Concealed Coronary Atherosclerosis In Idiopathic Paroxysmal Atrial Fibrillation is Associated with Imminent Cardiovascular Diseases.

BACKGROUND: Previous research showed a significant difference in the presence of subclinical coronary artery disease (CAD) on cardiac CT angiography (CTA) between patients with idiopathic paroxysmal atrial fibrillation (iAF) versus a matched sinus rhythm population (iSR). Here we present 5-year follow-up data and the consequences of subclinical CAD on baseline CTA on the development of cardiovascular disease in iAF. METHODS: In 99 iAF patients (who underwent CTA as part of work-up for pulmonary vein isolation) and 221 matched iSR controls (who underwent CTA for CAD assessment), the incidence of hypertension, diabetes and major cardiovascular events (MACCE) during follow-up was obtained. Multivariable Cox regression analysis was used to reveal predictors of incident cardiovascular disease in the iAF group. RESULTS: During a follow-up of 68±11 months, over one third of patients developed cardiovascular disease, with no difference between iAF and iSR (log-rank p=0.56), and comparable low rates of MACCE (4.0% vs 5.0%,p=0.71). Within the iAF group, age (HR1.12(1.03-1.20);p=0.006), left atrial diameter (HR1.16(1.03-1.31);p=0.01), Segment Involvement Score (total number of coronary segments with atherosclerotic plaque; HR1.43(1.09-1.89);p=0.01) and the number of calcified plaques on CTA (HR0.53(0.30-0.92);p=0.01) were independent predictors of incident cardiovascular disease. CONCLUSIONS: Subclinical coronary disease on CTA may be useful to identify the subset of patients with iAF that harbour concealed cardiovascular risk factors and need intensive clinical follow-up to ensure timely initiation of appropriate therapy once CV disease develops, including anticoagulation and vascular prophylactic therapy.

Effects of tailored telemonitoring on functional status and health-related quality of life in patients with heart failure.

BACKGROUND: Functional status and health-related quality of life (HRQoL) are important in patients with heart failure (HF). Little is known about the effect of telemonitoring on functional status and HRQoL in that population. METHODS AND RESULTS: A total of 382 patients with HF (New York Heart Association class 2-4) were included in a randomised controlled trial to investigate the effect of tailored telemonitoring on improving HRQoL and functional status in HF patients. Randomisation was computer-generated with stratification per centre. At baseline and after 12 months, patients' functional status was determined by metabolic equivalent scores (METS). HRQoL was measured with the EuroQol five dimensions questionnaire (EQ-5D), visual analogue scale (VAS) and Borg rating of perceived exertion scale (Borg). Additional outcome data included number of HF-related outpatient clinic visits and mortality. Telemonitoring was statistically significantly related to an increase in METS after 1 year (regression coefficient 0.318; p = 0.01). Telemonitoring did not improve Borg, EQ-5D or VAS scores after 1 year. EQ-5D [hazard ratio (HR) 0.20, 95% confidence interval (CI) 0.07-0.54], VAS (HR 0.98, 95% CI 0.96-0.99), Borg (HR 1.21, 95% CI 1.11-1.31) and METS (HR 0.73, 95% CI 0.58-0.93) at baseline were significantly associated with survival after 12 months. CONCLUSIONS: Tailored telemonitoring stabilised the functional status of HF patients but did not improve HRQoL. Therefore, telemonitoring may help to prevent deterioration of exercise capacity in patients with HF. However, because our study is a reanalysis of a randomised controlled trial (RCT), this is considered hypothesis-generating and should be confirmed by adequately powered RCTs.

Are premature ventricular contractions always harmless?

INTRODUCTION: Premature ventricular contractions (PVCs) are among the most prevalent arrhythmias. PVCs lead to haemodynamically insufficient heartbeats. Their presence is considered rather insignificant, but this widespread assumption is not supported by research evidence. CASES: We present three cases of patients commonly seen in daily general practice, with a range of presentations, varying from incidental (harmless) PVCs to frequent and potentially symptomatic PVCs. DISCUSSION: In more frequent PVCs (> 10% heart beats) fatigue and exertional dyspnoea may occur. When > 20% of heart beats are PVCs, patients may develop cardiomyopathy and heart failure. Incidental PVCs are harmless. Anti-arrhythmic drug treatment should be considered in case of frequent PVCs but also catheter ablation appears an effective treatment option. CONCLUSION: Altogether, PVCs may not be harmless, depending on their occurrence rate. Research data from primary care settings on epidemiology and natural course is needed.

RESPONSE study: Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists: Study design, objectives and expected results.

Background. Patients with coronary artery disease are at high risk of coronary events and death, but effective secondary prevention can reduce this risk. There is a gap between guidelines on secondary prevention and the implementation of these measures, which could potentially be reduced by nurse led prevention clinics (NLPC).Objectives. The aim of the current study is to quantify the impact of NLPC on the risk of cardiovascular events in patients with established coronary artery disease.Methods. A randomised, multicentre clinical trial of NLPC in addition to usual care or usual care alone in post-acute coronary syndrome patients. (Neth Heart J 2009;17:322-8.).

[Cardiac symptoms due to pectus excavatum in a man over the age of 55]. / Cardiale klachten door een pectus excavatum bij een 55-plusser.

A healthy 59-year-old man, a retired general practitioner, suffered from increasing palpitations, fatigue and postural dyspnoea: bending over led to a significant increase in his shortness of breath. Cardiological and pulmonological examination, performed at regular intervals, showed occasional supraventricular arrhythmia and nodal tachycardia but did not yield a satisfactory explanation for the symptoms. In the years that followed, the physical impairment became a considerable handicap. Finally, the patient himself suggested a possible explanation on the basis of an Internet search: his pectus excavatum. A literature search confirmed this hypothesis. A lateral chest X-ray in bending position and a CT-scan of the chest revealed compression of the heart by the sternum. Ten years after the onset of symptoms, a modified Ravitch operation finally brought nearly complete recovery.

[Complete atrioventricular block during galantamine therapy]. / Totaal atrioventriculair blok tijdens behandeling met galantamine.

A 77-year-old man who for 5 months had been being treated with galantamine for early Alzheimer's disease, suddenly became unwell. He was bradycardic and his ECG showed a complete atrioventricular block. This was treated by implantation of a pacemaker. Treatment with galantamine was continued. A month later he had no cardiac symptoms and his dementia score on a cognitive scale had improved. Cholinesterase inhibitors may have adverse effects on the heart. Patients starting treatment with cholinesterase inhibitors should be screened for an increased risk of cardiac arrhythmias by investigating their potassium concentrations and running an ECG.

Tolerability of beta-blockers in elderly patients with chronic heart failure: the COLA II study.

BACKGROUND: Beta-blockers are recommended therapy for patients with chronic heart failure (CHF). However, there remains concern regarding tolerability of these agents in the elderly, which has contributed to the limited uptake of these agents in clinical practice. AIMS: We conducted a multi-national, prospective evaluation of tolerability to carvedilol in 1030 CHF patients aged >70 years selected by their treating physician to receive this agent in everyday practice. METHODS AND RESULTS: NYHA Class II-IV CHF patients were assessed at baseline for key demographic parameters that may predict tolerability, then followed for 6 months after starting carvedilol. Tolerability was defined as being on >or=6.25 mg bd of carvedilol at 6 months having received a total of >or=3 months therapy. Tolerability overall was 80% with age 70-75 years 84.3%, 76-80 years 76.8% and >80 years 76.8%. Mean carvedilol dose achieved was 31.2 mg. In multivariate analysis, advanced age, low diastolic BP, LVEF, obstructive airways disease and presence of diabetes were predictors of tolerability. CONCLUSIONS: Carvedilol appears to be well tolerated in this elderly CHF patient cohort. Therefore, elderly CHF patients should not be denied treatment with carvedilol because of concerns regarding tolerability.

Non-invasive assessment of local arterial pulse pressure: comparison of applanation tonometry and echo-tracking.

OBJECTIVES: Pulse pressure is not constant throughout the arterial tree. Use of pulse pressure at one arterial site as surrogate for pulse pressure at another arterial site may be erroneous. The present study compares three non-invasive techniques to measure local pulse pressure: (i) internally calibrated readings from applanation tonometry, (ii) alternative calibration of pressure waves obtained with applanation tonometry and (iii) alternative calibration of arterial distension waves obtained with echo-tracking. Alternative calibration assumes mean and diastolic blood pressure constant throughout the large artery tree. DESIGN AND METHODS: Study 1 used invasive measurements in the ascending aorta as a reference method and internally calibrated tonometer readings and alternatively calibrated pressure waves at the common carotid artery as test methods. Study 2 used alternatively calibrated pressure waves as a reference method and alternatively calibrated distension waves and internally calibrated applanation tonometer readings as test methods. RESULTS: In study 1, pulse pressure from internally calibrated tonometer readings was 10.2+/-14.3 mmHg lower and pulse pressure from alternatively calibrated pressure waves was 1.8+/-5.2 mmHg higher than invasive pulse pressure. Pulse pressure from calibrated distension waves was 3.4+/-6.9 mmHg lower than pulse pressure from alternatively calibrated pressure waves. According to British Hypertension Society criteria, pulse pressure from the internally calibrated tonometer achieved grade D and pulse pressure from alternatively calibrated pressure waves achieved grade A. Pulse pressure from calibrated distension waves achieved grade B when alternatively calibrated pressure waves were used as a reference method. CONCLUSIONS: Pulse pressure obtained from alternatively calibrated tonometer-derived pressure waves and echo-tracking-derived distension waves demonstrates good accuracy. Accuracy of pulse pressure from internally calibrated applanation tonometer readings at the carotid artery is poor.

Effect of acute phase response on cumulative troponin T release.

UNLABELLED: We studied a possible effect of the extent of the acute phase response after acute myocardial infarction on the cumulative release of troponin T. The height of the acute phase response might influence the cumulative release of troponin T, bound to the myofibrillar structures of the heart, in a different way compared to the free cytoplasmic cardiac marker hydroxybutyrate dehydrogenase (EC 1.1.1.27). To investigate this, the cumulative amount of C-reactive protein in plasma, i.e. the quantified acute phase response, was related to the cumulative plasma release of hydroxybutyrate dehydrogenase (an established method for infarct sizing) on the one hand and to that of troponin T on the other hand. The study was performed in patients receiving (n=16) and in patients not receiving (n=6) thrombolytic therapy. Cumulative protein release was calculated using a two-compartment model for circulating proteins. CONCLUSIONS: The cumulative amount of plasma C-reactive protein is significantly higher in the patients not receiving thrombolytic therapy, as is in accordance with earlier studies. The cumulative amount of troponin T released is significantly related to the cumulated concentration of C-reactive protein, especially in patients not receiving thrombolytic therapy. The intensity of the acute phase response, estimated from cumulative plasma C-reactive protein response, has no effect on the relative proportions of troponin T and hydroxybutyrate dehydrogenase released into plasma.

Clopidogrel-rt-PA-heparin combination in the treatment of acute myocardial infarction.

The safety and tolerability of clopidogrel coadministration to patients with recent acute myocardial infarction (AMI) treated with recombinant tissue plasminogen activator (rt-PA) and heparin were assessed. Patients of either sex who had a recent uncomplicated AMI with ischemic pain lasting at least 20 minutes and ST-segment elevation, and with indication for thrombolysis were included. Treatment was started within 12 hours after the onset of pain. Clopidogrel 75 mg was administered within 3 hours of starting the rt-PA infusion, and was continued at 75 mg once daily over the next 6 days. Heparin was administered as a 5000 IU intravenous bolus followed by a 1000 IU/h infusion for at least 48 hours to maintain an activated partial thromboplastin time at 1.8 to 2.2 times the control value. rt-PA was administered as a 15 mg bolus injection, followed by a 0.75 mg/kg (up to 50 mg) infusion over 30 minutes and a subsequent 0.50 mg/kg (up to 35 mg) infusion over 60 minutes. The patients were hospitalized at least during the 7-day study period, after which they were followed for 10 days. The primary end point of the study was the occurrence of bleeding complications validated by a data monitoring and safety committee as severe (intracerebral or with substantial hemodynamic alteration requiring treatment), moderate (need for transfusion), or minor (other bleeding). Based on the statistical assumption, at alpha = 0.05 of a true probability of severe bleeding < or =0.06, the required minimum number of patients was calculated as 45, 65, or 94 if no, one, or two moderate-to-severe bleeding events occurred, respectively. Efficacy was assessed based on mortality, reinfarction, or need for emergency revascularization procedures. One intracranial hemorrhage occurred among the first 49 patients included, and one after the inclusion of 16 additional patients (total of 65). After further increase in the number of patients to 94, then to 116 in order to secure a number of 94 evaluable patients for safety, there were no additional cases of severe bleeding. Hence, the observed rate of moderate-to-severe bleeding was estimated at 1.7%, with a 95% probability that the underlying rate was below 7.5%. Deaths occurred in 3.6% compared to 6.3% in the GUSTO trial. Recurrent myocardial infarctions occurred in 4.5% and emergency revascularization procedures in 14.5% of the 110 patients deemed evaluable for efficacy, rates which are similar in this study and the GUSTO trial. The results of the study compare favorably with historical data showing a moderate-to-severe bleeding rate of 6% with aspirin given concomitantly with rt-PA and suggest that clopidogrel could be safely given as platelet aggrega

Treatment of elderly patients with isolated systolic hypertension with isosorbide dinitrate in an asymmetric dosing schedule.

Nitrates decrease pulse pressure more than mean arterial pressure (MAP) and are advocated for the treatment of isolated systolic hypertension (ISH). Nitrates show drug tolerance during chronic treatment so an asymmetric dosing regimen may prevent loss of effect of nitrates. This study investigates the anti-hypertensive effect of isosorbide dinitrate (ISDN) given in a twice daily asymmetric dosing regimen in elderly patients with ISH. After a 6-week placebo run-in period, patients entered the double-blind study. Ten patients received placebo and 11 patients ISDN 20 mg b.i.d. for 8 weeks. This dose could be doubled once. Office systolic and diastolic blood pressures (SBP/DBP) and ambulatory BP were measured. Pulse pressure was calculated as SBP-DBP. Office pulse pressure was more reduced during ISDN (17.9%) than with placebo (5%; P < 0.05). SBP and MAP decreased compared to baseline, but the changes were not statistically significant between the two groups. DBP tended to increase with ISDN compared to placebo. Mean 24-h, mean daytime and mean night-time pulse pressure decreased after treatment with ISDN (10.7%, 12.1%, 7.9%, respectively). Pulse pressure tended to decrease more during the day than during the night with ISDN. No changes could be demonstrated with placebo. In conclusion, pulse pressure decreased with ISDN, resulting in a lower SBP without a decrease in DBP. The latter may preserve coronary perfusion in ISH. With the asymmetric dosing regimen the decrease in pulse pressure was not clear at night. Whether a decrease in nocturnal BP, in addition to the spontaneous decrease, is advisable in ISH remains a matter of debate.

Thrombolytic therapy does not change the release ratios of enzymatic and non-enzymatic myocardial marker proteins.

Measurements of cardiac marker proteins in plasma from patients with acute myocardial infarction (AMI) have become important in the evaluation of recanalization therapy. The validity of this approach has however been questioned, because it was claimed that coronary reperfusion may increase the recovery in plasma of cardiac enzymes, such as creatine kinase (CK). In the present study, possible effects of thrombolytic therapy on the release of enzymatic and nonenzymatic marker proteins were investigated. Activities of CK and lactate dehydrogenase (LDH), and concentrations of myoglobin (Mb) and fatty acid-binding protein (FABP) were determined in serial plasma samples obtained from 50 patients with confirmed AMI, of whom 36 received thrombolytic therapy, and 14 did not. Treatment delay was 2.8+/-1.6 (mean+/-SD) h, and hospital delay in untreated patients was 2.7+/-1.8 h. Average infarct size, expressed in gram-equivalents of heart muscle per litre of plasma (g-eq/l), varied between 5.5 and 7.2 g-eq/l for the four marker proteins in patients treated with thrombolytic therapy, and between 4.6 and 6.4 g-eq/l in untreated patients, with a tendency to larger infarct sizes for Mb and FABP than for CK and LDH. Thrombolytic therapy, although significantly accelerating protein release rates, did not influence the release ratios. These results indicate that thrombolytic therapy has no significant effects on the recovery of cardiac marker proteins in plasma.

Fatty acid-binding protein and the early detection of acute myocardial infarction.

Fatty acid-binding protein (FABP) is a newly introduced plasma marker of acute myocardial infarction (AMI). The plasma kinetics of FABP (15 kD) closely resemble those of myoglobin (18 kD) in that elevated plasma concentrations are found within 3 h after AMI and return to normal generally within 12 to 24 h. This makes both myoglobin and FABP useful biochemical markers for the early assessment or exclusion of AMI. The myocardial tissue content of FABP (0.5 mg/g) is about five-fold lower than that of myoglobin (2.5 mg/g), but the reference plasma concentration of FABP (ca. 2 microg/l) is about 15-fold lower than that of myoglobin (ca. 32 microg/l), together suggesting a superior performance of FABP for the early detection of AMI. Indeed, in a study including blood samples from 83 patients with confirmed AMI, taken immediately upon admission to the hospital (< 6 h after AMI), the diagnostic sensitivity was significantly greater for FABP (78%, confidence interval 67-87%) than for myoglobin (53%, CI 40-64%) (P < 0.05). In addition, the differences in contents of myoglobin and FABP in heart and skeletal muscles and their simultaneous release upon muscle injury allow the plasma ratio of myoglobin/FABP to be applied for discrimination of myocardial (ratio 4-5) from skeletal muscle injury (ratio 20-70). Rapid and sensitive immunochemical assay systems for FABP in plasma are now being developed and soon will enable the introduction of this marker in clinical practice.

Cumulative troponin T release after acute myocardial infarction. Influence of reperfusion.

UNLABELLED: For troponin T a characteristic biphasic change in the plasma time-concentration curve has been described, especially in patients with early reperfusion after thrombolytic therapy. As troponin T is bound to myofibrillar structures, treatment strategy or treatment outcome could influence the cumulative plasma release of this protein in a different way compared to the cumulative release of free cytoplasmic cardiac enzymes. The present study is the first study comparing the total quantity of troponin T released by the heart during the first 168 hours after acute myocardial infarction, both in patients treated with thrombolytic therapy (n = 16) and in patients not treated with thrombolytic therapy (n = 7). On the basis of clinical symptoms and coronary arteriogram within 24 hours, the patients treated with thrombolytic therapy were divided into two groups, reperfused (n = 9) and non-reperfused (n = 7). In the patients not treated with thrombolytic therapy, absence of spontaneous early reperfusion was judged only from clinical symptoms. Cumulative troponin T release into plasma was compared to the cumulative release of the cytoplasmic cardiac enzymes creatine kinase (EC 2.7.3.2) and hydroxybutyrate dehydrogenase (EC 1.1.1.27). Cumulative release, i. e., infarct size, was calculated using a two-compartment model for circulating proteins. Mean tissue contents, per gram wet weight, of 156 U/g for hydroxybutyrate dehydrogenase, 2.163 U/g for creatine kinase and 234 microg/g for troponin T, were used to express infarct size in gram-equivalents of healthy myocardium per litre plasma (g-eq/l). Release rates were represented by the ratio of cumulative quantities released in 10 hours and 72 hours for creatine kinase and hydroxybutyrate dehydrogenase and in 10 hours and 168 hours for troponin T. CONCLUSIONS: - Plasma time-concentration curves and release rates of troponin T in patients treated with thrombolytic therapy showing reperfusion differ significantly from those of patients not treated with thrombolytic therapy, showing no reperfusion. - Creatine kinase and hydroxybutyrate dehydrogenase release is completed within 72-100 hours in all patients, whereas troponin T release still continues after 168 hours. - Cumulative troponin T release at 168 hours is only a fraction (around 8%) of cumulative cytoplasmic enzyme release and the percentage released is not influenced by the treatment strategy or outcome, i. e., vessel patency. - Although troponin T release is only a fraction of the cumulative enzyme release (infarct size) there is a highly significant correlation between both, independent of the treatment strategy or treatment outcome.

Estimation of myocardial infarct size from plasma myoglobin or fatty acid-binding protein. Influence of renal function.

Myoglobin (M(r) 18,000) and fatty acid-binding protein (M(r) 15,000), are low molecular mass cytoplasmic proteins that are considered useful biochemical markers for early detection or exclusion of acute myocardial infarction, and also for early estimation of infarct size. As each of these proteins shows renal clearance, we studied the influence of renal function on the estimation of infarct size from their plasma concentration curves. For this, infarct size estimated from plasma myoglobin or fatty acid-binding protein release curves was compared with that estimated with the established infarct size markers hydroxybutyrate dehydrogenase and creatine kinase, which are not influenced by changes in renal function. The discordance between infarct size estimates was related to renal function. Creatine kinase (EC 2.7.3.2), hydroxybutyrate dehydrogenase (EC 1.1.1.27), myoglobin, fatty acid-binding protein and creatinine were assayed serially in plasma samples obtained frequently and for at least 72 hours after the start of thrombolytic therapy in 20 patients with acute myocardial infarction. Cumulative release of the different cardiac markers was calculated by using a two-compartment model for circulating proteins. Mean tissue contents of 156 U/g for hydroxybutyrate dehydrogenase, 2163 U/g for creatine kinase, 2.79 mg/g for myoglobin and 0.57 mg/g wet weight for fatty acid-binding protein, were used to express infarct size in gram-equivalents of healthy myocardium per litre of plasma (g-eq/l). Mean plasma creatinine was obtained by averaging the creatinine concentrations measured in all plasma samples taken during the first 24 hours after acute myocardial infarction. A relation was found between the mean plasma creatinine concentration during the first 24 hours after acute myocardial infarction and the discordance between infarct size estimated from cumulative hydroxybutyrate dehydrogenase release, compared to infarct size estimated from cumulative myoglobin or fatty acid-binding protein release. For patients with mean plasma creatinine concentrations within the reference interval for creatinine (group 1, n = 15) a good agreement was found between infarct size estimated from myoglobin or fatty acid-binding protein plasma curves and that estimated with either hydroxybutyrate dehydrogenase or creatine kinase. However, for patients with a mean creatinine concentration above the upper reference limit (group 2, n = 5), infarct size calculated from plasma myoglobin or fatty acid-binding protein release curves was markedly overestimated, especially for larger infarcts. Estimation of infarct size from serial plasma myoglobin or fatty acid-binding protein concentrations is possible in the first 24 hours after the onset of symptoms, but only in patients with normal renal function, as estimated from plasma creatinine concentrations.

Right heart failure: diagnosis via ultrasonography of the inferior vena cava and hepatic veins.

PURPOSE: To determine the efficiency of ultrasonographic measurements of the inferior vena cava (IVC) and hepatic vein (HV) in the detection of elevated systemic venous pressure due to right heart failure. MATERIAL AND METHODS: Measurements of the Collapsibility Index (CI) of the Inferior vena cava (IVC) and hepatic vein (HV) was obtained from 95 persons without right failure. The CI values of 32 patients with clinically documented right heart failure and the data of a subgroup of 24 patients who received therapy, were statistically compared to those of the group without right heart failure. RESULTS: There were statistical significant differences between the CI of the persons without and the patients with right heart failure and between the patients before and after therapy (two-sample T-test: p < 0.05). The position of the ROC curve indicates that measurements of the CI of the IVC and HV enables to distinguish very well patients with right heart failure from those without right heart failure. If the cut-off CI value between normal and abnormal of the IVC was set at 0.22, the sensitivity was 78% and the specificity 98%. When the cut-off value of the CI of the HV was set at 0.25 the sensitivity was 78% and the specificity 96%. There was good interobserver agreement with regard to the CI values of the IVC (correlation coefficient 0.65), but poor interobserver agreement with regard to the CI values of the HV (correlation coefficient 0.35). CONCLUSION: Ultrasonographic measurement of the CI of the inferior vena cava is particularly useful to exclude systemic venous congestion in right heart failure and to monitor the effect of therapy.

Cardiac troponin T release into plasma after acute myocardial infarction: only fractional recovery compared with enzymes.

After acute myocardial infarction (AMI) cardiac enzymes and proteins are released into plasma and are used as biochemical markers of cardiac muscle injury. We studied the completeness of the release of troponin T, a cardiac protein that is largely bound to myofibrillar structures and compared it with the release of cytoplasmic cardiac enzymes in 22 patients with AMI, who were treated with thrombolytic therapy. Creatine kinase (CK; EC 2.7.3.2), hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH; EC 1.1.1.27) and troponin T were assayed serially in plasma samples obtained frequently and for at least 168 h after the start of thrombolytic therapy. Cumulative release of enzymes and troponin T in plasma were calculated by using a two-compartment model for circulating proteins. In order to express the cumulative plasma releases in gram equivalent (g-eq) healthy myocardium per litre plasma (infarct size), we determined HBDH, LDH and total troponin T contents per gram net weight of tissue in 17 human hearts obtained post-mortem from patients who died from non-cardiac causes. Mean (SD) tissue contents per gram wet weight of, respectively, 156 +/- 25 U/g, 385 +/- 59 U/g and 234 +/- 65 micrograms/g were found. For the cardiac enzymes CK, HBDH and LDH the mean (SEM, n = 22) total release over 72 h, was, respectively, 5.9 +/- 1.5, 5.9 +/- 1.6 and 6.1 +/- 1.7 g-eq/L. There was no further increase after 72 h and the differences between enzymes were not significant. The mean (SEM) cumulative troponin T release, expressed in gram equivalents of myocardium per litre of plasma was only 0.30 +/- 0.09 g-eq/L after 72 h and 0.51 +/- 0.61 g-eq/L after 168 h. After 72 h total recovery of troponin T in g-eq/L was only 5% and after 168 h only 8.5% of the total recovery of cytoplasmic cardiac enzymes after 72 h. Cumulative troponin T release after 72 h and after 168 h correlates well with infarct size, estimated from cumulative cytoplasmic enzyme release. However, quantification of infarct size should preferably be performed from plasma release curves of cytoplasmic cardiac enzymes or proteins in order to prevent underestimation of infarct size, caused by incomplete release of the non-cytoplasmic proteins.

Economic aspects of treatment with captopril for patients with asymptomatic left ventricular dysfunction in The Netherlands.

OBJECTIVE: To estimate the costs and effects of preventive treatment with captopril compared with the current treatment policy in patients with asymptomatic left ventricular dysfunction after a myocardial infarction. METHODS: Estimates of effects are based on the results of the SAVE trial. Costs are estimated on the basis of current treatment patterns in four Dutch hospitals. All knowledge is incorporated in a mathematical model extrapolating the SAVE results to 20 years. RESULTS AND CONCLUSIONS: Captopril treatment is expected to increase survival at certain costs. The average additional costs per patient are estimated at DF1 2,491 in 4 years and at DF1 8,723 in 20 years of treatment. Costs per additional survivor after 4 years are estimated at DF1 69,126. After extrapolation of the results of the SAVE trial to 20 years, costs per life-year gained can be estimated at DF1 15,799. From univariate sensitivity analysis it appears that the results are highly sensitive for the costs of treatment with captopril and the occurrence and prevention of clinical heart failure. Varying all estimates randomly between upper and lower limits-in 5,000 simulations-an estimate of costs per life-year gained of DF1 15,729 is made for 20 years of treatment, with 95% of all estimates between DF10 and DF1 50, 000. On a national level, undiscounted costs are expected to increase up to approximately DF1 42 million annually during the first 40 years after introduction of the preventative strategy.