Hypertension-Mediated Organ Damage and Long-term Cardiovascular Outcomes in Asian Hypertensive Patients without Prior Cardiovascular Disease

Background@#Hypertension-mediated organ damage (HMOD), comprising structural and functional changes in arteries or end organs, is a marker of cardiovascular (CV) disease.However, there are limited data on evaluation of risk of CV disease regarding HMOD, especially in Asians. We sought to investigate the association between CV events and HMOD, and we tried to determine the most important diagnostic marker among the component of HMOD for prevention of mortality and CV events in treated Korean hypertensive patients. @*Methods@#From January 2008 to December 2010, a total of 35,000 hypertensive Vietnamese War veterans who consecutively visited our hospital for medical check-up were reviewed, and 6,158 patients without established CV disease were enrolled. The patients were divided into two groups as follows: HMOD group (n = 766) and non-HMOD group (n = 5,392). The primary outcome was all-cause death. @*Results@#Median age was 63.3 years (interquartile range [IQR], 61.4–65.4), and median follow-up was 6.6 years (IQR, 5.9–7.2). Patients with old age, diabetes, and chronic kidney disease were more prevalent in the HMOD group than in the non-HMOD group (all P < 0.05).The lipid profiles were not significantly different between the two groups. Nephropathy was the most prevalent (54.7%) organ damage in the HMOD group. The 6-year incidence of all-cause death was higher in the HMOD group than in the non-HMOD group (22.5% vs.9.0%; adjusted hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.01–2.00; P = 0.04). The incidence of cardiac death, ischemic heart disease, and ischemic and hemorrhagic stroke were also significantly higher in the HMOD group than in the non-HMOD group (P < 0.05, respectively). In multivariate analysis, proteinuria (adjusted HR, 2.21; 95% CI, 1.52–3.20; P < 0.001) was the most powerful independent risk factor to predict all-cause death among components of HMOD. As the degree of proteinuria increased, the rate of all-cause death also increased (long-rank P < 0.001). @*Conclusion@#HMOD was associated with increased risk of mortality and CV events.Proteinuria was the most powerful independent risk factor for all-cause death, and the degree of proteinuria and mortality rate were proportional. Our data suggest that monitoring of the proteinuria is important to predict long-term CV events in hypertensive patients.

Hypertension-Mediated Organ Damage and Long-term Cardiovascular Outcomes in Asian Hypertensive Patients without Prior Cardiovascular Disease

Background@#Hypertension-mediated organ damage (HMOD), comprising structural and functional changes in arteries or end organs, is a marker of cardiovascular (CV) disease.However, there are limited data on evaluation of risk of CV disease regarding HMOD, especially in Asians. We sought to investigate the association between CV events and HMOD, and we tried to determine the most important diagnostic marker among the component of HMOD for prevention of mortality and CV events in treated Korean hypertensive patients. @*Methods@#From January 2008 to December 2010, a total of 35,000 hypertensive Vietnamese War veterans who consecutively visited our hospital for medical check-up were reviewed, and 6,158 patients without established CV disease were enrolled. The patients were divided into two groups as follows: HMOD group (n = 766) and non-HMOD group (n = 5,392). The primary outcome was all-cause death. @*Results@#Median age was 63.3 years (interquartile range [IQR], 61.4–65.4), and median follow-up was 6.6 years (IQR, 5.9–7.2). Patients with old age, diabetes, and chronic kidney disease were more prevalent in the HMOD group than in the non-HMOD group (all P < 0.05).The lipid profiles were not significantly different between the two groups. Nephropathy was the most prevalent (54.7%) organ damage in the HMOD group. The 6-year incidence of all-cause death was higher in the HMOD group than in the non-HMOD group (22.5% vs.9.0%; adjusted hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.01–2.00; P = 0.04). The incidence of cardiac death, ischemic heart disease, and ischemic and hemorrhagic stroke were also significantly higher in the HMOD group than in the non-HMOD group (P < 0.05, respectively). In multivariate analysis, proteinuria (adjusted HR, 2.21; 95% CI, 1.52–3.20; P < 0.001) was the most powerful independent risk factor to predict all-cause death among components of HMOD. As the degree of proteinuria increased, the rate of all-cause death also increased (long-rank P < 0.001). @*Conclusion@#HMOD was associated with increased risk of mortality and CV events.Proteinuria was the most powerful independent risk factor for all-cause death, and the degree of proteinuria and mortality rate were proportional. Our data suggest that monitoring of the proteinuria is important to predict long-term CV events in hypertensive patients.

Long-term Survival in Korean Elderly Patients with Symptomatic Severe Aortic Stenosis Who Refused Aortic Valve Replacement

BACKGROUND AND OBJECTIVES: Aortic valve replacement (AVR) is the treatment of choice in severe symptomatic aortic stenosis (AS) patients. However, a substantial number of elderly patients refuse AVR and treated medically. We investigated their long-term prognosis. METHODS: From January 2005 to December 2016, we analyzed elderly patients with severe symptomatic AS who refused to have AVR. RESULTS: After screening of total 534 patients, we analyzed total 180 severe symptomatic AS patients (78±7 years old, 96 males). Hypertension was the most common cardiovascular risk factor (72%) and the most common symptom was dyspnea (66%). Calculated aortic stenosis area was 0.73±0.20 cm2 and mean left ventricular ejection fraction (LVEF) was 57.8±12.2%. Total 102 patients died during follow-up period (39.1±31.0 months). One-, 3-, and 5-year all-cause mortality rate was 21.1±3.0%, 43.1±3.8%, and 56.5±4.2%, respectively. Of them, 87 died from cardiac causes, and 1-, 3-, and 5-year cardiac mortality rate was 18.0±2.9%, 38.2±3.8%, and 50.7±4.3%, respectively. Their all-cause mortality and cardiac mortality were significantly higher than those of controls. Univariate analysis showed that age, anemia, LVEF, and Log N-terminal pro B-type natriuretic peptide (NT-proBNP) were significant parameters in all-cause mortality (p < 0.001, p=0.001, p=0.039, and p=0.047, respectively) and in cardiac mortality (p < 0.001, p < 0.001, p=0.046, and p=0.026, respectively). Multivariate analysis showed that age and anemia were significant prognostic factors for cardiac and all-cause mortality. CONCLUSIONS: In elderly severe symptomatic AS patients who treated medically, their 1-, 3- and 5-year all-cause mortality rate was 21.1±3.0%, 43.1±3.8%, and 56.5±4.2%, respectively. Age and anemia were significant prognostic factors for cardiac and all-cause mortality.

Long-term Survival in Korean Elderly Patients with Symptomatic Severe Aortic Stenosis Who Refused Aortic Valve Replacement

BACKGROUND AND OBJECTIVES@#Aortic valve replacement (AVR) is the treatment of choice in severe symptomatic aortic stenosis (AS) patients. However, a substantial number of elderly patients refuse AVR and treated medically. We investigated their long-term prognosis.@*METHODS@#From January 2005 to December 2016, we analyzed elderly patients with severe symptomatic AS who refused to have AVR.@*RESULTS@#After screening of total 534 patients, we analyzed total 180 severe symptomatic AS patients (78±7 years old, 96 males). Hypertension was the most common cardiovascular risk factor (72%) and the most common symptom was dyspnea (66%). Calculated aortic stenosis area was 0.73±0.20 cm2 and mean left ventricular ejection fraction (LVEF) was 57.8±12.2%. Total 102 patients died during follow-up period (39.1±31.0 months). One-, 3-, and 5-year all-cause mortality rate was 21.1±3.0%, 43.1±3.8%, and 56.5±4.2%, respectively. Of them, 87 died from cardiac causes, and 1-, 3-, and 5-year cardiac mortality rate was 18.0±2.9%, 38.2±3.8%, and 50.7±4.3%, respectively. Their all-cause mortality and cardiac mortality were significantly higher than those of controls. Univariate analysis showed that age, anemia, LVEF, and Log N-terminal pro B-type natriuretic peptide (NT-proBNP) were significant parameters in all-cause mortality (p < 0.001, p=0.001, p=0.039, and p=0.047, respectively) and in cardiac mortality (p < 0.001, p < 0.001, p=0.046, and p=0.026, respectively). Multivariate analysis showed that age and anemia were significant prognostic factors for cardiac and all-cause mortality.@*CONCLUSIONS@#In elderly severe symptomatic AS patients who treated medically, their 1-, 3- and 5-year all-cause mortality rate was 21.1±3.0%, 43.1±3.8%, and 56.5±4.2%, respectively. Age and anemia were significant prognostic factors for cardiac and all-cause mortality.

Embolic Stroke of Undetermined Source Accompanied by Lipomatous Hypertrophy of Interatrial Septum

No abstract available.

Left Ventricular Metastasis From Renal Cell Carcinoma Causing Left Ventricular Outflow Tract Obstruction

Most cases of cardiac metastasis from renal cell carcinoma (RCC) involve the vena cava or right atrium. Left ventricular metastases from RCC without involving the vena cava or right atrium are extremely rare. Herein we report a case of RCC with left ventricular metastasis causing left ventricular outflow obstruction (LVOT).

Non-Ischemic Cardiomyopathy Attributed to Adult Myotonic Dystrophy

In patients with myotonic dystrophy (MD), impairment of the conduction system is a common and progressive finding. However, only a few cases of MD with cardiomyopathy have been reported. Herein we report a case of MD with progressive non-ischemic cardiomyopathy and severe electrocardiographic abnormalities.

Carotid Sinus Syncope in an Elderly Patient With Unexplained Syncope

Carotid sinus syndrome is the most commonly reported cause of falls and syncope in elderly adults. However, it has been rarely reported in Koreans, and the reason of this ethnic difference is unknown. We report here on an Korean unusual case of carotid sinus syncope and this was induced by carotid sinus massage.

Infective Endocarditis with Isolated Double Chambers of the Right Ventricle during Adulthood

Isolated double chambers of the right ventricle (DCRV) are a rare variant of congenital heart disease. We report here on a case of right-sided infective endocarditis with isolated DCRV that presented in adulthood.

Thrombolysis in the Obstructed Prosthetic Tricuspid Valve: Importance of the Site of Prosthetic Valve and the Patient's Adherence with Anticoagulation Therapy

A prosthetic valve thrombus that occludes the blood flow or interferes with the valvular function is a rare, but life-threatening complication after prosthetic valve replacement. The patient's adherence with taking his anticoagulant medication is most critical. However, as seen in this presentation, the location of the prosthetic valve at the supra coronary sinus site may also be important. For the patient in this study, the blood flow and the speed of the flow through the valve were significantly reduced because the flow from the coronary sinus bypassed the prosthetic valve. This particular location of the prosthetic valve may be one of the risk factors that caused the thrombus. The right-sided prosthetic valve thrombus was successfully treated by thrombolysis with using urokinase, and there was no evidence of pulmonary embolism.

Spontaneous Closure of Iatrogenic Coronary Artery Fistula to Left Ventricle After Septal Myectomy for Hypertrophic Obstructive Cardiomyopathy

Cases of iatrogenic coronary artery fistulas draining into the left ventricle after surgical myectomy for hypertrophic obstructive cardiomyopathy have been published as sporadic reports. However, its management scheme and prognosis are not clear because of the low incidence. A 46-yr-old woman was hospitalized for evaluation of chest pain and shortness of breath for 3 months. Transthoracic echocardiographic examination showed typical hypertrophic obstructive cardiomyopathy with a peak pressure gradient of 71 mmHg across the left ventricular outflow tract. The patient underwent surgical septal myectomy. Postoperative color Doppler imaging revealed a diastolic blood flow from the interventricular septal myocardium to the left ventricular cavity, i.e. iatrogenic coronary artery fistula to the left ventricle. Ten days later, the fistula closed spontaneously which was diagnosed by transthoracic echocardiography and confirmed by coronary angiography.

hVEGF121 transfection and animal model for in vivo angiogenesis / 대한내과학회지

BACKGROUND: This study was designed to prove the superiority of ACP vector containing ITR, and to establish animal model quantifying angiogenesis in vivo. METHODS: hVEGF121, therapeutic gene, was inserted to various vectors (pcDNA3.1, pcDNA 3.2, pActin, pDesm, pACP vector), and these vectors were transfected to various cells using FuGENE6. We cultured for 48hrs, and then quantified amounts of hVEGF121 of supernatants by ELISA. The long-term transfection was assessed for 14 days. Optimal condition of transfection was evaluated by change of the ratio of DNA to FuGENE6, amount of DNA, and confluence of cells. ACP-hVEGF121 was transfected to C2C12 and these transfected C2C12 cells were mixed with Matrigel, and then injected to C3H mouse subcutaneously. Seven days later, hemoglobin assay and pathology of Matrigel were reviewed for angiogenesis. RESULTS: The level of hVEGF121 gene expression using pACP vector was significantly higher than those of others. In 2 weeks culture study, pACP vector showed the highest gene expression and produced VEGF until 2 weeks. The highest gene expression was obtained when the concentration of DNA was 7 microgram, the confluence was up to 80% and the ratio of DNA to FuGENE6 was 1:3. The hemoglobin level in Matrigel of VEGF group was significantly higher than the one of the control group, and active angiogenesis was noted in the VEGF group. CONCLUSIONS: pACP vector might be an efficient vector for angiogenic gene delivery, and animal model using Matrigel and transfected C2C12 cell could be a useful tool for quantitative angiogenesis assay.

Mechanical Circulatory Supports in the Treatment of Fulminant Myocarditis

BACKGROUND AND OBJECTIVES: Although fulminant myocarditis (FM) is known as a fatal disease, once patients have recovered, with aggressive pharmacologic therapy and/or mechanical circulatory supports (MCS), including intra-aortic pump, temporary ventricular assist device and percutaneous cardiopulmonary support, they may return to normal life with an excellent long-term prognosis. Elevated C-reactive protein, Creatinine phosphokinase and cytokine concentrations, decreased left ventricular ejection fraction and intraventricular conduction disturbances on admission may predict the progress of acute myocarditis to fulminant course. Early MCS helps save life and prevent multi-organ failures in patients with FM. The type of MCS may not affect the outcome of the clinical course when its complications are managed properly. Since other managements with immunoglobulin, antiviral agent or monoclonal antibody remain to be confirmed, aggressive hemodynamic support with MCS is the best management for patients with FM, who once recovered from the acute phase can return to normal life.

Risk Factors and Predictors for the Progression of Carotid Atherosclerotic Stenosis in Korean Adults

BACKGROUND AND OBJECTIVES: The goals of this study were to investigate the prevalence and risk factors of carotid atherosclerotic stenosis and also the predictors for the progression of carotid atheroslcerotic stenosis in Korean adults. SUBJECTS AND METHODS: Carotid ultrasonography was performed for 22,782 adults who volunteered for a routine health check-up. Carotid atheroslcerotic stenosis was defined as a finding of at least one lesion of an intima-media thickness greater than 1.2 mm with atherosclerotic plaque. Among the 22,782 people, 4,077 persons underwent follow-up carotid ultrasonography at an average interval of 27.6 months. The past medical history and information on the cardiovascular risk factors were obtained from standardized questionnaires and the subjects' blood chemistry. RESULTS: Carotid atheroslcerotic stenosis was detected in 1,875 adults (8.2%) and it was significantly associated with a history of stroke, hypertension, heart disease, hyperlipidemia, higher HbA1C, older age, a wider pulse pressure, lower HDL-cholesterol and a large amount of smoking (p<0.05). In the subjects without history of stroke (22,444 persons), those with more than 5 risk factors showed a higher prevalence (36.8%) of carotid atherosclerotic stenosis than those with a history of stroke (29.0%). The independent predictors of stenosis progression were older age, male gender, hypertension, a large amount of smoking, a high LDL cholesterol level, a low HDL-cholesterol level and a high fibrinogen level (p<0.05). CONCLUSION: Carotid ultrasonographic screening for a population with these risk factors will lead to a more efficient screening process and our identification of the predictors of disease progression may help to design therapeutic trials for preventing the progression of carotid atherosclerotic stenosis.

Vascular endothelial growth factor-induced angiogenic gene therapy in patients with peripheral artery disease

This phase 1 clinical trial tested the safety of intramuscular gene transfer by using naked plasmid DNA encoding the gene for VEGF, and analyzed the potential therapeutic benefits in patients with severe peripheral arterial disease (PAD). This study was an open-labeled, dose- escalating, single-center trial on nine male patients with severe debilitating PAD who had not responded to conventional therapy. Seven had Buerger's disease and two had arteriosclerosis obliterans. Plasmid DNA (pCK) containing human VEGF165 was given by eight intramuscular injections in and around the area in need of new blood vessels. The study evaluated three escalating total doses (2, 4, and 8 mg of pCK- VEGF165), with half of each total dose given four weeks apart. The follow-up duration was nine months. The gene injections were well tolerated without significant side effects or laboratory abnormalities related to gene transfer. Three patients showed transient edema in their extremities. Ischemic pain of the affected limb was relieved or improved markedly in six of seven patients. Ischemic ulcers healed or improved in four of six patients. The mean ankle-brachial index (ABI) improved significantly. Six of nine patients showed an increase in collateral vessels around the injection sites demonstrated by digital subtraction angiography. However, there was no relationship between the degree of ABI improvement and the dose given. Mean plasma levels of VEGF did not increase significantly. In conclusion, intramuscular injections of pCK- VEGF165 can be performed safely to induce therapeutic angiogenesis in patients with severe PAD.

Heart Rate Variability in Stable Angina Patients without History of Myocardial Infarction

BACKGROUND AND OBJECTIVES: Heart rate variability(HRV) reflects the autonomic integration of heart. There were many reports that HRV in patients with myocardial infarction or heart failure is an independent prognostic factor to predict fatal arrhythmia and sudden cardiac death. But, the role of HRV is still controversial in stable angina patients without history of myocardial infarction. In this study, we tried to compare HRV indices between stable angina patients and normal subjects. MATERIALS AND METHODS: Twenty-one stable anginal patients without history of myocardial infarction (mean age : 57 +/- 2 years) and twenty-one relatively healthy persons without history of coronary heart disease (mean age : 53 +/- 2 years) were included in the study and underwent 24-hour ambulatory ECG monitoring. In patients group, all underwent coronary angiography after 24-hour ambulatory ECG monitoring. HRV was analyzed over the whole 24 hours, using time and frequency domain parameters, according to time phases and coronary angiographic severity. RESULTS: There were no significant differences in age, sex and cardiovascular risk factors, except hypertension (p=.001) between two groups. HRV indices such as rMSSD, pNN50, LF, HF, LFnorm and HFnorm were significantly decreased (p<0.05) in patients group. But the angiographic severity of coronary arteries did not show any significant effect on the HRV indices in patients group. CONCLUSIONS: We observed significantly reduced HRV indices in patients with stable angina without history of myocardial infarction.

Dose-dependent Effect of Benidipine in Patients with mild moderate Hypertension

BACKGROUND AND OBJECTIVES: This study was designed to evaluate the appropriate dose and dose-dependent effect of benidipine hydrochloride, a Ca+ +/- channel blocker, in patients with mild-moderate essential hypertension. Material and MethodsBenidipine was administered in 2 mg, 4 mg and 8 mg once daily with 1 month interval in 41 hypertensive patients with diastolic blood pressure over 90 mmHg and systolic blood pressure from 140 to 210 mmHg. Blood pressure, heart rate, subjective symptoms and adverse effects were checked every 4 weeks after benidipine administration. Laboratory examinations were performed before and after benidipine administration. RESULTS: The dose-dependent, antihypertensive effect of benidipine was evaluated in 41 patients. The blood pressure significantly reduced from 166+/-15 mmHg/103+/-7 mmHg to 13815 mmHg/88+/-11 mmHg at 12 weeks administration of benidipine and overall effective rate was 95%. The systolic and diastolic blood pressure was reduced significantly in proportion to dose of benidipine (p<0.0001). Antihypertensive effect was prominent at 4mg of benidipine. The heart rate was not affected by benidipine. No significant laboratory changes were observed. CONCLUSION: Benidipine has a dose-dependent effect in the treatment of mild-moderate hypertension, and the dosage to be needed may be 4mg or more for sufficient antihypertensive effect.

Genetic relatedness of Vancomycin-Resistant Enterococci Isolated from Clinical Specimens / 감염

BACKGROUND: Vancomycin-resistant enterococci (VRE) infection has become one of the important nosocomial infections in the United States. Recently, increasing number of patients with VRE infection have been reported in Korea. We performed this study to investigate the clinical manifestations, genetic relatedness and mechanism of transmission of VRE in our hospital. METHODS: We retrospectively reviewed the medical records of patients with VRE which were isolated from clinical specimens in Samsung Medical Center from July 1997 through September 1997. The minimal inhibitory concentrations (MIC, microgram/mL) of vancomycin and teicoplanin were determined by the agar dilution method. As for VRE isolated, PCR and pulsed-field gel electrophoresis (PFGE) for molecular epidemiologic analysis were performed. RESULTS: During the study period, 5 strains of VRE were isolated from clinical specimens. All of 5 strains belonged to VanA phenotypically and genotypically. Among the five strains, one was E. faecalis and four were E. faecium. Four strains of E. faecium showed the same PFGE pattern. CONCLUSION: This study demonstrated the unexpectedly high rate of VRE isolates during relatively short-term period. Four out of 5 strains of VRE had the same PFGE patterns, which suggested the possibility of dissemination of one clone. To prevent the emergence and spread of VRE, practical guidelines including restriction of vancomycin usage and surveillance are warranted.

Association of Angiotensin-Converting Enzyme Gene Polymorphism and Angiotensin-Converting Enzyme Activity in Korean patients with Coronary Artery Disease

BACKGROUND: Insertion/Deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene has been postulated as a risk factor for coronary artery disease. However, controversies exist whether deletion polymorphism in the ACE gene and/or high levels of ACE activity may be a risk factor for coronary artery disease (CAD). We investigated the association of the I/D polymorphism of the ACE gene and serum ACE activity in Korean patients with CAD. METHODS: Study subjects were 629 patients who underwent coronary angiography. CAD group (n=77) was subdivided according to either clinical manifestation or the number of diseased vessels on angiography. The control group comprised 152 patients who did not have a significant coronary lesion. Low risk group (n=5) was defined as subjects with age <55 years, a body mass index (BMI) <26 kg/m2 and a plasma ApoB <125 mg/dl. RESULTS: 1) The genotype and allele frequencies of ACE gene polymorphism were not different between control (DD:DI:II=.20:0.48:0.32, D:I=.44:0.56) and CAD group (DD:DI:II=.18:0.46:0.36, D:I=.41:0.59). 2) When the CAD group was subdivided into stable angina (SA) and acute coronary syndrome (ACS) group, neither ACE genotype nor allele frequencies differed between the SA and ACS group. 3) There was no significant association between the ACE polymorphism and the severity of CAD, as assessed by the number of diseased coronary vessels. 4) A significant difference in serum ACE activity was apparent among ACE genotypes in both controls and CAD subjects. Serum ACE activity in individuals with the DD genotype was significantly greater than that in individuals with DI or II genotypes. 5) There was no difference in serum ACE activity between controls and the CAD subjects of all genotypes or of the same genotype. 6) There was no association between the ACE polymorphism or serum AC activity and CAD in the low risk group. CONCLUSIONS: We have shown that neither the ACE I/D polymorphism nor serum ACE activity act as an independent risk factor in the development of CAD in Korean. This result indicates that the gene polymorphism and variation in serum ACE activity are not risk factors for CAD in this population.

Minimal Change Disease and Focal Segmental Glomerulosclerosis in Identical Twin Brothers / 대한신장학회잡지

The simultaneous occurrence of primary glomerulonephritis in identical twins has been rarely reported previously. It has suggested that genetic factors may play an important role in the pathogenesis of primary glomerulonephritis. We describe a pair of 17-year-old identical twin brothers with asymptomatic proteinuria, one with histologically proven minimal change disease and the other with focal segmental glomerulosclerosis. HLA typing in twin brothers revealed an identical phenotype consisting of A25, A33, B44, B54, Cwl, Cw7, DR7 and DRB1. To our knowledge, this is the first case of glomerulonephritis in identical twins in Korea.