Third heart sound in hospitalised patients with acute heart failure: insights from the ATTEND study.

BACKGROUND: Several previous studies have suggested that detection of a third heart sound (S3) in patients with chronic congestive heart failure is associated with adverse long-term outcomes. However, the short-term prognostic value of identifying an S3 on admission in patients with acute heart failure (AHF) is not well established. We therefore analysed the in-hospital prognostic value of detecting an S3 on admission in hospitalised patients with AHF. METHODS: The Acute Decompensated Heart Failure Syndromes (ATTEND) study investigators enrolled 4107 patients hospitalised with AHF. Investigators evaluated the presence or absence of an S3 during routine physical examination. RESULTS: On admission to hospital, 1673 patients (41%) had an S3. Patients with an S3 had a higher heart rate, higher serum level of B-type natriuretic peptide and higher creatinine levels than patients without an S3. However, there were no significant differences of systolic blood pressure, serum sodium, haemoglobin, C-reactive protein and total bilirubin between the two groups. Multivariate analysis adjusted for various markers of disease severity revealed that only the presence of an S3 was independently associated with an increase of in-hospital all cause death [adjusted odds ratio (OR), 1.69; 95% confidence interval (CI), 1.19-2.41; p = 0.003] and cardiac death (adjusted OR, 1.66; 95% CI, 1.08-2.54; p = 0.020) among the congestive physical findings related to heart failure (S3, rales, jugular venous distension and peripheral oedema). CONCLUSIONS: Detecting an S3 on admission was independently associated with adverse in-hospital outcomes in patients with AHF. Our findings suggest that careful bedside assessment is clinically meaningful.

Benefit of bilateral over single internal mammary artery grafts for multiple coronary artery bypass grafting.

BACKGROUND: The aim of this study was to evaluate the performance of bilateral internal mammary artery (BIMA) grafts in isolated CABG. METHODS AND RESULTS: Beginning in April 1985, elective primary multiple CABG for multivessel disease was performed in 1131 patients. The early and late results of 688 patients who received single internal mammary artery (SIMA) grafts and 443 patients who received BIMA grafts were compared (median follow-up, 6.15 years). Hospital mortality was not significantly different in the SIMA (0.9%) and BIMA (0.9%) groups. Graft patency was 97.3% in the BIMA group and 94.3% in the SIMA group (P<0.0001). The 7-year repeated CABG-free rate was significantly higher in the BIMA group (P=0.026). The 7-year new myocardial infarction-free rate in all patients tended to be higher in the BIMA group (P=0.06). The hazard ratio for all death or repeated CABG in patients with ejection fractions >0.4 and age <71 years was lower in the BIMA group (P=0.0499). CONCLUSIONS: Our data suggest that the use of BIMA grafts in patients with in situ coronary artery anastomoses achieves a significantly higher repeated CABG-free rate in all patients compared with the use of SIMA.

Coronary artery bypass with only in situ bilateral internal thoracic arteries and right gastroepiploic artery.

BACKGROUND: With the rapid advance of catheter intervention, the direction taken by surgeons is not only to make conventional CABG less invasive but also to pursue better long-term results by using more arterial conduits. METHODS AND RESULTS: Between July 1989 and April 2000, 239 patients (218 men, 21 women) with a mean age of 59.7 (range 39 to 79) years underwent CABG with exclusive use of both internal thoracic arteries (ITAs) and the right gastroepiploic artery (RGEA). ITA grafts were harvested by using the skeletonization technique. Most patients (96%) had either triple-vessel or left main disease. Fifty percent of the patients were diabetic, and 16 were being treated with insulin. The left ventricular ejection fraction was

Clinical potential of intravascular ultrasound for physiological assessment of coronary stenosis: relationship between quantitative ultrasound tomography and pressure-derived fractional flow reserve.

BACKGROUND: Little is known regarding intravascular ultrasound (IVUS) criteria to determine the functional severity of coronary stenosis. Recently, fractional flow reserve (FFR) has emerged as a lesion-specific index of the functional severity of a coronary stenosis that is independent of systemic hemodynamic variability. The present study was undertaken to determine the IVUS parameters for the physiological severity of coronary stenosis. METHODS AND RESULTS: Fifty-one lesions in 42 patients were evaluated by means of quantitative coronary angiogram, IVUS, and intracoronary pressure measurements. The FFR was calculated as the ratio of the distal coronary pressure divided by the proximal coronary pressure under hyperemia. We considered a value of the FFR <0.75 as significant in determining inducible ischemia, according to the previous studies. The minimal luminal area (MLA) and the area stenosis were measured by IVUS. By regression analysis, the MLA showed a positive correlation with the FFR value (r(2)=0.62, P<0.0001). The area stenosis had a significant inverse correlation with the value of FFR (r(2)=0.60, P<0.0001). The IVUS thresholds that maximized the sensitivity and specificity were MLA <3.0 mm(2) (sensitivity, 83.0%; specificity, 92.3%) and area stenosis >0.6 (sensitivity, 92.0%; specificity, 88.5%). The combination of both criteria (MLA <3.0 mm(2) and area stenosis <0.6) without exception met a value of the FFR <0.75. CONCLUSIONS: Anatomic parameters obtained by IVUS showed a significant correlation to the FFR values. The present study demonstrated that the combination of the MLA and area stenosis measured by IVUS can be an anatomic predictor for the physiological impact of coronary epicardial stenosis.

Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis in cystic medial degeneration associated with Marfan's syndrome.

BACKGROUND: Cystic medial degeneration (CMD) is a histological abnormality that is common in the aortic diseases associated with Marfan's syndrome (MFS). Although little known about the mechanism underlying CMD, several recent reports have demonstrated that vascular smooth muscle cell (VSMC) apoptosis could play a substantial role in CMD. On the other hand, angiotensin II (Ang II) has been reported to play an important role in the regulation of VSMC growth and apoptosis via the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R). METHODS AND RESULTS: To elucidate the role of Ang II signaling via the Ang II receptors in CMD, we investigated AT1R and AT2R mRNA expression and tissue concentration of Ang II in MFS aortas (n=10) and control aortas (n=12). Furthermore, we examined the effects of an ACE inhibitor, an AT1R blocker, and an AT2R blocker on serum deprivation-induced VSMC apoptosis by organ culture system. AT1R expression was significantly decreased (P<0.01) and AT2R expression was significantly increased (P<0.001) in MFS aortas compared with control aortas, and tissue Ang II concentration was significantly higher in CMD than in the control condition (P<0.01). Both the ACE inhibitor and AT2R blocker significantly inhibited serum deprivation-induced VSMC apoptosis (P<0.05), although the AT1R blocker did not inhibit apoptosis in cultured aortic media from MFS patients. CONCLUSIONS: Accelerated ACE-dependent Ang II formation and signaling via upregulated AT2R play a pivotal role in VSMC apoptosis in CMD, and the ACE inhibitor could have clinical value in the prevention and treatment of CMD.

Novel mechanism associated with an inherited cardiac arrhythmia: defective protein trafficking by the mutant HERG (G601S) potassium channel.

BACKGROUND: The congenital long-QT syndrome (LQTS) is an inherited disorder characterized by a prolonged cardiac action potential and a QT interval that leads to arrhythmia. Mutations in the human ether-a-go-go-related gene (HERG), which encodes the rapidly activating component of the delayed rectifier current (IKr), cause chromosome 7-linked LQTS (LQT2). Studies of mutant HERG channels in heterologous systems indicate that the mechanisms mediating LQT2 are varied and include mutant subunits that form channels with altered kinetic properties or nonfunctional mutant subunits. We recently reported a novel missense mutation of HERG (G601S) in an LQTS family that we have characterized in the present work. METHODS AND RESULTS: To elucidate the electrophysiological properties of the G601S mutant channels, we expressed these channels in mammalian cells and Xenopus oocytes. The G601S mutant produced less current than wild-type channels but exhibited no change in kinetic properties or dominant-negative suppression when coexpressed with wild-type subunits. To examine the cellular trafficking of mutant HERG channel subunits, enhanced green fluorescent protein tagging and Western blot analyses were performed. These showed deficient protein trafficking of the G601S mutant to the plasma membrane. CONCLUSIONS: Our results from both the Xenopus oocyte and HEK293 cell expression systems and green fluorescent protein tagging and Western blot analyses support the conclusion that the G601S mutant is a hypomorphic mutation, resulting in a reduced current amplitude. Thus, it represents a novel mechanism underlying LQT2.

Effect of cimetidine and probenecid on pilsicainide renal clearance in humans.

OBJECTIVE: To investigate the effect of cimetidine and probenecid on the renal clearance of pilsicainide in healthy subjects. METHODS: Nine healthy men (age range, 21 to 38 years) were given oral doses of 50 mg pilsicainide hydrochloride alone, with coadministration of 800 mg oral cimetidine, or with coadministration of 1,500 mg oral probenecid on three occasions in a Latin-square order. Urine and venous blood samples were collected on a timely basis. The concentration of pilsicainide in plasma and urine were determined by an HPLC method. RESULTS: Concomitant administration of cimetidine significantly increased the area under the plasma concentration-time curve of pilsicainide by a mean of 33%, prolonged elimination half-life by a mean of 24% (from 5 to 6.2 hours), reduced apparent oral clearance by a mean of 26% (from 14.7 +/- 0.1 to 10.8 +/- 0.8 L/h) and reduced renal clearance by a mean of 28% (from 196.8 +/- 53.9 to 141.8 +/- 25.9 mL/min). The net renal clearance by tubular secretion was significantly reduced by a mean value of 38%, from 151.4 +/- 62.9 to 93.0 +/- 31.1 mL/min. Coadministration of probenecid did not show any changes in plasma concentrations of pilsicainide, pharmacokinetics, or the net renal clearance by tubular secretion of pilsicainide. CONCLUSIONS: Pilsicainide appeared to be secreted by the active transport system for organic bases in the proximal tubule, and the excretion of pilsicainide was inhibited by cimetidine.

Retinoic acid suppresses endothelin-1 gene expression at the transcription level in endothelial cells.

Retinoids have been shown to inhibit cell growth, which can result in an anti-atherosclerotic action in the vasculature. Endothelin-1 (ET-1), a potent vasoconstrictor peptide produced in endothelial cells, plays an important role in inducing proliferation of vascular smooth muscle cells. In this study, we investigated the effect of retinoids on the mRNA expression and transcriptional activity of the ET-1 gene in endothelial cells. All-trans retinoic acid (ATRA) suppressed ET-1 mRNA expression in cultured endothelial cells. Synthetic retinoids, Ch55 and Am580 (retinoic acid receptor (RAR) agonists) markedly enhanced this effect, and an RAR antagonist, LE540, blocked this inhibitory effect on ET-1 gene expression. ATRA did not change ET-1 mRNA half-life. Transfection experiments using 5 kb of the ET-1 promoter-reporter gene construct which contains 5 kb of the preproET-1 promoter revealed that ATRA and Ch55 suppressed ET-1 promoter activity, resulting in down-regulation of ET-1 gene transcription. Taken together, retinoids may be another modulator of endothelial cell function through regulation of vasoactive substances at the transcription level.

Total and partial cardiac sympathetic denervation after surgical repair of ascending aortic aneurysm.

UNLABELLED: Sympathetic cardiopulmonary nerves arise from the cervical sympathetic trunks and travel alongside the great arteries to innervate the ventricles. Because of the proximity of the nerve and artery, cardiac sympathetic denervation may occur in patients who have just undergone surgery for the repair of an ascending aortic aneurysm. METHODS: To evaluate the cardiac sympathetic activity in aortic aneurysm, we performed cardiac 123I-metaiodobenzylguanidine (MIBG) imaging on 12 patients (mean age +/- SD, 47 +/- 17 y) before and after the surgical repair of an aneurysm. Seven patients scheduled for coronary artery bypass grafting also underwent 123I-MIBG imaging as controls for open-chest surgery. Planar images were obtained at 15 min (early) and 4 h (delayed) after injection of 111 MBq 123I-MIBG, and the cardiac 123I-MIBG uptake was graded quantitatively and visually. The quantitative evaluation was based on the heart-to-mediastinum ratio (H/M), and visual evaluation was performed by assigning a score of 0-3 (0 = absent, 1 = severely reduced, 2 = reduced, and 3 = normal). Heart rate variability using 24-h Holter electrocardiography was analyzed before and after the operation to generate a time-domain index of heart rate variability as an index of autonomic balance. RESULTS: In patients with aortic aneurysms, both early and delayed H/Ms were significantly decreased after the operation (early H/M: 1.84 +/- 0.16 before vs. 1.40 +/- 0.16 after, P = 0.001; delayed H/M: 1.79 +/- 0.38 before vs. 1.27 +/- 0.18 after, P = 0.004). Visual analysis of 123I-MIBG accumulation in early images showed absence of 123I-MIBG accumulation in 3 of 12 patients, a score of 1 in 7 patients, and a score of 2 in 2 patients. In contrast, no significant difference between H/M before surgery and H/M after surgery was seen in patients who underwent coronary artery bypass grafting. The time-domain index of heart rate variability was significantly lower after the operation than before (135 +/- 40 after vs. 96 +/- 27 before, P < 0.05). CONCLUSION: Cardiac sympathetic nerves are totally or partially denervated after the surgical repair of ascending aortic aneurysm.

Differentiation and mechanisms of prevention and termination of verapamil-sensitive sustained ventricular tachycardia.

The purpose of this study was to differentiate by means of electrophysiologic study, a drug's ability to terminate or to prevent ventricular tachycardia (VT). Differences between the 2 effects were examined in patients with VT and the underlying mechanisms were studied in verapamil-responsive idiopathic sustained VT. The clinical significance of the distinction for chronic oral drug therapy is discussed. Thirty-five cases of inducible sustained VT were studied. A drug was considered "preventive" if it prevented VT induction and repetitive ventricular response, and "terminating" if it stopped induced VT within 15 complexes or could stop VT after its intravenous administration. Prevention and termination occurred together in 13 of 19 cases (68%) with disopyramide, in 10 of 19 cases (53%) with procainamide, in 8 of 12 cases (67%) with lidocaine, in 11 of 15 cases (73%) with mexiletine, and in 10 of 16 cases (63%) with verapamil. In the 16 in which verapamil terminated VT, VT rate immediately before termination slowed markedly from 167 +/- 33 to 134 +/- 28 beats/min. In the 6 cases without preventative effects, minimal and maximal premature intervals for VT induction increased significantly, from 291 +/- 70 to 335 +/- 85 ms and 323 +/- 68 to 423 +/- 109 ms, respectively, after verapamil administration. In 2 cases in which verapamil had a terminating effect, 5 mg of verapamil restored sinus rhythm but 10 mg caused premature beats resembling VT complexes. In another 2, 5 mg of verapamil lengthened the minimal premature interval; 10 mg increased both minimal and maximal premature intervals and lengthened the VT cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of propafenone on K currents in human atrial myocytes.

1. The class Ic anti-arrhythmic agent, flecainide is known to inhibit the transient outward K current (Ito) selectively in human atrium. We studied the effects of propafenone, another class Ic antiarrhythmic agent, on K currents in human atrial myocytes using a whole-cell voltage-clamp method. 2. Propafenone inhibited both Ito and the sustained or ultra-rapid delayed rectifier K current (Isus or Ikur) evoked by depolarization pulses. The concentration for half-maximal inhibition (IC50) was 4.9 microM for Ito and 8.6 microM for Isus. Propafenone blocked Ito and Isus in a voltage- and use-independent fashion and accelerated the inactivation time constant of Ito [from 28.3 to 6.7 ms at 10 microM propafenone]. 3. The steady-state inactivation curve for Ito was unaffected by propafenone. Propafenone did not affect the initial current at depolarizing potentials, but it did produce a block that increased as a function of time after depolarization (time constant of 3.4 ms). This suggests that propafenone preferentially blocked Ito in the open state. 4. Propafenone had no significant effect on the rate at which Ito recovered from inactivation at -80 mV suggesting that propafenone dissociates rapidly from the channel. 5. The steady-state activation curve for Isus was not affected by propafenone. Propafenone slowed the time course of the onset of the Isus tail current. This suggests that propafenone blocked Isus in the open state. 6. The present results suggest that, unlike flecainide, propafenone blocks both Ito and Isus in human atrial myocytes in the open state at clinically relevant concentrations.

Contribution of phosphodiesterase isozymes to the regulation of the L-type calcium current in human cardiac myocytes.

1. To determine the contribution of the various phosphodiesterase (PDE) isozymes to the regulation of the L-type calcium current (ICa(L)) in the human myocardium, we investigated the effect of selective and non-selective PDE inhibitors on ICa(L) in single human atrial cells by use of the whole-cell patch-clamp method. We repeated some experiments in rabbit atrial myocytes, to make a species comparison. 2. In human atrial cells, 100 microM pimobendan increased ICa(L) (evoked by depolarization to +10 mV from a holding potential of -40 mV) by 250.4 +/- 45.0% (n = 15), with the concentration for half-maximal stimulation (EC50) being 1.13 microM. ICa(L) was increased by 100 microM UD-CG 212 by 174.5 +/- 30.2% (n = 10) with an EC50 value of 1.78 microM in human atrial cells. These two agents inhibit PDE III selectively. 3. A selective PDE IV inhibitor, rolipram (1-100 microM), did not itself affect ICa(L) in human atrial cells. However, 100 microM rolipram significantly enhanced the effect of 100 microM UD-CG 212 on ICa(L) (increase with UD-CG 212 alone, 167.9 +/- 33.9, n = 5; increase with the two agents together, 270.0 +/- 52.2%; n = 5, P < 0.05). Rolipram also enhanced isoprenaline (5 nM)-stimulated ICa(L) by 52.9 +/- 9.3% (n = 5) in human atrial cells. 4. In rabbit atrial cells, ICa(L) at +10 mV was increased by 22.1 +/- 9.0% by UD-CG 212 (n = 10) and by 67.4 +/- 12.0% (n = 10) by pimobendan (each at 100 microM). These values were significantly lower than those obtained in human atrial cells (P < 0.0001). Rolipram (1-100 microM) did not itself affect ICa(L) in rabbit atrial cells. However, ICa(L) was increased by 215.7 +/- 65.2% (n = 10) by the combination of 100 microM UD-CG 212 and 100 microM rolipram. This value was almost 10 times larger than that obtained for the effect of 100 microM UD-CG 212 alone. 5. These results imply a species difference: in the human atrium, the PDE III isoform seems dominant, whereas PDE IV may be more important in the rabbit atrium for regulating ICa(L). However, PDE IV might contribute significantly to the regulation of intracellular cyclic AMP in human myocardium when PDE III is already inhibited or when the myocardium is under beta-adrenoceptor-mediated stimulation.

Cryosurgical ablation of accessory atrioventricular pathways without cardiopulmonary bypass: an epicardial approach for Wolff-Parkinson-White syndrome.

An epicardial approach has been developed and applied to 31 Kent bundles (23 parietal, 1 right anteroseptal, and 7 posteroseptal bundles) in 28 patients with Wolff-Parkinson-White syndrome. Our technique consists of dissection of the atrioventricular fat pad of the Kent bundle site using an ultrasonic aspirator and subsequent cryosurgical ablation. For the left parietal and posteroseptal pathways, the apex of the heart has to be retracted upward, but this maneuver was well tolerated in all patients. Moreover, even through a narrow operative field, the ultrasonic aspirator permitted deliberate dissection on the beating heart without injury to major coronary vessels or the atrial wall. In 89% of the patients, operation was performed without the use of heart-lung bypass. All patients were free from preexcitation. With this technique, all Kent bundles except that adjacent to the atrioventricular node can be ablated on the beating heart, usually without heart-lung bypass.

Amiodarone-induced thyrotoxicosis associated with thyrotropin receptor antibody.

Since amiodarone was first marketed in 1992 in Japan, the incidence of amiodarone-induced thyrotoxicosis (AIT) has been increasing. Among 12 thyrotoxic patients, a patient with arrhythmogenic right ventricular dysplasia, who had been taking amiodarone for 4 years, developed thyrotoxicosis with subacute onset, accompanied by transiently positive thyrotropin (TSH) receptor antibody (TRAb), or thyrotropin-binding inhibiting immunoglobulin (TBII). The immunoglobulin G (IgG) obtained from the TRAb-positive serum of the patient elicited no thyroid hormone-releasing activity in cultured human thyroid follicles, whereas all IgGs obtained from untreated Graves' disease elicited positive results. These in vitro findings and clinical course suggest that TRAb/TBII without thyroid-stimulating activity may develop in patients with amiodarone-induced destructive thyroiditis, as reported in patients with destructive thyroiditis, such as subacute and silent thyroiditis.

Recurrent pulmonary adenoid cystic carcinoma presenting as a cardiac tumor.

A 58-year-old patient is presented who had a pulmonary adenoid cystic carcinoma which recurred 10 years after sleeve left pneumonectomy. The patient developed acute heart failure because the lesion obstructed blood flow by compressing the left atrium. Transesophageal echocardiography and magnetic resonance imaging demonstrated a solid mass arising from the pericardium which displaced the posterior wall of the left atrium. The mass was resected. Postoperative radiation was not performed.

Rheumatoid arthritis and simultaneous aortic, mitral, and tricuspid valve incompetence.

We describe a 72-year-old woman with aortic, mitral, and tricuspid valve incompetence secondary to a rheumatoid granulomata. The cardiac valvular lesions developed simultaneously and deteriorated rapidly. The patient died after a transient relief of symptoms by high dose steroid therapy.

Perinuclear-antineutrophil cytoplasmic antibodies are associated with vasculitis.

We describe a 62-year-old man with perinuclear-antineutrophil cytoplasmic antibodies-associated vasculitis, which involved the heart, lung, and kidneys. The patient's care was complicated by total occlusions of the brachiocephalic and right renal arteries and a stenosis of the left renal artery. Involvement of large-sized vessels has not been reported in patients with perinuclear-antineutrophil cytoplasmic antibodies-associated vasculitis.

Malfunction of a Hancock bioprosthesis in the mitral position 24 years after initial implantation.

BACKGROUND AND AIMS OF THE STUDY: Although many types of cardiac bioprosthetic valves are currently available, the major disadvantage of their use is limited durability due to progressive structural valve deterioration. Few such valves function beyond 20 years. METHODS: A 61-year-old man was admitted urgently to our institute with acute mitral insufficiency, 24 years after undergoing mitral valve replacement with a 25-mm standard Hancock porcine bioprosthesis for mitral stenosis. RESULTS: Mitral valve reoperation was performed successfully with a mechanical valve. The explanted bioprosthesis showed leaflet perforations and a commissural tear, moderate calcification on the commissures, and pannus overgrowth. CONCLUSION: The findings in this case suggest that individual patient variables, as well as the design and the construction of the valve are major determining factors in the rate of valve failure.

Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy.

BACKGROUND: The concurrent use of amiodarone and warfarin inhibits metabolism of S-warfarinby cytochrome P450 (CYP) 2C9, thereby increasing the anticoagulant effect of warfarin. Amiodarone primarily inhibits CYP1A2 and CYP3A4, and desethylamiodarone primarily inhibits CYP2C9. We investigate whether a relationship exists between the plasma concentration of desethylamiodarone and anticoagulation when amiodarone is administered to patients receiving warfarin therapy. METHODS AND RESULTS: The correlation between the plasma concentration of either amiodarone or desethylamiodarone, and prolongation of prothrombin time-international normalized ratio/dose of warfarin (Delta INR/Dose) on day 7 of amiodarone administration was studied in 25 patients (22-74 years old) with structural heart disease and refractory arrhythmias receiving stable warfarin therapy. RESULTS: No correlation was found between the plasma concentration of amiodarone and Delta INR/Dose, but a correlation was found between the plasma concentration of desethylamiodarone and Delta INR/Dose. CONCLUSIONS: It was suggested that inhibition of CYP2C9 by desethylamiodarone, the active metabolite of amiodarone, plays an important role in the interaction of warfarin and amiodarone.

Evaluation of regional cardiac sympathetic innervation in congenital long QT syndrome using 123I-MIBG scintigraphy.

The aim of this study was to determine whether sympathetic imbalance in congenital long QT syndrome (LQTS) can be identified by cardiac sympathetic neuronal dysinnervation. 123I-metaiodobenzylguanidine (MIBG) is a tracer of the norepinephrine analogue which reflects the regional innervation and norepinephrine kinetics in cardiac sympathetic nerves. Sixteen patients with LQTS, who were members of 12 families, and 7 normal controls underwent MIBG scintigraphy. Myocardial SPET and planar images were obtained 15 min and 4 h after the injection of MIBG in each patient. The relative regional uptake (RRU) and regional washout rate (rWR) of MIBG at 4 h in each of nine regions were compared with those in the control group. The heat-to-mediastinum ratio (H/M) and global washout rate (GWR) were also calculated. The RRU, rWR, H/M and GWR showed no significant difference between LQTS patients and normal controls. Furthermore, the RRU in 96% of all regions in LQTS was within the mean +/- 2 standard deviations of that in the control group. Patients with LQTS have normal cardiac sympathetic innervation, as assessed by MIBG. The sympathetic imbalance hypothesis is unlikely to be attributed to an abnormal distribution and different regional norepinephrine kinetics of cardiac sympathetic nerves.