Clinical development and trial operations in COVID-19 era

no abstract available.

Safety and efficacy of fimasartan with essential hypertension patients in real world clinical practice: data from a post marketing surveillance in Korea

The safety and efficacy of fimasartan have been evaluated through post-marketing surveillance in real world clinical practice. The multi-center, prospective, open-label and non-interventional study. A total of 3,945 patients (3,729 patients for safety assessment and 3,473 patients for efficacy assessment) were screened in patients with essential hypertension in 89 study centers from 9 September 2010 through 8 September 2016. Among the total patients, 2,893 patients (77.6%) were administered fimasartan for 24 weeks or longer and were classified as ‘patients with long-term follow-up’, and the additional safety and efficacy analysis were performed. The improvement was defined as systolic blood pressure (SBP) controlled to ≤ 140 mmHg or decreased SBP differences ≥ 20 mmHg after treatment or diastolic blood pressure (DBP) controlled to ≤ 90 mmHg or decreased DBP differences ≥ 10 mmHg after treatment. Adverse drug reactions (ADRs) were reported in 3.8% patients; dizziness, and hypotension were the most frequently reported ADRs in total patients. The results of patients with long-term follow-up were comparable with total patients. The overall improvement rate in all efficacy assessment at the last visit was 87.1% (3,025/3,473 patients). The overall improvement rate of the patients with long-term follow-up was 88.9%. Fimasartan was well tolerated, with no new safety concerns identified and an effective treatment in the real world clinical practice for Korean patients with hypertension.

Use of Oral Antibiotics in Elderly Gastrointestinal Patients

Oral antibiotics are usually prescribed for geriatric patients for the treatment of infectious diarrhea and management of hepatic encephalopathy. But oral antibiotics have systemic adverse events, so many doctors face the issue of choosing the right antibiotics. Rifaximin, an intestinal topical antibiotic that exhibits a wide antimicrobial activity against both aerobic and anaerobic bacteria, has various indications, such as acute bacterial diarrhea caused by Gram positive and negative bacteria, traveler's diarrhea, small intestine bacterial overgrowth, prevention of infection after gastrointestinal surgery, and the management of hepatic encephalopathy with hyperammoniemia. But there are few clinical trial data on the geriatric population. Hence we reviewed the clinical study data that included geriatric patients in their clinical trials. Based on our literature searches, only one clinical trial on acute bacterial diarrhea was performed only for geriatric patients. Other clinical trials for various indications usually recruited elderly patients, but the number of elderly patients was limited. However, generally speaking, rifaximin showed good efficacy and safety profile in acute bacterial diarrhea caused by Gram positive and negative bacteria, traveler's diarrhea, small intestine bacterial overgrowth, prevention of infection after gastrointestinal surgery, and the management of hepatic encephalopathy with hyperammoniemia; and there were no differences in efficacy and safety, compared to the nongeriatric population. We concluded that rifaximin is a good therapeutic option for various gastrointestinal indications, and shows good efficacy and an excellent safety profile, compared to other oral agents. For more evidence on the geriatric population, we propose clinical trials on elderly patients for each indication.

Myocardial injury occurs earlier than myocardial inflammation in acute experimental viral myocarditis

Endomyocardial biopsy often fails to show myocardial inflammation for patients with clinically suspected myocarditis. The serum isoforms of troponin T (cTnT) level is a very sensitive marker of myocardial injury and it is elevated even in the absence of myocardial inflammation. We investigated the correlations for myocardial injury, virus titers and inflammation in acute viral infection. Using the murine coxsackievirus group B3 (CVB3) myocarditis model, the histopathologic findings and virus titers in mouse hearts were compared with the serum cTnT levels measured by ELISA at various time points. Viable virus titers in the hearts peaked at 3 days after infection (8.22+/-0.13 log10 PFU/100 mg of heart); they decreased at day 7 and no viable virus was detected from day 14. Myocardial inflammation was minimal at day 3, peaked at day 7 and markedly decreased at day 14. The individual serum TnT levels were significantly increased at day 3 (7.37+/-1.46 ng/ml), persisted to day 7 (0.73+/-0.08 ng/ml), and normalized at day 14. Serum cTnT levels were correlatable with virus titers in the heart (r=0.744, P <0.01), but the serum cTnT levels were not correlated with the degrees of inflammation. Using the less myocarditic strain of CVB3, similar relationships were observed between the changes for the serum cTnT levels and the heart virus titers. During the course of viral infection, myocardial injury precedes the pathologic evidence of inflammation, and the elevated cTnT levels provide evidence of myocardial injury even in the absence of any histologic findings of myocarditis.

Treatment of Hypercholesterolemia in Elderly Patients; From the Viewpoint of Statins

No abstract available.

Incidence of eNOS gene mutationin Korean patients with coronary artery spasm

BACKGROUND: Coronary artery spasm is an important mechanism in producing myocardial ischemia. But the exact mechanism of the spasm is not well known. We investigated the mutation of endothelial nitric oxide synthase (eNOS) that produce nitric oxide and relationship between eNOS mutation and coronary artery spasm. MATERIALS AND METHODS: Blood were drawn from the patients with angiographically proven coronary artery spasm and normal controls. DNA were extracted and polymerase chain reaction and restriction analysis with Nae I were performed to find T-786--

Incidence of eNOS gene mutationin Korean patients with coronary artery spasm

BACKGROUND: Coronary artery spasm is an important mechanism in producing myocardial ischemia. But the exact mechanism of the spasm is not well known. We investigated the mutation of endothelial nitric oxide synthase (eNOS) that produce nitric oxide and relationship between eNOS mutation and coronary artery spasm. MATERIALS AND METHODS: Blood were drawn from the patients with angiographically proven coronary artery spasm and normal controls. DNA were extracted and polymerase chain reaction and restriction analysis with Nae I were performed to find T-786--

Screening of the Presence of Hepatitis B and C Virus Infections in Terminally Failing Human Hearts

In order to evaluate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in terminally failing hearts, we screened the explanted hearts of transplantation recipients for the presence of HBV DNA and HCV RNA. DNA and RNA extractions were taken from explanted failing hearts (N=7) and normal hearts (N=). Polymerase chain reaction (PCR) and in situ PCR of HBV or reverse transcription-polymerase chain reaction (RT-PCR) and in situ RT-PCR of HCV were performed. The positivity of HBV in failing hearts was 63% (17/27) and it was 50% (3/6) in normal hearts in PCR. There was no significant difference in the positivity of HBV DNA between failing and normal hearts. The positivity of HCV in failing hearts was 18.5% (5/27) and it was 16.7% (1/6) in normal hearts in nested RT-PCR. There was no significant difference in the positivity of HCV RNA between failing and normal hearts. HCV was very rarely observed in explanted terminally failing hearts and HBV was frequently found in both explanted failing hearts and normal hearts. We concluded that these viruses have little direct causal relationship with the development of heart failure.

A Case of Dilated Cardiomyopathy Associated with Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease is a systemic disorder with cystic manifestations in the kidneys, liver, pancreas, seminal vesicles, and meninges; its noncystic manifestations affect mostly the vascular, cardiac, and connective tissues. Cardiovascular abnormalities, including mitral and aortic valvular prolapse and regurgitation and annuloaortic ectasia, have been considered important extrarenal manifestations of autosomal dominant polycystic kidney disease. But there were no reports with dilated cardiomyopathy in patients with polycystic kidney disease yet. We have experienced a case of dilated cardiomyopathy that is associated by autosomal dominant polycystic kidney disease in 40 year old male patient. Abdominal ultrasonography revealed variable sizes of multiple cysts in both kidneys and echocardiography showed the marked dilatation of left ventricle and severely depressed left ventricular systolic function (ejection fraction=19%). He was treated with diuretics intravenously and orally. Then dyspnea and abdominal distension was improved. This is the first case of dilated cardiomyopathy with autosomal dominant polycystic disease in Korea.

Thrombolytic Therapy Followed by Myotomy of Gastrocnemius Muscle in Popliteal Artery Entrapment Syndrome

Popliteal artery entrapment syndrome (PAES) is rare, but increasingly reported in the literature as a cause of lower limb arterial impairment. Management of a patient with PAES depends on the clinical pictures. Currently, myotomy of the medial head of gastrocnemius muscle with interposition grafting or bypass of diseased popliteal artery has been widely used in cases with a demaged or occluded artery. But, other less extensive therapeutic approaches were also performed instead of it. We present a case of type II popliteal entrapment syndrome in an 36-year-old male. Presenting symptom was exercise- induced pain in his right calf since one month ago. Arteriography showed occlusion in short segment of right popliteal artery and intact distal run-off arteries. After overnight urokinase thrombolysis, residual focal stenosis and medial deviation of popliteal artery were observed. CT scan showed abnormal structure between right popliteal artery and popliteal vein, so, diagnosis was established. After myotomy of the medial head of gastrocnemius muscle, the symptom resolved completely. Post-operative duplex scan showed normal blood flow, even in active plantar flexion of the foot. In our case, early diagnosis and combined approach of endovascular thrombolytic therapy followed by surgical release of popliteal artery enabled to avoid direct vascular surgery such as bypass or interposition grafting with resolution of ischemic symptoms. This thrombolytic therapy does not obviate surgery but may permit a less extensive procedure to be performed in PAES.

A Case of Histologically Confirmed Coxsackiviral Myocarditis Supported by a Left Ventricular Assist Device

Enteroviruses are the most common agents of myocarditis and have been implicates in the pathogenesis of dilated cardiopmyopathy. There are still discrepancies in the association of enterovirus and myocardial disease, partially due to lack of data on detection of virus antigen or viral culture in the tissue. For the treatment of fulminant myocarditis, aggressive hemodynamic support is warranted because of its excellent long-term prognosis. This 16 year-old girl was admitted because of anterior chest pain for a day. She had flu-like symptoms such as fever, sore throat and cough at 2 weeks ago. Electrocardiogram showed sinus tachycardia and ST segment elevations in lead II, III, aVF and V1-V4. Troponin T was positive and creatinine phosphokinase was elevated (1323 IU/L) at emergency room. On emergency echocardiogram, inferior wall motion was decreased and the ejection fraction (EF) was 70%. Coronary angiogram showed no thrombus and no significant stenosis in coronary artery, and spasm was not induced with ergonovine. Conventional treatment for congestive heart failure with digoxin (0.25 mg daily) and furosemide (20 mg t.i.d) was started under the impression of myocarditis. On the first hospital day, pulmonary edema and signs of shock were developed. The whole left ventricular(LV) wall motion were markedly decreased and EF was less than 20% on echocardiogram. Despite of intra-aortic balloon pump (IABP) for 4 hours, shock and pulmonary edema was progressed. Mechanical circulatory support was started with left ventricular assist device (LVAD, Bio-pump, Medtronic Bio-Medicus, USA). At the time of operation, central venous pressure was 24cmH20, systolic blood pressure was 75mmHg, left atrium(LA) and LV was dilated and the whole wall of LV showed almost akinesia , and LA appendage was biopsied. After 126 hours of LVAD, LV wall motion was restored and EF was 79% on echocardiogram. LVAD was removed 10 days after operation and she was discharged on 23 days of hospitalization without any heart failure symptoms. Immunohistochemistry of LA showed enteroviral VP1 capsid protein (primary antibody; NoVo Castra Laboratory, UK) over the entire LA wall. Her serum neutralized coxsackievirus B3 (CVB3, H3 variant of Woodruff strain) in neutralization test using horse anti-CVB3 (Nancy strain) antibody (ATCC, V030-501-560) as a positive control. The titer of neutralization Ab in her serum of 21 days increased more than 4 times than that of 2 days.

A Case Report of Infective Endocarditis that Caused by Gemella Haemolysans in a Patient with Ventricular Septal Defect

Infective endocarditis is the infectious disease that produces vegetation on endocardium. Acute bacterial endocarditis is most frequently caused by Staphylococcus aureus, occurs on a normal heart valve, and subacute endocarditis usually caused by Streptococcus viridans occurs on damaged valves. Gemella haemolysans are gram-positive cocci that is placed in the family Streptococcaceae. As opportunistic pathogen, Gemella haemolysans are able to cause severe localized and generalized infections and it is known that this organism very rarely causes infective endocarditis. The paucity of reports concerning Gemella haemolysans is probably related to the difficulties associated with their identification. Several laboratory tests to prevent misinterpretation of this organism are now suggested. We have experienced a case of infective endocarditis that is caused by Gemella haemolysans in 37 year old male patient with ventricular septal defect. Gemella haemolysans were detected by blood culture and he was treated with intravenous vancomycin with gentamicin and ceftriaxone, and also underwent cardiac surgery. This is the first case of Gemella haemolysans endocarditis of ventricular septal defect in Korea.

The Frequency Distribution of Apolipoprotein E Genetic Polymorphism and Relationship of Apolipoprotein E Genetic Polymorphism with Development of Coronary Artery Disease in Patients with Familial Hypercholesterolemia / 대한내과학회지

OBJECTIVES: Apolipoprotein E genetic polymorphism was screened in subjects with FH to determine the genetic effects of Apo E polymorphism on basal cholesterol levels, severity of coronary atherosclerosis and response to lipid lowering therapy using HMG CoA reductase inhibitor. METHODS: Total 45 unrelated patients with FH (M:F= 24:21, 48.0/11.5yr.) were included in this study. Apolipoprotein E genetic polymorphism was screened. Clinical parameters were checked. Change of lipid profile to lovastatin,; 20mg/d (n=19), 40mg/d (n=12), and of Achilles tendon thickness were analysed. RESULTS: 1) Genotype frequencies of E2/3, 3/3, 4/3 were 8.9, 60.0, 31.1% respectively, and allele frequencies of epsilon2, epsilon3, and epsilon4 were 0.044, 0.800, and 0.155 respectively.2) Presence and degree of coronary atherosclerosis, the thickness of Achilles tendon and lipid levels were not significantly different by apolipoprotein E genotype.3) On multivariate study, age, triglyceride and cholesterol /high density lipoprotein were significantly related to presence of coroanry atherosclerosis. 4) Percent reduction of LDL-cholesterol by lovastatin was significantly low in subjects having E4/3 genotype than those having E3/3 genotype (p=0.05; 40mg/d), and the percent reduction of Achilles tendon thickness was significantly low in subjects having E4/3 genotype than those having E3/3 genotype (p=0.037; 20mg/d). CONCLUSION: The distribution of apolipoprotein E genotype in patients with familial hypercholesterolemia was not significantly different with that in normal subjects. But apolipoprotein E polymorphism may affect the reduction of LDL-cholesterol and Achilles tendon xanthoma with medication of HMG CoA reductase inhibitor in patients with familial hypercholesterolemia.

Long-term Follow-up of the Patients with Permanent Antibradycardia Pacemaker

BACKGROUND: Antibradycardia pacemaker is one of the treatment modalities for bradyarrhythmia. We present the clinical results of 440 implantations of permanent pacemaker between August 1984 and December 1997 at Department of Internal Medicine in Seoul National University Hospital. METHOD: We investigated the indication of permanent pacing, the pacing modes, the complications of permanent pacing, and the chronic pacing threshold. RESULT: The study was comprised of 440 patients (M/F : 179/261, mean age : 59+/-12 years, 58+/-14 years, respectively). Indications of the primary pacemaker implantations were sinus node dysfun-ction in 53% and atrioventricular conduction disorders in 47%. Twelve percent of total pacemaker procedures were pulse-generator replacements. Pacing modes were VVI in 59.1%, VVIR in 10.2%, DDD in 30.2%, and others in 0.5%. Complications developed in 21 cases (4.8%) during long-term follow-up. They included 8 cases of pacing failure due to increased pacing threshold, 2 cases of early power depletion, 2 cases of lead dislodgement, 6 cases of lead fracture, 3 cases of skin erosion, 3 cases of hematoma, 3 cases of infection, and 1 case of skeletal muscle stimulation. Chronic pacing thresholds at pacing width of 0.5 msec were 1.9+/-0.4 V for the epicardial ventricular leads (n=11), 1.3+/-0.5 V for the endocardial ventricular leads (n=36), and 1.1+/-0.2 V for the atrial leads (n=4) after 7 to 10 years of implantation. CONCLUSION: Sinus node dysfunction was the more common indication than atrioventricular block for the antibradycardia pacemaker implantation. Long-term follow-up of the pacemaker patients would be very useful to detect the pacing system abnormalities and to maximize the battery longevity by adjustment of pacing output according to the level of chronic pacing threshold.

Long-term Follow-up of the Patients with Permanent Antibradycardia Pacemaker

BACKGROUND: Antibradycardia pacemaker is one of the treatment modalities for bradyarrhythmia. We present the clinical results of 440 implantations of permanent pacemaker between August 1984 and December 1997 at Department of Internal Medicine in Seoul National University Hospital. METHOD: We investigated the indication of permanent pacing, the pacing modes, the complications of permanent pacing, and the chronic pacing threshold. RESULT: The study was comprised of 440 patients (M/F : 179/261, mean age : 59+/-12 years, 58+/-14 years, respectively). Indications of the primary pacemaker implantations were sinus node dysfun-ction in 53% and atrioventricular conduction disorders in 47%. Twelve percent of total pacemaker procedures were pulse-generator replacements. Pacing modes were VVI in 59.1%, VVIR in 10.2%, DDD in 30.2%, and others in 0.5%. Complications developed in 21 cases (4.8%) during long-term follow-up. They included 8 cases of pacing failure due to increased pacing threshold, 2 cases of early power depletion, 2 cases of lead dislodgement, 6 cases of lead fracture, 3 cases of skin erosion, 3 cases of hematoma, 3 cases of infection, and 1 case of skeletal muscle stimulation. Chronic pacing thresholds at pacing width of 0.5 msec were 1.9+/-0.4 V for the epicardial ventricular leads (n=11), 1.3+/-0.5 V for the endocardial ventricular leads (n=36), and 1.1+/-0.2 V for the atrial leads (n=4) after 7 to 10 years of implantation. CONCLUSION: Sinus node dysfunction was the more common indication than atrioventricular block for the antibradycardia pacemaker implantation. Long-term follow-up of the pacemaker patients would be very useful to detect the pacing system abnormalities and to maximize the battery longevity by adjustment of pacing output according to the level of chronic pacing threshold.

4G/5G Polymorphism of Plasminogen Activator Inhibitor-1 Gene and Its Effects on Coronary Artery Disease

BACKGROUND: 4G allele of one base pair insertion/deletion polymorphism (4G/5G) at plasminogen activator inhibitor-1 (PAI-1) was associated with increased plasma activity of PAI-1. Increased plasma PAI-1 activity was associated with increase risk of coronary artery disease (CAD). However, there was a controversy whether 4G allele increases the risk of CAD. We investigated relationship between 4G/5G genetic polymorphism and CAD in Korean population. METHODS: We studied 453 patients-145 patients with normal coronary angiogram (NL), 106 with stable angina (SA), 104 with unstable angina (UA) and 98 with myocardial infarction (MI)-characterized by coronary angiography. RESULTS: 1) Korean had higher 4G allele frequency than Caucasian (4G:5G=0.60:0.40 in Korean). 2) There were no allele or gene frequency difference of 4G/5G polymorphism between CAD group and NL group (4G:5G=0.61:0.39 in CAD, 0.59:0.41 in NL, p=0.58). 3) 4G allele was not associated with increased risk of acute coronary syndrome (4G:5G=0.60:0.40 in SA, 0.59:0.41 in UA, and 0.57:0.43 in MI, p=0.84). 4) 4G allele had no influence on progression of coronary artherosclerosis (4G:5G=0.58:0.42 in single vessel disease, 0.58:0.42 in two vessel disease, and 0.56:0.44 in three vessel disease, p=0.82). 5) 4G was not an independent risk factor of CAD even after adjusted with other risk factors. CONCLUSION: In Korean, 4G/5G polymorphism of PAI-1 gene has no relationship with development, progression of coronary artery disease.

Antiatherogenic Effect of Naringin Independent of Lipid-Lowering Action in Hypercholesterolemic Rabbits

BACKGROUND: Naringin, one of the flavonoids in citrus fruit peels, is known to have antioxidant and hepatotonic effects in animal studies. We evaluated the effect of naringin on 1) blood lipid profiles, 2) regression of fatty streak of aorta, and 3) liver toxicity in diet-induced hypercholesterolemic rabbits. METHODS: New Zealand White Rabbits (2.0 - 2.5 Kg) were divided to three groups; group without treatment, group treated with 100 mg/kg/d or 500 mg/kg/d naringin, and group treated with 1 mg/kg/d or 20 mg/kg/d lovastatin. They were fed on 0.25% or 1.0% cholesterol-containing diet for 8 weeks and then sacrificed. Blood samples were collected for measurement of total cholesterol, HDL-cholesterol, triglyceride, serum GOT and GPT. Aortas and livers were harvested for evaluation of fatty streak and pathologic examination. RESULTS: 1)Feeding of 1% cholesterol diet for eight weeks significantly increased the cholesterol level upto 20 folds. Neither lovastatin nor naringin did lower these marked hypercholesterolemia. But both naringin (500 mg/kg/d) and lovastatin (1 mg/kg/d) significantly reduced the area of fatty streak by 75% and 58%, respectively. Naringin was more effective in inhibition of fat infiltration into liver than lovastatin which showed hepatotoxicity as increase of serum GPT level (p=0.01). 2)Feeding of 0.25% cholesterol diet for eight weeks significantly increased the cholesterol level upto 17 folds. Total cholesterol and triglyceride levels tended to decrease by treatment with naringin (500 mg/kg/d) and lovastatin (20 mg/kg/d), but this decreases were not statistically significant. However, areas of fatty streak significantly decreased by treatment with naringin and lovastatin by 64 and 82%, respectively (p<0.05). Microscopic analysis revealed that foam cell infiltration into intima was significantly reduced by naringin and lovastatin. In contrast to lovastatin, naringin significantly reduced the level of serum GPT (p<0.05). CONCLUSION: Like lovastatin, naringin has strong antiatherogenic action which may not be associated with its very mild lipid lowering action. In contrast to lovastatin, naringin does have hepatoprotective effect.

Permanent pacemaker implantation via coronary sinus

We report a case of successful ventricular pacing via the coronary sinus in a 34 year-old female patient admitted because of repetitive dizziness and syncope. She had rheumatic valvular disease with mitral valve replacement 14 years earlyer. and the mitral, aortic and tricuspid valves were subsequently replaced with prosthetic mechanical valves 4 years ago. Two years after the triple valve replacement, complete AV block developed with the symptoms of dizziness and syncope. A permanent pacemaker was implanted epicardially. Six months later the epicardial lead was replaced because of increased pacing threshold. A year later the epicardial lead had to be replaced because of increased threshold and capture failure to pace. To avoid further thoracotomy, a 'Medtronic 2188' electrode was implanted in the posterior left ventricular vein via the coronary sinus. Pacing threshold was 1.2 volt/0.4 msec. Five days later, the pacing threshold increased to 3.0 volt/0.4 msec. Prednisolone had been given for 10 months. The new system has been functioning well and the pacing threshold was 1.0 volt/0.4 msec at 11 months after implantation. Ventricular pacing via the coronary sinus can be an alternative to the epicardial pacemaker system in patient whose tricuspid valve have been replaced with mechanical prosthetic valve.

Permanent pacemaker implantation via coronary sinus

We report a case of successful ventricular pacing via the coronary sinus in a 34 year-old female patient admitted because of repetitive dizziness and syncope. She had rheumatic valvular disease with mitral valve replacement 14 years earlyer. and the mitral, aortic and tricuspid valves were subsequently replaced with prosthetic mechanical valves 4 years ago. Two years after the triple valve replacement, complete AV block developed with the symptoms of dizziness and syncope. A permanent pacemaker was implanted epicardially. Six months later the epicardial lead was replaced because of increased pacing threshold. A year later the epicardial lead had to be replaced because of increased threshold and capture failure to pace. To avoid further thoracotomy, a 'Medtronic 2188' electrode was implanted in the posterior left ventricular vein via the coronary sinus. Pacing threshold was 1.2 volt/0.4 msec. Five days later, the pacing threshold increased to 3.0 volt/0.4 msec. Prednisolone had been given for 10 months. The new system has been functioning well and the pacing threshold was 1.0 volt/0.4 msec at 11 months after implantation. Ventricular pacing via the coronary sinus can be an alternative to the epicardial pacemaker system in patient whose tricuspid valve have been replaced with mechanical prosthetic valve.

Screening of the Presence of Enterovirus and Cytomegalovirus Infections in Terminally Failing Human Hearts

BACKGROUND: In order to evaluate the prevalence of enterovirus and cytomegalovirus infections to terminally failing hearts, the presence of enteroviral RNA and cytomegaloviral DNA was screened in the explanted hearts of transplantation recipients. METHODS: RNA and DNA extractions were performed from explanted failing hearts (N=22) and normal hearts (N=5). Reverse transcription-polymerase chain reaction (RT-PCR) of enterovirus and polymerase chain reaction (PCR) of cytomegalovirus were performed. In situ RT-PCR and in situ PCR were performed with positive nucleic acids of viruses. RESULTS: The positivity of enterovirus in failing hearts was 4.4% (1/22) and 0% (0/5) in normal hearts in nested RT-PCR. There was no significant difference in positivity of enteroviral RNA between failing and normal hearts. Nuclei of myocardium was stained in dark-violet color with in situ RT-PCR. The positivity of cytomegalovirus in failing hearts was 45% (10/22) and 40% (2/5) in nested PCR. There was no significant difference in positivity of cytomegaloviral DNA between failing and normal hearts. Nuclei of myocardium was stained in dark-violet color with in situ PCR. Positive chambers of cytomegalovirus were in decreasing tendency according to increasing patient's age. CONCLUSION: Enterovirus was very rarely observed in explanted terminally failing hearts and cytomegalovirus was frequently found both in explanted failing hearts and normal. These viruses have little direct causal relationship with the development of heart failure.