Yong-Seog Oh

Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients.

Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboembolic disorders. We investigated the contribution of genetic variations of four genes and clinical factors to warfarin dose requirement and provided a warfarin-dosing algorithm based on genetic and clinical variables in Korean patients. We recruited 564 Korean patients on stable anticoagulation. Single nucleotide polymorphisms (SNPs) for the VKORC1, CYP2C9, CYP4F2 and GGCX were analyzed. Using multiple regression analysis, we developed a model to predict the warfarin requirement. The SNPs of VKORC1, CYP2C9, CYP4F2 and GGCX showed significant correlation with warfarin dose. Patients with the 3730AA genotype received significantly higher doses of warfarin than those with the 3730GG (P=0.0001). For CYP2C9, the highest maintenance dose was observed in the patients with wild-type genotype compared with the variant allele carriers (P<0.0001). The multiple regression model including age, gender, body surface area (BSA), international normalized ratio (INR) and four genetic polymorphisms accounted for 35% of total variations in warfarin dose (R2=0.3499; P<0.0001). This study shows that age, gender, BSA, INR and VKORC1, CYP2C9 and CYP4F2 polymorphism affect warfarin dose requirements in Koreans. Translation of this knowledge into clinical guidelines for warfarin prescription may contribute to improve the efficacy and safety of warfarin treatment for Korean patients.

Comparison of Magnetic Navigation System and Conventional Method in Catheter Ablation of Atrial Fibrillation: Is Magnetic Navigation System Is More Effective and Safer Than Conventional Method?

Background and Objectives Although there have been so many reports of catheter ablation of atrial fibrillation (AF) with magnetic navigation system (MNS), it is not necessarily obvious that MNS is more effective than conventional ablation. We performed AF ablation with MNS and compared the clinical outcomes and radiofrequency ablation parameters with those of conventional ablation. Subjects and Methods One hundred eleven consecutive patients (conventional group, n=70 vs. MNS group, n=41) undergoing catheter ablation of AF were enrolled. We compared and analyzed the procedural parameters, namely fluoroscopic time, procedural time, acute procedural success and 3 months success rate of both groups. Results The MNS group was associated with slightly larger left atrial size (43.7±6.3 mm vs. 41.2±6.3 mm, p=0.04), significantly longer total procedure time (352±50 minutes vs. 283±75 minutes, p<0.0001), and shorter total fluoroscopic time (99±28 minutes vs. 238±45 minutes, p<0.0001) than the conventional group. The MNS and conventional group did not differ with respect to acute procedural success, AF recurrence, atrial flutter/atrial tachycardia recurrence, or total arrhythmia recurrence. While no complications were observed in the MNS group, eight cases of significant pericardial effusion occurred in the conventional group. Conclusion The MNS system seems to be effective and safe in the catheter ablation of AF, particularly in the population of patients with persistent AF and slightly dilated left atria.

Age is an Independent Risk Factor for the Early Morning Blood Pressure Surge in Patients Never-Treated for Hypertension

Background and Objectives The early morning blood pressure surge (EMBPS) has been reported to be associated with cardiovascular events. The aim of this study was to investigate the relationship between 24-hour ambulatory BP monitoring (ABPM) parameters and conventional cardiovascular risk factors. Subjects and Methods Patients (n=346) never-treated for essential hypertension with no other cardiovascular risk factors, such as diabetes, dyslipidemia, and nephropathy were enrolled. The EMBPS was defined as the early morning systolic BP minus the lowest night systolic BP. We compared the 24-hour ABPM parameters in two groups divided by age (<60 and ≥60 years) and examined the association between the 24-hour ABPM parameters and cardiovascular risk factor. Results The EMBPS (18±14 vs. 24±14 mmHg, p=0.002), 24-hour mean blood pressure {MBP; 102±9 vs. 105±11 mmHg, p=0.044}, and 24-hour mean pulse pressure (PP; 52±10 vs. 58±11 mmHg, p<0.001) were significantly increased in the elderly subjects compared to the younger subjects. The degree of decrease was less in the elderly subjects (10±8 vs. 7±10%, p=0.002). Based on multivariate analysis, age was an independent risk factor for the highest quartile of EMBPS (>28 mmHg) after adjusting for gender differences, body mass index, and various 24-hour ABPM parameters (odds ratio, 1.051; 95% confidence interval, 1.028-1.075; p<0.001). Conclusion Age is an independent risk factor for EMBPS in patients with never-treated hypertension. BP control in the early morning period is more important in elderly patients so as to prevent cardiovascular events.

Effect of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Patients Following Ablation of Atrial Fibrillation

Background and Objectives It is known that angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor blockers (ACEIs and ARBs, respectively) are effective in preventing atrial fibrillation (AF) in high-risk patients. However, it is not known whether ACEIs and ARBs are effective in preventing the recurrence of AF after catheter ablation. Subjects and Methods One hundred fifty-two patients (mean age, 57±10 years; M : F=94 : 58) who underwent catheter ablation due to drug-refractory paroxysmal (mean age, 57±10 years; M : F=58 : 43) or persistent AF (mean age, 56±10 years; M : F=36 : 15) were enrolled. We compared the recurrence rates between the groups with and without ACEIs or ARBs use in paroxysmal and persistent AF. The mean duration of follow-up was 18±14 months. Results The overall recurrence rate after ablation therapy was 26% (n=39). The recurrence rate was significantly decreased in the patients with persistent AF with the use of ACEIs or ARBs (12.1% vs. 61.1%, p<0.01), but this difference was not observed in the patients with paroxysmal AF (24.2% vs. 22.9%, p=0.87). In patients with persistent AF with and without recurrence, the size of the left atrium (44.2±8.4 mm vs. 44.3±5.8 mm, respectively, p=0.45) and the ejection fraction (62±6.5% vs. 61.5±6.2%, respectively, p=0.28) were not significantly different. In multivariate analysis, the use of ACEIs or ARBs was independently associated with recurrence after adjusting for the size of the left atrium and the ejection fraction {odds ratio (OR)=0.078, 95% confidence interval (CI)=0.02-0.35, p<0.01}. Conclusion ACEIs and ARBs were shown to be effective in preventing AF recurrence after catheter ablation in patients with persistent AF.

Assessment of the structural remodeling of the left atrium by 64-multislice cardiac CT: comparative studies in controls and patients with atrial fibrillation.

BACKGROUND To assess the functional differences among the three anatomic compartments of the left atrium (LA) using 64-multislice cardiac CT in controls and patients with atrial fibrillation (AF). METHODS We examined 144 individuals (105 males, mean age 56.42 ± 12.04 years) undergoing 64-multislice cardiac CT and divided them into 48 control, 53 paroxysmal AF (PAF), and 43 persistent AF (PeAF) patients. The LA was divided into three anatomic compartments according to their embryologic origins: venous LA (VLA), anterior LA (ALA), and LA appendage (LAA). Each volume was calculated using a threshold-based, three-dimensional segmentation. The LA parameters were defined as maximum and minimum LA volume indices, emptying volume, and ejection fraction. We compared the LA parameters of each compartment in controls, PAF patients, and PeAF patients. RESULTS In each of the three LA compartments, the maximum LA volume index was lowest in controls (LAA, 4.8 ml/m(2); VLA, 18.3 ml/m(2); ALA, 37.1 ml/m(2)) and highest in PeAF patients (LAA, 9.8 ml/m(2); VLA, 30.0 ml/m(2); ALA, 67.3 ml/m(2)). Regarding the three LA compartments, the ejection fraction was highest in the LAA and lowest in the VLA in controls (LAA, 58.3%; VLA, 29.0%; ALA, 47.4%) and in PAF patients (LAA, 47.3%; VLA, 18.3%; ALA, 39.2%). In PeAF patients, the emptying volumes and ejection fractions of the VLA were approximately zero. CONCLUSIONS The anatomic compartments of the LA play different roles in AF patients. The LAA has both highest contractility and independent function, and the VLA is the most severely affected by LA dysfunction. Our results may be helpful in understanding the pathophysiology of AF and predicting treatment responses to radiofrequency ablation in the future.

The Measurement of Opening Angle and Orifice Area of a Bileaflet Mechanical Valve Using Multidetector Computed Tomography

Background and Objectives The aim of this study was to assess mechanical valve function using 64-slice multidetector computed tomography (MDCT). Subjects and Methods In 20 patients (mean age, 50±12 years; male-to-female ratio, 10:10), 30 St. Jude bileaflet mechanical valves (15 aortic and 15 mitral valves) were evaluated using MDCT. We selected images vertical and parallel to the mechanical valve. The valve orifice area (OA) and valve length were determined by manual tracing and the opening and closing angles were measured using a protractor. The OA and length of the mechanical valves were compared with the manufacturers values. Results The geometric orifice areas (GOAs) based on the manufacturers values and the OAs determined by MDCT were 3.4±0.2 cm2 and 3.4±0.3 cm2 for the mitral valves and 2.1±0.3 cm2 and 2.1±0.4 cm2 for the aortic valves, respectively. The correlation coefficients between the OA measures were 0.433 for the mitral valves and 0.874 for the aortic valves (both p<0.001). The lengths based on the manufacturers values and determined by MDCT were 29.3±1.99 mm and 29.6±1.65 mm for the mitral valves and 21.5±2.1 mm and 20.7±2.3 mm for the aortic valves, respectively. The correlation coefficients between the measures were 0.651 for the mitral valve and 0.846 for the aortic valve (both p<0.001). The opening and closing angles determined by MDCT were 10.9±0.6° and 131.1±3.2° for the mitral valves and 11.1±0.9° and 120.6±1.7° for the aortic valves, respectively. Conclusion MDCT is an accurate modality with which to assess the function and morphology of bileaflet mechanical valves.

Optimal antithrombotic strategy in patients with atrial fibrillation after coronary stent implantation.

Background and Objectives Little evidence is available on the optimal antithrombotic therapy following percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). We investigated the outcomes of antithrombotic treatment strategies in AF patients who underwent PCI. Subjects and Methods Three hundred sixty-two patients (68.0% men, mean age: 68.3±7.8 years) with AF and who had undergone PCI with stent implantation between 2005 and 2007 were enrolled. The clinical, demographic and procedural characteristics were reviewed and the stroke risk factors as well as antithrombotic regimens were analyzed. Results The accompanying comorbidities were as follows: hypertension (59.4%), diabetes (37.3%) and congestive heart failure (16.6%). The average number of stroke risk factors was 1.6. At the time of discharge after PCI, warfarin was prescribed for 84 patients (23.2%). Cilostazol was used in addition to dual antiplatelet therapy in 35% of the patients who did not receive warfarin. The mean follow-up period was 615±385 days. The incidences of major adverse cardiac events (MACE), stroke and major bleeding were 11.3%, 3.6% and 4.1%, respectively. By Kaplan-Meier survival analysis, warfarin treatment was not associated with a lower risk of MACE (p=0.886), but it was associated with an increased risk of major bleeding (p=0.002). Conclusion Oral anticoagulation therapy after PCI may increase hemorrhagic events in Korean AF patients.

Measurement of the intimal thickness of the carotid artery: comparison between 40 MHz ultrasound and histology in rats.

Common carotid artery intimal thickness (IT) has been shown to be as useful as a measurement of the whole layer of intima-media thickness (IMT) for evaluating the early phase of atherosclerosis. The aim of this study was to elucidate the relationship between high echogenic intimal thickening (HEIT), which was measured using a 40 MHz ultrasound biomicroscope (UBM), and the histologically determined IT in rat carotid arteries. HEIT was estimated in 10 Wistar-Kyoto rats (group I), 15 spontaneous hypertensive rats (SHR) fed a standard diet (group II) and 10 SHR fed a high-fat diet (group III). IT and IMT measurements were determined in Masson trichrome-stained tissues and were compared with the HEIT and IMT evaluated using the UBM. In group I, the HEIT and the IT were 33 +/- 4 microm and 12 +/- 1 mirom, respectively. In group II, the HEIT and the IT were 68 +/- 8 microm and 16 +/- 2 microm, respectively. In group III, the HEIT and the IT were 65 +/- 26 microm and 33 +/- 14 microm, respectively. In SHR, the HEIT and the mean IMT measured with echography were significantly correlated with the IT and the IMT that were determined by histologic measurement (r = 0.60, p = 0.003 and r = 0.53, p = 0.01, respectively). Moreover, HEIT may be associated with the intimal pathology and atherosclerotic burden. The HEIT measurement is a noninvasive method that may be used to assess atherosclerosis in humans.

The Relationship Between the Acute Changes of the Systolic Blood Pressure and the Brachial-Ankle Pulse Wave Velocity

Background The brachial-ankle pulse wave velocity (baPWV) is a useful parameter to assess arterial stiffness. However, it is difficult to evaluate arterial stiffness in hypertensive patients because the baPWV is affected by the blood pressure itself. This study was designed to estimate the relationship between the change of the blood pressure parameters and the baPWV (ΔbaPWV) when hypertensive patients were subjected to an acute reduction of blood pressure. Methods Thirty patients with essential hypertension and whose blood pressure was higher than 140/90 mmHg were enrolled. In all the patients, the blood pressure and baPWV were measured using an automatic waveform analyzer with the patients at a resting state. When the reduction of blood pressure was more than 10 mmHg after sublingual administration of nifedipine 10 mg, then the blood pressure and baPWV were measured again in the same manner and then they were compared with the baseline values. Spearmans correlation and multiple linear regression tests were performed to estimate the relationship between the change of the blood pressure parameters (ΔSBP, ΔDBP, ΔMAP and ΔPP) and the ΔbaPWV. Results The baPWV was significantly decreased shortly after the administration of nifedipine (1903.6±305.2 cm/sec vs. 1716±252.0 cm/sec, respectively, p<0.01). The ΔbaPWV was correlated with the ΔSBP (r=0.550, p<0.01), ΔDBP (r=0.386, p<0.05), ΔMAP (r=0.441, p<0.05), and ΔPP (r=0.442. p<0.05). On the multiple regression analysis, the ΔSBP was the only significant variable for predicting the ΔbaPWV, and the linear equation was ΔbaPWV=8.7×SBP-48. Conclusions The baPWV is affected by the systolic blood pressure level to a large degree and careful attention must be paid to the blood pressure level when evaluating arterial stiffness with using the baPWV.

Impact of Left Anterior Line on Left Atrial Appendage Contractility in Patients Who Underwent Catheter Ablation for Chronic Atrial Fibrillation

Left anterior line (LAL) has been used as a substitute for mitral isthmus line for catheter ablation of chronic atrial fibrillation (AF). However, it results in left anterolateral conduction delay and might affect left atrial (LA) contractility. We aimed to investigate whether LAL decreases LA appendage function.