Clinical profiles of patients with surgically resected pheochromocytoma and paraganglioma.

BACKGROUND/AIMS: Pheochromocytoma and paraganglioma (PPGL) are catecholamine-producing tumors that can cause blood pressure (BP) elevation and cardiovascular complications. Clinical presentation of these tumors may be changed through widespread use of imaging studies, which enables detection of PPGLs before onset of symptoms. We investigated clinical profiles of patients with surgically resected PPGLs. METHODS: From 2005 to 2017, 111 consecutive patients with surgically resected PPGLs in two tertiary hospitals in Korea were studied. RESULTS: Mean age was 52 ± 16 years, 57 patients (51.4%) were male and 54 (48.6%) were hypertensive. Twenty-nine PPGLs (26.1%) were extra-adrenal paragangliomas. Sixteen (14.4%) and seven patients (6.3%) (Group 1, n = 23) were diagnosed during work-up of hypertension and transient cardiomyopathy respectively, and the remainder (Group 2, n = 88) were incidentalomas detected during routine abdominal imaging. Patients in the Group 1 were younger and more frequently symptomatic, and had higher BPs, heart rates and levels of urinary catecholamines than those in the Group 2. Paragangliomas were less frequent and secretion of epinephrine and metanephrine was more predominant in the Group 1 than in Group 2. After the surgical resections, 18.2% of patients still needed antihypertensive medications. CONCLUSION: Out of 111 patients with surgically resected PPGLs, 88 (79.3%) were diagnosed as incidentalomas. Seven patients presented with transient cardiomyopathy and 16 with hypertension. Tumor location and secretion of catecholamine may vary depending on the presence of symptoms.

ECG features and proarrhythmic potentials of therapeutic hypothermia.

OBJECTIVE: Hypothermia can induce ECG J waves. Recent studies suggest that J waves may be associated with ventricular fibrillation (VF) in patients with structurally normal hearts. However, little is known about the ECG features, clinical significance or arrhythmogenic potentials of therapeutic hypothermia (TH)-induced J waves. METHODS: We analysed ECGs from 240 patients who underwent TH at six major university hospitals in Korea between August 2010 and December 2013. The prevalence, amplitudes and distributions of the J waves and the development of malignant arrhythmia were analysed. RESULTS: The average patient body temperature was 33.5±1.0°C during TH. J waves were observed in 98 patients (40.8%). They were newly developed in 91 cases, and pre-existing J waves were augmented in seven patients. J waves during TH were primarily observed in leads II, III, aVF and V4-6. The average amplitude of the J waves was 0.239±0.152 mV. There were four VF events during TH. These events occurred in three patients who were finally diagnosed with Brugada syndrome, idiopathic VF or early repolarisation syndrome, respectively, and in one patient with non-cardiac aetiology (asphyxia). CONCLUSIONS: J waves were recorded in about 40% of the patients who received TH. They were most frequently observed in the inferior limb leads or lateral precordial leads. Life-threatening VF occurred only rarely (1.7%) during TH and were mainly observed in patients with primary arrhythmic disorder. Although a causal relationship between TH-induced J waves and VF remains unknown, administering TH to this potentially susceptible, high-risk population may require careful attention.

Temporal variation and morphologic characteristics of J-waves in patients with early repolarisation syndrome.

OBJECTIVE: Electrocardiographic markers identifying malignant forms of early repolarisation (ER) from ER of normal variants are of prime clinical importance. We compared the ECG parameters of ER patterns in patients with early repolarisation syndrome (ERS) proximate to the ventricular fibrillation (VF) episodes, remote from the events and those with normal controls with ER. DESIGN: A retrospective, case-control study. SETTING: University hospital. PATIENTS: This study included 12 patients with ERS and 36 age-matched, gender-matched controls with ER. MAIN OUTCOME MEASURES: Dynamic change of J-wave. RESULTS: The highest amplitude of J-wave, sum of the J-wave amplitudes or the number of leads with ER showed a dramatic change during the perievent period. J-wave amplitudes (2.0±1.3 vs 4.0±1.7, p=0.004) and the number of leads with ER (3.3±1.7 vs 5.3±2.0, p=0.021) were significantly higher around the time of VF. In particular, the characteristic morphology of 'giant' (wide, >80 ms) J-waves were observed during the perievent period in 5/12 patients with ERS. However, there were no significant differences in the electrocardiographic parameters of ER pattern remote from VF events between the patients with ERS and normal control subjects with ER. CONCLUSIONS: Although the extent of and amplitude of J-wave or ST segment elevation (STE) increased significantly around VF episodes, the electrocardiographic parameters of ER remote from VF episodes were not significantly different from those of normal controls. The narrow time window of these ECG changes limits early detection of ER patients at risk of developing VF or sudden cardiac death.

Sympathetic nerve fibers and ganglia in canine cervical vagus nerves: localization and quantitation.

BACKGROUND: Cervical vagal nerve (CVN) stimulation may improve left ventricular ejection fraction in patients with heart failure. OBJECTIVES: To test the hypothesis that sympathetic structures are present in the CVN and to describe the location and quantitate these sympathetic components of the CVN. METHODS: We performed immunohistochemical studies of the CVN from 11 normal dogs and simultaneously recorded stellate ganglion nerve activity, left thoracic vagal nerve activity, and subcutaneous electrocardiogram in 2 additional dogs. RESULTS: A total of 28 individual nerve bundles were present in the CVNs of the first 11 dogs, with an average of 1.87±1.06 per dog. All CVNs contain tyrosine hydroxylase-positive (sympathetic) nerves, with a total cross-sectional area of 0.97±0.38 mm(2). The sympathetic nerves were nonmyelinated, typically located at the periphery of the nerve bundles and occupied 0.03%-2.80% of the CVN cross-sectional area. Cholineacetyltransferase-positive nerve fibers occupied 12.90%-42.86% of the CVN cross-sectional areas. Ten of 11 CVNs showed tyrosine hydroxylase and cholineacetyltransferase colocalization. In 2 dogs with nerve recordings, we documented heart rate acceleration during spontaneous vagal nerve activity in the absence of stellate ganglion nerve activity. CONCLUSIONS: Sympathetic nerve fibers are invariably present in the CVNs of normal dogs and occupy in average up to 2.8% of the cross-sectional area. Because sympathetic nerve fibers are present in the periphery of the CVNs, they may be susceptible to activation by electrical stimulation. Spontaneous activation of the sympathetic component of the vagal nerve may accelerate the heart rate.

Guggulsterone inhibits melanogenesis in B16 murine melanoma cells by downregulating tyrosinase expression.

In the present study, we investigated the effect of guggulsterone on melanogenesis in B16 melanoma cells and elucidated its possible mechanism of action. The effects of guggulsterone on melanogenesis were determined by assaying melanin synthesis and cellular tyrosinase activity in B16/F10 mouse melanoma cells. Guggulsterone dose-dependently inhibited isobutylmethylxanthine (IBMX)-induced melanogenesis and cellular tyrosinase activity with no cytotoxicity. Decreased melanin biosynthesis was accompanied by the reduced expression of melanogenesis-related genes, such as tyrosinase, microphthalmia-associated transcription factor, tyrosinase-related protein (TRP)-1 and TRP-2. Guggulsterone also inhibited α-melanocyte stimulating hormone- or forskolin-induced increases in melanogenesis, suggesting an action on the cAMP-dependent melanogenic pathway. Co-incubation with chenodeoxycholic acid, a well-known farnesoid-X receptor agonist, did not affect IBMX-induced melanogenesis. These results suggest that guggulsterone exerts a melanogenic inhibitory effect through the downregulation of tyrosinase expression.

Effect of substrate modification in catheter ablation of paroxysmal atrial fibrillation: pulmonary vein isolation alone or with complex fractionated electrogram ablation.

Catheter ablation of atrial fibrillation that targets complex fractionated electrogram sites has been widely applied in the management of persistent atrial fibrillation. The clinical outcomes of pulmonary vein isolation alone and pulmonary vein isolation plus the use of complex fractionated electrogram-guided ablation (CFEA) have not been fully compared in patients with paroxysmal atrial fibrillation.This prospective study included 70 patients with symptomatic paroxysmal atrial fibrillation that remained inducible after pulmonary vein isolation. For radio-frequency catheter ablation, patients were nonrandomly assigned to a control group (pulmonary vein isolation alone, Group 1, n=35) or a CFEA group (pulmonary vein isolation plus additional CFEA, Group 2, n=35). The times to first recurrence of atrial tachyarrhythmias were compared between the 2 groups.In Group 2, CFEA rendered atrial fibrillation noninducible in 16 patients (45.7%) and converted inducible atrial fibrillation into inducible atrial flutters in 12 patients (34.3%). Atrial fibrillation remained inducible in 7 patients (20%) after the combined ablation procedures. After a mean follow-up of 23 months, freedom from recurrence of atrial tachyarrhythmias was significantly higher in Group 2 than in Group 1 (P=0.037). In Group 1, all of the recurrent tachyarrhythmias were atrial fibrillation, whereas regular tachycardia was the major mechanism of recurrent arrhythmias in Group 2 (atrial tachycardia or atrial flutter in 5 of 6 patients and atrial fibrillation in 1 patient).We found that CFEA after pulmonary vein isolation significantly reduced recurrent atrial tachyarrhythmia and might modify the pattern of arrhythmia recurrence in patients with paroxysmal atrial fibrillation.

Effects of slow pathway ablation on fast pathway function in patients with atrioventricular nodal reentrant tachycardia: cryo- vs. radiofrequency ablation.

BACKGROUND: In typical atrioventricular nodal reentrant tachycardia, radiofrequency (RF) ablation of the slow pathway (SP) is known to change the effective refractory period of the fast pathway (ERP(FP)) after successful RF ablation of the SP. The purpose of this study was to ascertain the mechanism of the ERP(FP) changes after SP ablation by comparing the results of both cryo- and RF ablation. METHODS AND RESULTS: A total of 112 patients were enrolled prospectively and their electrophysiological properties analyzed before and after successful SP ablation. Patients were grouped into cryoablation (n=54) and RF ablation (n=58) groups and each group was subdivided into complete ablation (CG) and modification (MG) based on the presence of the SP after successful ablation. CG was performed in 64 patients: 30 by cryoablation and 34 by RF ablation. In patients who underwent complete SP ablation, the ERP(FP) was shortened significantly after cryoablation (375 ± 74 vs. 281 ± 39 ms, P<0.01), without significant change in the atrio-His (AH) or sinus cycle length (SCL) interval. Similarly, the ERP(FP) was shortened significantly (358 ± 106 vs. 289 ± 84 ms, P=0.01) also after RF ablation without change in AH or SCL interval. CONCLUSIONS: ERP(FP) shortening was observed after complete SP ablation with both cryo- and RF ablation without significant changes in indices of autonomic activity.

Infective Endocarditis due to Streptococcus Agalactiae in Young and Immunocompetent Woman: A Case of Structurally Normal Valve Endocarditis Presented with Major Stroke.

We describe here a 26-year-old woman who presented confusion and right hemiparesis due to embolic obstruction of left internal carotid artery and middle cerebral artery. Transthoracic echocardiography showed structurally normal mitral valve with hypermobile echogenic material suggesting vegetation. The vegetation was disappeared after antimicrobial treatment without surgery.

Cardiovascular Behçet's Disease Presenting as a Subepicardial Hematoma: An Uneventful 2-Year Clinical Course.

Cardiovascular involvement in Behçet's disease is not uncommon and could be life-threatening. We describe here a 28-year-old man, who developed sudden onset chest pain during warfarinization due to deep vein thrombosis. Echocardiography and computed tomography showed a 60×60 mm-sized hematoma in the pericardial space compressing the right heart. Coronary angiography showed totally occluded proximal right coronary artery. The hematoma was located at the subepicardial plane of the right atrium on surgical view and successfully evacuated. Follow-up echocardiography revealed complete resolution of the hematoma. He is doing well for 24 months after surgery.

Periprocedural hemoglobin drop and contrast-induced nephropathy in percutaneous coronary intervention patients.

BACKGROUND AND OBJECTIVES: The development of contrast-induced nephropathy (CIN) is associated with an increased risk of death and late cardiovascular events after percutaneous coronary intervention (PCI). The relationship between CIN and hemoglobin drop has been controversial. The aim of this study was to evaluate the clinical usefulness of periprocedural hemoglobin drop as a nontraditional risk factor for CIN. SUBJECTS AND METHODS: Five-hundred thirty-seven patients who underwent PCI were divided into 2 groups: Group I (486 patients: patients who did not develop CIN) and Group II (51 patients: patients who developed CIN). All patients were administered iodixanol as contrast media during coronary angiography. CIN is defined as a rise in serum creatinine of >/=25% or >/=0.5 mg/dL above the baseline value within 48 hours after contrast administration. RESULTS: BASELINE CLINICAL AND CARDIOVASCULAR RISK FACTORS WERE NOT SIGNIFICANTLY DIFFERENT BETWEEN THE TWO GROUPS, EXCEPT FOR LOW ABDOMINAL CIRCUMFERENCE (GROUP I : Group II=87.9+/-9.0 cm : 81.2+/-15.1 cm, p=0.024), body weight (Group I : Group II=63.5+/-10.6 kg : 59.7+/-9.2 kg, p=0.008), body mass index (BMI) (Group I : Group II=24.4+/-3.4 kg/m(2) : 23.4+/-2.8 kg/m(2), p=0.032), pre-PCI hemoglobin (Group I : Group II=13.2+/-2.0 g/dL : 12.3+/-2.0 g/dL, p=0.003), and post-PCI hemoglobin (Group I : Group II=12.4+/-1.9 g/dL : 11.5+/-1.8 g/dL, p=0.001). Multiple logistic regression analysis showed that a periprocedural drop in hemoglobin (>1 g/dL) was an independent predictor of CIN, like other known risk factors. CONCLUSION: A periprocedural drop in hemoglobin of more than 1 g/dL is another important independent predictor for CIN, even in patients administered the lowest nephrotoxic contrast agent, iodixanol, during PCI.

Huge primary pleomorphic leiomyosarcoma in the right ventricle with impending obstruction of both inflow and outflow tracts.

Primary cardiac leiomyosarcoma is an extremely rare disease entity that is associated with very poor prognosis. We describe here a 45-year-old man who had a huge pleomorphic leiomyosarcoma in the right ventricle (RV) that presented with signs of acute pressure and volume overload and impending obstruction of both outflow and inflow tracts of the RV. The tumor was attached to the RV apex and the interventricular septum, and extended into the main pulmonary trunk just above the pulmonary valve as well as into the right atrium through the tricuspid valve. We evaluated the extent of the tumor using various imaging modalities including transthoracic and transesophageal echocardiography, magnetic resonance imaging, computed tomography, and positron emission tomography-computed tomography. Although he underwent urgent debulking surgery to relieve the obstruction, the tumor could not be resected completely because of its extensive local invasion. The tumor has shown aggressive regrowth after surgery despite adjuvant chemotherapy.

Different response of ANP secretion to adrenoceptor stimulation in renal hypertensive rat atria.

Sympathetic nervous system and atrial natriuretic peptide (ANP) system play fundamental roles in the regulation of cardiovascular functions. Overactivity of sympathetic nervous system can lead into cardiovascular diseases such as heart failure and hypertension. The present study aimed to define which adrenergic receptors (ARs) affect atrial contractility and ANP release and to determine their modification in renal hypertensive rat atria. An alpha(1)-AR agonist, cirazoline increased ANP release with positive inotropism. These alpha(1)-AR agonist-mediated responses were attenuated by the alpha(1A)-AR antagonist, but not by the alpha(1B)- or alpha(1D)-AR antagonist. An alpha(2)-AR agonist, guanabenz and clonidine increased ANP release with negative inotropism and decreased cAMP level. The order of potency for the increased ANP release was cirazoline>>phenylephrine=guanabenz>>clonidine. In contrast, a beta-AR agonist, isoproterenol decreased ANP release with positive inotropism and these responses were blocked by the beta(1)-AR antagonist but not by the beta(2)-AR antagonist. The increased cAMP level by isoproterenol was suppressed by pretreatment with both beta(1)- and beta(2)-AR antagonists. In renal hypertensive rat atria, the effects of isoproterenol on atrial contractility, ANP release, and cAMP level were attenuated whereas the effect of cirazoline on ANP release was unaltered. Atrial beta(1)-AR mRNA level but not alpha(1A)-AR mRNA level was decreased in renal hypertensive rats. These findings suggest that alpha(1A)- and beta(1)-AR oppositely regulate atrial ANP release and that atrial beta(1)-AR expression/function is impaired in renal hypertensive rats.

Bail-out stenting for left main coronary artery dissection during catheter-based procedure: acute and long-term results.

BACKGROUND: The optimal treatment of patients with left main coronary artery (LMCA) dissection during catheter-based procedure remains uncertain. HYPOTHESIS: In cases with significant LMCA dissection occurring during catheter-based procedure, prompt stent implantation may be safe and associated with favorable clinical outcome. METHODS: We evaluated the acute and long-term results of bail-out stenting for LMCA dissection occurring during a catheter-based procedure in 10 patients. RESULTS: Initially, there was no significant stenosis of LMCA segments in these patients. Catheter-induced dissection occurred in eight patients (during diagnostic angiography in three patients and during guiding catheter manipulation in five patients). Two patients suffered dissection in the setting of stent deployment in other vessels. Therefore, bail-out stenting for LMCA dissection was performed in a total of 10 patients. In four patients, hypotension developed and an intra-aortic balloon pump was placed during the procedure. Stents were successfully deployed in all patients; there was no in-hospital mortality. Six-month angiographic follow-up was performed in eight patients. No angiographic restenosis (diameter stenosis > or = 50%) was observed in any patient at follow-up study. During a mean follow-up of 31 +/- 25 months after hospital discharge, there was no major adverse cardiac event (death, myocardial infarction, and target lesion revascularization). CONCLUSIONS: Bail-out LMCA stenting is technically feasible and showed good acute and long-term results in a small series of patients.

Clinical characteristics of Brugada syndrome in a Korean population.

The objective of this study was to investigate the clinical features of Korean patients with Brugada syndrome (BS). Between June 1998 and April 2002, 15 consecutive patients with BS (13 men, 2 women; mean age, 44+/-10 years) were identified. Eight patients had experienced at least 1 episode of aborted sudden death, 5 patients had had an episode of syncope or chest pain, and 2 patients were asymptomatic at diagnosis. The electrocardiographics (ECGs) of all patients showed spontaneous ST-segment elevation in leads V(1-3) at baseline and 13 patients (87%) showed transient normalization of the ST-segment elevation during follow-up. Twelve patients received an implantable cardioverter-defibrillator (6 patients with aborted sudden death, 5 patients with syncope or chest pain, 1 asymptomatic patient). During a mean follow-up of 19+/-14 months, arrhythmic events occurred in 5 of the 6 patients with aborted sudden death and in 1 of the 5 patients with syncope or chest pain. None of the asymptomatic patients developed any symptoms suggestive of an arrhythmic event. The clinical and ECG manifestation of BS in Korean patients is diverse, but the dynamic nature of the ST segment provides an important clue to the diagnosis of BS. Recurrence of malignant arrhythmia is extremely high in those patients who initially present with aborted sudden death.

Open channel block by KCB-328 [1-(2-amino-4-methanesulfonamidophenoxy)-2-[N-(3,4-dimethoxyphenethyl)-N-methylamino]ethane hydrochloride] of the heterologously expressed human ether-a-go-go-related gene K+ channels.

KCB-328 [1-(2-amino-4-methanesulfonamidophenoxy)-2-[N-(3,4-dimethoxyphenethyl)-N-methylamino]ethane hydrochloride] is a newly synthesized class III antiarrhythmic drug and is known to be highly effective against various types of arrhythmias induced by coronary artery ligation, reperfusion, and programmed electrical stimulation. To understand the potential ionic mechanisms, we examined the effects of KCB-328, which encodes the rapidly activating delayed rectifier K(+) current in cardiac tissues, on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes. The amplitudes of steady-state currents and tail currents of HERG were decreased by KCB-328 dose dependently. The decrease became more pronounced at more positive potential, suggesting that the block of HERG by KCB-328 is voltage-dependent. IC(50) values at -30, -20, -10, 0, +10, +20, +30, and +40 mV were 7.6 +/- 0.5, 4.8 +/- 0.4, 3.2 +/- 0.3, 2.1 +/- 0.3, 1.7 +/- 0.2, 1.4 +/- 0.2, 1.3 +/- 0.1, and 1.2 +/- 0.1 microM, respectively. Induction of block depended on depolarization beyond the threshold for channel opening. In addition, time-dependent block developed slowly, with tau = 1.7 +/- 0.3 s (100 microM) at 0 mV, and was delayed by a stronger depolarization to +80 mV, at which HERG channel is inactivated. We can conclude that KCB-328 preferentially blocks open (or activated) HERG channels. The block of HERG current might in part explain the underlying ionic mechanism for the antiarrhythmic and proarrhythmic effect of KCB-328.