Comparing learning curves of two established "single-shot" devices for ablation of atrial fibrillation.

PURPOSE: We compared the contour of learning curves of two "single-shot" devices used for pulmonary vein isolation (PVI) for safety and procedural data. METHODS: We performed a retrospective analysis comparing the first 60 PVI performed at our center using a pulmonary vein ablation catheter (PVAC) array (39 male, mean age 57 years, 42 paroxysmal AF) to the first 60 first PVI using the Cryoballoon (44 male, mean age 59 years, 22 paroxysmal AF). Both groups were further divided into tertiles, where T1 regroups the first 20 ablations, T2 the following 20, and T3 the last 20 ablations. RESULTS: The mean total procedure time was reduced by 24 min between T1 and T3 for the PVAC and 15 min for the Cryoballoon (p = 0.01). Fluoroscopy increased by 5 min, total ablation time was reduced by 7 min for PVAC (p = 0.02), and both times decreased respectively by 7 and 1 min for the Cryoballoon (p = ns). In the PVAC group, a mean rate of 0.16 (T1: n = 5; T2: n = 2; T3: n = 3) complications was observed while a rate of 0.16 (T1: n = 2; T2: n = 3; T3: n = 4) occurred in the CRYO group (p = ns). Severe complications defined as stroke, pericardial tamponade with need of pericardiocentesis and phrenic nerve palsy occurred in n = 4 in both groups (6.6%). CONCLUSIONS: With either of the systems, no significant differences in the effect of the learning curve on the occurrence of adverse events were observed. However, the PVAC array seemed to have a steeper learning curve for procedure, as well as fluoroscopy time.

Safety profile of multielectrode-phased radiofrequency pulmonary vein ablation catheter and irrigated radiofrequency catheter.

BACKGROUND: Silent cerebral lesions with the multielectrode-phased radiofrequency (RF) pulmonary vein ablation catheter (PVAC(®)) have recently been investigated. However, comparative data on safety in relation to irrigated RF ablation are missing. METHODS AND RESULTS: One hundred and fifty consecutive patients (58 ± 12 years, 56 female) underwent first pulmonary vein isolation (PVI) for atrial fibrillation (61% paroxysmal) using PVAC(®) (PVAC). Procedure data as well as in-hospital complications were compared with 300 matched patients who underwent PVI using irrigated RF (iRF). Procedure duration (148 ± 63 vs. 208 ± 70 min; P < 0.001), RF duration (24 ± 10 vs. 49 ± 25 min; P < 0.001), and fluoroscopy time (21 ± 10 vs. 35 ± 13 min; P < 0.001) were significantly shorter using PVAC. Major complication rates [major bleeding, transitoric ischaemic attack (TIA), and pericardial tamponade] were not significantly different between groups (PVAC, n = 3; 2% vs. iRF n = 17; 6%). Overall complication rate, including minor events, was similar in both groups [n = 21 (14%) vs. n = 48 (16%)]. Most of these were bleeding complications due to vascular access [n = 8 (5.3%) vs. n = 22 (7.3%)], which required surgical intervention in five patients [n = 1 (0.7%) vs. n = 4 (1.3%)]. Pericardial effusion [n = 4 (2.7%) vs. n = 19 (6.3%); pericardial tamponade requiring drainage n = 0 vs. n = 6] occurred more frequently using iRF. Two patients in each group developed a TIA (1.3% vs. 0.6%). Of note, four of five thromboembolic events in the PVAC group (two TIAs and three transient ST elevations during ablation) occurred when all 10 electrodes were used for ablation. CONCLUSION: Pulmonary vein isolation using PVAC as a 'one-shot-system' has a comparable complication rate but a different risk profile. Pericardial effusion and tamponade occurred more frequently using iRF, whereas thromboembolic events were more prevalent using PVAC. Occurrence of clinically relevant thromboembolic events might be reduced by avoidance of electrode 1 and 10 interaction and uninterrupted anticoagulation, whereas contact force sensing for iRF might minimize pericardial effusion.

Neuropsychological impact of cerebral microemboli in ablation of atrial fibrillation.

BACKGROUND: Clinically silent lesions on cerebral magnet resonance imaging have been found in larger numbers after pulmonary vein isolation (PVI) especially with phased radio frequency (pRF) using all ten electrodes. However, the neuropsychological effects of cerebral microembolism during the procedure remain unclear and data regarding this issue so far are inconsistent. METHODS: Between August 2011 and June 2012, 76 patients undergoing their first PVI were randomized to ablation with either phased (40) or irrigated (36) radio frequency (iRF). A comprehensive neuropsychological test battery was performed the day before and after PVI as well as 6 months after ablation. The occurrence of cerebral microemboli during the procedure was performed via a transcranial Doppler ultrasound device. RESULTS: PVI using pRF was associated with increased number of microembolic signals (MES) compared to iRF (1530.0 ± 979.8 vs. 645.7 ± 448.7; p < 0.001). Neuropsychological assessment did not reveal any changes in correlation with the used ablation technique. Besides an age-related effect there was a diffuse, sub-clinical impairment of neurologic function depending on age and the number of MES. CONCLUSIONS: There was no clinical overt cognitive deficit and no significant difference in cognitive function correlating with the used ablation technique. The number of MES correlated with a subtle, diffuse post-procedural impairment of neuropsychological function highlighting the need to reduce microemboli during ablation.

Idiopathic ventricular outflow tract arrhythmias from the great cardiac vein: challenges and risks of catheter ablation.

INTRODUCTION: Catheter ablation for idiopathic ventricular arrhythmia is well established but epicardial origin, proximity to coronary arteries, and limited accessibility may complicate ablation from the venous system in particular from the great cardiac vein (GCV). METHODS: Between April 2009 and October 2010 14 patients (56 ± 15 years; 9 male) out of a total group of 117 patients with idiopathic outflow tract tachycardias were included undergoing ablation for idiopathic VT or premature ventricular contractions (PVC) originating from GCV. All patients in whom the PVC arose from the GCV were subject to the study. In these patients angiography of the left coronary system was performed with the ablation catheter at the site of earliest activation. RESULTS: Successful ablation was performed in 6/14 (43%) and long-term success was achieved in 5/14 (36%) patients. In 4/14 patients (28.6%) ablation was not performed. In another 4 patients (26.7%), ablation did not abolish the PVC/VT. In the majority, the anatomical proximity to the left coronary system prohibited effective RF application. In 3 patients RF application resulted in a coronary spasm with complete regression as revealed in repeat coronary angiography. CONCLUSION: A relevant proportion idiopathic VT/PVC can safely be ablated from the GCV without significant permanent coronary artery stenosis after RF application. Our data furthermore demonstrate that damage to the coronary artery system is likely to be transient.

Risk stratification in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiomyopathy characterized by myocyte death and fibrofatty replacement mostly in the right ventricle. It is a leading cause of sudden cardiac death (SCD) in individuals under the age of 35 years. The main goal in the treatment of the disease is the prevention of SCD. An implantable cardioverter-defibrillator (ICD) is the only proven life-saving therapeutic option able to improve survival in ARVC patients. This therapy is not free from side effects and it accounts for a relatively high rate of morbidity because of the occurrence of inappropriate ICD interventions and of complications, both at implantation and during the follow-up. In recent years, the approach to ICD implantation has been changing on the basis of new emerging data on risk stratification. The usefulness of ICD implantation for secondary prevention has been definitively proven; the most challenging question is how to treat patients with no history of previous cardiac arrest or hemodynamically unstable ventricular tachycardia (VT). The value of ECG abnormalities, syncope, VT, and right/left ventricular involvement as predictors of SCD has been assessed in different studies with the purpose of better defining risk stratification in ARVC. Nevertheless, in spite of the growing amount of data, primary prevention in ARVC patients remains mostly an individual decision.

[Atrial fibrillation : new anticoagulants and antiarrhythmic drugs]. / Vorhofflimmern : Neue Antiarrhythmika und Antikoagulanzien.

Atrial fibrillation is the most common form of arrhythmia and one of the most frequent causes of ischemic stroke. Several new anticoagulants have recently been introduced as alternatives to vitamin-K antagonists for prophylaxis of ischemic stroke and tested in phase-3 studies for efficacy and safety. Identifying patients who will profit in particular from the new anticoagulant therapy is crucial to the clinical application of these drugs. Vernakalant and dronedarone are new antiarrhythmic drugs for rhythm control of atrial fibrillation. However, therapeutic efficacy of the new agents still has to be proven.

Blockade of I(Ca) suppresses early afterdepolarizations and reduces transmural dispersion of repolarization in a whole heart model of chronic heart failure.

BACKGROUND AND PURPOSE Chronic heart failure (CHF) is associated with action potential prolongation and Ca(2+) overload, increasing risk of ventricular tachyarrhythmias (VT). We therefore investigated whether I(Ca) blockade was anti-arrhythmic in an intact perfused heart model of CHF. EXPERIMENTAL APPROACH CHF was induced in rabbits after 4 weeks of rapid ventricular pacing. Hearts from CHF and sham-operated rabbits were isolated and perfused (Langendorff preparation), with ablation of the AV node. VT was induced by erythromycin and low [K(+) ] (1.5mM). Electrophysiology of cardiac myocytes, with block of cation currents, was simulated by a mathematical model. KEY RESULTS Repolarization was prolonged in CHF hearts compared with sham-operated hearts. Action potential duration (APD) and overall dispersion of repolarization were further increased by erythromycin (300 µM) to block I(Kr) in CHF hearts. After lowering [K(+) ] to 1.5mM, CHF and sham hearts showed spontaneous episodes of polymorphic non-sustained VT. Additional infusion of verapamil (0.75 µM) suppressed early afterdepolarizations (EAD) and VT in 75% of sham and CHF hearts. Verapamil shortened APD and dispersion of repolarization, mainly by reducing transmural dispersion of repolarization via shortening of endocardial action potentials. Mathematical simulations showed that EADs were more effectively reduced by verapamil assuming a state-dependent block than a simple block of I(Ca) . CONCLUSIONS AND IMPLICATIONS Blockade of I(Ca) was highly effective in suppressing VT via reduction of transmural dispersion of repolarization and suppression of EAD. Such blockade might represent a novel therapeutic option to reduce risk of VT in structurally normal hearts and also in heart failure. LINKED ARTICLE This article is commented on by Stams et al., pp. 554-556 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01818.x.

[Class I antiarrhythmic drugs: mechanisms, contraindications, and current indications]. / Klasse-I-Antiarrhythmika: Wirkmechanismen, Kontraindikationen und aktuelle Indikationen.

Class I antiarrhythmic drugs are sodium channel inhibitors that act by slowing myocardial conduction and, thus, interrupting or preventing reentrant arrhythmia. Due to proarrhythmic effects and the risk of ventricular tachyarrhythmia, class I antiarrhythmics should not be administered in patients with structural heart disease. Nevertheless, there remains a broad spectrum of arrhythmias--among the most common being atrial fibrillation--that can successfully be treated with class I antiarrhythmic drugs. This review gives an overview on the classification, antiarrhythmic mechanisms, indications, side effects, and application modes of class I antiarrhythmic drugs.

QT interval prolongation and risk for cardiac events in genotyped LQTS-index children.

Congenital long-QT syndrome (LQTS) is an inherited cardiac disorder with a disturbance in repolarization characterized by a prolonged QT interval on the surface electrocardiogram and life-threatening ventricular tachycardia. Publications from the International LQTS Registry have provided information that the cardiac risk may be influenced by gender, genotype, exposure to arrhythmia triggers, and previous cardiac events. In children, early-onset of disease, changes in life style, and medical treatment is a sensitive issue and significant, gender-related differences of a first life-threatening event were reported. Thus, we investigated the clinical features of a large genotyped population of LQTS-index children (age < or =16 years) upon a single-center experience and determined risk factors for symptoms. Of 83 children [mean corrected QT interval (QTc) 510 +/- 74 ms], 89% had LQT1, -2, or -3. Nine patients (11%) were identified as having Jervell and Lange-Nielsen syndrome. Among symptomatic children (n = 51, 61%), syncope was the most prevalent symptom at initial presentation (49%); however, aborted cardiac arrest (ACA) occurred in 33% and sudden cardiac death (SCD) in 18%, respectively, as the initial manifestation. During a mean follow-up period of 5.9 +/- 4.7 years, 31% of the children developed symptoms while on therapy (86% syncope, 9% ACA, 5% SCD). Statistical analyses of risk factors for cardiac events showed that the QTc >500 ms was a strong and significant predictor for cardiac events during follow-up (p = 0.02). Furthermore, a prior syncope [hazard ratio (HR), 4.05; 95% confidence interval (CI), 1.1 to 15.0; p = 0.03] or an ACA (HR, 11.7; 95% CI, 3.1 to 43.4; p = <0.001) identified children with an increased risk for recurrent cardiac events compared to asymptomatic LQT children. LQTS-index children manifest with a high percentage of severe symptoms. Among presently validated risk factors for LQTS, a QTc interval >500 ms and a history of prior syncope or ACA were strong predictors for recurrent cardiac events.

Verapamil prevents torsade de pointes by reduction of transmural dispersion of repolarization and suppression of early afterdepolarizations in an intact heart model of LQT3.

BACKGROUND: In long QT syndrome (LQTS), prolongation of the QT-interval is associated with sudden cardiac death resulting from potentially life-threatening polymorphic tachycardia of the torsade de pointes (TdP) type. Experimental as well as clinical reports support the hypothesis that calcium channel blockers such as verapamil may be an appropriate therapeutic approach in LQTS. We investigated the electrophysiologic mechanism by which verapamil suppresses TdP, in a recently developed intact heart model of LQT3. METHODS AND RESULTS: In 8 Langendorff-perfused rabbit hearts, veratridine (0.1 microM), an inhibitor of sodium channel inactivation, led to a marked increase in QT-interval and simultaneously recorded monophasic ventricular action potentials (MAPs) (p < 0.05) thereby mimicking LQT3. In bradycardic (AV-blocked) hearts, simultaneous recording of up to eight epi- and endocardial MAPs demonstrated a significant increase in total dispersion of repolarization (56%, p < 0.05) and reverse frequency-dependence. After lowering potassium concentration, veratridine reproducibly led to early afterdepolarizations (EADs) and TdP in 6 of 8 (75%) hearts. Additional infusion of verapamil (0.75 microM) suppressed EADs and consecutively TdP in all hearts. Verapamil significantly shortened endocardial but not epicardial MAPs which resulted in significant reduction of ventricular transmural dispersion of repolarization. CONCLUSIONS: Verapamil is highly effective in preventing TdP via shortening of endocardial MAPs, reduction of left ventricular transmural dispersion of repolarization and suppression of EADs in an intact heart model of LQT3. These data suggest a possible therapeutic role of verapamil in the treatment of LQT3 patients.

Atrioventricular nodal re-entrant tachycardia in a patient with Ebstein anomaly.

The first case of successful slow pathway modulation is reported in a patient with Ebstein anomaly and recurrent atrioventricular nodal re-entrant tachycardia. Typical signals were recorded during electrophysiological study at the slow pathway region between the His bundle and the coronary sinus where ablation was performed successfully. Thus, slow pathway modulation seems to be a safe procedure even in selected patients with Ebstein anomaly.

Long QT syndrome and life threatening arrhythmia in a newborn: molecular diagnosis and treatment response.

Intrauterine and neonatal manifestations of congenital long QT syndrome are associated with a high cardiac risk, particularly when atrioventricular block and excessive QT prolongation (> 600 ms(1/2)) are present. In a female newborn with these features, treatment with propranolol and mexiletine led to complete reduction of arrhythmia that was maintained 1.5 years later. High throughput genetic analysis found a sodium channel gene (LQT3) mutation. Disappearance of the 2:1 atrioventricular block and QTc shortening (from 740 ms(1/2) to 480 ms(1/2)), however, was achieved when mexiletine was added to propranolol. This effect was considered to be possibly genotype related. Early onset forms of long QT syndrome may benefit from advanced genotyping.

[Clinical aspects and molecular genetics of the Jervell- and Lange-Nielsen Syndrome]. / Klinik und Molekulargenetik des Jervell- und Lange-Nielsen-Syndroms.

In contrast to the Romano-Ward (R-W) syndrome, the Jervell and Lange-Nielsen (J-LN) syndrome is an autosomal recessive inherited disease characterized by QT-prolongation in the electrocardiogram (ECG) and recurrent syncopal attacks which are also typical for the R-W syndrome, but also by congenital deafness. Recently, defect alleles in the genes for KCNQ1 and KCNE1 have been identified in patients with the J-LN syndrome. These genes may be causative for the R-W syndrome as well but in J-LN patients, they are only present in the homozygote or compound heterozygote form. In the present paper, we review the clinical and genetic similarities and differences of the J-LN and the R-W syndrome as well as the diagnostic and therapeutic management of these patients and their family members.

Torsade de pointes induced by ajmaline.

Ajmaline, a reserpine derivative, is an effective class I antiarrhythmic agent. Herein we report two cases of ajmaline-induced abnormal QT prolongation accompanied by polymorphic ventricular tachycardia of the torsade de pointes type. Since ajmaline is increasingly used for the acute termination of wide complex tachycardia and as a diagnostic tool after syncope and in patients with idiopathic ventricular tachyarrhythmias, our observations suggest that caution should be exercised with regard to the effects of the drug on the QT interval and its potency to induce proarrhythmia of the torsade de pointes type.

Prolonged QRS duration increases QT dispersion but does not relate to arrhythmias in survivors of acute myocardial infarction.

QT dispersion has been suggested and disputed as a risk marker for ventricular arrhythmias after myocardial infarction. Delayed ventricular activation after myocardial infarction may affect arrhythmic risk and QT intervals. This study determined if delayed activation as assessed by (1) QRS duration in the 12-lead ECG and by (2) late potentials in the signal-averaged ECG affects QT dispersion and its ability to assess arrhythmic risk after myocardial infarction. QT duration, JT duration, QT dispersion, and JT dispersion were compared to QRS duration in the 12-lead ECG and to late potentials in the signal-averaged ECG recorded in 724 patients 2-3 weeks after myocardial infarction. Prolonged QRS duration (> 110 ms) and high QRS dispersion increased QT and JT dispersion by 12%-15% (P < 0.05). Presence of late potentials, in contrast, did not change QT dispersion. Only the presence of late potentials (n = 113) was related to arrhythmic events during 6-month follow-up. QT dispersion, JT dispersion, QRS duration, and QRS dispersion were equal in patients with (n = 29) and without arrhythmic events (QT disp 80 +/- 7 vs 78 +/- 1 ms, JT disp 80 +/- 6 vs 79 +/- 2 ms, mean +/- SEM, P > 0.2). In conclusion, prolonged QRS duration increases QT dispersion irrespective of arrhythmic events in survivors of myocardial infarction. Presence of late potentials, in contrast, relates to arrhythmic events but does not affect QT dispersion. Therefore, QT dispersion may not be an adequate parameter to assess arrhythmic risk in survivors of myocardial infarction.

Modification of stretch-induced shortening of repolarization by streptomycin in the isolated rabbit heart.

The exact mechanism of mechano-electrical feedback and stretch-induced arrhythmias is unknown, but the role of stretch-activated ion channels and specific calcium channels has been proposed. The aim of the present study was to test the hypothesis that stretch-activated ion channels and not calcium channels contribute to stretch-related alterations of repolarization and that these effects can be neutralized by stretch-activated channel block. We studied the interaction of acute ventricular dilatation and the stretch-activated channel blocker streptomycin and the specific calcium channel blocker verapamil in an isolated retrogradely perfused rabbit heart model in which the left ventricular size is modified by abruptly changing the volume of a fluid-filled balloon placed in the left ventricle. Acute ventricular dilatation led to a rate-dependent decrease in repolarization. The mean effective refractory period (ERP) and monophasic action potential duration (MAP90) for cycle lengths between 300 and 1,000 ms decreased from 174.2+/-9 ms and 178.9+/-7 ms to 161.6+/-11 ms and 169.7+/-5 ms, respectively. Streptomycin (80 microM) inhibited this stretch-related shortening of repolarization (ERP: 175.4+/-8 ms; MAP90: 179.7+/-8 ms, p < 0.05) but had almost no effect on already dilated ventricles. Counteraction of the observed electrophysiologic changes could only be achieved by increasing the streptomycin concentration to 200 microM. Streptomycin nearly completely suppressed stretch-related ectopic ventricular complexes. In contrast, verapamil (1 microM) had no effect on stretch-related changes in repolarization and stretch-induced arrhythmias. The present study indirectly implicates stretch-activated ion channels in the genesis of stretch-related changes in repolarization and arrhythmias. The electrophysiologic changes after ventricular dilatation to a degree that increases left ventricular pressure in a clinically relevant range can be influenced by the stretch-activated channel blocker streptomycin but not by specific calcium channel block. This may have clinically important implications for the development of new antiarrhythmic drugs.

Multislice cardiac spiral CT evaluation of atypical hypertrophic cardiomyopathy with a calcified left ventricular thrombus.

We report a case of a 43-year-old male patient with an atypical nonobstructive hypertrophic cardiomyopathy and a calcified left ventricular thrombus, and present results of multislice computed tomography (MSCT) using retrospective electrocardiograph gating, which is a new modality in cardiac imaging. Obtaining virtually motion-free images with a temporal resolution of 250 ms in an optimized heart scan MSCT allows functional imaging with evaluation of impaired systolic and diastolic left ventricular wall motion.

A patient with "atrial torsades de pointes".

A patient with long QT syndrome and a history of palpitations underwent electrophysiologic study. Runs of polymorphic self-terminating atrial tachyarrhythmias were easily induced and occurred spontaneously several times. Atrial monophasic action potential (MAP) durations were prolonged at short pacing cycle lengths. Premature high right atrial extrastimuli prolonged MAP durations in the low right atrium, resulting in an inverse electrical restitution curve, and increased dispersion of repolarization. MAP morphology showed gradually increasing early afterdepolarizations. When the arrhythmia was initiated, a new action potential reproducibly emerged from these afterdepolarizations. To the knowledge of the authors, this is the first reported case of "atrial torsades de pointes" in a patient.

Molecular genetics of arrhythmias--a new paradigm.

The molecular genetic background of inherited cardiac arrhythmias has only recently been uncovered. This late development in comparison to other inherited cardiac disorders has partly been due to the high mortality and early disease onset of these arrhythmias resulting in mostly small nucleus families. Thus, traditional genetic linkage studies, which are based on the genetic information obtained from large multi-generation families, were made difficult. Inherited arrhythmogenic disorders can be divided into 'primary electrical disorders' (e.g., long-QT [LQT] syndrome) in which a detectable, organic heart disease is not evident, and into inherited diseases of the myocardial structure (e.g., hypertrophic cardiomyopathies) in which the arrhythmias occur combined with the structural alterations. To date, all inherited arrhythmogenic disorders in which the causative genes have been identified turned out to be channelopathies, since the genes encode channel subunits that regulate important ion currents that tune the cardiac action potential. The discovery of the genetic bases of the LQT syndrome became a new methodologic paradigm; because with the use of 'classical' genetic linkage strategies (named [positional] candidate strategies) not only the causative genes have been found, but moreover, functional components with a previously unknown but fundamental role for a normal repolarization process were discovered. Disease mutations turned out to be not only a family-specific event with a distinct phenotype and the potential of an additional diagnostic tool, but also, when expressed in heterologous expression systems, characterize the defective ion channel in a topological way and lead to a more specific understanding of ion channel function. Most, if not all, primary electrical cardiac disorders show a high genetic diversity. For the LQT syndromes, sixth disease loci and the responsible gene have been recently discovered (so-called locus or genetic heterogeneity). Within all disease genes, the mutations are spread over the entire gene (allelic heterogeneity); in addition, more than one disease mutation may be present. This complexity requires, at least, complete mutation analysis of all LQT genes before medical advice should be given. Meanwhile, genotype-phenotype correlations in large families are being used to evaluate intergene, interfamilial and intrafamilial differences in the clinical phenotype, reflecting gene specific, gene-site specific and individual consequences of a given mutation. A widespread phenotypic heterogeneity even within mutation carriers in the same family raises the importance of modifying factors and genes that are mostly unknown to date. The reduced penetrance and variable expressivity associated with the LQT mutations remain still to be explained. First insights into the complex actions of mutations are being extracted, from expression data; these preliminary results may lead to potential implications for a specific (gene-site directed) therapy. This paper discusses the current data on molecular genetics and genotype-phenotype correlations in LQT syndrome and related disorders and the potential implications for diagnosis and treatment.

Insulin-like growth factor-binding protein-3 is associated with the presence and extent of coronary arteriosclerosis

Aging is associated with the progression of arteriosclerosis and the decline of several endocrine functions. We therefore investigated the association of coronary arteriosclerosis with hormones, the serum concentrations of which change during aging. Coronary angiograms of 189 men <70 years old were evaluated by 3 semiquantitative score systems to estimate the extent of focal and diffuse vessel wall alterations. Fasting sera were analyzed for levels of glucose, lipids, thyroid-stimulating hormone, insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone-binding globulin (SHBG). After adjustment for age, body mass index, and waist-to-hip ratio, 92 patients with >/=1 stenoses >70% differed from 97 patients without such focal lesions by higher serum levels of glucose, total and LDL cholesterol, and apolipoprotein (apo) B, as well as by lower serum levels of IGFBP-3. Multivariate analyses revealed significant and independent correlations of all 3 coronary scores with LDL cholesterol (or apoB) and IGFBP-3; of 2 coronary scores with age, glucose, and insulin; and of 1 score with IGF-I. No significant correlations existed for waist-to-hip ratio (or body mass index) and DHEAS (or testosterone or SHBG). IGFBP-3 explained 9% to 14% and 3.5% to 10% of the variances of focal and diffuse lesions, respectively. In conclusion, IGFBP-3 and, with much less strength and consistency, insulin and IGF-I, but not markers of hypothyroidism, adrenopause, and andropause, have statistically significant and independent associations with coronary arteriosclerosis in men.