The Role of Preoperative NT-proBNP in Elderly Orthopedic Patients with Normal Left Ventricular Systolic Function / 대한내과학회지

BACKGROUND/AIMS: Preoperative N-terminal pro-brain natriuretic peptide (NT-proBNP) is a useful predictor of postoperative cardiovascular complications. The present study investigated whether blood NT-proBNP values are suitable for predicting postoperative cardiovascular complications after non-cardiac surgery in elderly patients showing normal left ventricular (LV) function on preoperative echocardiograms. METHODS: This study was performed by analyzing the medical records of elderly patients referred to the cardiology department for the purpose of assessing their cardiac function before orthopedic surgery. Of the patients who underwent echocardiography and NT-proBNP assessment simultaneously, 275 patients aged > or = 70 years and with an LV ejection fraction of > or = 55% were included in the study. RESULTS: Major adverse cardiac and cerebrovascular events (MACCEs) occurred in 33 (12%) of the 275 patients, and the NT-proBNP concentration was higher in patients with complications than in those without complications (1,904.20 +/- 2,300.23 vs. 530.58 +/- 882.27 pg/mL, p 80 years (odds ratio, 2.313; p = 0.047) and an increased blood NT-proBNP concentration (odds ratio, 3.189; p = 0.009) were independent risk factors for the prediction of MACCEs. CONCLUSIONS: Although elderly patients scheduled to undergo non-cardiac surgery may show normal LV systolic function on echocardiography, measurement of their preoperative blood NT-proBNP concentration is useful for predicting MACCEs occurring after non-cardiac surgery.

Fatal Delayed Coronary Artery Perforation After Coronary Stent Implantation

Most type I and II perforations are predominately caused by hydrophilic and stiff wires, often presented in the delayed form, and do not require pericardial drainage or surgical interventions. However, we report a type III delayed coronary artery perforation at the site of stent implantation after intervention without any evidence of immediate perforations. To the best of our knowledge, this is the first case report of angiographic documentation and treatment of delayed coronary perforation at the site of stent, presented as a cardiac arrest.

Pulmonary tumor thrombotic microangiopathy in a patient with breast cancer / 대한내과학회지

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related complication causing severe pulmonary hypertension, right heart failure, and death. PTTM is characterized by diffuse fibrocellular intimal proliferation and multiple thrombi formation in the pulmonary arteries and arterioles, which result from invasion of the pulmonary blood vessels by tumor cells. Establishing the diagnosis of PTTM is very difficult and few cases are diagnosed ante mortem. We report the case of a 48-year-old woman diagnosed with PTTM before death who developed breast cancer and presented with persistent dyspnea on exertion.

The Usefulness of B-type Natriuretic Peptide test in Critically Ill, Noncardiac Patients / 결핵

BACKGROUND: Previous studies have suggested that a B-type natriuretic peptide(BNP) test can provide important information on diagnosis, as well as predicting the severity and prognosis of heart failure. Myocardial dysfunction is often observed in critically ill noncardiac patients admitted to the Intensive Care Unit, and the prognosis of the myocardial dysfunction needs to be determined. This study evaluated the predictability of BNP on the prognosis of critically ill noncardiac patients. METHODS: 32 ICU patients, who were hospitalized from June to October 2002 and in whom the BNP test was evaluated, were enrolled in this study. The exclusion criteria included the conditions that could increase the BNP levels irrespective of the severity, such as congestive heart failure, atrial fibrillation, ischemic heart disease, and renal insufficiencies. A triage B-Type Natriuretic Peptide test with a RIA-kit was used for the fluorescence immunoassay of BNP test. In addition, the acute physiology and the chronic health evaluation (APACHE)IIscore and mortality were recorded. RESULTS: There were 16 males and 16 females enrolled in this study. The mean age was 59 years old. The mean BNP levels between the ICU patients and control were significantly different (186.7+/-274.1pg/mL vs. 19.9+/-21.3 pg/mL, p=0.033). Among the ICU patients, there were 14(44%) patients with BNPlevels above 100 pg/mL. The APACHEIIscore was 16.5+/-7.6. In addition, there were 11 mortalities reported. The correlation between the BNP and APACHEIIscore, between the BNP and mortality were significant (r=0.443, p=0.011 & r=0.530, p=0.002). The mean BNP levels between the dead and alive groups were significantly different (384.1+/-401.7 pg/mL vs. 83.2+/-55.8 pg/mL p=0.033). However, the PaO2/FiO2 did not significantly correlate with the BNP level. CONCLUSION: This study evaluated the BNP level was elevated in critically ill, noncardiac patients. The BNP level could be a useful, noninvasive tool for predicting the prognosis of the critically ill, noncardiac patients.

A Case of Primary Pulmonary Hypertension Diagnosed in Puerperium

Primary pulmonary hypertension is a condition characterized by sustained elevations of pulmonary artery pressure without demonstrable cause. It is incurable and progressive clinical entity. The incidence has been estimated at approximately 1 to 2 cases per million people in the general population. The maternal mortality of primary pulonary hypertension in pregnancy was said to be 30% and the first month after delivery represents the period of highest risk. We experienced a 27-year-old women with primary pulmonary hypertension diagnosed in postpartum period. She was transferred from the department of obstetrics to internal medicine due to dyspnea on the first day of postpartum. She was diagnosed by perfusion lung scan, chest CT and confirmed by echocardiography. This diagnosis were supported by findings of pulmonary angiogram and cardiac catheterization. Initially she was treated with diuretics, aspirin and anticoagulant therapy, and as a result of the treatment, her symptoms improved. However after 8months has elapsed, exertional dyspnea was worsening. Thus she was treated with calcium channel blocker, aspirin and diuretics and was followed at 1 month interval on the outpatient clinics.

A Serial Echocardiograhic Obesrvation of Acute Myocardial Injury Associated with Pheoechromocytoma Crisis

Pheochromocytoma may cause anatomic and functional cardiac abnormalities. Various echocardiographic abnormalities have been observed, including systolic anterior movement, global hypokinesis as well as hypokinesis of the base and the apex of LV. There are no previous reports of serial echocardiographic finding in patients with pheochromocytoma. We experienced a 38-year-old woman with pheochromocytoma who suffered from acute myocardial injury. Echocardiography revealed that the acute myocardial injury started in the base in the early phase and subsequently extended to the mid-portion of left ventricule. The injury persisted longer in the base than the mid-portion. than 1.5 times the adjacent normal coronary artery.

A Case of Aortic Dissection with Compromised Superior Mesenteric Artery Treated with Stents Insertion at Origin of the Artery

The treatment of a thoracic aortic dissection is guided by prognostic and anatomical information. Stanford type A aortic dissection requires surgery, but the appropriate treatment of a Stanford type B aortic dissection has not been determined, especially in patients with visceral artery compromise associated with the aortic dissection due to the failure of surgery to improve the prognosis.We report a case of a 35-year-old man, with a Stanford type B aortic dissection, where the superior mesenteric artery was obstructed. This condition was successfully treated with stents inserted at the origin of the artery.

Expression of leptin receptor (Ob-R) in human atherosclerotic lesions: potential role in intimal neovascularization

Neovascularization of the adventitial vasa vasorum with extension into the intima of atherosclerotic lesions is frequently observed, but its pathophysiological significance is still subject to debate. Recently, leptin, the product of the Ob gene, was identified. Leptin, via activation of the endothelial receptor (Ob-R), generates a growth signal involving a tyrosine kinase-dependent intracellular pathway and promotes angiogenic processes. We hypothesized that a high concentration of leptin within vasa vasorum and plaque itself, may influence inflammatory and vascular neovascularization coupling with functional upregulation of the vascular endothelial growth factor (VEGF). Microscopic computerized tomography was utilized for the spatial distribution of vasa vasorum and intimal neovascularization from atherosclerotic human coronary arteries. Atherosclerotic coronary arteries showed a dense plexus of microvessels in the adventitia and plaque itself. Microscopic analysis from human atherosclerotic aortas revealed an increase in the intimal thickness with neovascularization. The immunoreactivity for Ob-R, VEGF and matrix metalloproteinase (MMP) increased in atherosclerotic plaque, predominantly in the endothelial lining of the intimal neovessel and macrophages/foam cells. Our observation of a prominent colocalization between Ob-R, VEGF and MMP supports this hypothesis and these factors participate in the neovascularization of atherosclerotic lesions. The present study is the first report on vascular tissue and it opens a promising perspective concerning future investigations of leptin-dependent modulation of atherogenesis and vascular neovascularization under pathophysiolgical conditions.

Coexpression of cyclooxygenase-2 and matrix metalloproteinases in human aortic atherosclerotic lesions

Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study aimed to investigate atherosclerosis in human aortas for in situ tissue distribution of COX-2, MMPs including MMP-9 and membrane type 1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemical studies were performed on atherosclerotic lesions of aortas from patients with aortic aneurysms (n = 4) and dissections (n = 3) by using antibodies to COX-2, MMP-9, MT1-MMP, and TIMP-2. Control tissues were obtained from traumatically dissected aortas (n = 2). All specimens from diseased aortas had atherosclerotic lesions ranging from fatty streak to atheromatous plaques. In control, there was no expression of COX-2, MMP-9, and MT1-MMP in all aortic layers. Immunoreactivity for COX-2 was predominantly noted in macrophages and smooth muscle cells (SMCs) of the intima including atherosclerotic plaque itself and the medial layer of the plaque base, as well as in SMCs and endothelial lining of the vasa vasorum in the adventitia. Immunoreactivity for MMP-9 and MT1-MMP was found in the same distribution as that of COX-2. Additionally, the expression of TIMP-2 increased in relation to MMP-9 expression. This study demonstrates that COX-2 is coexpressed with MMP-9 and MT1-MMP, not only by macrophages and SMCs in atherosclerotic lesions, but also in endothelial lining of the vasa vasorum of human aortas. Thus, vascular inflammatory reactions may influence extracellular matrix remodeling by coactivation of MMPs in the development of atherosclerosis and, in turn, the progression of disease.

Analysis of Heart Rate Variability in 24-Hour Holtor onitoring of Patients with Vasovagal Syncope

BACKGROUND AND OBJECTIVES: Syncope is defined as a sudden temporary loss of consciousness associated with a loss of postural tone with spontaneous recovery. It is a common clinical problem with complex and heterogeneous etiologies, but vasovagal syncope is the main cause of unexplained syncope. Bradycardia and hypotension by transient dysfunction of cardiac autonomic nervous system have been cited as the main pathophysiology of the vasovagal syncope. Therefore, we studied whether analysis of heart rate variability (HRV) by 24-hour ambulatory ECG monitoring would reflect autonomic imbalance between cardiac sympathetic and vagal efferent activity in the patients of vasovagal syncope. MATERIALS AND METHOD: 45 patients (male=2, female=3, mean age=2.214 years) with syncope were enrolled, and divided into 2 subgroups according to the results of head-up tilt test: head-up tilt test positive (group S1) and negative (group S0). A sex-matched control group consisted of 9 healthy volunteers (male=, female=, mean age=16 years, Group C). The 24-hour ambulatory ECG monitoring was performed in all groups, and R-R intervals were analyzed by time- and frequency-domain methods. The time-domain measurements of HRV were mean NN(mean of all coupling intervals between normal beat), ASDNN(mean of the standard deviations of all normal R-R intervals for 5-minute segments of the entire recording), SDNN(standard deviation of all normal R-R intervals over 24 hours), SDANN(standard deviation of average R-R intervals in all 5 minutes segments of the entire recording), rMSSD(square root of the mean squared differences of successive R-R interval) and pNN50(percent of differences between adjacent normal R-R intervals more than 50ms during 24 hours), and frequency-domain measurements were low frequency (LF), high frequency (HF) components and LF/HF ratio. RESULTS: The LF/HF ratio was significantly higher in syncope patients with positive results of head-up tilt test and syncope patients with negative results than in control (p<0.05). The LF, HF, mean NN, ASDNN, SDNN, SDANN, rMSSD, and pNN50 were not significantly different among these three groups. CONCLUSION: These results suggest that the cardiac autonomic nervous system in patients with vasovagal syncope has sympathetic-activated balanced without changes of total power of both sympathetic and parasympathetic components.

Apolipoprotein E polymorphism in non-diabetic patients with acute coronary syndrome

Since a decade ago, apolipoprotein (apo) E polymorphism has been focussed as a risk factor for cardiovascular disease. ApoE plays a central role as a receptor ligand for the uptake of lipoproteins from the circulation. There was an agreement on apoE polymorphism being one of the major risk factors for coronary artery disease (CAD) by its effects on lipid profiles. However, the effects of apoE have not been noted in all populations and conflicting results in the risk of CAD have been noted. Recently, in situ expression of apoE on the atherosclerotic plaque has been studied. We, therefore, investigated the effects of apoE genotype on patients with acute coronary syndrome, including unstable angina and acute myocardial infarction, in non-diabetic patients. While we could not find significant risk effects of apoE on coronary artery disease and lipid profiles on simple comparison with the normal control group, we could find significantly decreased frequencies of apo epsilon 3 allele in patients with acute coronary syndrome compared with stable angina patients (77.8% vs 88.8%). We suggest that the apoE genotype could be associated with acute coronary events in CAD and further study with in situ biochemical methods will be needed on the effects of apoE polymorphism on plaque stability.

A Randomized Comparison of Cilostazol and Ticlopidine after Coronary-artery

BACKGROUND AND OBJECTIVES: Combination of ticlopidine and aspirin has been accepted as a standard antiplatelet regimen after coronary stenting because it reduced the rate of cardiac events and hemorrhagic-vascular compli-cations compared with intensive anticoagulation. Ticlopidine use, however, may accompany serious side effects such as neutropenia or liver dysfunction. Cilostazol, a c-AMP phosphodiesterase inhibitor, is a novel antiplatelet agent which is known to have less side effects. MATERIALS AND METHODS: We compared the efficacy and safety of ci lostazol plus aspirin (CA) with ticlopidine plus asprin (TA) after elective coronary stenting. Patients were randomly assigned to receive either CA or TA two days before stenting. The primary end point was a composite of angiographic stent thrombosis, death, myocardial infarction (Q or Non-Q), repeat intervention or bypass su rgery at 30 days. The secondary end points were hemorrhagic-vascular complications, or drug side effects such as neutropenia, thrombocytopenia, or any side effects requiring cessation of drugs at 30 days. RESULTS: After randomization of 300 patients equally to each group, 4 patients were excluded from the analysis: 1 failure of stenting, 3 follow-up loss. The primary end point was reached in 2 patients (1.4% ) in CA group and 3 patients (2.0% ) in TA group (p=1.0). The rate of hemorrhagic-vascular complications was not different between the gr oups (1.4% vs 2.0%, p=1.0). The incidence of significant drug-related side effects was not statistically different between CA group and TA group (0.7% vs 2.7%, p=0.37). However, serious side effect such as neutropenia was seen only in TA group. CONCLUSION: Compared with TA, CA has comparable effect for the prevention of stent thrombosis and major cardiac events with similar rate of hemorrhagic-complications and drug-related side effects after elective coronary-artery stenting. Thus CA regimen can be a safe alternative to TA in elective implantation of coronary artery stent.

Percutaneous transmyocardial revascularization induces angiogenesis: a histologic and 3-dimensional micro computed tomography study

The purpose of this study was to visualize the spatial patterns and connection of channels created after percutaneous transmyocardial revascularization (PTMR) in normal porcine hearts, and to estimate the relative contributions of transmyocardial and coronary perfusion. Six pigs underwent PTMR creating channels using radiofrequency ablative energy. Three-dimensional computed tomography imaging of channels 1 hr after PTMR showed the direct connection of PTMR channels to the myocardial capillary network and to epicardial coronary vessels. In the heart, examined 28 day after PTMR, there was a fine, extensive, network of microvessels originating from the site of the original PTMR channel, also connecting the left ventricular cavity to myocardial capillaries. Histopathologic examination of the 1-hr specimens showed numerous regions of myocardial hemorrhage and associated inflammatory cell infiltration. In the 28-day specimens, newly developed new vascular network suggested neovascularization within the core of these channel remnants. The immunoreactivity for basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were intense within myocardium and neovascular structure surrounding PTMR channel remnants. The vascular connections occur by direct communication with existing myocardial vasculature acutely, and angiogenesis in these channel remnant chronically.

Experimental hypercholesterolemia induces ultrastructural changes in the elastic laminae of rabbit aortic valve

Atherosclerosis is the most severe problem in the high-pressure systemic circulation and similar changes also occur in the high-pressure loading valve. This study was designed to test the hypothesis that early atherosclerosis, induced by a high cholesterol diet in rabbits, is characterized by significant ultrastructural change in the elastic laminae of the aortic valve. However, it is not known whether this process is also taking place in the cardiac valve at the early stage of atherosclerosis. Animals were fed either a high cholesterol diet (n = 5) or a control diet (n = 5) for 10-12 weeks. Histologic analysis demonstrated that subendothelial thickening and foam-cell infiltration were evident in the arterialis of aortic valves. Confocal microscopy revealed an altered pattern characterized by fragmentation and disorganization of the arterialis elastic laminae of hypercholesterolemic valves. Computerized digital analysis of the images obtained by confocal scanning microscopy demonstrated that compared to normal valves, the arterialis elastic laminae of hypercholesterolemic valves decreased in percentage of their elastin content (29.03 +/- 1.10% vs. 42.94 +/- 1.35%, p = 0.023). Immunohistochemical staining for matrix metalloproteinase-3 (MMP-3) revealed MMP-3 immunoreactivity was increased in hypercholesterolemic valves, predominantly in the arterialis. This study demonstrated that early atherosclerosis, induced by a high cholesterol diet in rabbits, is characterized by significant ultrastructural change in the elastic laminae of the aortic valve. The arterialis endothelium of the aortic valve may be a more atherosclerosis-prone area compared with the ventricularis. The presence of ultrastructural defect in the elastic laminae may play a role in chronic degenerative change and a resultant valvular dysfunction.

A Case of Beneficial Effect of Short-Term Growth Hormone Treatment for Intractable Heart Failure in Cardiomyopathy Combined with Neuromuscular Dystrophy

We report a case of 15-year-old man with beneficial effects of short term growth hormone treatment presenting with cardiomyopathy combined with neuromuscular dystrophy. Transthoracic echocardiography revealed that LV chamber was markedly dilated and global LV systolic function was severely reduced. The findings of electromyography were compatible with neuromuscular dystrophy. Under the impression of cardiomyopathy combined with neuromuscular disease, maximal medical treatments such as inotropic agents, diuretics and ACE inhibitor were tried but we could not attain remarkable clinical improvement. Finally, we started growth hormone injection and after treatment for 3 months, we could attain remarkable clinical and hemodynamic improvement without any side effect.

Computed numerical analysis of the biomechanical effects on coronary atherogenesis using human hemodynamic and dimensional variables

The objectives of this investigation were to evaluate biomechanical factors in the atherosclerotic process using human in vivo hemodynamic parameters and computed numerical simulation qualitatively and quantitatively. The three-dimensional spatial patterns of steady and pulsatile flows in the left coronary artery were simulated, using a finite volume method. Coronary angiogram and Doppler ultrasound measurement of the proximal left coronary flow velocity were performed in humans. Inlet wave velocity distribution obtained from in vivo data of the intravascular Doppler study allowed for input of in vitro numerical simulation. Hemodynamic variables, such as flow velocity, pressure and shear stress of the left anterior descending coronary bifurcation site were calculated. We found that there were spatial fluctuation of flow-velocity and recirculation areas at the curved outer wall of the left anterior descending coronary artery, which were due to the differences of flow-velocity and shear stress, especially during the declaration phase of pulsatile flow. This study suggests that rheologic properties may be a part of the atherogenic process in the coronary bifurcated and curved areas.

Primary empty sella syndrome / 대한내분비학회지

BACKGROUND: Primary empty sella syndrome (PES) is thought to arise from an incompetent diaphragma allowing progressive herniation of arachnoid membrane with secondary compression and atrophy of the pituitary gland. As a consequence of the improvement and widespread use of neuroradiological techniques, such as computerized tomography (CT) and magnetic resonance imaging (MRI), empty sella is more frequently disclosed. The aim of this study is to assess the associated clinical characteristics and endocrinologic disturbance in empty sella syndrome. METHODS: From January 1986 to June 1996, 171 patients with empty sella syndrome have undergone analysis for clinical characteristics and associated disease. RESULT: In our study, PES was diagnosed in 131 of the 171 patients (77%). Primary empty sella syndrome was frequent in middle aged women (female:male 115:16, mean age: 50.6+12.6 years). The common clinical features were headache (80.2%), obesity (72.5%), and hypertension (27.5%). Most of patients with PES have normal pituitary function (75%). The frequent pituitary dysfunction was hyperprolactinemia in PES (21%). Partial and total emptiness of sella on sella CT or MRI were in 111 (84.7%) patients, and in 20 (15.4%) patients, respectively. The most common associated disease with empty sella syndrome was pituitary adenoma. CONCLUSION: PES should be considered as a possible cause in obese middle aged women with unexplained headache. The combined pituitary function test should be considered for evaluation of pituitary dysfunction when clinically suspected.

Effect of Low Dose Enteric-coated Aspirin Alone or Combination with Ticlopidine on Platelet

BACKGROUND: The role of platelet in the pathogenesis of acute coronary syndrome and cerebral thrombosis is well known and the platelet inhibitors are used widely for primary and sccondary prevention of cardiovascular disease. Aspirin is the least expensive and most widely used antiplatelet agent and its effect is associated with its ability to inhibit plateletthromboxane A2 synthesis. The effectiveness of aspirin is dependent on its ability to block the formation of thromboxane A2. Ticlopidine is another popular antiplatelet agent used today in the era of stent implantation for treating coronary artery obstructive disease(CAOD) with aspirin. The mechanism of action of ticlopidine is clearly different from that of aspirin. It is concluded recently that ticlopidine is an inhibitor of ADP binding to platelets. The inhibition of ADP binding to platelets by ticlopidine is very nicely correlated with its does and the inhibition of platelet aggregation. Therefore, in this study, antiplatelet effect of low dose enteric-coated aspirin in place of aspirin and combined therapy with low does enteric-coated aspirin plus ticlopidine were evaluated in the normal subjects. METHOD: IN twenty normal subjects, platelet aggregation tests with adenosine diphosphate(ADP) and collagen were performed baseline, after I week adminisrtation of enteric-coated aspirin, and in randomly selected ten among twenty normal subjects, I week administration of enteric-coated aspirin and ticlopidine. The maximal aggregation rate was calculated by measuring the maximal change of the light transmittance after addition of aggregating agents. RESULT: Low does enteric-coated aspirin inhibited platelet aggregation in response to collagen significantly. Less than 25% of antiaggregation effect was noted in about 50% of subjects with low dose enteric-coated aspirin when platelet aggregation was induced by ADP. Ticlopidine in combination with low does enteric-coated aspirin potentiated the inhibitory effect significantly on platelet aggregation in response to ADP. CONCLUSION: Effect of low dose enteric-coated aspirin alone on platelet aggregation in response to ADP stimulation was weak and showed variablity, comparing to collagen stimulation. The combined treatment of ticlopidine plus aspirin was synergistically inhibited platelet aggregation responding to ADP stimulation. Therefore to achieve the synergistic inhibition of platelet aggregation to ADP and collagen stimulation, combination theraphy might be a effective regimen.