Hong-Won Shin

Trends in Oral Anticoagulation Therapy Among Korean Patients With Atrial Fibrillation: The KORean Atrial Fibrillation Investigation

Background and Objectives Anticoagulation with vitamin K antagonists (VKAs) such as warfarin provides effective stroke prophylaxis in patients with atrial fibrillation (AF). We conducted a large multicenter survey of Korean patients with AF to determine trends in VKA use. Subjects and Methods Eligible patients were adults with AF that had been prescribed VKAs. Medical records from a total of 5616 patients {mean age 63.6±12.2 years, male 3150 (56.1%)} in 27 hospitals from Jan. 2001 to Oct. 2007 were reviewed. Results The mean international normalized ratio (INR) was 2.04±0.64, and mean dosage of VKA was 3.66±1.50 mg. Individuals in their sixties (1852 patients) accounted for about one third of patients studied. As patients grew older, INR increased and VKA dosage decreased. The dosage of VKA in male patients was larger than that in females for all ages. A total of 2146 (42.4%) patients had an INR of 2-3, and less than 40% patients in their sixties had an INR within optimal range. The dosage of oral anticoagulant for optimal INR level was 3.71 mg. Conclusion In this study, less than half of the Korean patients with AF on VKA reached the therapeutic range of INR. Mean dosage of VKA was 3.66±1.50 mg, and the dosage of oral anticoagulant for optimal INR level was 3.71 mg, which decreased with age.

Combination of Uric Acid and NT-ProBNP: A More Useful Prognostic Marker for Short-Term Clinical Outcomes in Patients with Acute Heart Failure

Background/Aims In patients with heart failure (HF), N-terminal prohormone brain natriuretic peptide (NT-ProBNP) is a standard prognostic indicator. In addition, uric acid (UA) was recently established as a prognostic marker for poor outcome in chronic HF. The aim of this study was to determine the combined role of UA and NT-ProBNP as prognostic markers for short-term outcomes of acute heart failure (AHF). Methods The levels of UA and NT-ProBNP were determined in 193 patients (age, 69 ± 13 years; 76 males) admitted with AHF. Patients were followed for 3 months and evaluated for cardiovascular events, defined as cardiac death and/or readmission for HF. Results Of the 193 patients, 23 (11.9%) died and 20 (10.4%) were readmitted for HF during the 3-month follow-up period. Based on univariate analysis, possible predictors of short-term cardiovascular events were high levels of UA and NT-ProBNP, low creatinine clearance, no angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and old age. Multivariate Cox hazard analysis showed that UA levels were independently associated with increased incidence of cardiovascular events (hazard ratio, 1.115; 95% confidence interval, 1.006 to 1.235; p = 0.037). Kaplan-Meier survival analysis revealed that patients with UA levels > 8.0 mg/dL and NT-ProBNP levels > 4,210 pg/mL were at highest risk for cardiac events (p = 0.01). Conclusions The combination of UA and NT-ProBNP levels appears to be more useful than either marker alone as an independent predictor for short-term outcomes in patients with AHF.

Intracardiac foreign body caused by cement leakage as a late complication of percutaneous vertebroplasty.

To the Editor, Percutaneous vertebroplasty (PVP) is a simple, convenient, and minimally invasive procedure for the management of back pain and spinal instability associated with osteoporotic compression fractures and other osteolytic spinal lesions [1]. Although very rare, cement leakage into the spinal canal or the vascular system has been reported as a troublesome late complication. In this report, we present a case of a foreign body in the heart revealed by transthoracic echocardiography and removed by open heart surgery. A 75-year-old female patient was admitted for evaluation of progressively worsening dyspnea for 2 months. However, there was no medical history of dyspnea and intermittent palpitation, because she had been fairly active without diff iculty 2 months prior to admission. On examination, her vital signs were blood pressure 110/70 mmHg, heart rate 148 beats/min, respiratory rate 20 breaths/min, and body temperature 37.3℃. Physical examinations were unremarkable. Electrocardiography revealed atrial flutter with rapid ventricular response, whereas it had shown normal sinus rhythm 4 years prior to admission. Chest radiography showed an increased cardiothoracic ratio with mild pulmonary vascular congestion; in addition, radiographic high density was noted in the third lumbar vertebral body (Fig. 1A). With respect to her past medical history, she had undergone PVP at the level of the third and fourth lumbar spine 5 years previously for chronic back pain and had been asymptomatic since that time. Figure 1 (A) Chest radiography shows the high density (arrows) of the 3rd lumbar vertebral body. (B) Coronary view in the chest computed tomographic scan shows linear high attenuating material (arrow heads) in the right atrium. Transthoracic echocardiography exhibited severe global decreased wall motion abnormalities of the left ventricle (LV), poor systolic function (ejection fraction [EF], 27%), with rapid heart rate (136 beats/min) and normal LV end-diastolic dimension of 4.6 cm and dilated left atrium (LA) of 4.6 cm. However, moderate-to-severe tricuspid insufficiency (pulmonary artery systolic pressure [PASP], 57 mmHg) was noted, while there were no evidence of LA thrombus or pericardial effusion. Moreover, a calcified linear structure (approximately 6 cm), which was also conf irmed by chest computed tomography (CT) (Fig. 1B), was found in the right atrium (RA) and right ventricle (RV). It was anchored in the RA adjacent to the inferior vena cava opening, passed through the tricuspid valve, and reached around the posterior wall of the RV outflow tract (Fig. 2). As a result of malcoaptation of the tricuspid valve caused by the linear structure passing through the tricuspid opening, a laterally directed eccentric jet flow of moderate-to-severe tricuspid insufficiency was demonstrated. With regard to the increased pulmonary artery pressure, any pulmonary complications of foreign body embolism could not be found by chest CT. Figure 2 (A) In the subcostal view, the foreign body (arrow heads) is attached to right atrium (RA) near the opening site of inferior vena cava. (B) Parasternal short axis view reveals that the echogenic linear structure (arrow heads) in the RA passed through ... The patient had commenced diuretics with furosemide (increased to 80 mg daily) and β-blockers with carvedilol (up to 12.5 mg twice daily) for dyspnea and atrial flutter. The symptoms of chest discomfort and dyspnea seemed to be related at least in part to the foreign body in the heart. We considered the foreign body in the RA and RV to be a potential source of pulmonary thromboembolism or infarction in the near future and thus recommended surgical removal, even if the etiology of the clinical symptoms was not entirely correlated with the foreign body. Surgical findings revealed that the 6 cm long linear intracardiac foreign body was a calcified and fragile material (Fig. 3), and that it was attached to the confluence site of the inferior vena cava and RA, and reached to the RV. The foreign body was excised at its attachment, preserving the tricuspid valve. Figure 3 (A) Operation photograph showing a linear material (arrowheads) in the right ventricle and right atrium. (B) Photograph of gross specimens showing cement materials that were removed from right atrium and ventricle; foreign body was broken into two pieces. ... On follow-up echocardiography, systolic function was not much improved (EF 33%); however, the severity of tricuspid regurgitation was decreased from moderate to mild. The patient subsequently became free from dyspnea and chest discomfort, while atrial flutter remained. After discharge, she visited the outpatient clinic regularly for management of heart failure. PVP is an effective, minimally invasive procedure used mainly for the treatment of vertebral fractures in osteoporosis and metastasis. During the procedure, polymethylmethacrylate is injected into the lesion of the vertebral body, and organizes within a short time. Complications after PVP include bleeding at the puncture site, inaccurate needle placement, pain exacerbation, local infection, leakage of polymethylmethacrylate cement into the spinal canal or paravertebral tissues, perivertebral venous leakage, and pulmonary embolism [2]. There is always a risk of cement migration into the vena cava, which may result in pulmonary embolism. Vasconcelos et al. [3] have reported an incidence of 16.6% for minor passage of cement into perivertebral veins, including one case in which a minute amount of cement reached the inferior vena cava. Other cases have reported multiple cardiac perforations after PVP [4]. Usually, symptoms or signs of cement leakage complications occur during, immediately or within several months after the procedure. However, in the present case, the foreign body could not enter the pulmonary circulation because of the length and rigid nature of the material; otherwise, there would have been catastrophic complications. Thus, we speculated that the pathological process of heart failure progressed gradually, taking 5 years for the clinical manifestation of dyspnea to become apparent. As regards the cause of heart failure, there was a possibility of acute exacerbation of chronic heart failure, and some explanations seem possible. Other than the conventional risk factors, such as old age, hypertension and diabetes, the shortening of ejection time or diastolic relaxation time in rapid heart rate could cause heart failure, such as tachycardia-induced heart failure [5], as is frequently seen in patients with atrial flutter or fibrillation. Although the foreign body might have increased tricuspid insufficiency, it was not the only cause of the heart failure. In other words, we do not know the cause of the aggravation of dyspnea. However, in this case, the symptom improved after heart rate control. The foreign body could increase PASP and tricuspid insufficiency severity. High pulmonary artery pressure can be caused by left heart failure. The foreign body was not solely responsible for dyspnea and could not have been an immediate cause of dyspnea. When the cause of heart failure is unknown, the symptom may be attributed to tricuspid insufficiency exacerbated by a foreign body, although pharmacological treatments such as diuretics and digoxin are used in heart failure. A definite relationship between the foreign body and atrial flutter with tricuspid insufficiency leading to heart failure could not be demonstrated in the present case. Although the foreign body was found incidentally, it might have been the source of pulmonary thromboembolism, valvular heart disease, or cardiac perforation in the near future. Because of the jamming caused by the linear structure in the tricuspid valve, we assumed that the heart failure with atrial flutter in our patient could be partly attributed to the foreign body; this is supported by the patients clinical course after removal of the foreign body. Thus, given the deleterious effects of a foreign body on cardiovascular complications, surgical removal of the foreign body should be performed. Here, we report a foreign body in the RA and RV complicating PVP 5 years previously. In this case, we exerted effort to prevent complications arising due to the foreign body. It is important to consider the possibility of late manifestation of complications; a high index of suspicion is also required in patients who have a cardiac foreign body, especially those with a history of PVP.

Zotarolimus-eluting stent-induced hypersensitivity pneumonitis

To the Editor, Drug-eluting stents (DESs) have revolutionized the treatment of coronary artery disease, as shown by the significant reductions in rates of repeat revascularization and major adverse cardiac events in randomized studies; however, concerns have been raised about the safety of these stents in relation to the occurrence of stent thrombosis [1]. Another area of debate regarding DES safety is related to hypersensitivity. Almost all of the hypersensitivity reactions reported to date have been seen in association with the standard adjunct drug therapy used with stent implantation. Nevertheless, on occasion, components of a DES, such as the metal stent backbone, the polymer coating, or the eluted drug, have been associated with hypersensitivity reactions in other settings [2]. To our knowledge, zotarolimuseluting stent (ZES)-induced hypersensitivity pneumonitis has not been reported previously. Here, we report a case of hypersensitivity pneumonitis, which was proven by lung biopsy and computed tomography, after coronary stenting using a ZES. A 60-year-old man was admitted with resting chest pain. As a cardiovascular risk factor, he had a history of type 2 diabetes mellitus. He did not have any allergy history. Electrocardiography on admission showed T-wave inversion in the inferior leads. Diagnostic coronary angiography was performed due to his unstable clinical presentation. The results revealed significant stenosis in the mid-portion of the right coronary artery, and the patient underwent percutaneous coronary intervention. Aspirin (200 mg), clopidogrel (75 mg after a 300-mg loading dose), and carvedilol (12.5 mg) were prescribed for 2 days. Using standard angioplasty, a ZES (Endeavor, Medtronic, Santa Rosa, CA, USA) was implanted in the right coronary artery. There were no adverse events during the hospital stay. Thirteen days after the index procedure, the patient developed nonproductive cough, dyspnea, and malaise, and after 10 days with these symptoms, he returned to the hospital appearing acutely ill. On examination, he was febrile (39℃), had a respiratory rate of 22 breaths per minute, and had an oxygen saturation of 94.9% while breathing room air. Fine inspiratory crepitations were audible on both lower lung fields. Chest X-rays showed perihilar peribronchial nodular opacities and diffuse ground-glass opacities in both lung fields as compared with the pre-procedural chest X-ray findings (Fig. 1). A complete blood analysis revealed a white blood cell count of 9,770/mm3, an eosinophil count of 780/mm3, and a hemoglobin level of 12.1 g/dL. The immunoglobulin E level was 242.0 IU/mL, the erythrocyte sedimentation rate was 56 mm in the first hour, and the C-reactive protein level was elevated to 71.9 mg/L. Empiric antibiotic therapy consisting of cefoxitin and roxithromycin was initiated to cover for community-acquired pneumonia. The patient continued to have intermittent fever, dry cough, and moderate dyspnea. On high-resolution computed tomography, diffuse ground-glass opacity and centrilobular nodules were observed throughout both lungs (Fig. 2). Open lung biopsy was performed to determine the cause of pneumonitis in this case, and it revealed diffuse involvement of chronic bronchiolar lesions with peribronchiolar fibrosis, inflammatory infiltration, and foci of luminal narrowing. There were a few areas of vague granulomas showing multinucleated giant cells around the bronchiolar lesions (Fig. 3A and 3B). The findings were therefore compatible with chronic bronchiolitis with peribronchiolar, probably hypersensitivity pneumonitis. Figure 1 (A) Chest X-ray after coronary angiogram. It shows increase of computed tomography ratio, but no active pulmonary pathology, nor bony abnormality. (B) Chest X-ray upon presentation with respiratory symptoms. Chest X-ray reveals perihilar peribronchial ... Figure 2 High resolution computed tomography view of the chest reveals diffuse ground-glass opacities throughout both lungs (white arrow) and centrilobular nodules (yellow arrows). Figure 3 (A) Histological features of the open lung biopsy. Light micrograph of the case shows bronchial and peribronchial patchy inflammatory infiltration of lymphocytes (white arrow), and vague granuloma with multinucleated giant cells (black arrow) (H&E, ... Bacterial, viral, and fungal cultures from sputum and blood were negative. Serological test results were not consistent with acute infection caused by Mycoplasma species, and Legionella and Pneumococcus urinary antigens were negative. There was no evidence of infection on slides prepared for bacterial, fungal, or acid-fast organisms. Based on the biopsy results, the patient was treated with high-dose steroids for 2 weeks. Chest X-rays revealed improvement of the ground-glass appearance in both lung fields as compared with the previous films. The patient received steroid treatment with tapering for 2 months. Four months later, follow-up high-resolution computed tomography showed significant improvement of the hypersensitivity pneumonitis. The patient had no history of significant inhalational exposure. His medications, including clopidogrel, were not discontinued during management of the complication, and the pneumonitis did not recur. We concluded that the ZES could have caused the hypersensitivity pneumonitis. There were no adverse clinical events during the 10-month follow-up period. Hypersensitivity pneumonitis is an allergic lung disease characterized by lymphocytic and granulomatous inflammation of the lung parenchyma and bronchioles caused by repeated exposure to a variety of etiological agents as well as genetic factors [3]. When considering the possibility of hypersensitivity pneumonitis after DES implantation, the essential first step in the differential diagnosis is a more detailed questioning about the patients potential exposures. Local and systemic hypersensitivity manifestations can develop in response to implantation of DES in coronary arteries. The numerous potential antigens include not only many different complex organic particles from chemicals, including medications, but also stent components such as metal, polymer coating, or eluted drug [2]. The differential diagnosis of hypersensitivity pneumonitis is based on history, clinical features, laboratory and radiographic evidence, pulmonary function test results, and histological findings [3]. In the present case, the patient had no history of allergies. Symptoms, including cough and dyspnea, developed 2 weeks after stent implantation. The results of laboratory tests, including eosinophil count, immunoglobulin E level, and erythrocyte sedimentation rate, were consistent with a hypersensitivity reaction. Chest radiography and high-resolution computed tomography showed a multifocal ground-glass appearance in both lung fields. Pulmonary function tests revealed a moderately restrictive ventilatory defect. Histological features on open lung biopsy were characteristic of hypersensitivity pneumonitis. The patients illness was unresponsive to standard broad-spectrum antibacterial treatment, but responded rapidly to steroid therapy. Based on the clinical course and pathological findings, a diagnosis of hypersensitivity pneumonitis was made in this case. Compared with bare-metal stents, DESs-including the ZES used here-are safe and reduce the rates of clinical and angiographic restenosis. However, they may be a cause of systemic and intrastent hypersensitivity reactions. Respiratory hypersensitivity reactions may develop hours to weeks after DES insertion. There are three potential causal agents after DES insertion, i.e., anti-platelet agents, intravenous agents such as intravenous iodinated contrast agents used at implantation, and the DES itself [2]. In the present case, anti-platelet agents can be excluded as causal agents because the patient had previously taken anti-platelet agents without evidence of hypersensitivity. If the culprit were intravenous agents used at implantation, the reaction would have been expected to begin on the day of implantation and to resolve within 2 days; however, the patient showed evidence of a hypersensitivity reaction 13 days post-implantation. We concluded that DES was the most likely cause of the hypersensitivity response in this case. Drugs used in other stents, including sirolimus and paclitaxel, can cause hypersensitivity pneumonitis [4,5]. Non-drug components of DES are also potential causes of hypersensitivity. The polymer coating can fragment and expose the metal struts, and nickel and molybdenum in the stainless steel may cause hypersensitivity [2]. Therefore, the hypersensitivity reaction in the present case could have been caused by zotarolimus, the polymer, or the metal struts. This is the first report of a case of hypersensitivity pneumonitis in association with implantation of a ZES in a coronary artery. In summary, hypersensitivity pneumonitis is a rare complication of DES implantation. The diagnosis of ZES-induced hypersensitivity pneumonitis should be considered in patients who develop nonspecific respiratory symptoms and a diffuse bilateral interstitial pattern on chest radiography hours to weeks after insertion of a ZES.

The Efficacy of the Cystatin C Based Glomerular Filtration Rate in the Estimation of Safe Contrast Media Volume

Background and Objectives The risk of contrast-induced nephropathy (CIN) is significantly influenced by baseline renal function and the amount of contrast media (CM). We evaluated the usefulness of the cystatin C (CyC) based estimated glomerular filtration rate (eGFRCyC) in the prediction of CIN and to determine the safe CM dosage. Subjects and Methods We prospectively enrolled a total of 723 patients who received percutaneous coronary intervention (PCI) and investigated the clinical factors associated with the development of CIN. Renal function was calculated as eGFRCyC and a modified diet in the renal disease (MDRD) equation, respectively. Systemic exposure of CM was calculated as CM volume to eGFR ratio. We conducted a regression analysis to evaluate the predictive role of CM volume to eGFRCyC for the risk of CIN. Results The incidence of CIN was 4.0% (29/723). The patients with CIN had a lower hemoglobin level, decreased renal function, and a higher CyC value, and had greater CM exposure. Through multivariate regression analyses, hemoglobin {odds ratio (OR) 0.743, p=0.032}, CM volume/eGFRCyC (OR 1.697, p=0.006) and CM volume/MDRD (OR 2.275, p<0.001) were found to be independent predictors for CIN. In the receiver operating characteristic curve analysis, fair discrimination for CIN was found at a CM volume/eGFRCyC level of 4.493 (C-statics=0.814), and at this value, the sensitivity and specificity were 79.3% and 80.0%, respectively. Conclusion Both the CM volume/MDRD and CM volume/eGFRCyC method would be simple, useful indicators for determining the safe CM-dose based on eGFR value before PCI. However, there was no significantly different predictive value between creatinine and CyC based GFR estimations.

Fever after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction is associated with adverse outcomes

BACKGROUND Fever is a common finding after primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, its prognostic value is not validated yet. OBJECTIVES This study sought to evaluate the impact of fever after PPCI in STEMI on adverse clinical outcomes. METHODS Five hundred fourteen consecutive patients who underwent PPCI due to STEMI were enrolled. Body temperature (BT) was checked every 6 h for 5 days after PPCI. Patients were divided into two groups according to the highest quartile of peak BT; peak BT≤37.6 °C (control group) and peak BT>37.6 °C (fever group). Rates of 1-year major adverse cardiovascular events (MACE; death, myocardial infarction, any revascularization) were compared. RESULTS The prevalence of fever group (peak BT>37.6 °C) was 24.7% (127/514). White blood cell count, highly sensitive C-reactive protein and serum cardiac troponin I level were higher in fever group than control group (12,162±4199/μL vs. 10,614±3773/μL, p<0.001; 22.9±49.4 mg/L vs. 7.4±2.5 mg/L, p=0.001, 16.7±36.9 ng/dl vs. 8.70±26.2 ng/dl, p=0.027, respectively). The frequency of a history of previous myocardial infarction and left ventricular ejection fraction was lower in fever group (0.0% vs. 4.7%, p=0.010; 47±8 % vs. 49±9 %, p=0.002, respectively). There was no significant difference in angiographic characteristics between 2 groups. 1-year MACE rates were higher in fever group (11.0% vs. 4.7%, p=0.010). Multivariate analysis revealed fever (OR 2.358, 95% CI 1.113-4.998, p=0.025), diabetes mellitus as risk factor (2.227, 1.031-4.812, 0.042), and left anterior descending artery as infarct related artery (2.443, 1.114-5.361, 0.026) as independent predictors for 1-year MACE. CONCLUSIONS Fever after PPCI in patients with STEMI is frequently developed and it can predict adverse clinical outcome.

Left ventricular twist and ventricular-arterial coupling in hypertensive patients.

Left ventricular (LV) twist is usually influenced by LV hypertrophy resulting from hypertension or vascular stiffness. Vascular stiffness would increase arterial elastance (Ea), whereas LV end‐systolic stiffness (Ees) could be influenced by LV hypertrophy. Therefore, in hypertensive patients, we assessed the extent to which ventricular–arterial coupling (VAC; Ea/Ees) affects LV twist, which may be a compensatory mechanism for systolic dysfunction.