Clinical Characteristics and Outcome of Immediate-Release Versus SLOW-Release Carvedilol in Heart Failure Patient (SLOW-HF): a Prospective Randomized, Open-Label, Multicenter Study.

PURPOSE: Carvedilol demonstrated therapeutic benefits in patients with heart failure and reduced ejection fraction (HFrEF). However, it had a short half-life time mandating twice a day administration. We investigated whether slow-release carvedilol (carvedilol-SR) is non-inferior to standard immediate-release carvedilol (carvedilol-IR) in terms of clinical efficacy in patients with HFrEF. METHODS: We randomly assigned patients with HFrEF to receive carvedilol-SR once a day or carvedilol-IR twice a day. The primary endpoint was the change in N-terminal pro B-natriuretic peptide (NT-proBNP) level from baseline to 6 months after randomization. The secondary outcomes were proportion of patients with NT-proBNP increment > 10% from baseline, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance. RESULTS: A total of 272 patients were randomized and treated (median follow-up time, 173 days). In each group of patients taking carvedilol-SR and those taking carvedilol-IR, clinical characteristics were well balanced. No patient died during follow-up, and there was no significant difference in the change of NT-proBNP level between two groups (-107.4 [-440.2-70.3] pg/mL vs. -91.2 [-504.1-37.4] pg/mL, p = 0.101). Change of systolic and diastolic blood pressure, control rate and response rate of blood pressure, readmission rate, and drug compliance rate were also similar. For safety outcomes, the occurrence of adverse reactions did not differ between carvedilol-SR group and carvedilol-IR group. CONCLUSION: Carvedilol-SR once a day was non-inferior to carvedilol-IR twice a day in patients with HFrEF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03209180 (registration date: July 6, 2017).

PRE-OPerative ECHOcardiograhy for prevention of cardiovascular events after non-cardiac surgery in intermediate- and high-risk patients: protocol for a low-interventional, mixed-cohort prospective study design (PREOP-ECHO).

BACKGROUND: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. METHODS: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. DISCUSSION: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. TRIAL REGISTRATION: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

Neutrophil-Lymphocyte Ratio as a Predictor of Venous Thromboembolism after Total Knee Replacement.

Venous thromboembolism (VTE) is a potentially serious complication after total knee replacement (TKR), and recent guideline recommends thromboprophylaxis for VTE after TKR. The neutrophil-lymphocyte ratio (NLR) has emerged as a simple and new prognostic biomarker for several cardiovascular diseases. This study was performed to investigate the precise incidence of postoperative VTE and the role of NLR for predicting VTE in patients receiving thromboprophylaxis after TKR. We retrospectively enrolled 264 patients undergoing TKR who underwent routine screening enhanced pulmonary artery and lower extremity venography computed tomography (CT) scan within 7 postoperative days. Biochemical tests were performed within 2 weeks prior to surgery, and the NLR was defined as the absolute neutrophil count in peripheral blood divided by lymphocyte count. All patients received thromboprophylaxis with enoxaparin postoperatively. Of 264 patients, 102 (38.6%) were diagnosed with deep vein thrombosis (DVT) or pulmonary embolism on CT scan. Preoperative NLR was significantly higher in patients with postoperative VTE compared with that in patients without VTE (2.57 ± 1.59 vs. 2.11 ± 1.10, p = 0.011). Receiver operating characteristic curve analysis showed that a preoperative NLR of 1.90 was the best cutoff value for the prediction of postoperative VTE (sensitivity 57.8%, specificity 55.6%, and area under curve 0.589). In the multivariate analysis, a preoperative NLR ≥1.90 was a sole independent predictor of postoperative VTE (odds ratio: 1.95, 95% computed tomography: 1.16-3.31, p = 0.013). The present study shows a higher incidence of VTE (38.6%) after TKR in patients receiving thromboprophylaxis than that reported in previous studies. Furthermore, preoperative NLR was significantly higher in patients with postoperative VTE, and a high preoperative NLR (≥1.90) was an independent predictor of VTE after TKR. NLR measurement may be a simple and useful method for the prediction of VTE in patients undergoing TKR.

Efficacy and Tolerability of Telmisartan/Amlodipine and Rosuvastatin Coadministration in Hypertensive Patients with Hyperlipidemia: A Phase III, Multicenter, Randomized, Double-blind Study.

PURPOSE: Dyslipidemia and hypertension increase the risk for cardiovascular disease. Combination therapy improves patient compliance. This study was conducted to compare the efficacy and tolerability of the combination therapies telmisartan/amlodipine + rosuvastatin, telmisartan/amlodipine, and telmisartan + rosuvastatin in patients with hypercholesterolemia and hypertension. METHODS: In this Phase III, multicenter, 8-week randomized, double-blind study, participants with hypertension and dyslipidemia (defined as a sitting systolic blood pressure [sitSBP] of ≥140 mm Hg, a low-density lipoprotein-cholesterol [LDL-C] level of ≤250 mg/dL, and a triglyceride level of ≤400 mg/dL) were screened. After a 4-week washout/run-in period involving therapeutic lifestyle changes and telmisartan 80 mg once a day, eligible patients had a sitSBP of ≥140 mm Hg and met the LDL-C level criteria according to the National Cholesterol Education Program Adult Treatment Panel III cardiovascular disease risk category. Patients were randomly assigned to 1 of 3 groups: (1) telmisartan/amlodipine 80/10 mg + rosuvastatin 20 mg (TAR group); (2) telmisartan/amlodipine 80/10 mg (TA group); or (3) telmisartan 80 mg + rosuvastatin 20 mg (TR group). The primary efficacy end points were the percentage changes from baseline in LDL-C in the TAR and TA groups and the mean changes in sitSBP in the TAR and TR groups at week 8 compared to baseline. Continuous variables were compared using the unpaired t test or the Wilcoxon rank sum model, and categorical variables were compared using the χ2 or Fisher exact test. Tolerability was assessed based on adverse events found on physical examination including vital sign measurements, laboratory evaluations, and 12-lead ECG. FINDINGS: A total of 134 patients were enrolled. The least squares mean percentage changes in LDL-C at 8 weeks after administration of the drug compared to baseline were -51.9% (3.0%) in the TAR group and -3.2% (2.9%) in the TA group (P < 0.001). At 8 weeks after baseline, the least squares mean (SE) changes sitSBP were -28.3 (2.4) mm Hg in the TAR group and -10.7 (2.1) mm Hg in the TR group (P < 0.001). The prevalence rates of treatment-emergent adverse events were 15.0%, 25.0%, and 12.2% in the TAR, TA, and TR groups, respectively; those of adverse drug reactions were 15.0%, 22.7%, and 10.2%. None of the differences in rates were significant among 3 groups. IMPLICATIONS: Triple therapy with TAR can be an effective treatment in patients with dyslipidemia and hypertension. The TAR combination has value for hypertensive patients with hyperlipidemia in terms of convenience, tolerability, and efficacy. ClinicalTrials.gov identifier: NCT03566316.

Assessment of clinical effect and treatment quality of immediate-release carvedilol-IR versus SLOW release carvedilol-SR in Heart Failure patients (SLOW-HF): study protocol for a randomized controlled trial.

BACKGROUND: Carvedilol is a non-selective, third-generation beta-blocker and is one of the cornerstones for treatment for patients with heart failure and reduced ejection fraction (HFrEF). However, due to its short half-life, immediate-release carvedilol (IR) needs to be prescribed twice a day. Recently, slow-release carvedilol (SR) has been developed. The aim of this study is to evaluate whether carvedilol-SR is non-inferior to standard carvedilol-IR in terms of its clinical efficacy in patients with HFrEF. METHODS/DESIGN: Patients with stable HFrEF will be randomly assigned in a 1:1 ratio to the carvedilol-SR group (160 patients) and the carvedilol-IR group (160 patients). Patients aged ≥ 20 years, with a left ventricular ejection fraction ≤ 40%, N-terminal pro B-natriuretic peptide (NT-proBNP) ≥ 125 pg/ml or BNP ≥ 35 pg/ml, who are clinically stable and have no evidence of congestion or volume retention, will be eligible. After randomization, patients will be followed up for 6 months. The primary endpoint is the change in NT-proBNP level from baseline to the study end. The secondary endpoints include the proportion of patients with NT-proBNP increment > 10% from baseline, composite of all-cause mortality and readmission, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance. DISCUSSIONS: The SLOW-HF trial is a prospective, randomized, open-label, phase-IV, multicenter study to evaluate the therapeutic efficacy of carvedilol-SR compared to carvedilol-IR in HFrEF patients. If carvedilol-SR proves to be non-inferior to carvedilol-IR, a once-daily prescription of carvedilol may be recommended for patients with HFrEF. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03209180 . Registered on 6 July 2017.

A Randomized, Multicenter, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and the Tolerability of a Triple Combination of Amlodipine/Losartan/Rosuvastatin in Patients With Comorbid Essential Hypertension and Hyperlipidemia.

PURPOSE: The objective of this study was to evaluate the efficacy and tolerability of a triple combination of amlodipine/losartan/rosuvastatin in patients with hypertension and hypercholesterolemia. METHODS: A randomized, multicenter, double-blind, placebo-controlled study was conducted. Eligible patients with hypertension and a sitting diastolic blood pressure (SiDBP) of >90 mm Hg and LDL-C levels <250mg/dL were screened. After a 4-week run-in period with therapeutic lifestyle changes and losartan potassium 100mg once daily, patients who met both blood pressure criteria (80 mm Hg ≤ SiDBP < 110 mm Hg) and the LDL-C level criteria (defined in the National Cholesterol Education Program Adult Treatment Panel III cardiovascular risk categories) were randomized to 1 of 3 groups and treated once daily for 8 weeks: losartan potassium 100mg + rosuvastatin 20mg treatment (L/R 100/20) group, amlodipine camsylate 5mg + losartan potassium 100mg treatment (A/L 5/100) group, and amlodipine 5mg+ losartan potassium 100mg + rosuvastatin 20mg (A/L/R 5/100/20) group. The primary efficacy variables were the percent change in LDL-C in the A/L/R 5/100/20 and A/L 5/100 groups and the mean change of SiDBP in the A/L/R 5/100/20 and L/R 100/20 groups after 8 weeks of treatment, relative to baseline values. FINDINGS: A total of 146 patients were enrolled and the demographic characteristics were similar among the 3 treatment groups. After 8 weeks of treatment, the mean (SD) percent change in LDL-C was significantly greater in the A/L/R group than in the A/L group (-48.40% [2.77%] vs -6.70% [3.00%]; P < 0.0001). Moreover, the mean change in SiDBP was significantly greater in the A/L/R group than in the L/R group (-9.75 [0.92] mm Hg vs -1.73 [1.03] mm Hg; P < 0.0001). SiDBP and LDL-C reductions in the A/L/R group were comparable to reductions in the A/L and L/R groups, respectively. Ten adverse events were reported in 7 patients (4.83%), and 1 patient from the A/L group (0.69%) experienced 2 adverse drug reactions (tachycardia and face edema), which were mild and resolved without specific treatment. There were no clinically significant tolerability issues during the treatment period. IMPLICATIONS: Triple combination therapy with amlodipine/losartan/rosuvastatin can be an effective therapeutic strategy in patients with hypertension combined with dyslipidemia. These findings will form the foundation of the future development of a single-pill triple combination. ClinicalTrials.gov identifier: NCT02899455.

Systematic Review of Treatment for Trapped Thrombus in Patent Foramen Ovale.

BACKGROUND AND OBJECTIVES: Trapped thrombus in patent foramen ovale (PFO) is a rare complication of pulmonary embolism that may lead to tragic clinical events. The aim of this study was to identify the optimal treatment for different clinical situations in patients with trapped thrombus in a PFO by conducting a literature review. SUBJECTS AND METHODS: A PubMed database search was conducted from 1991 through 2015, and 194 patients (185 articles) with trapped thrombus in a PFO were identified. Patient characteristics, paradoxical embolic events, and factors affecting 60-day mortality were analyzed retrospectively. RESULTS: Among all patients, 112 (57.7%) were treated with surgery, 28 with thrombolysis, and 54 with anticoagulation alone. Dyspnea (79.4%), chest pain (33.0%), and syncope (17.5%) were the most common presenting symptoms. Pretreatment embolism was found in 37.6% of cases, and stroke (24.7%) was the most common event. Surgery was associated with fewer post-treatment embolic events than were other treatment options (p=0.044). In the multivariate analysis, initial shock or arrest, and thrombolysis were independent predictors of 60-day mortality. Thrombolysis was related with higher 60-day mortality compared with surgery in patients who had no initial shock or arrest. CONCLUSION: This systematic review showed that surgery was associated with a lower overall incidence of post-treatment embolic events and a lower 60-day mortality in patients with trapped thrombus in a PFO. In patients without initial shock or arrest, thrombolysis was related with a higher 60-day mortality compared with surgery.

Korean Guidelines for Diagnosis and Management of Chronic Heart Failure.

The prevalence of heart failure (HF) is skyrocketing worldwide, and is closely associated with serious morbidity and mortality. In particular, HF is one of the main causes for the hospitalization and mortality in elderly individuals. Korea also has these epidemiological problems, and HF is responsible for huge socioeconomic burden. However, there has been no clinical guideline for HF management in Korea. The present guideline provides the first set of practical guidelines for the management of HF in Korea and was developed using the guideline adaptation process while including as many data from Korean studies as possible. The scope of the present guideline includes the definition, diagnosis, and treatment of chronic HF with reduced/preserved ejection fraction of various etiologies.

Myocardial contrast echocardiography for the detection of coronary artery disease in patients with global hypokinesis admitted for first-onset acute heart failure: pilot study.

BACKGROUND: The non-invasive differentiation of ischemic and nonischemic acute heart failure (AHF) not resulting from acute myocardial infarction is difficult and has therapeutic and prognostic implications. The aim of this study was to assess whether resting myocardial contrast echocardiography (MCE) can detect coronary artery disease (CAD) in patients with decreased left ventricular (LV) systolic function and global hypokinesis presenting with AHF. METHODS: Twenty-one consecutive patients underwent low-power real-time MCE based on color-coded pulse inversion Doppler. Standard apical LV views were acquired during contrast IV infusion of Definity®. Following transient microbubbles destruction, the contrast replenishment rate (ß), reflecting myocardial blood flow velocity, was derived by plotting signal intensity vs. time and fitting data to the exponential function: y (t) = A (1 - e(-ß(t-t0))) + C. RESULTS: Of the 21 (mean age 56.6 ± 13.6 years) patients, 5 (23.8%) demonstrated flow-limiting CAD (> 70% of luminal diameter narrowing). The mean ± standard deviation of LV ejection fraction was 29.6 ± 8.6%. Quantitative MCE analysis was feasible in 258 of 378 segments (68.3%). There were no significant difference in "ß" and "Aß" in patients without and with CAD (0.48 ± 0.27 vs. 0.45 ± 0.25, p = 0.453 for ß and 2.99 ± 2.23 vs. 3.68 ± 3.13, p = 0.059 for Aß, respectively). No contrast-related side effects were reported. CONCLUSION: Resting quantitative MCE analysis in patients with AHF was feasible, however, the parameters did not aid in detecting of CAD.

Echocardiographic serial changes of hypertensive cardiomyopathy with severely reduced ejection fraction: comparison with idiopathic dilated cardiomyopathy.

BACKGROUND: Hypertensive cardiomyopathy with reduced ejection fraction (HTCMREF) is known as an important cause of reversible cardiomyopathy, but its serial changes on echocardiography is yet to be elucidated. HYPOTHESIS: HTCMREF on serial echocardiography has distinctive points as compared to idiopathic dilated cardiomyopathy (idDCM). METHODS: We retrospectively studied 18 hypertensive patients (mean age, 63 ± 13 years, 56% women) admitted with severe left ventricular (LV) systolic dysfunction and heart failure. We compared clinical characteristics and echocardiographic parameters at admission and follow-up between the patients with HTCMREF and 18 age-matched patients with idDCM. Left ventricular mass (LVM) and left atrial volume (LAV) were calculated by a formula using echocardiographic measurement. RESULTS: In HTCMREF, left ventricular ejection fraction improved to 52.3 ± 8.8% during a mean follow-up of 574 days. In HTCMREF, initial left atrial diameter was greater than in idDCM (43.6 ± 5.8 mm vs 38.9 ± 6.3, p = 0.027). At follow-up, LAV index decreased in HTCMREF (from 31.9 ± 8.3 mL/m(2) to 21.0 ± 8.9, P < 0.001), as opposed to a significant increase in idDCM (from 28.5 ± 10.9 mL/m(2) to 31.9 ± 8.3, P < 0.001). There was no significant difference in initial LVM index between the 2 groups, but only in HTCMREF did LVM index decrease significantly (151.4 ± 42.1 g/m(2) from 192.2 ± 43.7, P < 0.01) at follow-up. In HTCMREF, LV wall on M-mode was thicker than in idDCM. CONCLUSIONS: Hypertensive cardiomyopathy with severe LV systolic dysfunction might be characterized by eccentric left ventricular hypertrophy and enlarged left atrium in comparison with idDCM.

Normalization of negative T-wave on electrocardiography and right ventricular dysfunction in patients with an acute pulmonary embolism.

BACKGROUND/AIMS: Right ventricular dysfunction (RVD) is associated with poor prognosis in patients with acute pulmonary embolism (APE). Echocardiography and computed tomography (CT)-angiography may be difficult to perform in a serial follow up, unlike electrocardiography (ECG). Many ECG findings specific for APE have been reported, and many studies have found that negative T-waves (NTW) in precordial leads are most frequently observed in patients with APE. We analyzed serial changes in precordial NTW to detect RVD and predict the recovery of RVD in patients with APE. METHODS: We examined 81 consecutive patients diagnosed with APE using CT-angiography or echocardiography. ECG, transthoracic echocardiography, and laboratory tests were performed within 24 hours of admission, and daily ECG follow-up was performed. Precordial NTWs were defined by the new development of pointed and symmetrical inverted T-waves in at least three leads. Recovery of NTW was defined as flattening or upright inverted T-waves in more than two leads. RESULTS: Of the 81 patients with APE, 52 (64%) had RVD according to echocardiography. Among the patients with RVD, 33 (63%) showed precordial NTW. The multivariate logistic regression analysis revealed that NTW was the strongest independent predictor for RVD (odds ratio, 22.8; 95% confidence interval, 2.4 to 221.4; p = 0.007). Time to normalization of NTW was associated with improvement of RVD on echocardiography (r = 0.84, p < 0.01). CONCLUSIONS: Precordial NTW was a reliable finding to identify RVD in patients with APE. Improvements in RVD can be predicted by normalizing precordial NTW.

Utility of B-type natriuretic Peptide for predicting perioperative cardiovascular events in patients without history of cardiovascular disease undergoing major non-cardiac surgery.

BACKGROUND AND OBJECTIVES: Patients without previous history of cardiac disease can be regarded as low-risk when undergoing major non-cardiac surgery. The aim of this study was to examine whether preoperative B-type natriuretic peptide (BNP) level predicted postoperative cardiac events in these patients. SUBJECTS AND METHODS: Preoperative BNP level was measured in 163 patients whose risk was considered low according to the Revised Cardiac Risk Index. Postoperative cardiac events, including death during hospitalization, myocardial injury, arrhythmia, cerebrovascular accidents and congestive heart failure were assessed. RESULTS: Postoperative cardiac events occurred in 8 patients (4.9%). Preoperative BNP levels were significantly higher among patients who experienced postoperative cardiac events, compared to those who did not (130.6±148.8 vs. 57.9±70.8 pg/mL, p=0.009). CONCLUSION: Preoperative BNP level may provide prognostic information in low-risk patients undergoing major non-cardiac surgery.

Acute Myocardial Infarction by Right Coronary Artery Occlusion Presenting as Precordial ST Elevation on Electrocardiography.

It is rare to observe ST-segment elevation in only the anterior leads and not the inferior leads during right coronary artery occlusion. We describe a case with acute myocardial infarction (MI) by right coronary artery occlusion who developed ST-segment elevation only in the precordial leads V1 to V3.

The correlation between left ventricular failure and right ventricular systolic dysfunction occurring in thyrotoxicosis.

BACKGROUND AND OBJECTIVES: Heart failure rarely occurs in patients with thyrotoxicosis (6%), with half of the cases having left ventricular dysfunction (LVD). Although a few studies reported isolated right heart failure in thyrotoxicosis, there has been no evaluation of relationship between LVD and right ventricular dysfunction (RVD). SUBJECTS AND METHODS: We enrolled 12 patients (mean age: 51+/-11 years, 9 females) diagnosed as having thyrotoxicosis with heart failure and LVD {left ventricular ejection fraction (LVEF) <40%}, and divided them into two groups {Group I with RVD defined as tricuspid annular plane excursion (TAPSE) less than 15 mm and Group II without RVD}. Clinical features, laboratory variables, and echocardiographic parameters were compared between two groups. RESULTS: RVD was found in 6 (50%) patients. On admission, there were no significant differences between the two groups in clinical features, laboratory variables, or echocardiographic parameters including atrial fibrillation {6 vs. 5, not significant (NS)}, heart rate (149+/-38 vs. 148+/-32/min, NS), LVEF (36.7+/-9.5 vs. 35.1+/-6.3%, NS), or the tricuspid regurgitation peak pressure gradient (TRPPG, 30.9+/-2.0 vs. 36.3+/-9.3 mmHg, NS). After antithyroid treatment, all achieved an euthyroid state and both ventricular functions were recovered. All data, including the recovery time of LVEF and the change of heart rate between two groups, displayed no significant differences. CONCLUSION: In half of patients, RVD was combined with thyrotoxicosis-associated LVD. There were no differences in clinical factors or hemodynamic parameters between patients with and without RVD. This suggests that RVD is not secondary to thyrotoxicosis-associated LVD.

A multicenter, eight-week treatment, single-step titration, open-label study assessing the percentage of Korean dyslipidemic patients achieving LDL cholesterol target with atorvastatin starting doses of 10 mg, 20 mg and 40 mg.

BACKGROUND: This study was designed to evaluate the safety and efficacy of algorithm-based atorvastatin therapy initiated at different starting doses of 10, 20, and 40 mg in Korean dyslipidemic patients. METHODS: Five hundred seventy-four patients were screened, and 425 were enrolled (low risk, n = 29; intermediate risk, n = 45; high risk, n = 351). The starting dose depended on a patient's cardiovascular risk and LDL-cholesterol (LDL-C) levels. RESULTS: Of the patients, 253 (59.5%), 63 (14.8%) and 109 (25.6%) patients were assigned at baseline to 10 mg, 20 mg and 40 mg atorvastatin, respectively. 390 patients (91.8%) completed the study, and 35 discontinued prematurely. No patient in the low or intermediate risk groups was titrated to 80 mg at Week 4, whereas, 26 in the high risk group were. 81.9% of patients achieved their LDL-C target at Week 4, which was sustained through to Week 8 (86.0%). 89.1% of patients who were not titrated achieved their LDL-C target at Week 8, and 82.1% of patients who were titrated 1 step up achieved their LDL-C target at Week 8. Overall, about 40% reduction in LDL-C, non-HDL-C levels, and LDL-C/HDL-C ratio was observed during the follow-up. Triglyceride was reduced by approximately 10% by Week 8. HDL cholesterol was slightly increased over 8 weeks (2.6%). Atorvastatin was well tolerated at all dose levels. CONCLUSIONS: Patient-tailored statin therapy according to an individual's risk category and LDL-C levels was safe and effective with a quick achievement of LDL-C target in Korean dyslipidemic patients.

Impact of chronotropic effect of cilostazol after acute myocardial infarction: insights from change in left ventricular volume and function.

BACKGROUND: Cilostazol, a phosphodiesterase inhibitor, is an antiplatelet agent with positive chronotropic effect, the impact of which on left ventricular (LV) volume and function in acute myocardial infarction (AMI) was evaluated in the present study. METHODS AND RESULTS: In 56 patients with AMI treated with primary coronary stenting, serial echocardiographic studies within 24 h and at 6 months were performed. Patients received a conventional antiplatelet regimen either without cilostazol (group 1, n=29) or with cilostazol (group 2, n=27). At 6 months, the difference in the change in heart rate between group 1 and group 2 was statistically significant (9.9 beats/min; p=0.04). However, changes in LV end-systolic volume (LVESV) (7.1+/-8.2 vs 10.0+/-21.7 ml, p=0.60), LV ejection fraction (EF) (8.2+/-9.9 vs 9.0+/-12.6%, p=0.85) and the ratio of early mitral inflow velocity to the mitral annular velocity (E/E') (0.6+/-3.7 vs -1.7+/-3.2) were not different between the 2 groups. Cardiac event rate was similar between the 2 groups. On multivariate regression analyses, cilostazol therapy had no significant influence on the changes in LVESV, LVEF or E/E'. CONCLUSIONS: In this study, the addition of cilostazol on conventional drug therapy had no adverse influence on LV remodeling or LV function after AMI.

Ultrasonic biophysical measurements in the normal human fetus for optimal design of the monolithic fetal pacemaker.

Ultrasound measurements, including xiphoid-to-pericardial distance and deployment angle, were made on human fetuses as a function of gestational age for the purpose of assessing the likelihood of 3 failure modes of a monolithic fetal pacemaker, including primary positioning failure due to device length and secondary dislodgement failure due to somatic growth. The small variation of the measurements over the gestational age range relevant to device implantation for the major indications of the device (for complete heart block complicated by hydrops and for bradycardia risk after fetal surgery or intrauterine intervention) predicts a small likelihood of these failure modes.

The monolithic fetal pacemaker: prototype lead design for closed thorax deployment.

Prenatal sudden cardiac death and hydrops fetalis are often due to complete heart block. However, no pacing modality exists for intrauterine application for fetal bradycardia. A prototype lead for a novel fetal pacemaker has been developed and used in a direct pacing model. It has been demonstrated that the lead can be safely and successfully deployed using a hypochondriac and transdiaphragmatic or subxiphoid approach. Pacing with ventricular capture was evident with the widening of QRS duration from 50.2 +/- 9.8 to 95.1 +/- 12.8 ms (P = 0.0001). Further studies by echocardiogram revealed an increase in the pulse with pacing, confirming pacing. This study documents proof-of-concept for closed thorax over-the-wire deployment of a novel lead design applicable to fetal pacing. By combining the lead design with microcircuitry and a small power source, it is possible to create a monolithic fetal pacemaker system capable of being deployed in utero.

Effects of the calcineurin dependent signaling pathway inhibition by cyclosporin A on early and late cardiac remodeling following myocardial infarction.

BACKGROUND: The calcineurin-mediated signaling pathway has been implicated as one of the crucial pathways in cardiac hypertrophy. However, the role of calcineurin pathway on cardiac remodeling after myocardial infarction (MI) has not been well defined. METHODS: Infarcted rats (n = 45) were randomized into calcineurin inhibitor, cyclosporin A (CsA) or vehicle groups, 3 days after MI and treated for 2 weeks (early post-MI cardiac remodeling stage), or randomized 17 days after MI and treated for 2 weeks (late remodeling stage). RESULTS: Calcineurin pathway inhibition during the early cardiac remodeling stage attenuated the myocardial hypertrophy after MI (P < 0.05). However, left ventricular dimensions were further increased and fractional shortening deteriorated with calcineurin inhibition during this stage (P < 0.05, each). During late remodeling stage, CsA treatment did not affect myocardial hypertrophy and cardiac dilation following MI. CONCLUSION: Our results strongly support the hypothesis that calcineurin pathway mediates compensatory myocardial hypertrophy during the early remodeling stage after MI. However, the calcineurin pathway does not seem to affect the late remodeling after MI.