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Aims: The prevalence and the natural course of iron deficiency (ID) in acute heart failure (AHF) are still unclear. We investigated the prevalence of ID in unselected patients admitted with AHF on admission, at discharge and up to 3 months thereafter., Methods and Results: In this prospective, multicentre, observational study, 742 patients admitted with AHF were enrolled. The main study outcome was the percentage of patients with ID (ferritin <100 μg/L = absolute ID or ferritin 100-299 μg/L and transferrin saturation <20% = functional ID) at admission (T0), after clinical stabilization prior to discharge (T1), and 10 ± 6 weeks after discharge (T2). At T0, ID was present in 71.8% of the patients (44.1% absolute and 27.7% functional ID). At T1 and T2, ID was present in 56.4% (32.4% absolute and 24% functional ID) and 50.3% (36.8% absolute and 13.5% functional ID), respectively. Absolute ID persisted from T0 to T2 in 66% of the patients, while functional ID resolved in 56% of the patients. Ferritin (median [interquartile range] 124 μg/L [56-247] to 150 μg/L [73-277]), transferrin saturation (15% [10-20] to 18% [12-27]), and iron levels (9 μmol/L [6-13] to 11 μmol/L [8-16]) increased significantly (all P < 0.001) from T0 to T1. Transferrin saturation (to 21% [15-29]) and iron levels (to 13 μmol/L [9-17]) also increased significantly (both P < 0.01) from T1 to T2 without iron supplementation., Conclusions: Iron deficiency is highly prevalent in patients with AHF, but resolves during treatment in some patients, even without iron supplementation. Absolute ID is more likely to persist over time, whereas functional ID often resolves during treatment of AHF, representing probably a reduced iron availability rather than a true deficiency., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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.

Background: Patients with pectus excavatum which is unsuitable for minimally invasive repair are usually treated by modified Ravitch procedure. For fixation of the sternal osteotomy, mesh and wires are mostly used. To decrease non-union risk, we introduced a technique with double locking plate fixation of the osteotomy and compared this to fixation using mesh and wires., Methods: Patients undergoing a modified Ravitch procedure for pectus excavatum between 2006 and 2016 were included. From 2006 to 2012, the sternum was fixated with mesh and wires. From 2012 to 2016, locking compression plates (LCP) were used. Baseline parameters, symptomatic non-union and total number of complications were retrospectively compared. Statistical analysis was performed using Mann-Whitney or Fisher's exact test. Data are presented as means +/- SD., Results: Forty-four patients were included. In 18 patients, the sternum was fixed with mesh and wires, in 26 patients with LCP. Mean follow-up was 35 months in the mesh and 30 months in the LCP group, P=0.71. Haller index was similar in both groups (mesh 3.8±1.3 vs. LCP 3.9±1.1, P=0.81). Symptomatic non-union occurred in 17% (n=3) in the mesh group and did not occur after LCP, P=0.062. Total number of complications was 33% (n=6) in the mesh group and 15% (n=4) after LCP, P=0.27., Conclusions: After modified Ravitch procedure, union of the sternal osteotomy is challenging. In this retrospective cohort study, a lower incidence of symptomatic non-union was observed after fixation of the sternum with LCPs, with a trend towards statistical significance., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-527). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: Historically, the majority of insertable cardiac monitor (ICM) procedures were performed in the cardiac catheterization (cath) lab, electrophysiology (EP) lab, or operating room (OR). The miniaturization of ICMs allows the procedure to be relocated within the hospital without compromising patient safety. We sought to estimate the rate of untoward events associated with procedures performed within the hospital but outside the traditional settings and to characterize resource utilization, procedure time intervals, and physician experience., Methods: The Reveal LINQ in-Office 2 (RIO 2) International study was a single arm, multicenter, prospective study. Patients indicated for an ICM and willing to undergo device insertion outside the cath/EP lab or OR were eligible and followed for 90 days after insertion., Results: A total of 191 patients (45.5% female aged 63.8 ± 26.9 years) underwent successful Reveal LINQ ICM insertion at 17 centers in Europe, Canada and Australia. The median total visit duration was 106 min (interquartile range [IQR]: 55-61). Patient preparation and patient education accounted for 10 min (IQR: 5-20) and 10 min (IQR: 8-15) of total visit duration, respectively. Preparation and education occurred in the procedure room for 90.6 and 60.2% of patients, respectively. There were no untoward events (0.0, 95% CI: 0.0-2.1%) though four patients presented with procedure-related adverse events that did not require invasive intervention. Physicians rated procedure location as convenient or very convenient., Conclusions: The Reveal LINQ™ ICM insertion can be safely and efficiently performed in the hospital outside the cath/EP lab or OR., Trial Registration: ClinicalTrials.gov identifier NCT02412488 ; registered on April 9, 2015.

This study was performed to gain further insight in the heterogeneity of monocytes in the different categories of acute coronary syndrome (ACS), especially between patients with unstable angina pectoris, ST-elevation myocardial infarction (STEMI), and non-ST-elevation myocardial infarction (NSTEMI). For this purpose, blood samples were collected in the acute phase from patients presenting with an ACS. These samples were examined with multiparameter flow cytometry to identify the different monocyte subsets and to analyze the expression of monocyte-associated molecules. Leukocytes, as well as an absolute number of monocytes, showed a clear and significant increase in patients with STEMI. This increase was seen in all subtypes of monocytes. The classical monocytes (CD14++CD16-) of patients with an NSTEMI had a significantly increased CD11b expression when compared to the control group, while these cells showed a decreased expression pattern in STEMI patients. This increased CD11b-expression was also seen in the intermediate monocytes of NSTEMI, while it was almost completely downregulated on the intermediate monocytes of STEMI. Finally, CX3CR1, which is almost exclusively expressed on intermediate and nonclassical monocytes, showed a significant decrease in expression in patients with STEMI. In conclusion, intermediate and nonclassical monocytes have a different immunophenotypic pattern in patients with STEMI versus NSTEMI. These differences reflect the pro-inflammatory state of the monocytes in NSTEMI and can be used as target molecules for novel therapeutic strategies to diminish the migration of proinflammatory monocytes into the myocardial tissue. © 2017 International Society for Advancement of Cytometry., (© 2017 International Society for Advancement of Cytometry.)

Objective: In acute coronary syndrome (ACS) cardiac cell damage is preceded by thrombosis. Therefore, plasma coagulation markers may have additional diagnostic relevance in ACS. By using novel coagulation assays this study aims to gain more insight into the relationship between the coagulation system and ACS., Methods: We measured plasma thrombin generation, factor XIa and D-dimer levels in plasma from ACS (n = 104) and non-ACS patients (n = 42). Follow-up measurements (n = 73) were performed at 1 and 6 months. Associations between coagulation markers and recurrent cardiovascular events were calculated by logistic regression analysis., Results: Thrombin generation was significantly enhanced in ACS compared to non-ACS patients: peak height 148±53 vs. 122±42 nM. There was a significantly diminished ETP reduction (32 vs. 41%) and increased intrinsic coagulation activation (25 vs. 7%) in ACS compared to non-ACS patients. Furthermore, compared to non-ACS patients factor XIa and D-dimer levels were significantly elevated in ACS patients: 1.9±1.1 vs. 1.4±0.7 pM and 495(310-885) vs. 380(235-540) μg/L. Within the ACS spectrum, ST-elevated myocardial infarction patients had the highest prothrombotic profile. During the acute event, thrombin generation was significantly increased compared to 1 and 6 months afterwards: peak height 145±52 vs. 100±44 vs. 98±33 nM. Both peak height and factor XIa levels on admission predicted recurrent cardiovascular events (OR: 4.9 [95%CI 1.2-20.9] and 4.5 [1.1-18.9])., Conclusion: ACS patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events.

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.

This study was performed to gain further insight in pro- and anticoagulant characteristics of leukocytes in acute coronary syndrome (ACS). For this purpose, patients presenting on the emergency department (ED) with anginal chest pain were included in this study. In peripheral blood, procoagulant tissue factor (TF) expression was measured in the different blood-borne phagocytes, i.e. neutrophilic granulocytes and the three different monocyte subsets based on expression of CD14 and CD16. Simultaneously, intracellular presence of platelet-(CD41) and/or endothelial cell-remnants (CD62e) was analysed in these different leukocyte subsets. Neutrophils showed a weak intracellular staining of CD62e and CD41 that increased with severity of ACS. Monocytes, and especially the classical (CD14++CD16-) and intermediate monocytes (CD14++CD16+) showed a clear and significant increase in intracellular CD41-staining after coronary damage. The different monocyte subsets showed an increase in expression of TF in severe ACS. Finally, it appeared that also neutrophils showed a significant increase in expression of TF on their membrane. In conclusion, this study showed an increased intracellular staining in blood-borne phagocytes for CD62e and CD41 in patients with ACS compared to non-cardiac related control patients. This indicates that at least in the acute phase of ACS phagocytosis of platelet and endothelial cell-remnants is increased. These data support the recent hypothesis that neutrophils protect against further thrombotic processes by clearing platelet and endothelial cell-remnants. In addition, this study shows that the different monocyte subsets are also involved in this process. Furthermore, both monocytes and neutrophils show increased TF expression in ACS.

Background: Idiopathic atrial fibrillation (AF) refers to a clinically lacking cardiovascular or pulmonary disease generating the pathophysiologic substrate for the arrhythmia. However, because idiopathic AF is associated with an increased event rate, it could be a harbinger of as-yet undetected underlying heart disease., Objective: The purpose of this study was to determine the prevalence of coronary artery disease (CAD) in patients diagnosed with idiopathic paroxysmal AF., Methods: Of the 3243 patients who underwent cardiac computed tomographic angiography (CTA) in our center between January 2008 and March 2011, we identified a total of 115 consecutive idiopathic paroxysmal AF patients who underwent CTA before electrophysiologic ablation. Patients were compared with 275 age-, sex-, and PROCAM risk score-matched healthy controls in permanent sinus rhythm. All patients were free of hypertension, diabetes, congestive heart failure, previous known coronary artery and peripheral vascular disease, previous stroke, thyroid, pulmonary, and renal disease, and structural abnormalities on echocardiography., Results: Controls more often showed a family history of CAD (38% vs 15%, P <.001), had a higher prevalence of smoking (25% vs 14%, P = .021), higher fasting blood glucose levels (5.5 ± 0.7 mmol/L vs 5.4 ± 0.6 mmol/L, P = .025), and smaller atrial diameters (37 ± 4 mm vs 40 ± 5 mm, P <.001) compared to AF patients. Notwithstanding the above, idiopathic AF patients significantly more often suffered from subclinical CAD compared to controls (49% vs 34%, P = .008). Multivariable regression analysis revealed that beside (as expected) age and gender, a history of AF and left atrial diameter were significant predictors of underlying CAD., Conclusion: Half of patients originally diagnosed with idiopathic paroxysmal AF show concealed underlying CAD. The detection and treatment of CAD at an early stage could improve the prognosis of these patients., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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.).

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.

Background: Anaemia may affect B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) levels, but this has not been well described in heart failure (HF) patients without the exclusion of patients with renal dysfunction., Aims: To study the influence of both anaemia and renal function on BNP and NT-proBNP levels in a large group of hospitalised HF patients., Methods and Results: We studied 541 patients hospitalised for HF (mean age 71+/-11 years, 62% male, and left ventricular ejection fraction 0.33+/-0.14). Of these patients, 30% (n=159) were anaemic (women: Hb<7.5 mmol/l, men: Hb<8.1 mmol/l). Of the 159 anaemic patients, 73% had renal dysfunction (eGFR<60 ml/min/1.73 m2) and of the non-anaemic patients, 57% had renal dysfunction. BNP and NT-proBNP levels were measured in all patients before discharge. In multivariable analyses both plasma haemoglobin and eGFR were independently related to the levels of BNP and NT-proBNP (standardised beta's of -0.16, -0.14 [BNP] and -0.19, -0.26 [NT-proBNP] respectively, P-values<0.01)., Conclusion: Anaemia and renal dysfunction are related to increased BNP and NT-proBNP levels, independent of the severity of HF. These results indicate that both anaemia and renal dysfunction should be taken into consideration during the interpretation of BNP and NT-proBNP levels in HF patients.

Since the 1960s, calcium antagonists have been available for the treatment of angina pectoris and hypertension. The first of this class, nifedipine, was introduced and readily accepted as the third treatment option for angina, alongside beta-blockers and nitrates. However, the short-acting formulations of nifedipine had pharmacokinetic properties that were far from ideal and in 1995, several studies involving various dosing regimens reported possible dangerous effects in secondary prevention. Since then, large-scale, randomized controlled trials with new controlled-released formulations of nifedipine have demonstrated the effectiveness and safety of this drug. As a consequence of these results, guidelines for both hypertension and angina pectoris have been recently reconsidered, and have put the modern formulations of calcium channel blockers in a pole position. Within this group of therapeutics, nifedipine gastrointestinal therapeutic system has a unique position and it cannot be replaced by other controlled-release formulations of nifedipine, the pharmaceutical properties of which have yet to be tested in large-scale outcome trials.

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.

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.

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.

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.

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 (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.

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.

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.

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.

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.

Nebivolol is a selective beta 1-adrenoceptor antagonist with a particular hemodynamic profile, suggesting an ancillary vasodilating property. The nature of this ancillary property is still unknown. The present double-blind placebo-controlled multicenter study investigated the effect of 4 and 8 weeks treatment with nebivolol 5 mg once daily on blood pressure (BP), heart rate (HR), blood parameters, and ECG. The effect on quality of life perception and the adverse effect profile were also studied. Nebivolol 5 mg once daily had a good antihypertensive effect in supine (10/8 mm Hg) as well as in standing position (16/10 mm Hg). Of 114 patients studied, 65% had either normalization of or > 10% reduction in diastolic BP (DBP). No evidence of drug tolerance was observed during the 8-week treatment period. Quality of life perception, as measured with the Inventory of Subjective Health (ISH) and the perceived health rating scale, was not impaired with nebivolol during the entire 8-week study. Nebivolol showed a favorable adverse effect profile and appeared to be devoid of central nervous system (CNS) adverse effects. The total number of complaints with nebivolol treatment did not differ from the number of complaints with placebo treatment. ECG and blood analyses, also show that nebivolol is safe and well tolerated. This study also shows that absolute drug-induced changes in quality of life perception can be assessed only in a placebo-controlled study and that comparison with baseline might be incorrect and misleading.

In a randomized, double-blind, cross-over, multicenter study with a placebo run-in phase, the efficacy and safety of two oral formulations of diltiazem, standard three or four times daily (t.i.d. or q.i.d.) and controlled release twice daily (b.i.d.), were compared in 49 patients with stable angina pectoris. ST-segment depression at maximum exercise 12 h after tablet intake was less frequently observed with diltiazem controlled release than with standard diltiazem (34 of 49, 69% vs. 43 of 49, 88%, p = 0.007). In patients with ST-segment depression after both treatments (n = 33), the average time to 1-mm ST-segment depression was 55.4 +/- 19.9 s longer with diltiazem controlled release than with standard diltiazem [476 +/- 195 vs. 422 +/- 163 s, p = 0.009; 95% confidence interval (CI) 14.8-96 s]. Reduction in mean number of anginal attacks and nitroglycerin (NTG) intake was not significantly different between treatment with standard diltiazem and diltiazem controlled release. The incidence of side effects was low and not different between the two treatments. Both formulations are equally effective in reducing the number of anginal attacks and are well tolerated. Diltiazem controlled release is more effective than standard diltiazem in preventing myocardial ischemia 12 h after tablet intake. Thus, diltiazem controlled release allows twice-daily intake frequency and may therefore be preferable to standard diltiazem in treatment of stable angina pectoris.

Continuous 24-hour ECG monitoring was performed as an additional objective in 87 patients from 5 centres in the VISA 1 study. The aim of the study was to compare the continuous 24-hour ECG recordings before the study and during treatment with epanolol ('Visacor') or metoprolol. Parameters of particular interest were heart rate and premature ventricular contractions (PVCs). Using the Oxford 4000 system with a 5-lead recorder, 24-hour monitoring was carried out on entry to the study (no antianginal therapy was allowed, with the exception of short acting nitrates), and at the end of both treatment periods. Measurements included the total number of heart beats and PVCs and the incidence of bradycardia. 87 patients, of mean age 59 (range 32 to 80) years, were included in the study. 62 patients had evaluable tapes available on both active treatment periods. The mean heart rate during 24 hours was significantly lower with metoprolol compared with epanolol treatment (64 vs 72 beats/min, respectively, p less than 0.001). The total number of PVCs in 24 hours was similar in both treatment groups and not significantly different from the value recorded at entry. The median total duration of bradycardia (heart rate less than 60 beats/min) in 24 hours was significantly (p less than 0.001) less for epanolol (60 minutes) than metoprolol (428 minutes). Plots of the mean hourly heart rates show that during daytime, epanolol was associated with a mean heart rate in between the rate observed without treatment and with metoprolol treatment. At night-time, almost identical values were found in the groups treated with epanolol compared with the non-treatment period, whereas the metoprolol treatment induced significant lower heart rate levels. Thus, it was shown that there was greater heart rate reduction with metoprolol than with epanolol (p less than 0.001), and that there was no heart rate reduction at night with epanolol. No arrhythmogenic effect was seen for either drug.