Early efficacy and safety of statin therapy in Korean patients with hypercholesterolemia: Daegu and Gyeongbuk Statin Registry.

BACKGROUND/AIMS: To date, prospective data are limited on efficacy and safety profiles of statin therapy in Korean hypercholesterolemic patients. Hence, the aim of this study was to evaluate the practice patterns of statin therapy and its efficacy and safety through the prospective Daegu and Gyeongbuk statin registry. METHODS: Statin naïve patients who were prescribed statins according to the criteria of Korean Guidelines for Management of Dyslipidemia were enrolled. Clinical and laboratory evaluations were performed at baseline and at week 8, where the efficacy was assessed with the same guidelines. RESULTS: Of 908 patients, atorvastatin and rosuvastatin were most frequently prescribed statins (63.1% and 29.3%, respectively). High intensity statins (atorvastatin 40 mg or rosuvastatin 20 mg) were prescribed in 24.7% of all patients and in 79.5% of high and very high risk groups. The total and low density lipoprotein (LDL) cholesterol levels decreased from 203.7 ± 43.0 to 140.6 ± 28.6 mg/dL and 134.4 ± 35.7 to 79.5 ± 21.3 mg/dL, respectively. The achievement rate of the LDL target goal was 98.6% in low risk, 95.0% in moderate risk, 88.1% in high risk, and 42.1% in very high risk patients (59.7% in overall). There was no significant difference in the efficacy between atorvastatin and rosuvastatin. Adverse events were observed in 12.0% of patients and led to 1.4% of treatment cessation. CONCLUSION: The efficacy of the usual starting dose of statins in daily practice was relatively insufficient for Korean hypercholesterolemic patients with high or very high risks. Short-term adverse events of statin therapy were not common in Korean patients with a low discontinuation rate.

Comparison of the efficacy between impedance-guided and contact force-guided atrial fibrillation ablation using an automated annotation system.

BACKGROUND: This study compared the efficacy of catheter ablation of atrial fibrillation (AF) between impedance (IMP)-guided and contact force (CF)-guided annotation using the automated annotation system (VisiTag™). METHODS: Fifty patients undergoing pulmonary vein isolation (PVI) for AF were randomized to the IMP-guided or CF-guided groups. The annotation criteria for VisiTag™ were a 10 second minimum ablation time and 2 mm maximum catheter movement range. A minimum CF of 10 g was added to the criteria in the CF-guided group. In the IMP-guided group, a minimum IMP drop of over 5 Ω was added to the criteria. RESULTS: The rates of successful PVI after an initial ablation line were higher in the CF-guided group (80% vs 48%, P = .018). Although average CF was similar between two groups, the average force-time integral (FTI) was significantly higher in the CF-guided group (298.3 ± 65. 2 g·s vs 255.1 ± 38.3 g·s, P = .007). The atrial arrhythmia-free survival at 1 year demonstrated no difference between the two groups (84.0% in the IMP-guided group vs 80.0% in the CF-guided group, P = .737). If the use of any antiarrhythmic drug beyond the blanking period was considered as a failure, the clinical success rate at 1 year was 52.0% for the CF-guided group vs 56.0% for the IMP-guided group (P = .813). CONCLUSIONS: Atrial fibrillation ablation using an automated annotation system guided by CF improved the success rate of PVI after the initial circumferential ablation. An IMP-guided annotation combined with catheter stability criteria showed similar clinical outcomes as compared to the CF-guided annotation.

The Melatonin Signaling Pathway in a Long-Term Memory In Vitro Study.

The activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) via phosphorylation in the hippocampus is an important signaling mechanism for enhancing memory processing. Although melatonin is known to increase CREB expression in various animal models, the signaling mechanism between melatonin and CREB has been unknown in vitro. Thus, we confirmed the signaling pathway between the melatonin receptor 1 (MT1) and CREB using melatonin in HT-22 cells. Melatonin increased MT1 and gradually induced signals associated with long-term memory processing through phosphorylation of Raf, ERK, p90RSK, CREB, and BDNF expression. We also confirmed that the calcium, JNK, and AKT pathways were not involved in this signaling pathway by melatonin in HT-22 cells. Furthermore, we investigated whether melatonin regulated the expressions of CREB-BDNF associated with long-term memory processing in aged HT-22 cells. In conclusion, melatonin mediated the MT1-ERK-p90RSK-CREB-BDNF signaling pathway in the in vitro long-term memory processing model and increased the levels of p-CREB and BDNF expression in melatonin-treated cells compared to untreated HT-22 cells in the cellular aged state. Therefore, this paper suggests that melatonin induces CREB signaling pathways associated with long-term memory processing in vitro.

Prognostic Usefulness of Tricuspid Annular Diameter for Cardiovascular Events in Patients With Tricuspid Regurgitation of Moderate to Severe Degree.

Functional tricuspid regurgitation (TR) is frequently encountered. Current guidelines recommend the surgical correction of severe TR only at the time of left valve surgery despite emphasizing the enlarged tricuspid annulus (TA) dimension. We attempted to evaluate the relation between TA dimension and clinical outcomes of moderate or severe TR. A total of 213 patients (mean age 68 years, women 68%) with moderate or severe TR secondary to left-sided valve surgery, nonvalvular disease, or isolated primary TR were retrospectively identified and classified into tertiles of TA dimension. Cardiovascular (CV) outcomes were defined as a composite of hospitalization for worsening heart failure (HF), stroke, and CV death over a median follow-up of 3.4 years. Upper and lower tertiles of TA dimension had high frequencies of left-sided valve surgery and isolated primary TR, respectively. TA dimension was correlated with TR severity assigned as color Doppler grade and systolic tissue Doppler imaging of the tricuspid valve (TDI s'). During follow-up, there were 87 (41%) occurrences of primary outcomes: 65 HFs (31%), 13 CV deaths (6%), and 9 strokes (4%). There was a high frequency of adverse outcomes in the upper tertile. TA dimension and TDI s' were independently related to outcomes. An enlarged TA dimension was associated with outcomes irrespective of subgroups according to type or severity of TR and TDI s' (p = 0.21, p = 0.77, p = 0.15 for interaction). A cut-off value of 4.0 cm for TA dimension was best for CV event occurrence. When assessing clinical CV outcomes, TA dimension should be considered, even in moderate TR.

Heart rate at first postdischarge visit and outcomes in patients with heart failure.

OBJECTIVE: Heart rate control is important to prevent adverse outcomes in patients with heart failure (HF). However, postdischarge activity may worsen heart rate control, resulting in readmission. This study aimed to explore the implications of the heart rate differences between discharge and the first outpatient visit (D-O diff). METHODS: We retrospectively identified 458 patients (male: 46%; mean age: 72 years) discharged after HF. The heart rates at admission, discharge and first outpatient visit were analysed. The primary outcome was a composite of cardiovascular (CV) death and readmission of non-fatal myocardial infarction (MI), non-fatal stroke or non-fatal HF over a mean follow-up of 16 months. RESULTS: During follow-up, the clinical outcomes were noted in 223 patients (49%): HF, 199; stroke, 9; MI, 6; CV death, 9. The heart rate at the first outpatient visit (r=-0.311, P<0.001) and D-O diff (r=0.416, P<0.001) showed a better correlation with the time-to-clinical event than the heart rate at admission or discharge. The events group displayed a pronounced heart rate increase (13 beats/min) from discharge to the first outpatient visit compared with the event-free group (a decrease of 2 beats/min). A decrease less than -15 in the D-O diff showed a 4.5-fold risk of clinical outcomes during follow-up (P<0.001). CONCLUSIONS: A decreased D-O diff was related to the adverse outcomes of HF. The failure of heart rate control within more than 15 beats/min at the first outpatient visit was an independent factor for CV events.

Supraventricular tachyarrhythmias in patients with a persistent left superior vena cava.

Aims: A persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly. This venous anomaly can impact the evaluation and treatment of supraventricular tachyarrhythmia (SVA). The aim of this study was to assess the proportion and characteristics of PLSVC in adult SVA patients. Methods and results: From July 2002 to July 2012, clinical and procedural data from databases of 10 cardiac electrophysiology laboratories in the Yeungnam region of the Republic of Korea were reviewed. Of 6662 adult SVA patients who underwent an EP study or catheter ablation of SVA during the 10-year study period, 18 patients had PLSVC (mean age 47.6 ± 14.8 years, 10 men). The proportion of PLSVC in adult SVA patients was 0.27% (18/6662). SVA type and procedural outcomes of radiofrequency (RF) catheter ablation in these patients were investigated and the results were as follows: successful slow pathway modification in six of seven patients with atrioventricular nodal reentrant tachycardia (AVNRT), successful ablation of accessory pathway in three of four patients with atrioventricular reentrant tachycardia, and successful ablation of atrial tachycardia (cavotricuspid isthmus-dependent in two, septal macroreentry in one, focal from the PLSVC in one) in three of four patients. In one patient with junctional tachycardia, catheter ablation failed. In two patients with atrial fibrillation, catheter ablation was successful. Conclusion: Among adult SVA patients who underwent an EP study or RF catheter ablation during the 10-year study period, 0.27% had PLSVC. The most common type of SVA was AVNRT. The success rate of catheter ablation was 82% in SVA patients with PLSVC. There were no procedure-related complications.

Induction of Inflammation In Vivo by Electrocardiogram Sensor Operation Using Wireless Power Transmission.

Prolonged monitoring by cardiac electrocardiogram (ECG) sensors is useful for patients with emergency heart conditions. However, implant monitoring systems are limited by lack of tissue biocompatibility. Here, we developed an implantable ECG sensor for real-time monitoring of ventricular fibrillation and evaluated its biocompatibility using an animal model. The implantable sensor comprised transplant sensors with two electrodes, a wireless power transmission system, and a monitoring system. The sensor was inserted into the subcutaneous tissue of the abdominal area and operated for 1 h/day for 5 days using a wireless power system. Importantly, the sensor was encapsulated by subcutaneous tissue and induced angiogenesis, inflammation, and phagocytosis. In addition, we observed that the levels of inflammation-related markers increased with wireless-powered transmission via the ECG sensor; in particular, levels of the Th-1 cytokine interleukin-12 were significantly increased. The results showed that induced tissue damage was associated with the use of wireless-powered sensors. We also investigated research strategies for the prevention of adverse effects caused by lack of tissue biocompatibility of a wireless-powered ECG monitoring system and provided information on the clinical applications of inflammatory reactions in implant treatment using the wireless-powered transmission system.

Extension of catheter ablation and outcome for ventricular tachycardia or premature ventricular contractions from the right ventricular outflow tract.

Objective We aimed to determine whether the extension of ablation could influence the ablation outcome for ventricular tachycardia (VT)/premature ventricular contractions (PVCs) from the right ventricular outflow tract (RVOT). Methods and results The radiofrequency catheter ablation results of 33 VT/6 frequent PVCs from the RVOT were analysed. The ablation extension was divided into 3 categories from the final successful ablation point with the earliest activation: (I) focal ablation (15 cases); ablation at 1 or 2 points; (II) focal with extended ablation (12 cases); focal and surrounding area ablation (maximum ≤1 cm) after elimination of clinical VT/PVCs; and (III) broad ablation (12 cases); continued broad ablation (maximum >1 cm) after elimination of clinical VT/PVCs. Acute termination was defined as the complete elimination and non-inducibility of clinical VT/PVCs during the procedure. For the mean follow-up of 12.8 months, the recurrence rate was not significantly different among the groups (P = 0.49). The mean procedure time was longer in group II, but ablation times and complication rates were not different among the groups. When acute termination was achieved, the overall recurrence rate was 7.6%. However, when confirming absence of the clinical VT/PVCs using 24-hour Holter monitoring immediately after the procedure, the recurrence rate was 2.7%. Conclusions Ablation extension did not affect ablation outcome of VT/PVCs from the RVOT. Confirmation of absence of clinical VT/PVCs using 24-hour Holter monitoring immediately after the procedure could guarantee long-term success.

Predictors of an adverse clinical outcome in patients with long-term right ventricular apical pacing.

BACKGROUND: Right ventricular (RV) apical pacing can result in progressive left ventricular (LV) dysfunction and contribute to the development of heart failure (HF). This study aimed to predict the outcome after long-term RV apical pacing in patients with acquired atrioventricular (AV) block who required permanent pacing. METHODS: We included 247 patients who underwent long-term (>90% ventricular pacing with atrioventricular synchrony for more than 1 year) RV apical pacing for acquired AV block. We excluded patients with a reduced LV systolic function [ejection fraction (EF) <50%]. The paced QRS duration, degree of the axis, clinical characteristics, laboratory findings, and echocardiographic parameters were recorded. We evaluated the mortality and hospitalization due to HF. RESULTS: The mean follow-up duration was 6.9 years. Mortality and hospitalization due to HF occurred in 8.1% and 17%, respectively. In a multivariate analysis, a wider paced QRS duration and less superior paced QRS axis at the time of the implantation were independent risk factors for adverse events. The patients with a paced QRS duration of ≥163ms and axis of ≥-65° had a 5.8 times higher risk for adverse events compared to those with a paced QRS duration of <163ms and axis of <-65°. CONCLUSIONS: The paced QRS duration and axis could help us predict adverse clinical outcomes after permanent RV apical pacing in patients with high-degree AV block.

Effectiveness of Implantable Cardioverter-Defibrillator Therapy for Heart Failure Patients according to Ischemic or Non-Ischemic Etiology in Korea.

BACKGROUND AND OBJECTIVES: This study was performed to describe clinical characteristics of patients with left ventriculars (LV) dysfunction and implantable cardioverter-defibrillator (ICD), and to evaluate the effect of ICD therapy on survival in Yeongnam province of Korea. SUBJECTS AND METHODS: From a community-based device registry (9 centers, Yeongnam province, from November 1999 to September 2012), 146 patients with LV dysfunction and an ICD implanted for primary or secondary prophylaxis, were analyzed. The patients were divided into two groups, based on the etiology (73 with ischemic cardiomyopathy and 73 with non-ischemic cardiomyopathy), and indication for the device implantation (36 for primary prevention and 110 for secondary prevention). The cumulative first shock rate, all cause death, and type and mode of death, were determined according to the etiology and indication. RESULTS: Over a mean follow-up of 3.5 years, the overall ICD shock rate was about 39.0%. ICD shock therapy was significantly more frequent in the secondary prevention group (46.4% vs. 16.7%, p=0.002). The cumulative probability of a first appropriate shock was higher in the secondary prevention group (p=0.015). There was no significant difference in the all-cause death, cardiac death, and mode of death between the groups according to the etiology and indication. CONCLUSION: Studies from this multicenter regional registry data shows that in both ischemic and non-ischemic cardiomyopathy patients, the ICD shock therapy rate was higher in the secondary prevention group than primary prevention group.

Implications of prescribing a fixed-dose combination in clinical cardiology practice: a retrospective observational study using a single medical centre database in Korea.

OBJECTIVE: Fixed-dose combination (FDC) prescribing enhances adherence to medication. However, there are limited data regarding the usefulness of FDC drugs across different risk groups. The aim of this study was to explore the relationship between FDC discontinuation and clinical outcomes. METHODS: From January 2008 to December 2014, patients with FDC prescriptions who visited a cardiology outpatient clinic at a tertiary university hospital in Daegu, Republic of Korea were retrospectively identified. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score and 20 conventional cardiovascular (CV) risk factors were assessed. Patients were classified according to FDC continuation, together with a tertile of 20 risks. CV events were defined as the composite of admission for worsening heart failure or diabetes, stroke, ischaemic heart disease, and CV death. RESULTS: 502 patients were prescribed with one of the following FDC products: calcium channel blocker (CCB) plus angiotensin receptor blockers (ARB), CCB plus statins, and ARB plus diuretics. During follow-up (mean 2.8±2.4 years), 203 discontinuations (40.4%) occurred. FDC-discontinued patients had lower ASCVD risk scores (24.8% vs. 28.8%, p<0.001), and patients with <6 risk factors discontinued FDC frequently. During follow-up, 57 events (11.4%) were reported: 30 (14.8%) in FDC-discontinued patients and 27 (9.1%) in FDC-continued patients (p=0.062). In multivariate models accounting for events, FDC discontinuation (p<0.001) and high ASCVD risk score (p=0.017) were associated with CV events. CONCLUSIONS: FDC discontinuation was common among patients attending the cardiology outpatient clinic. Our analyses suggest that FDC discontinuation in patients at high ASCVD risk may have an impact on CV event rates.

Clinical Outcomes in Patients with Deferred Coronary Lesions according to Disease Severity Assessed by Fractional Flow Reserve.

Data on the clinical outcomes in deferred coronary lesions according to functional severity have been limited. This study evaluated the clinical outcomes of deferred lesions according to fractional flow reserve (FFR) grade using Korean FFR registry data. Among 1,294 patients and 1,628 lesions in Korean FFR registry, 665 patients with 781 deferred lesions were included in this study. All participants were consecutively categorized into 4 groups according to FFR; group 1: ≥ 0.96 (n = 56), group 2: 0.86-0.95 (n = 330), group 3: 0.81-0.85 (n = 170), and group 4: ≤ 0.80 (n = 99). Primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, and target vessel revascularization. The median follow-up period was 2.1 years. During follow-up, the incidence of MACE in groups 1-4 was 1.8%, 7.6%, 8.8%, and 13.1%, respectively. Compared to group 1, the cumulative rate by Kaplan-Meier analysis of MACE was not different for groups 2 and 3. However, group 4 had higher cumulative rate of MACE compared to group 1 (log-rank P = 0.013). In the multivariate Cox hazard models, only FFR (hazard ratio [HR], 0.95; P = 0.005) was independently associated with MACE among all participants. In contrast, previous history of percutaneous coronary intervention (HR, 2.37; P = 0.023) and diagnosis of acute coronary syndrome (ACS) (HR, 2.35; P = 0.015), but not FFR, were independent predictors for MACE in subjects with non-ischemic (FFR ≥ 0.81) deferred coronary lesions. Compared to subjects with ischemic deferred lesions, clinical outcomes in subjects with non-ischemic deferred lesions according to functional severity are favorable. However, longer-term follow-up may be necessary.

Discrepancy between frequency domain optical coherence tomography and intravascular ultrasound in human coronary arteries and in a phantom in vitro coronary model.

BACKGROUND: This purpose of this study is to evaluate, concomitantly with quantitative coronary angiography (QCA), the potential discrepancy between frequency domain optical coherence tomography (FD-OCT) and intravascular ultrasound (IVUS) measurements in a phantom coronary model and in human coronary arteries within and outside stented segments. METHODS: FD-OCT and IVUS images sequentially obtained from a phantom coronary model and 57 stented human coronary arteries were compared between each other and with QCA. RESULTS: Lumen area (LA) by IVUS was 10.1% larger (6.43±0.09mm(2)) while by FD-OCT was similar (5.78±0.09mm(2)) to actual phantom LA (5.72mm(2)); IVUS vs. FD-OCT stent area (SA) was 4.2% larger. In human coronary artery, diameter by QCA was smaller than by IVUS and OCT in reference (by 10.5% and 3.5%, both p<0.001) and stented (3.6%, p<0.001; and 1.7%, p=0.012) segments. IVUS vs. FD-OCT distal reference LA was significantly larger (6.19±2.18mm(2) vs. 5.49±2.49mm(2), p<0.001, respectively), and SA was numerically larger (7.42±2.28mm(2) vs. 7.22±2.48mm(2), p=0.059) with larger discrepancy in reference (11.3%) than stented (2.7%) segments. IVUS vs. FD-OCT correlation for diameter was significantly higher for stented than reference segments (R(2)=0.8670 vs. 0.7351, p=0.047), while numerically higher for area (R(2)=0.8663 vs. 0.7806, p=0.157). CONCLUSIONS: In phantom model and human coronary arteries, IVUS vs. FD-OCT measurements were larger, particularly in non-stented than stented segments, and diameter was smaller by QCA vs. IVUS or FD-OCT. Despite undefined clinical significance, said discrepancy warrants consideration.

No Association of the rs17822931 Polymorphism in ABCC11 with Breast Cancer Risk in Koreans.

ABCC11 is reported to be associated with breast cancer. However, whether ABCC11 polymorphisms relate to breast cancer risk remains unclear. This study aimed to evaluate any association of a single nucleotide polymorphism (SNP), rs17822931, in ABCC11 with breast cancer in Koreans. Genomic DNA samples of 170 women with breast cancer and 100 controls were assessed for SNP rs17822931 of ABCC11 by single-strand conformation polymorphism (SSCP) and DNA sequencing. A 27-bp deletion (Δ27) of ABCC11 was analyzed by PCR amplification. The genotype of SNP rs17822931 was confirmed to be AA in all samples from breast cancer patients and Δ27 was found in none of the samples. Our finding indicated that the SNP rs17822931 in ABCC11 is not associated with breast cancer. However, this study does provide information on fundamental genetic aspects of ABCC11 with regard to breast cancer risk in Koreans.

Significance of apical cavity obliteration in apical hypertrophic cardiomyopathy.

OBJECTIVE: Apical hypertrophic cardiomyopathy (HCM) is characterised by apical systolic obliteration and is associated with atrial fibrillation (AF), stroke, heart failure (HF), and mortality. We investigated whether apical obliteration of the left ventricular (LV) cavity could have an unfavourable impact on the clinical course of apical HCM. METHODS: 188 patients with apical HCM (114 males, median age 67 years) were identified retrospectively from January 2008 to December 2010. The rate of apical obliteration was defined as the net obliteration to end-diastolic apical cap thickness, and the ratio of obliteration to cavity was defined as the end-systolic obliteration to cavity height. Events were defined as a composite of new onset of AF, stroke, HF, and cardiovascular (CV) death. RESULTS: There were 43 clinical events (19 AFs, 11 HFs, 9 strokes, and 4 deaths) during a follow-up of median 4.4 years. The events patients were older, had larger left atrial volume index (LAVI), lower late diastolic mitral annular tissue Doppler velocity (a'), and higher LV end-diastolic pressure (E/e'). They had greater apical thickness and obliteration, smaller systolic cavity height, higher rate of obliteration, and higher ratio of obliteration to cavity; events were significantly higher (54%) in the upper tertiles of the ratio of obliteration to cavity. Age, E/e', a', LAVI, apical thickness, rate of obliteration, and ratio of obliteration to cavity were associated with events. On multivariable analysis, the ratio of obliteration to cavity remained a significant predictor. CONCLUSIONS: The ratio of obliteration to cavity could provide useful information to predict the occurrence of adverse events in apical HCM.

Usefulness of Frequency Domain Optical Coherence Tomography Compared with Intravascular Ultrasound as a Guidance for Percutaneous Coronary Intervention.

OBJECTIVES: To compare outcomes and rates of optimal stent placement between optical coherence tomography (OCT) and intravascular ultrasound (IVUS) guided percutaneous coronary intervention (PCI). BACKGROUND: Unlike IVUS-guided PCI, rates of clinical outcomes and optimal stent placement have not been well characterized for OCT-guided PCI. METHODS: The study enrolled 290 patients who underwent implantation of a second generation drug eluting stent under OCT (122 patients) or IVUS (168 patients) guidance. The two groups were compared after adjusting for baseline differences using 1:1 propensity score matching (PSM) (114 patients in each group). Optimal stent placement was defined as achieving an adequate lumen (optimal minimum stent area [MSA > 4.85 mm(2) for OCT, >5 mm(2) for IVUS] or a final MSA ≥ 90% of the distal reference lumen area, without edge dissection, incomplete stent apposition, or tissue prolapse), or otherwise performing additional interventions to address suboptimal post-stenting OCT or IVUS findings. The primary endpoint was one-year cumulative incidence of major adverse cardiac events (MACE; cardiac death, myocardial infarction and target lesion revascularization). Definite or probable stent thrombosis (ST) rates were evaluated. RESULTS: In adjusted comparisons between OCT and IVUS groups, there was no significant difference in rates of MACE (3.5% vs. 3.5%, P = 1.000) and ST (0% vs. 0.9%, P = 1.000) at 1 year, optimal stent placement (89.5% vs. 92.1%, P = 0.492), and further intervention (7.9% vs.13.2%, P = 0.234), despite OCT significantly more frequently detecting tissue prolapse (97.4% vs. 47.4%, P < 0.001), and numerically more edge dissection (10.5% vs. 4.4%, P = 0.078) or incomplete stent apposition (48.2% vs. 36.8%, P = 0.082). CONCLUSIONS: OCT guidance showed comparable results to IVUS in mid-term clinical outcomes, suggesting that OCT can be an alternative tool for stent placement optimization.

Genetic Variation of SCN5A in Korean Patients with Sick Sinus Syndrome.

BACKGROUND AND OBJECTIVES: Due to recent studies that have shown an association between the genetic variation of SCN5A and sick sinus syndrome (SSS), we sought to determine if a similar correlation existed in Korean patients with SSS. SUBJECTS AND METHODS: We enrolled 30 patients with SSS who showed a sinus pause (longer than 3.0 s) in Holter monitoring, in addition to 80 controls. All exons including the putative splicing sites of the SCN5A gene were amplified by polymerase chain reaction and sequenced either directly or following subcloning. Wild-type and single nucleotide polymorphisms were expressed in human embryonic kidney cells, and the peak sodium current (INa ) was analyzed using the whole-cell patch-clamp technique. RESULTS: A total of 9 genetic variations were identified: 7 variations (G87A-A29A, IVS9-3C>A, A1673G-H558R, G3823A-D1275N, T5457C-D1819D, T5963G-L1988R, and C5129T-S1710L) had been previously reported, and 2 variants (A3075T-E1025D and T4847A-F1616Y) were novel; the potential structural effects of F1616Y were analyzed in a three-dimensional model of the SCN5A domain. Patch-clamp studies at room temperature demonstrated that the peak INa was significantly increased by 140% in HEK cells transfected with F1616Y compared with wild-type (-335.13 pA/pF±24.04, n=8 vs. -139.95 pA/pF±23.76, n=7, respectively). Furthermore, the voltage dependency of the activation and steady-state inactivation of F1616Y were leftward-shifted compared with wild-type (Vh activation=-55.36 mv±0.22, n=8 vs. Vh activation=-44.21 mV±0.17, n=7; respectively; Vh inactivation=-104.47 mV±0.21, n=7 vs. Vh inactivation=-84.89 mV±0.09, n=12, respectively). CONCLUSION: F1616Y may be associated with SSS.

Evaluation of the Efficacy and Safety of the Lercanidipine/Valsartan Combination in Korean Patients With Essential Hypertension Not Adequately Controlled With Lercanidipine Monotherapy: A Randomized, Multicenter, Parallel Design, Phase III Clinical Trial.

PURPOSE: The objective of this study was to evaluate the efficacy and safety of the lercanidipine/valsartan combination compared with lercanidipine monotherapy in patients with hypertension. METHODS: Part 1 of this study was the randomized, multicenter, double-blind, parallel group, Phase III, 8-week clinical trial to compare superiority of lercanidipine 10 mg/valsartan 80 mg (L10/V80) and lercanidipine 10 mg/valsartan 160 mg (L10/V160) combinations with lercanidipine 10 mg (L10) monotherapy. At screening, hypertensive patients, whose diastolic blood pressure (DBP) was >90 mm Hg after 4 weeks with L10, were randomized to 3 groups of L10, L10/V80, and L10/V160. The primary end point was the change in the mean sitting DBP from baseline (week 0) after 8 weeks of therapy. Patients who were randomly assigned to L10/V160 and whose mean DBP was still ≥ 90 mm Hg in part 1 were enrolled to the up-titration extension study with lercanidipine 20 mg/valsartan 160 mg (L20/V160) (part 2). FINDINGS: Of 772 patients screened, 497 were randomized to 3 groups (166 in the L10 group, 168 in the L10/V80 group, and 163 in the L10/V160 group). Mean (SD) age was 55 (9.9) years, and male patients comprised 69%. The mean (SD) baseline systolic blood pressure (SBP)/DBP were 148.4 (15.1)/94.3 (9.5) mm Hg. No significant differences were found between groups in baseline characteristics except the percentages of previous history of antihypertensive medication. The primary end points, the changes of mean (SD) DBP at week 8 from the baseline were -2.0 (8.8) mm Hg in the L10 group, -6.7 (8.5) mm Hg in L10/V80 group, and -8.1 (8.4) mm Hg in L10/V160 group. The adjusted mean difference between the combination groups and the L10 monotherapy group was -4.6 mm Hg (95% CI, -6.5 to -2.6; P < 0.001) in the L10/V80 group and -5.9 mm Hg (95% CI, -7.9 to -4.0, P < 0.001) in the L10/V160 group, which had significantly greater efficacy in BP lowering. A total of 74 patients were enrolled in the part 2 extension study. Changes of mean (SD) DBP and SBP from week 8 to week 12 and week 16 were -5.6 (7.9)/-8.0 (12.0) mm Hg and -5.5 (7.0)/-8.5 (11.3) mm Hg, respectively. For evaluation of the safety profile, the frequencies of adverse events between groups were also not significantly different. The most frequently reported adverse events were headache (6 cases, 20.7%) in the L10 group, dizziness (8 cases, 16.3%) in L10/V80 group, and nasopharyngitis (3 cases, 9.4%) in L10/V160 group, and the incidences of adverse events were not different between groups. IMPLICATIONS: Treatment of L10/V80 or L10/V160 combination therapy resulted in significantly greater BP lowering compared with L10 monotherapy. Moreover, the L20/V160 high dose combination had additional BP lowering effect compared with nonresponders with the L10/V160 combination. ClinicalTrials.gov: NCT01928628.

Randomized clinical trial to assess the effectiveness of remote patient monitoring and physician care in reducing office blood pressure.

The effectiveness of remote patient monitoring and physician care for the treatment of hypertension has not been demonstrated in a randomized clinical trial. The objective of this study was to evaluate the effectiveness of remote patient monitoring with or without remote physician care in reducing office blood pressure in patients with hypertension. A total of 374 hypertensive patients over 20 years of age were randomized into the following three groups: group (1) control, the patients received usual clinical care with home BP monitoring; group (2) the patients were remotely monitored and received office follow-up; and group (3) the patients received remote monitoring without physician office care using the remote monitoring device. For each group, in-office follow-up care was scheduled every 8 weeks for 24 weeks. The primary end point was the difference in sitting SBP at the 24-week follow-up. No difference between the three groups was observed in the primary end point (adjusted mean sitting SBP was as follows: group 1: -8.9±15.5 mm Hg, group 2: -11.3±15.9 mm Hg, group 3: -11.6±19.8 mm Hg, (NS). Significant differences in achieving the target BP at the 24th week of follow-up were observed between groups 1 and 2. The subjects over 55-years old had a significant decrease in the adjusted mean sitting SBP in groups 2 and 3 compared with that of the control group. Remote monitoring alone or remote monitoring coupled with remote physician care was as efficacious as the usual office care for reducing blood pressure with comparable safety and efficacy in hypertensive patients.