), the percent of RR intervals differing >50 ms from the preceding RR (pNN50), the low and high frequency components of the autoregressive power spectrum of the RR intervals and their ratio (LF/HF). At baseline, heart rate variability was similar in trained and untrained patients. In the short term (8 weeks after infarction), training increased RRSD by 25% (/><001), MSSD by 69% (P<001), pNN50 by 120% (/)<001), and reduced LF/HF ratio by 30% (/<001). The effects persisted after one year in trained patients. In untrained patients, the autonomic control of heart rate variability did not change 8 weeks after myocardial infarction and was only slightly modified by time. Thus, exercise training, performed for 8 weeks after a myocardial infarction, modifies the sympathovagal control of heart rate variability toward a persistent increase in parasympathet ic tone, known to be associated with a better prognosis. This may partly account for the favourable outcome of patients who undergo rehabilitation. (Eur Heart J 1996; 17: 532-538)

Reproducibility and automatic measurement of QT dispersion.

Abstract: This study investigated interobserver (two observers) and intrasubject (two measurements) reproducibility of QT dispersion from abnormal electrocardiograms in patients with previous myocardial infarction, and compared a user-interactive with an automatic measurement system. Standard 12-lead electrocardiograms, recorded at 25 mm. s−1, were randomly chosen from 70 patients following myocardial infarction. These were scanned into a personal computer, and specially designed software skeletonized and joined each image. The images were then available for user-interactive (mouse and computer screen), or automatic measurements using a specially designed algorithm. For all methods reproducibility of the RR interval was excellent (mean absolute errors 3–4 ms, relative errors 0·3–0·5%). Reproducibility of the mean QT interval was good; intrasubject error was 6 ms (relative error 1·4%), interobserver error was 7 ms (1·8%), and observers' vs automatic measurement errors were 10 and 11 ms (2·5, 2·8%). However QTc dispersion measurements had large errors for all methods; intrasubject error was 12 ms (17·3%), interobserver error was 15 ms (22·1%), and observers' vs automatic measurement were errors 30 and 28 ms (35·4, 31·9%). QT dispersion measurements rely on the most difficult to measure QT intervals, resulting in a problem of reproducibility. Any automatic system must not only recognize common T wave morphologies, but also these more difficult T waves, if it is to be useful for measuring QT dispersion. The poor reproducibility of QT dispersion limits its role as a useful clinical tool, particularly as a predictor of events.

Age-related transmural peak mean velocities and peak velocity gradients by Doppler myocardial imaging in normal subjects

Abstract: Doppler myocardial imaging is a new cardiac ultrasound technique based on the principles of colour Doppler imaging which can determine myocardial velocities by detecting the changes of phase-shift of the ultrasound signal returning directly from the myocardium. To determine the normal range of transmural velocities in healthy hearts a prospective study was carried out involving 42 normal subjects (age from 21 to 78, mean 47 +/- 16 years). Using M-mode Doppler myocardial imaging the peak values of the mean velocity and velocity gradient across the left ventricular posterior wall were measured during standardized phases of the cardiac cycle. Peak mean velocities had the following values during the cardiac cycle: isovolumic contraction - 1.3 +/- 1.2 cm. s-1, early ventricular ejection 4.2 +/- 1.2 cm. s-1, late ventricular ejection 1.8 +/- 1.1 cm. s-1, isovolumic relaxation -2.0 +/- 0.8 cm. s-1, rapid ventricular filling -6.6 +/- 2.2 cm. s-1, atrial contraction -2.8 +/- 1.8 cm. s-1, atrial relaxation 1.2 +/- 1.1 cm. s-1. Peak velocity gradients were: isovolumic contraction 1.3 +/- 1.9 s-1, early ventricular contraction 4.7 +/- 1.9 s-1, late ventricular contraction 1.1 +/- 1.0 s-1, isovolumic relaxation -0.6 +/- 0.5 s-1, rapid ventricular filling 6.1 +/- 3.4 s-1, atrial contraction 2.6 +/- 1.7 s-1, atrial relaxation 0.0 +/- 0.3 s-1. Linear regression analysis showed that with the increase of age, peak velocity gradient decreases during rapid ventricular filling (r = 0.83; P < 0.0001) and increases during atrial contraction (r = 0.86; P < 0.0001) while peak mean velocity increases only during atrial contraction (r = 0.80, P < 0.0001). Thus, there was no correlation between increasing age and systolic peak mean velocity and peak velocity gradient but both diastolic filling phases rapid ventricular filling and atrial contraction demonstrated age-related changes. In summary, this study has determined the age-related range of normal transmural myocardial velocities within the left ventricular posterior wall in healthy hearts during the cardiac cycle. We conclude that these measurements of peak mean velocities and peak velocity gradients, should form the baseline for subsequent Doppler myocardial imaging clinical studies on myocardial diseases processes.

Importance of the right ventricle in valvular heart disease

Abstract: The importance of the right ventricle as a determinant of clinical symptoms, exercise capacity, peri-operative survival and postoperative outcome has been underestimated for a long time. Right ventricular ejection fraction has been used as a measure of right ventricular function but has been found to be dependent on loading conditions, ventricular interaction as well as on myocardial structure. Altered left ventricular function in patients with valvular disease influences right ventricular performance mainly by changes in afterload but also by ventricular interaction. Right ventricular function and regional wall motion can be determined with right ventricular angiography, radionuclide ventriculography, two-dimensional echocardiography or magnetic resonance imaging. However, the complex structure of the right ventricle and its pronounced translational movements render quantification difficult. True regional wall motion analysis is, however, possible with myocardial tagging based on magnetic resonance techniques. With this technique a baso-apical shear motion of the right ventricle was observed which was enhanced in patients with aortic stenosis.

Determinants of delay between symptoms and hospital admission in 5978 patients with acute myocardial infarction

Abstract: The aim of this study was to analyse the influence of patient characteristics on delay between onset of symptoms and hospital admission (patient delay) in acute myocardial infarction, and especially to assess the impact of risk factors for acute myocardial infarction on patient delay. A group of 6676 consecutive patients with enzymeconfirmed acute myocardial infarction, admitted alive to 27 Danish hospitals over a 26 month period from 1990 to 1992, were studied. Due to missing information on delay or in-hospital acute myocardial infarction 698 patients were excluded, leaving 5978 patients for analysis. Mean patient delay was 9·1 h, median delay 3·25 h (5 to 95 percentiles: 0·67–40·0 h). Thirty-four percent were admitted within the first 2 h, 68% within 6 h and 81% within 12 h of onset of symptoms. In multivariate logistic regression analysis, a greater than 2 h patient delay was independently associated with male gender (odds ratio (OR)=0·809, P =0·003), increased age ( P =0·0001), diabetes mellitus (0R= 1·269, P =0·03) left ventricular systolic function (wall motion index) ( P =0·02), onset from midnight to 0600h (OR=1·434, P =0·0001), onset on a weekday (OR=0·862, P =0·04), history of angina pectoris (OR= 1·198, P =0·02), chest pain as initial symptom (OR=1.· 293, P =0·02), ventricular fibrillation (OR= 0·562, P =0·0001), ventricular tachycardia (OR=0·620, P =0·0001), Killip class ≥3(OR=0·709 P =0·002), presence of ST elevation (OR=0·810, P =0·01) and ST depressions (OR=0· 847, P =0·01). All these variables, except history of diabetes mellitus, angina pectoris, and chest pain as an initial symptom were also associated with a delay of more than 6 h. Thrombolytic therapy was administered to 55·8% of patients admitted within 2 h of an acute myocardial infarction, 48·5 of patients admitted within 2–6 h, 31·5% of patients admitted after 6–12 h and 11·9% of patients arriving later than 12 h after start of symptoms. Conclusion Patient delay continues to be disappointingly long. This also applies for patients at a high risk of acute myocardial infarction (notably those with a history of diabetes mellitus and angina pectoris). (Eur Heart J 1996; 17: 429%437)

Histological abnormalities of muscle from limb, thorax and diaphragm in chronic heart failure

Abstract: The aim of the study was to compare histological findings in limb and respiratory muscles from control subjects and patients with heart failure of two different aetiologies. Biopsies of the quadriceps femoris, strap, diaphragm and pectoralis major muscles were taken from each group. The control subjects all had normal left ventricular function, and comprised seven undergoing surgical ablation of electrical pathways and 10 undergoing coronary artery surgery. The heart failure group had severely impaired left ventricular function, and were undergoing cardiac transplantation in all except one case. Ten patients with idiopathic dilated cardiomyopathy and seven with heart failure of ischaemic origin were studied. Conventional histochemical techniques and specific anti-myosin immunofluorescent stains were used. There were no consistent differences in fibre type prevalence or diameter between the groups. There were no important histological abnormalities in the two control groups. There were minor/major changes in four of seven patients with ischaemic heart failure but no major abnormality, whilst in the dilated cardiomyopathy group there were five of 10 patients with minor/major changes and three of 10 with major abnormalities (P < 0.001 vs controls). A variety of changes were seen in both groups of heart failure subjects. These were more marked in the dilated cardiomyopathy than ischaemic group, and suggest the presence of fibre type regeneration and/or transformation. Amongst the findings were tubular aggregates, internalization of nuclei, bizzare staining of myosin and staining of neonatal myosin (seven of 14) and the presence of cores (five of 14). Such changes were more prominent in the diaphragm than in the other muscles. In conclusion, histological abnormalities are present in the limb and respiratory muscles from subjects with heart failure. The changes are most marked in subjects with idiopathic dilated cardiomyopathy, suggesting that there may be a generalized cardiac and skeletal myopathy in these subjects. The presence of histological abnormalities in the respiratory muscles may contribute to the pathogenesis of dyspnoea in heart failure.

The prognostic value of predischarge quantitative two-dimensional echocardiographic measurements and the effects of early lisinopril treatment on left ventricular structure and function after acute myocardial infarction in the GISSI-3 Trial

Abstract: Background Left ventricular dilatation and a low ejection fraction after acute myocardial infarction are independent indicators of a poor prognosis. ACE inhibitors have been shown to decrease left ventricular dilatation after myocardial infarction. In the GISSI-3 trial, patients were randomly assigned, within 24 h of onset of myocardial infarction symptoms, to 6 weeks of treatment with lisinopnl, nitroglycerin, both or neither, in an open, 2x2 factorial design. The study showed that early treatment in relatively unselected patients with lisinopril decreases mortality at 6 weeks and severe left ventricular dysfunction. We assessed (1) the prognostic value of pre-discharge 2-D echocardiographic variables, and (2) the effects of lisinopril on the progression of left ventricular dilatation. Methods and results 2-D echocardiograms were available pre-discharge in 8619 GISSI-3 trial patients discharged alive. In 6405 of these patients, a 2-D echocardiographic study was also available at 6 weeks, and at 6 months. Pre-discharge end-diastolic and end-systolic volumes, and ejection fraction predicted 6-month mortality and non-fatal clinical congestive heart failure (/" 27%. Patients with wall motion asynergy <27% showed no dilatation and lisinopril did not affect volumes at 6 months. Patients randomized to lisinopril also had smaller volumes after withdrawal of treatment at 6 weeks. Lisinopril did not affect left ventricular ejection fraction. Conclusions 2-D echocardiography independently contributes to pre-discharge risk stratification in terms of 6-month mortality and clinical heart failure after myocardial infarction, and early, short-term treatment with lisinopril in unselected myocardial infarction patients attenuates left ventricular dilatation; an effect evident in patients with larger infarcts. These results probably only partly explain the effect of lisinopril on total mortality concentrated in the first week after infarction. (Eur Heart J 1996; 17: 1646-1656)