Clinical consequences of hospital variation in use of oral anticoagulant therapy after first-time admission for atrial fibrillation.

OBJECTIVE: To analyse how hospital factors influence the use of oral anticoagulants (OAC) in atrial fibrillation (AF) patients and address the clinical consequences of hospital variation in OAC use. DESIGN AND SUBJECTS: By linkage of nationwide Danish administrative registers we conducted an observational study including all patients with a first-time hospitalization for AF between 1995 and 2004 as well as prescription claims for OAC. Multivariable logistic regression analysis was used to evaluate hospital factors associated with prescription of OAC therapy. Cox proportional-hazard models were used to estimate the risk of re-hospitalization for thromboembolism and haemorrhagic stroke with respect to discharge from a low, intermediate, or high OAC use hospital. RESULTS: Overall 40,133 (37%) out of 108,504 patients received OAC; ranging from 17% to 50% between the hospitals with the lowest and highest OAC use, respectively. Cardiology departments had the highest use of OAC, but neither tertiary university hospitals nor high volume hospitals had higher OAC use than local community hospitals and low volume hospitals. Risk of a thromboembolic event was significantly increased amongst patients from hospitals with a low OAC use (hazard ratio 1.16, confidence interval 1.10-1.22). Notably, higher OAC use was not associated with a higher risk of haemorrhagic stroke. CONCLUSION: In Denmark between 1995 and 2004, there was a major hospital variation in AF patients receiving OAC, and consequently, more thromboembolic events were observed amongst patients from low OAC use hospitals. Our study emphasizes the need for a continued vigilance on implementation of international AF management guidelines.

Diurnal monitoring of blood pressure and the renin-angiotensin system in hypertensive patients on long-term angiotensin converting enzyme inhibition.

The temporal blood pressure course and the diurnal profile of the renin-angiotensin system were examined in 13 patients with essential hypertension receiving hydrochlorothiazide and enalapril once daily. Blood samples were taken and blood pressure was measured before the habitual morning dose of hydrochlorothiazide and enalapril (at 8.00 a.m.) and at seven time points over the next 24 h. During the period of maximal effect of enalapril (from 11.00 a.m. to 2.00 p.m.), the increase in plasma renin concentration ranged from no change to an 800% increase. A negative correlation was observed between an increase in plasma renin and a decrease in immunoreactive plasma angiotensin II concentration (Spearman rank-order correlation coefficient = 0.83). Notably, the greatest changes in plasma renin and angiotensin II concentrations after enalapril were seen in those patients whose blood pressure fell most during the day. We conclude that hypertensive patients on long-term therapy with enalapril once daily vary widely in their between-dose biochemical response to the drug, and that there is a significant association between the responsiveness of the plasma renin-angiotensin system and the effect on 24 h blood pressure.

Bronchial artery perfusion scintigraphy to assess bronchial artery blood flow after lung transplantation.

UNLABELLED: The bronchial arterial system is inevitably interrupted in transplanted lungs when removing the organs from the donor, but it can be reestablished by direct bronchial artery revascularization (BAR) during implantation. The purpose of this study was to visualize and quantify the distribution of bronchial artery perfusion after en bloc double lung transplantation with BAR, by injecting radiolabeled macroaggregated albumin directly into the bronchial artery system. METHODS: BAR was performed using the internal mammary artery as conduit. Patients were imaged 1 mo (n = 13) or 2 y (n = 9) after en bloc double lung transplantation with BAR. Immediately after bronchial arteriography, 100 MBq macroaggregated albumin (45,000 particles) were injected through the arteriographic catheter. Gamma camera studies were then acquired in the anterior position. At the end of imaging, with the patient remaining in exactly the same position, 81mKr-ventilation scintigraphy or conventional intravenous pulmonary perfusion scintigraphy or both were performed. Images were evaluated by visual analysis, and a semiquantitative assessment of the bronchial arterial supply to the peripheral parts of the lungs was obtained with conventional pulmonary scintigraphy. RESULTS: The bronchial artery scintigraphic images showed that the major part of the bronchial arterial flow supplied central thoracic structures, but bronchial artery perfusion could also be demonstrated in the peripheral parts of the lungs when compared with conventional pulmonary scintigraphy. There were no differences between scintigrams obtained from patients studied 1 mo and 2 y post-transplantation. CONCLUSION: Total distribution of bronchial artery supply to the human lung has been visualized in lung transplant patients. This study demonstrates that this nutritive flow reaches even the most peripheral parts of the lungs and is present 1 mo as well as 2 y after lung transplantation. The results suggest that bronchial artery revascularization may be of significance for the long-term status of the lung transplant.

Continuous monitoring of global left ventricular ejection fraction during percutaneous transluminal coronary angioplasty.

Continuous monitoring of left ventricular (LV) function during percutaneous transluminal coronary angioplasty (PTCA) was performed in 40 patients (53 +/- 2 years) with a miniature, nuclear detector system after labeling the patients' red blood cells with technetium-99m. Balloon dilation (113 seconds, range 60 to 240) induced on average a 0.12 ejection fraction (EF) unit (19%) decrease in the LVEF, which was explained by a 34% increase in end-systolic counts. Balloon dilation of the left anterior descending artery (n = 23) produced a decrease in the LVEF of 0.17 +/- 0.13 EF units compared with the decrease of 0.06 +/- 0.07 EF units in patients undergoing dilation of the left circumflex artery (n = 9) and 0.05 +/- 0.04 EF units in patients treated for a stenosis of the right coronary artery (n = 8), (p = 0.02). Balloon deflation was associated with an immediate return to pre-PTCA levels. In 10 patients with 2 identical balloon occlusions, the second occlusion led to a significantly less decrease in the LVEF (0.41 +/- 0.14 vs 0.44 +/- 0.15) and electrocardiographic ST-segment deviation (88 +/- 54 microV vs 65 +/- 42 microV) than the first. We conclude that PTCA is associated with an abrupt transient decrease in the LVEF. The effect of balloon occlusion of the left anterior descending artery is more pronounced than balloon occlusion of the left circumflex and the right coronary arteries. Neither single nor multiple balloon occlusions were associated with post-PTCA global LV dysfunction, whereas the lesser degree of LV dysfunction and electrocardiographic signs of myocardial ischemia during the second of 2 identical balloon occlusions suggests that preconditioning can be induced during PTCA.

Late ventricular dilatation in survivors of acute myocardial infarction.

The purpose of this study was to assess the natural course of left ventricular (LV) volumes in the convalescent phase of acute myocardial infarction (AMI). Fifty-seven patients were examined 2 weeks and approximately 1 year after AMI by a radionuclide method allowing determination of absolute LV volumes. After 1 year the patients had fewer clinical and radiologic signs of heart failure, but median end-diastolic volume index had increased from 92 to 112 ml/m2 (p less than 0.001), median end-systolic volume index from 51 to 65 ml/m2 (p less than 0.001) and median stroke volume index from 39 to 47 ml/m2 (p less than 0.001). Patients with first anterior infarcts had significantly greater increases in end-diastolic volume index, end-systolic volume index and stroke volume index than patients with first inferoposterior infarcts. The increase in LV volumes was significantly greater in patients with clinical manifestations of heart failure than in those without these signs. Notably, changes in LV size had an unpredictable effect on LV ejection fraction.

Interobserver agreement and accuracy of bedside estimation of right and left ventricular ejection fraction in acute myocardial infarction.

Ninety-eight patients with acute myocardial infarction were examined by 3 clinicians who, independently of each other, gave an estimate of left ventricular (LV) and right ventricular (RV) ejection fraction (EF) in each patient. Their estimates were based on physical examination, chest x-ray, electrocardiogram, patient history and clinical course during admission. Ejection fractions were estimated as belonging to 1 of 4 categories: normal (LVEF greater than or equal to 0.53, RVEF greater than or equal to 0.57), mildly reduced (LVEF 0.40 to 0.52, RVEF 0.45 to 0.56), moderately reduced (LVEF 0.30 to 0.39, RVEF 0.35 to 0.44) or severely reduced (LVEF less than 0.30, RVEF less than 0.35). Radionuclide ventriculography was carried out immediately after the physical examination. LVEF was correctly estimated in 43% of all examinations, deviated from radionuclide LVEF by 1 LVEF category in 45% and by 2 LVEF categories in 12%. The 3 clinicians agreed on estimated LVEF in only 32% of the patients. RVEF was correctly estimated in 67% of the examinations, but none of the clinicians identified greater than 43% of the relatively few patients with reduced radionuclide RVEF and they greatly disagreed as to who among the patients had a reduced RVEF. Previous myocardial infarction, electrocardiographic infarct location, Killip class, physical signs of left- and right-sided heart failure, radiographic pulmonary congestion and cardiomegaly were analyzed to determine which were the most helpful in predicting LVEF and RVEF. The results disclosed that several variables, traditionally believed to be reliable indexes of reduced ventricular function, were surprisingly poor predictors of LVEF and RVEF.

Changes in left and right ventricular performance and volumes in seven-year survivors of acute myocardial infarction.

We describe the spontaneous long-term changes in right (RV) and left (LV) ventricular performance during a 7-year period after acute myocardial infarction (AMI). Radionuclide ventriculography was performed in the second week after AMI in 201 patients. RV and LV ejection fractions, and LV end-diastolic and end-systolic volumes were determined. A follow-up after 7 years was performed in 55 survivors. Of these, 16 patients were also examined after 1 year. During the 7-year follow-up period, LV ejection fraction decreased from 0.49 to 0.45 (p < 0.01). LV end-diastolic volume increased from 161 to 210 ml (30%) (p < 0.01), and LV end-systolic volume from 83 to 123 ml (48%) (p < 0.01). In patients without recurrent AMI, coronary artery bypass grafting surgery, or angiotensin-converting enzyme inhibitor therapy (n = 37) during follow-up, no change in average LV ejection fraction was observed. Nevertheless, this subgroup had substantial increases in LV end-diastolic volume, from 157 to 190 ml (21%) (p = 0.002) and in LV end-systolic volume, from 80 to 105 ml (31%) (p < 0.001). In a subgroup of patients also reinvestigated after 1 year (n = 16), there was a 15% increase in LV end-diastolic volume the first year after AMI with an additional 10% increase in LV end-diastolic volume between years 1 and 7. Corresponding figures for LV end-systolic volume were 20% and 12%, respectively. Hardly any association was apparent between LV ejection fraction, LV end-diastolic volume, and LV stroke volume at discharge for subsequent LV dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

In-hospital heart failure, first-year ventricular dilatation and 10-year survival after acute myocardial infarction.

BACKGROUND: Little is known about the factors that determine long-term prognosis in patients who have survived the first year after acute myocardial infarction (AMI). AIMS: To study the influence of left and right ventricular (LV and RV) dilatation during the first year after AMI on subsequent 10-year survival in comparison with in-hospital heart failure and other established prognostic indices. METHODS: Radionuclide ventriculography was performed before the era of thrombolysis and post-infarction ACE-inhibition in 57 patients with AMI at hospital discharge and again 1 year later, and compared with survival the ensuing 10 years. RESULTS: After 1 year significant LV-dilatation (>20%) had occurred in 32 (56%) patients. One year after the re-investigation the mortality in these was 19% vs. 0% in patients without dilatation (P=0.02); after 5 years the difference was 38 vs. 12% (P=0.02), whereafter it declined and became insignificant at 10 years. Neither RV-dilatation, nor LVEF determined at discharge or at the 1-year reinvestigation influenced long-term survival. In contrast, clinical heart failure recorded during the hospital stay had a sustained negative influence on long-term survival. CONCLUSION: Progressive LV dilatation after discharge and clinical heart failure during the hospital stay are both determinants of late survival after AMI, whereas LV ejection fraction at hospital discharge or 1 year later has little, if any, effect on survival beyond 1-year post-AMI.

[Is digoxin effective in the treatment of heart insufficiency in patients with sinus rhythm?]. / Er digoxin virksomt til behandling af hjerteinsufficiens hos patienter med sinusrytme?

Since its introduction in 1785, digitalis has been the cornerstone in the treatment of heart failure, although there during the last 20 years have been an increasing number of critical voices questioning its use in patients with sinus rhythm. In 1997 the Digitalis Investigation Group published the so far largest randomized trial on the use of digoxin in patients with heart failure (DIG-trial). All the included patients had sinus rhythm, and all received an ACE-inhibitor. Digoxin had no effect on mortality, but caused a decrease in hospitalizations. Based on the DIG-study, several minor clinical trials and two large withdrawal studies (RADIANCE and PROVED) it now seems clear that digoxin still has a role in the management of heart failure, not only in patients with atrial fibrillation, but also in patients with sinus rhythm.

Temporal decline in the prognostic impact of a recurrent acute myocardial infarction 1985 to 2002.

OBJECTIVE: To investigate trends in case-fatality and prognostic impact from recurrent acute myocardial infarction (re-AMI) during 1985-2002. DESIGN: Retrospective cohort study using nationwide administrative data from Denmark. SETTINGS: National registries on hospital admissions and causes of death were linked to identify patients with first AMI, re-AMI and subsequent prognosis. PATIENTS: Patients > or =30 years old with a discharge diagnosis of AMI during 1985-2002 were tracked for first hospital admission for re-AMI 1 year after discharge. MAIN OUTCOME MEASURES: One-year case-fatality. RESULTS: 166 472 patients were identified with a first AMI; 14 123 developed re-AMI. One-year crude case-fatality from first AMI/re-AMI was 39% versus 43% in 1985-1989 and 25% versus 29% in 2000-2002, respectively. In 1985-89, 35 795 patients survived to discharge (71%); of these 2.5% experienced reinfarction within 30 days (early reinfarction) and an additional 9.0% reinfarction within days 31-365 (late re-AMI). Re-AMI carried a poor prognosis in 1985-1989 compared to no re-AMI with age- and sex-adjusted relative risk of 1-year case-fatality of 7.5 (95% CI: 6.9 to 8.5) from early re-AMI and 11.7 (95% CI: 11.0 to 12.4) from late re-AMI. In 2000-2002, 23 552 patients (86%) survived to discharge; 4.4% had early re-AMI and 6.6% late re-AMI. Adjusted relative risk of 1-year case-fatality had declined to 2.1 (95% CI: 1.9 to 2.5) from early re-AMI and 5.6 (95% CI: 5.1 to 6.2) from late re-AMI compared to patients without reinfarction. CONCLUSION: Prognosis after AMI has improved substantially during the latest two decades and extends to patients with re-AMI.

Temporal trends in the prescription of vitamin K antagonists in patients with atrial fibrillation.

OBJECTIVES: Anticoagulation therapy is recommended in patients with atrial fibrillation (AF) and risk factors for stroke. We studied the temporal trends in the prescription of vitamin K antagonists (VKA) in patients with a first hospital diagnosis of AF in Denmark, 1995-2002. DESIGN: The Danish National Hospital Registry was used to identify subjects with a first hospital diagnosis of AF and the Danish Register of Medical Products Statistics to determine the proportion of these patients who claimed a prescription of VKA within 3 months from discharge. RESULTS: Amongst 68 546 patients aged 50-99 years with a diagnosis of AF who survived 3 months following discharge, 24 991 (36%) patients claimed a prescription of VKA within 3 months. In both men and women a gradual increase in the use of VKA with time was observed, the relative increase being largest amongst the 80- to 99-year olds. In all age groups, the prescription of VKA was lower in women than in men, including patients with a prior or concurrent stroke. CONCLUSIONS: From 1995 to 2002 the proportion of AF patients receiving VKA therapy increased significantly but the use of VKA therapy amongst women was lagging behind that of men. Even in patients with AF and prior stroke, the use of VKA seems to be less than optimal.

Technetium-99m sestamibi and tetrofosmin myocardial single-photon emission tomography: can we use the same reference data base?

The aim of this study was to compare technetium-99m labelled tetrofosmin and sestamibi myocardial perfusion single-photon emission tomography (SPET) with one common sestamibi reference file for bull's eye imaging, with quantitation of the extent and severity of perfusion defects. Twenty patients suspected or known to have coronary artery disease participated in the study. Patients first underwent routine sestamibi myocardial SPET over 2 days, receiving doses of 400-600 MBq at stress and 600-800 MBq at rest. Then within the same week a 1-day tetrofosmin myocardial SPET study was performed, with a dose of 300 MBq at stress, followed 2.5 h later by a dose of 750 MBq at rest. Bull's eye images were generated for visual evaluation. Black-out defects according to the Cequal software analysis were only recorded if they comprised more than 10 pixels in men and 20 in women. According to the Cequal program, extent score and severity scores were expressed as number of pixels and deviations below reference limits. Five patients had normal myocardial SPET imaging with both radiotracers, while 15 had reversible, irreversible or partially reversible defects. The concordance of the results was high. The only two significant differences were that one patient had a reversible defect which appeared to be located in different myocardial regions (LAD vs RCA), and another patient had a defect that was partially reversible with sestamibi but irreversible with tetrofosmin. The results showed very high correlation coefficients for the extent and severity scores (linear correlation coefficient values of 0.99 and 0.94, respectively). In conclusion, it appears that changing between sestamibi and tetrofosmin has little influence on the interpretation of bull's eye images from the data file of a common reference population using one of the tracers.

Cardiac function and maximal exercise capacity early after acute myocardial infarction.

The purpose of the study was to assess the relationship between left and right ventricular function measured at rest and maximal exercise capacity in patients with recent acute myocardial infarction (AMI). Forty-three male patients (Killip Class I, n = 36; Killip Class II, n = 7) with a wide range of left ventricular (LV) function and size underwent graded bicycle exercise testing less than 4 weeks after AMI (mean 21 days, 17-27). None of the patients had exercise limiting factors other than dyspnoea and fatigue. Left and right ventricular ejection fractions were determined by a radionuclide ventriculographic method which also allowed determination of absolute LV volumes and actual LV peak filling rate. LV ejection fraction had a weak association to estimated maximal oxygen uptake (VO2 max) (r = 0.37). No association was found between LV size, LV stroke volume, or LV peak filling rate and estimated VO2 max. Similarly, right ventricular ejection fraction showed no correlation to estimated VO2 max. Patients with well preserved LV function had a higher exercise induced increase in systolic blood pressure than patients with reduced LV function, but the increase in systolic blood pressure could not be used to estimate LV function with any reasonable accuracy. We conclude that the maximal exercise capacity of patients with recent AMI is virtually independent of their left and right ventricular function determined at rest, and that exercise testing and radionuclide ventriculography should be regarded as complementary procedures in the evaluation of patients with AMI.

Monitoring of left ventricular ejection fraction with a miniature, nonimaging nuclear detector: accuracy and reliability over time with special reference to blood labeling.

BACKGROUND: The purpose of this study was to determine the accuracy of determinations of left ventricular ejection fraction (LVEF) by a nonimaging miniature nuclear detector system (Cardioscint) and to evaluate the feasibility of long-term LVEF monitoring in patients admitted to the coronary care unit, with special reference to the blood-labeling technique. METHODS AND RESULTS: Cardioscint LVEF values were compared with measurements of LVEF by conventional gamma camera radionuclide ventriculography in 33 patients with a wide range of LVEF values. In 21 of the 33 patients, long-term monitoring was carried out for 1 to 4 hours (mean 186 minutes), with three different kits: one for in vivo and two for in vitro red blood cell labeling. The stability of the labeling was assessed by determination of the activity of blood samples taken during the first 24 hours after blood labeling. The agreement between Cardioscint LVEF and gamma camera LVEF was good with automatic background correction (r = 0.82; regression equation y = 1.04x + 3.88) but poor with manual background correction (r = 0.50; y = 0.88x - 0.55). The agreement was highest in patients without wall motion abnormalities. The long-term monitoring showed no difference between morning and afternoon Cardioscint LVEF values. Short-lasting fluctuations in LVEFs greater than 10 EF units were observed in the majority of the patients. After 24 hours, the mean reduction in the physical decay-corrected count rate of the blood samples was most pronounced for the two in vitro blood-labeling kits (57% +/- 9% and 41% +/- 3%) and less for the in vivo blood-labeling kit (32% +/- 26%). This "biologic decay" had a marked influence on the Cardioscint monitoring results, demanding frequent background correction. CONCLUSION: A fairly accurate estimate of LVEF can be obtained with the nonimaging Cardioscint system, and continuous bedside LVEF monitoring can proceed for hours with little inconvenience to the patients. Instability of the red blood cell labeling during long-term monitoring necessitates frequent background correction.

C-reactive protein in femoral head necrosis.

Serum concentrations of C-reactive protein (CRP), alpha 1-antitrypsin, orosomucoid, and haptoglobin were determined in 28 patients with a medial fracture of the femoral neck. The serum concentrations were compared with the result of hip scintigraphy with technetium-99m pyrophosphate, a method which can detect femoral head necrosis and predict the development of late segmental collapse. Serum concentrations of the four acute-phase proteins were measured immediately before osteosynthesis and at the time of hip scintigraphy 1 to 4, 8 to 13, and 37 to 47 days postoperatively. During the same period 15 patients had constantly normal, five varying abnormal/normal, and eight constantly abnormal scintigrams, the latter indicating femoral head necrosis. All four acute-phase proteins had a typical course of concentration changes, which were most pronounced for CRP. However, none of them were useful for the detection of femoral head necrosis or the prediction of late segmental collapse, since the observed serum concentrations could not be used to distinguish between the three scintigraphic groups.

Left ventricle haemodynamics and vaso-active hormones during graded supine exercise in healthy male subjects.

Left ventricle systolic and diastolic functional parameters were measured by gated equilibrium radionuclide cardiography in 12 healthy men (age 33-51 years) at rest and during graded supine exercise. The leftventricle end-diastolic volume showed an initial small (11%) increase during low submaximal exercise [from mean 163 (SD 40) at rest to mean 181 (SD 48) ml], while left ventricle end-systolic volume decreased successively [from mean 59 (SD 19) to mean 39 (SD 21) ml] with increasing exercise. Stroke volume was therefore elevated at all exercise levels compared with rest [mean 104 (SD 23) ml], and the peak value [mean 128 (SD 33) ml] was found at the lowest exercise level, contributing 40% to the initial increase in cardiac output. Cardiac output increased from mean 6.2 (SD 1.4) at rest to mean 20.2 (SD 5.0) l.min-1 at maximum. Left ventricle peak ejection and peak filling rates increased from mean 449 (SD 89) and mean 442 (SD 85) ml.s-1 at rest to mean 996 (SD 227) and mean 1255 (SD 333) ml.s-1, respectively, at maximum. The myocardium oxygen consumption, assumed to be proportional to the sum of the stroke work and the potential energy, increased fourfold, but absolute values were twice as high as expected, indicating that extrapolation from data obtained in dog hearts (as we have done) cannot be directly applied to humans. Selected vaso-active hormones were measured at all exercise intensities. Noradrenaline (NA), adrenaline (A) and angiotensin II (AII) concentrations showed a very pronounced increase at maximal exercise compared with the preceding lower intensites, while atrial natriuretic factor (ANF) and cyclic guanosinemonophosphate (cGMP) concentrations showed a more continuous increase, and dopamine (DA) remained almost unchanged. This speaks in favour of a crucial role for NA, A and AII in preserving blood pressure at maximum exercise, while DA probably has no importance for the cardiovascular homeostasis during exercise. Increases in concentrations of ANF and cGMP were highly correlated (r = 0.86). Our data supported the opinion that there is a cardiac limitation to maximal performance connected to the cardiac pumping capacity.

Atrial natriuretic factor: comparability of venous and arterial plasma measurements in man at rest and during exercise.

1. Simultaneously obtained arterial and venous plasma atrial natriuretic factor (ANF) concentrations were compared at supine rest and during graded dynamic leg exercise in 10 healthy male subjects (aged 33-51 years). 2. Arterial ANF concentrations ranged between 12 and 179 pg/ml and venous concentrations between 9 and 177 pg/ml. 3. A positive correlation between arterial and venous concentrations was found (r = 0.984). 4. Arterial ANF concentrations were higher than venous concentrations in all pairs of samples (n = 31), but the difference was small and changed little with exercise: the mean difference was 5 pg/ml at rest, 12 pg/ml during submaximal exercise and 6 pg/ml during maximal exercise. 5. The extraction ratios for ANF varied greatly, but were in general lower (P less than 0.05) during maximal exercise (median 0.07, range 0.01-0.32) than at rest (median 0.22, range 0.05-0.33). 6. It was concluded that the plasma ANF concentration in a peripheral arm vein is a good indicator of the systemic peptide concentration at rest as well as during dynamic leg exercise.

Clinical characteristics, left and right ventricular ejection fraction, and long-term prognosis in patients with non-insulin-dependent diabetes surviving an acute myocardial infarction.

Patients with diabetes mellitus have a high morbidity and mortality from acute myocardial infarction, the reason for which is not fully understood. The relationship between congestive heart failure symptoms, left ventricular ejection fraction, and long-term mortality was examined in 578 hospital survivors of acute myocardial infarction, 47 of whom had Type 2 (non-insulin-dependent) diabetes mellitus. None of the patients were treated with insulin. The prevalence of congestive heart failure during hospitalization was similar in patients with and without diabetes, although mean diuretic dose was higher in the former patients. Left and right ventricular ejection fraction was measured with radionuclide ventriculography in the second week after acute myocardial infarction. At discharge from the coronary care unit, patients with and without diabetes had similar left ventricular ejection fraction (with diabetes: median 46% vs without diabetes: median 43%; p = 0.89). Median right ventricular ejection fraction (62%) was within normal limits in both groups and did not differ statistically. Survival data were obtained for all patients. The 5-year mortality was increased in patients with diabetes compared with non-diabetic patients independent of left ventricular ejection fraction. Univariate analysis showed that the cumulative 5-year mortality rate was 53% in the group with diabetes compared with 43% in the non-diabetic group (p = 0.007). Using multivariate regression analysis presence of diabetes was found to have a significant association with long-term mortality after myocardial infarction, that was independent of age, history of hypertension, congestive heart failure symptoms during hospitalization or of either left or right ventricular ejection fractions at discharge. We conclude that the excess mortality in patients with non-insulin-dependent diabetes mellitus is not explained by available risk markers after myocardial infarction. Even though left ventricular ejection fraction and serum creatinine did not differ significantly, the apparent higher dose of Frusemide in patients with than without non-insulin-dependent diabetes mellitus might indicate that heart failure, it present, is more severe in patients with than in those without diabetes. The importance of diastolic dysfunction in this context needs to be determined.

Is digoxin an independent risk factor for long-term mortality after acute myocardial infarction?

The safety of treatment with digoxin in patients with acute myocardial infarction (MI) was investigated in 584 hospital survivors of MI. All patients were examined by radionuclide ventriculography, with determination of left ventricular ejection fraction (LVEF), close to the time of discharge. Clinical data were collected on admission. All patients were followed up with regard to death (median 6.2 years, range 3.9-7.8 years). Patients treated with digoxin (N = 172 (29%) were older (median 66 vs 59 years; (P < 0.001), had a higher incidence of diabetes (13% vs 7%; P = 0.025), and a lower LVEF (0.33 vs 0.49; P < 0.001). As expected, clinical heart failure was more frequent among them (84% vs 14%; P < 0.001), than in patients not receiving digoxin. The 1- and 5-year mortality of patients treated with digoxin was 38% and 74% compared to 8% and 26% in patients not receiving digoxin (P < 0.001). The increased risk associated with digoxin therapy remained statistically significant when patients were stratified according to the presence or absence of heart failure or atrial fibrillation/flutter during hospitalization, or to LVEF above or below 0.45 at discharge. In a proportional hazard model including age, LVEF, diabetes mellitus, heart failure, atrial fibrillation or flutter, ventricular fibrillation, gender, dose of furosemide at discharge and calcium antagonists and digoxin treatment as covariates, digoxin was independently associated with an increased risk of death (relative risk 1.8 (95% confidence limit 1.2-2.5)). We conclude that administration of digoxin may be harmful in hospital survivors of MI.