Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy

Background@#We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy. @*Methods@#Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit. @*Results@#G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro. @*Conclusion@#Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.

A First-in-Man Clinical Evaluation of Sirolimus and Ascorbic Acid-Eluting Stent Systems: a Multicenter, Subject-Blinded, Randomized Study

Background and Objectives@#This clinical trial was conducted to evaluate the safety and efficacy of D+Storm™ drug-eluting stent (DES) and BioMatrix Flex™ DES. @*Methods@#This study was a multicenter, subject-single-blind, randomized, and confirmed comparative clinical trial. According to the inclusion criteria, those diagnosed with stable angina, unstable angina, silent ischemia, or non-ST-segment myocardial infarction were selected among patients with coronary artery stenosis as subjects. Among the subjects with 50% stenosis on coronary angiography, the experiment was performed on those who had a lesion with reference vessel 2.5–4.0 mm in diameter and ≤40 mm in length. The primary endpoint was an in-segment late loss and the secondary endpoints were in-stent late lumen loss, stent malapposition, the incidence of mortality, myocardial infarction, reoperation, and stent thrombosis at 36 weeks. @*Results@#57 patients in the D+Storm™ DES group and 55 patients in the BioMatrix Flex™ DES group were enrolled in the study. Fifty-seven patients in the D+Storm™ DES group and Fifty-five patients in the BioMatrix Flex™ DES group were enrolled in the study. An average of in-segment late lumen loss was 0.08±0.13 mm in the D+Storm™ DES group and 0.14±0.32mm in the BioMatrix Flex™ DES group with no significant difference between the 2 groups (p=0.879). In addition, there was no significant difference in adverse events between D+Storm™ DES and BioMatrix Flex™ DES. @*Conclusions@#This study demonstrated the clinical effectiveness and safety of D+Storm™ DES implantation in patients with coronary artery disease over a 36-week follow-up period.

Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy

Background@#We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy. @*Methods@#Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit. @*Results@#G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro. @*Conclusion@#Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.

Role of MicroRNA-34a in Anti-Apoptotic Effects of Granulocyte-Colony Stimulating Factor in Diabetic Cardiomyopathy

BACKGROUND: Recent studies have shown that microRNAs (miRNAs) are involved in the process of cardiomyocyte apoptosis. We have previously reported that granulocyte-colony stimulating factor (G-CSF) ameliorated diastolic dysfunction and attenuated cardiomyocyte apoptosis in a rat model of diabetic cardiomyopathy. In this study, we hypothesized a regulatory role of cardiac miRNAs in the mechanism of the anti-apoptotic effect of G-CSF in a diabetic cardiomyopathy rat model.METHODS: Rats were given a high-fat diet and low-dose streptozotocin injection and then randomly allocated to receive treatment with either G-CSF or saline. H9c2 rat cardiomyocytes were cultured under a high glucose (HG) condition to induce diabetic cardiomyopathy in vitro. We examined the extent of apoptosis, miRNA expression, and miRNA target genes in the myocardium and H9c2 cells.RESULTS: G-CSF treatment significantly decreased apoptosis and reduced miR-34a expression in diabetic myocardium and H9c2 cells under the HG condition. G-CSF treatment also significantly increased B-cell lymphoma 2 (Bcl-2) protein expression as a target for miR-34a. In addition, transfection with an miR-34a mimic significantly increased apoptosis and decreased Bcl-2 luciferase activity in H9c2 cells.CONCLUSION: Our results indicate that G-CSF might have an anti-apoptotic effect through down-regulation of miR-34a in a diabetic cardiomyopathy rat model.

Two Distinct Responses of Left Ventricular End-Diastolic Pressure to Leg-Raise Exercise in Euvolemic Patients with Exertional Dyspnea

BACKGROUND AND OBJECTIVES: Few studies have invasively assessed diastolic functional reserve and serial changes in left ventricular hemodynamics in euvolemic patients with exertional dyspnea. In this study, sequential changes in left ventricular end-diastolic pressure (LVEDP) to leg-raise exercise were measured invasively in patients with early heart failure with preserved ejection fraction (HFpEF) to determine the association between these serial changes and echocardiographic results or clinical features. SUBJECTS AND METHODS: During their hospital stay, 181 patients with early HFpEF underwent left cardiac catheterization, coronary angiography, and transthoracic echocardiography (TTE). Leg-raise exercise was performed in two stages: during cardiac catheterization and again during TTE. RESULTS: Compared with the initial values, all the invasively measured LVEDP values increased significantly during the leg-raise exercise, whereas the septal e/e' ratio remained unchanged. Active leg-raise led to increased LVEDP, which caused dyspnea. The severity of symptoms correlated with the level and extent of changes in LVEDP. At the end of active leg-raise, LVEDP decreased in 40 patients (22.1%), who were younger and had significantly lower e/e' ratios. On multivariate analysis to predict the response of LVEDP to active leg-raise, age and the septal e/e' ratio remained significant predictors. CONCLUSION: Despite having similar LVEDP values at rest, patients may respond to exercise with different LVEDP levels and clinical manifestations, depending on their diastolic capacity. The leg-raise exercise in early HFpEF can elucidate individual diastolic profiles, and the LVEDP response to the leg-raise test may serve as a useful criterion in stratifying patients with early HFpEF with respect to functional reserve.

Radial Arteriovenous Fistula after Coronary Angiography / 대한내과학회지

A 67-year-old man underwent coronary angiography using a transradial approach. Three months after coronary angiography, the patient complained of a thrill detected in his right wrist. Localized compression was performed in the assumption of arteriovenous fistula formation. Since thrill was still detected after localized compression, surgical revision of an arteriovenous fistula was performed. Six days later, radial bruit was still reported. It was decided to perform upper extremity angiography. Upper extremity angiography revealed the remaining arteriovenous fistula from radial artery to cephalic vein, and surgical revision was performed again. This appears to be a very unusual complication related to the transradial approach for coronary angiography.

A Case of Stress-Induced Cardiomyopathy after Propofol Anesthesia / 대한내과학회지

Propofol is an intravenous hypnotic agent that is generally used for sedation in the intensive care unit and for induction of anesthesia during minimally invasive surgery, endoscopy, and plastic surgery in local clinics. Low blood pressure and transient apnea might occur under propofol sedation, whereas stress-induced cardiomyopathy is a very rare complication. We herein describe a case involving a 25-year-old woman without cardiovascular risk factors who developed stress-induced cardiomyopathy after propofol injection for anesthesia and was treated with conservative treatment. This case reminds us that clinicians should consider the possible occurrence of stress-induced cardiomyopathy after anesthesia using propofol, even in patients without cardiovascular risk factors.

The Extended Rapid Response System: 1-Year Experience in a University Hospital

The rapid response system (RRS) is an innovative system designed for in-hospital, at-risk patients but underutilization of the RRS generally results in unexpected cardiopulmonary arrests. We implemented an extended RRS (E-RRS) that was triggered by actively screening at-risk patients prior to calls from primary medical attendants. These patients were identified from laboratory data, emergency consults, and step-down units. A four-member rapid response team was assembled that included an ICU staff, and the team visited the patients more than twice per day for evaluation, triage, and treatment of the patients with evidence of acute physiological decline. The goal was to provide this treatment before the team received a call from the patient's primary physician. We sought to describe the effectiveness of the E-RRS at preventing sudden and unexpected arrests and in-hospital mortality. Over the 1-yr intervention period, 2,722 patients were screened by the E-RRS program from 28,661 admissions. There were a total of 1,996 E-RRS activations of simple consultations for invasive procedures. After E-RRS implementation, the mean hospital code rate decreased by 31.1% and the mean in-hospital mortality rate was reduced by 15.3%. In conclusion, the implementation of E-RRS is associated with a reduction in the in-hospital code and mortality rates.

Exercise Induced Left Bundle Branch Block Accompanied by Chest Pain

Exercise-induced left bundle branch block is a rare condition that has been reported along with and without demonstrable cardiac abnormalities. We describe the case of a 73-year-old female with chest pain on execration. Coronary angiography revealed normal findings. She underwent a treadmill stress test. During the exercise left bundle branch block with concomitant chest pain was demonstrated. Chest pain was relieved with cessation of exercise.

A Reverse Dipping Pattern Predicts Cardiovascular Mortality In a Clinical Cohort

An abnormal dipping pattern in ambulatory blood pressure monitoring (ABPM) is a cardiovascular (CV) risk factor. However, its impact on CV mortality has not been investigated sufficiently in clinical practice to be considered a standard parameter. We assessed the association between abnormal dipping patterns and increased CV mortality in a tertiary hospital in Korea. Our retrospective cohort study included 401 patients who underwent ABPM between 1994 and 1996 in Hanyang University Hospital, Seoul, Korea. The patients were classified as risers ( or =0% drop, n=294). The follow-up period was 120 months. The frequency of CV mortality was 14.0% in risers and 5.8% in others. A Cox regression analysis found a significant association between dipping pattern and CV mortality, after adjusting for age, gender, body mass index, hypertension, diabetes mellitus, smoking and hypercholesterolemia. Risers were at greater risk of CV death than others (RR, 3.02, P=0.022), but there was no difference in event rates between dippers and non-dippers. The reverse dipping pattern may be more frequent in clinical settings than in the population at large, and it is strongly associated with increased risk of CV mortality in Korea.

Correlation between Proximal Abdominal Aortic Stiffness Measured by Ultrasound and Brachial-Ankle Pulse Wave Velocity

BACKGROUND AND OBJECTIVES: The proximal portion of the abdominal aorta (AA) is characterized by minimal arteriosclerosis compared with other aortic segments. To assess the clinical usefulness of this characteristic, the correlation between ultrasonographically measured proximal AA stiffness and brachial-ankle pulse wave velocity (baPWV) was examined. SUBJECTS AND METHODS: 285 subjects were analyzed, half with hypertension and half with normal blood pressure. Proximal AA was examined using ultrasonography; strain, distensibility, elastic modulus, and the stiffness index were determined. After adjustment for age, gender, body mass index (BMI), systolic blood pressure (SBP), and heart rate, the relationships between baPWV and all these parameters were tested. RESULTS: The mean age of the study subjects was 58.1+/-12.8 years and the mean BMI was 24.3+/-3.8 kg/cm2. 58.9% of the subjects were female. 42.8% were hypertensive subjects. Among the hypertensive subjects, 56.0% were taking antihypertensive medication. Adjusted partial correlation coefficients for the relationship between baPWV with strain, distensibility, elastic modulus, and the stiffness index of the proximal AA were -0.203 (p=0.01), -0.121 (p=0.129), 0.304 (p=0.0001), and 0.299 (p=0.0001), respectively, in normotensive subjects. In the multivariate analyses, such correlations were observed mainly in the normotensive group, whereas there was no association among hypertensive subjects regardless of antihypertensive medication status. CONCLUSION: baPWV is moderately correlated with the stiffness parameters for the proximal AA, mainly in normotensive subjects.

A Case of Transient Ischemic Attack and Cardiomyopathy Presented with Pheochromocytoma / 대한내과학회지

Patients with pheochromocytoma show a variety of clinical symptoms secondary to excessive catecholamine secretion. Major symptoms include hypertension, headache, hyperhidrosis, and palpitation. Stroke and myocardial infarction are known to occur in patients with pheochromocytoma, but the incidence is low. Here, we describe a 45-year-old female with a previous history of transient ischemic attack and a clinical presentation mimicking acute myocardial infarction with transient takotsubo-like myocardial dysfunction. A subsequent diagnostic examination revealed a left adrenal pheochromocytoma. The patient recovered with intensive medical treatment, including alpha- and beta-adrenergic blockade. Follow-up echocardiography revealed normalized cardiac function and wall motion. Thereafter, the patient underwent a laparoscopic left adrenalectomy without complications.

A Comparison of Cornell and Sokolow-Lyon Electrocardiographic Criteria for Left Ventricular Hypertrophy in Korean Patients

BACKGROUND AND OBJECTIVES: Electrocardiography (ECG) is a cost-effective and useful method for diagnosing left ventricular hypertrophy (LVH) in a large-scale study or in clinical practice. Among ECG criteria, the Cornell product (Cor P) and Sokolow-Lyon criteria were adopted by the European Society of Hypertension-European Society of Cardiology Guidelines but have different performances among races. The aim of this study was to compare the diagnostic performance of two voltage criteria in Korean patients. SUBJECTS AND METHODS: Electrocardiography and echocardiographic LV mass of 332 (159 male, 173 female) consecutive patients were analyzed. Cornell voltage criteria and the Cor P were compared with Sokolow-Lyon voltage (Sok V) and the Sokolow-Lyon product (Sok P). The sensitivities and specificities were estimated using a receiver-operating characteristics (ROC) curve in relation to the LVH diagnosis. The sensitivities and revised cut-off values were derived at specificity levels of 90, 95, and 100%. RESULTS: The Cornell-based criteria generally showed better performance than that of the Sok V criteria and Sok P in the area under the ROC curve analysis. The revised cut-off values for the Cornell voltage criteria (20 and 16 mm for males and females, respectively) showed an improved sensitivity (19.7 and 30.3% for males and females, respectively), with a high specificity of 95%. CONCLUSION: The Cornell-based criteria had better performance than that of the Sokolow-Lyon criteria in both Korean men and women. However, revised cut-off values are needed to improve accuracy.

A Case of Acute Upper Airway Obstruction Caused by a Foreign Body in the Upper Esophagus of an Adult

Aspiration of the upper airway tract occurs most commonly in infants and children as a result of immature interaction between deglutition musculature and incomplete laryngeal reflex. Typically, the presence of a foreign body in the airway can cause difficulty in phonation, acute respiratory distress, and chronic airway infection. However, rarely, a foreign body lodged in the esophagus may also cause these problems. Although acute airway obstruction due to foreign body aspiration to the airway sometimes occurs in adults, cases involving these symptoms caused by the presence of a foreign body in the esophagus are very rare, and no such cases have been reported in Korea to date. The authors report a case of acute respiratory distress, during improving from an underlying alcoholic dilated cardiomyopathy. Stridor was observed on auscultation due to upper respiratory obstruction caused by an orthodontic prosthesis lodged within the upper esophagus.

Unilateral Pulmonary Edema: A Rare Initial Presentation of Cardiogenic Shock due to Acute Myocardial Infarction

Cardiogenic unilateral pulmonary edema (UPE) is a rare clinical entity that is often misdiagnosed at first. Most cases of cardiogenic UPE occur in the right upper lobe and are caused by severe mitral regurgitation (MR). We present an unusual case of right-sided UPE in a patient with cardiogenic shock due to acute myocardial infarction (AMI) without severe MR. The patient was successfully treated by percutaneous coronary intervention and medical therapy for heart failure. Follow-up chest Radiography showed complete resolution of the UPE. This case reminds us that AMI can present as UPE even in patients without severe MR or any preexisting pulmonary disease affecting the vasculature or parenchyma of the lung.

A Case of Transient Mid-Ventricular Ballooning Syndrome after Cardiac Arrest / 대한내과학회지

Stress-induced cardiomyopathy is characterized by transient wall-motion abnormalities involving the left ventricular apex. Emotional or physical stress might play a key role in this reversible form of cardiomyopathy, but the etiology remains unclear. Clinical features of stress-induced cardiomyopathyare similar to those of acute coronary syndrome, but there is no significant stenosis in the coronary arteries. Recently, transient mid-ventricular ballooning syndrome, a variant form of stress-induced cardiomyopathy in which only the mid-ventricle is affected, has been reported. Here, we report a case of a 42-year-old female patient who developed transient mid-ventricular ballooning syndrome after cardiac arrest during autologous fat transplantation.

Emergent Surgical Intervention for Embolization of Atrial Septal Defect Closure Device

The percutaneous transcatheter closure of secundum atrial septal defect has recently become an increasingly widespread alternative to surgical closure in many centers. Although immediate, short, and intermediate term results of percutaneous transcatheter septal closure are promising, the procedure is not free from inherent complications that could be lethal. We report a case of device embolization necessitating emergent surgical retrieval.

The Relationship between Diabetic Retinopathy and Macrovascular Complication in Patients with Type 2 Diabetes / 대한내과학회지

BACKGROUND/AIMS: Type 2 diabetes with microvascular complications is often accompanied by macrovascular complications. However, the relationship between the two complications is unclear. In this study, we determined the relationship between diabetic retinopathy and morphological changes of the carotid artery. METHODS: We analyzed the presence of plaque and mean carotid intima-media thickness (CIMT) in patients with type 2 diabetes (n = 133) using high-resolution ultrasound. The presence and severity of retinopathy were graded according to fundus photographs. RESULTS: The mean CIMT of the diabetic retinopathy (DR) group (0.111 +/- 0.048 cm) was significantly greater than that of the nondiabetic retinopathy (No DR) group (0.074 +/- 0.039 cm, p = 0.007). An abnormal mean CIMT (> 0.08 cm) was more frequently observed in the DR group (76%) than that in the No DR group (23.1%; odds ratio, 10.609; 95% confidence interval, 3.072-36.639; adjusted by age, body mass index, hypertension, and diabetes duration). Although the mean CIMT in patients with plaque was significantly greater than that of patients without plaque, no significant difference was observed between the DR (36%, 17 patients) and NoDR (18.5%, 20 patients) groups in the presence of plaque. CONCLUSIONS: Diabetic retinopathy was associated with an increased CIMT but not with atherosclerotic plaques. However, the increases in IMT were associated with the presence of plaques, which predispose patients to cardiovascular disease. These results imply that the microvascular complications of diabetes have indirect relationships with the cardiovascular complications of diabetes.

The Relationship Between Coronary Artery Calcification and Bone Mineral Density in Patients According to Their Metabolic Syndrome Status

BACKGROUND AND OBJECTIVES: The extent of coronary artery calcification (CAC) is closely related to total atherosclerotic plaque burden. However, the pathogenesis of CAC is still unclear. Conditions such as diabetes mellitus, renal failure, smoking, and chronic inflammation have been suggested to link vascular calcification and bone loss. In the present study, we hypothesized that bone loss can contribute to the pathogenesis of CAC in patients with the chronic inflammatory condition that accompanies metabolic syndrome (MetS). The objective of this study was to investigate the relationship between CAC and bone mineral density (BMD) in patients with MetS and in patients without MetS, by using coronary multidetector-row computed tomography (MDCT). SUBJECTS AND METHODS: Data from 395 consecutive patients was analyzed retrospectively. From the MDCT database, only those patients who underwent both coronary MDCT and dual-energy X-ray absorptiometry within an interval of one month, were selected. The presence of MetS was determined by the updated criteria as defined by the Third Adult Treatment Panel Report of the National Cholesterol Education Program. RESULTS: In patients with MetS, a significant correlation was found between CAC and age {odds ratio (OR)=1.139, 95% confidence interval (CI) 1.080 to 1.201, p<0.001}, CAC and male sex (OR=3.762, 95% CI 1.339 to 10.569, p=0.012), and CAC and T-score of L-spine (OR=0.740, 95% CI 0.550 to 0.996, p=0.047) using a forward multiple logistic regression analysis model including clinical variables of gender, age, lipid profile, body mass index, diabetes mellitus, hypertension, smoking, and BMD. But in patients without MetS, BMD by itself was not found to contribute to CAC. CONCLUSION: BMD was inversely correlated with CAC only in patients with MetS. This finding suggests that low BMD accompanied by MetS, may have significant clinical implications.

The Relationship Between Coronary Artery Calcification and Bone Mineral Density in Patients According to Their Metabolic Syndrome Status

BACKGROUND AND OBJECTIVES: The extent of coronary artery calcification (CAC) is closely related to total atherosclerotic plaque burden. However, the pathogenesis of CAC is still unclear. Conditions such as diabetes mellitus, renal failure, smoking, and chronic inflammation have been suggested to link vascular calcification and bone loss. In the present study, we hypothesized that bone loss can contribute to the pathogenesis of CAC in patients with the chronic inflammatory condition that accompanies metabolic syndrome (MetS). The objective of this study was to investigate the relationship between CAC and bone mineral density (BMD) in patients with MetS and in patients without MetS, by using coronary multidetector-row computed tomography (MDCT). SUBJECTS AND METHODS: Data from 395 consecutive patients was analyzed retrospectively. From the MDCT database, only those patients who underwent both coronary MDCT and dual-energy X-ray absorptiometry within an interval of one month, were selected. The presence of MetS was determined by the updated criteria as defined by the Third Adult Treatment Panel Report of the National Cholesterol Education Program. RESULTS: In patients with MetS, a significant correlation was found between CAC and age {odds ratio (OR)=1.139, 95% confidence interval (CI) 1.080 to 1.201, p<0.001}, CAC and male sex (OR=3.762, 95% CI 1.339 to 10.569, p=0.012), and CAC and T-score of L-spine (OR=0.740, 95% CI 0.550 to 0.996, p=0.047) using a forward multiple logistic regression analysis model including clinical variables of gender, age, lipid profile, body mass index, diabetes mellitus, hypertension, smoking, and BMD. But in patients without MetS, BMD by itself was not found to contribute to CAC. CONCLUSION: BMD was inversely correlated with CAC only in patients with MetS. This finding suggests that low BMD accompanied by MetS, may have significant clinical implications.