Prognostic and Safety Implications of Renin-Angiotensin-Aldosterone System Inhibitors in Hypertrophic Cardiomyopathy: A Real-World Observation Over 2,000 Patients

Background and Objectives@#The prognostic or safety implication of renin-angiotensinaldosterone system inhibitors (RASi) in hypertrophic cardiomyopathy (HCM) are not well established, mainly due to concerns regarding left ventricular outflow tract (LVOT) obstruction aggravation. We investigated the implications of RASi in a sizable number of HCM patients. @*Methods@#We enrolled 2,104 consecutive patients diagnosed with HCM in 2 tertiary university hospitals and followed up for five years. RASi use was defined as the administration of RASi after diagnostic confirmation of HCM. The primary and secondary outcomes were all-cause mortality and hospitalization for heart failure (HHF). @*Results@#RASi were prescribed to 762 patients (36.2%). During a median follow-up of 48.1months, 112 patients (5.3%) died, and 94 patients (4.5%) experienced HHF. Patients using RASi had less favorable baseline characteristics than those not using RASi, such as older age, more frequent history of comorbidities, and lower ejection fraction. Nonetheless, there was no difference in clinical outcomes between patients with and without RASi use (log-rank p=0.368 for all-cause mortality and log-rank p=0.443 for HHF). In multivariable analysis, patients taking RASi showed a comparable risk of all-cause mortality (hazard ratio [HR], 0.70, 95% confidence interval [CI], 0.43–1.14, p=0.150) and HHF (HR, 1.03, 95% CI, 0.63–1.70, p=0.900). In the subgroup analysis, there was no significant interaction of RASi use between subgroups stratified by LVOT obstruction, left ventricular (LV) ejection fraction, or maximal LV wall thickness. @*Conclusions@#RASi use was not associated with worse clinical outcomes. It might be safely administered in patients with HCM if clinically indicated.

Clinical Practice Guideline: Clinical Efficacy of Nasal Surgery in the Treatment of Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a common disorder characterized by upper airway obstruction during sleep. To reduce the morbidity of OSA, sleep specialists have explored various methods of managing the condition, including manifold positive airway pressure (PAP) techniques and surgical procedures. Nasal obstruction can cause significant discomfort during sleep, and it is likely that improving nasal obstruction would enhance the quality of life and PAP compliance of OSA patients. Many reliable studies have offered evidence to support this assumption. However, few comprehensive guidelines for managing OSA through nasal surgery encompass all this evidence. In order to address this gap, the Korean Society of Otorhinolaryngology-Head and Neck Surgery (KORL-HNS) and the Korean Society of Sleep and Breathing designated a guideline development group (GDG) to develop recommendations for nasal surgery in OSA patients. Several databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers using a predefined search strategy. The types of nasal surgery included septoplasty, turbinate surgery, nasal valve surgery, septorhinoplasty, and endoscopic sinus surgery. When insufficient evidence was found, the GDG sought expert opinions and attempted to fill the evidence gap. Evidence-based recommendations for practice were ranked according to the American College of Physicians’ grading system. The GDG developed 10 key action statements with supporting text to support them. Three statements are ranked as strong recommendations, three are only recommendations, and four can be considered options. The GDG hopes that this clinical practice guideline will help physicians make optimal decisions when caring for OSA patients. Conversely, the statements in this guideline are not intended to limit or restrict physicians’ care based on their experience and assessment of individual patients.

Pneumothorax Induced by Automatic Positive Airway Pressure Therapy for Obstructive Sleep Apnea: A Rare Case Report and Review of the Literature

Positive airway pressure (PAP) therapy is known to be an effective treatment for obstructive sleep apnea (OSA) that does not generally have serious complications. However, pneumothorax following lung barotrauma with the use of PAP has rarely been reported. We recently experienced the case of a 72-year old male patient with chronic obstructive pulmonary disease who developed pneumothorax after the use of automatic PAP (APAP). After 4 months of APAP use with a pressure of 4–8 cm H2O, he complained of sudden severe dyspnea at midnight. He eventually underwent surgical repair for pneumothorax. After 4 months, continuous PAP with low pressure of 5 cm H2O was applied without any complications. In summary, we emphasize the risk of barotrauma when PAP is used by OSA patients with lung disease.

A Rare Adult Case of Choristoma in Nasopharynx Obstructing the Eustachian Tube: Case Report and Review of the Literature / 대한이비인후과학회지

Choristoma, also known as a hairy polyp, is a rare benign mass that commonly occurs in the nasopharynx and oropharynx in the head and neck region. It is usually diagnosed in children and has rarely been reported in adults. In this study, we describe a nasopharyngeal choristoma in an adult man. The mass was located at the lateral nasopharyngeal wall, and the patient expressed intermittent nasal stuffiness and ear fullness. The mass was successfully removed using an endoscopic approach. Since nasopharyngeal choristoma in adults is rare, it is important to distinguish it from other benign tumors located in the nasopharynx or nasal cavity. In this report, we describe the radiologic characteristics of nasopharyngeal choristoma and summarize the importance of differential diagnosis from other benign masses.

J-curve relationship between corrected QT interval and mortality in acute heart failure patients

Background/Aims@#This study investigated the prognostic power of corrected QT (QTc) interval in patients with acute heart failure (AHF) according to sex. @*Methods@#We analyzed multicenter Korean Acute Heart Failure registry with patients with AHF admitted from 2011 to 2014. Among them, we analyzed 4,990 patients who were followed up to 5 years. Regarding QTc interval based on 12 lead electrocardiogram, patients were classified into quartiles according to sex. @*Results@#During follow-up with median 43.7 months, 2,243 (44.9%) patients died. The relationship between corrected QT interval and all-cause mortality followed a J-curve relationship. In Kaplan-Meier analysis, both sex had lowest mortality in the second QTc quartile. There were significant prognostic differences between the second and the fourth quartiles in male (log-rank p = 0.002), but not in female (log-rank p = 0.338). After adjusting covariates, the third (hazard ratio [HR], 1.185; 95% confidence interval [CI], 1.001 to 1.404; p = 0.049) and the fourth (HR, 1.404; 95% CI, 1.091 to 1.535; p = 0.003) quartiles demonstrated increased risk of mortality compared to the second quartile in male. In female, however, there was no significant difference across quartiles. QTc interval was associated with 5-year all-cause mortality in J-shape with nadir of 440 to 450 ms in male and 470 to 480 ms in female. @*Conclusions@#QTc interval was an independent predictor of overall death in male, but its significance decreased in female. The relationship between QTc interval and all-cause mortality was J-shaped in both sex.

Angiotensin II Type 1 Receptor Blocker, Fimasartan, Reduces Vascular Smooth Muscle Cell Senescence by Inhibiting the CYR61 Signaling Pathway

BACKGROUND AND OBJECTIVES@#Angiotensin II (Ang II) has been suggested to accelerate vascular senescence, however the molecular mechanism(s) remain unknown.@*METHODS@#We cultured human coronary artery smooth muscle cells (hCSMCs) and treated Ang II and/or fimasartan. Or we transfected adenoviral vectors expressing CYR61 (Ad-CYR61) or antisense CYR61 (Ad-As-CYR61). Cellular senescence was evaluated senescence-associated β-galactosidase (SA-β-gal) assay. The molecular mechanisms were investigated real-time PCR and western blots.@*RESULTS@#SA-β-gal-positive cells significantly increased in Ang II-treated hCSMCs (5.77±1.43-fold compared with the control). The effect of Ang II was significantly attenuated by pretreatment with the Ang II type 1 receptor blocker, fimasartan (2.00±0.92-fold). The expression of both p53 and p16 senescence regulators was significantly increased by Ang II (p53: 1.39±0.17, p16: 1.19±0.10-fold vs. the control), and inhibited by fimasartan. Cysteine-rich angiogenic protein 61 (CYR61) was rapidly induced by Ang II. Compared with the control, Ad-CYR61-transfected hCSMCs showed significantly increased SA-β-gal-positive cells (3.47±0.65-fold). Upon transfecting Ad-AS-CYR61, Ang II-induced senescence (3.74±0.23-fold) was significantly decreased (1.77±0.60-fold). p53 expression by Ang II was significantly attenuated by Ad-AS-CYR61, whereas p16 expression was not regulated. Ang II activated ERK1/2 and p38 MAPK, which was significantly blocked by fimasartan. ERK and p38 inhibition both regulated Ang II-induced CYR61 expression. However, p53 expression was only regulated by ERK1/2, whereas p16 expression was only attenuated by p38 MAPK.@*CONCLUSIONS@#Ang II induced vascular senescence by the ERK/p38 MAPK–CYR61 pathway and ARB, fimasartan, protected against Ang II-induced vascular senescence.

Usefulness of Measuring Airway Length with Cephalometry in Pediatric Subjects with Obstructive Sleep Apnea

Angiotensin II Type 1 Receptor Blocker, Fimasartan, Reduces Vascular Smooth Muscle Cell Senescence by Inhibiting the CYR61 Signaling Pathway

BACKGROUND AND OBJECTIVES: Angiotensin II (Ang II) has been suggested to accelerate vascular senescence, however the molecular mechanism(s) remain unknown. METHODS: We cultured human coronary artery smooth muscle cells (hCSMCs) and treated Ang II and/or fimasartan. Or we transfected adenoviral vectors expressing CYR61 (Ad-CYR61) or antisense CYR61 (Ad-As-CYR61). Cellular senescence was evaluated senescence-associated β-galactosidase (SA-β-gal) assay. The molecular mechanisms were investigated real-time PCR and western blots. RESULTS: SA-β-gal-positive cells significantly increased in Ang II-treated hCSMCs (5.77±1.43-fold compared with the control). The effect of Ang II was significantly attenuated by pretreatment with the Ang II type 1 receptor blocker, fimasartan (2.00±0.92-fold). The expression of both p53 and p16 senescence regulators was significantly increased by Ang II (p53: 1.39±0.17, p16: 1.19±0.10-fold vs. the control), and inhibited by fimasartan. Cysteine-rich angiogenic protein 61 (CYR61) was rapidly induced by Ang II. Compared with the control, Ad-CYR61-transfected hCSMCs showed significantly increased SA-β-gal-positive cells (3.47±0.65-fold). Upon transfecting Ad-AS-CYR61, Ang II-induced senescence (3.74±0.23-fold) was significantly decreased (1.77±0.60-fold). p53 expression by Ang II was significantly attenuated by Ad-AS-CYR61, whereas p16 expression was not regulated. Ang II activated ERK1/2 and p38 MAPK, which was significantly blocked by fimasartan. ERK and p38 inhibition both regulated Ang II-induced CYR61 expression. However, p53 expression was only regulated by ERK1/2, whereas p16 expression was only attenuated by p38 MAPK. CONCLUSIONS: Ang II induced vascular senescence by the ERK/p38 MAPK–CYR61 pathway and ARB, fimasartan, protected against Ang II-induced vascular senescence.

The Relationship between the Causative Allergens of Allergic Diseases and Environments in Korea Over a 8-Year-Period: Based on Skin Prick Test from 2006 to 2015

BACKGROUND AND OBJECTIVES: The present study evaluated the results of skin prick test using 55 allergens at 20 centers in the Republic of Korea in 2006, 2010, and 2014–2015. The aim was to assess changes in the positive rate of allergens according to temporal, regional, and environmental factors. MATERIALS AND METHODS: In total, 20 hospitals were selected based on the population distribution in the Republic of Korea. A skin prick test panel comprising 55 aeroallergens was distributed to 18 hospitals for this prospective study. The 2006 and 2010 skin prick test results were collected and analyzed retrospectively from 20 hospitals, while the 2014/2015 skin prick test results (from June 2014 to May 2015) were collected prospectively from 18 hospitals. RESULTS: A total of 14,897 SPT test results were analyzed: 4,319 in 2006, 7,431 in 2010, and 1,852 in 2014/2015. The overall rate of skin prick test positivity to more than two allergens was significantly higher in males than females. The positive rates of alder pollens and birch, oak and ragweed pollen positivity were increased in older patients. Several positive rates were increased according to the temperature in spring. The positive rates for beech pollen, birch pollen, hazel pollen, oak pollen, Tyrophagus putrescentiae, mugwort, cat, Acarus siro, Lepidoglyphus destructor and Tyrophagus putrescentiae were significantly increased, while those of Cult rye pollen and dandelion were significantly decreased over the three test periods. The overall positive rate for allergens in Jeju province varied significantly from Seoul and other cities. CONCLUSION: Change in the positive rate of multiple aeroallergens was evaluated in the Republic of Korea over time. Our findings can be used to recommend aeroallergens suitable for inclusion in skin prick test panels in the Republic of Korea and will facilitate further investigation of changes in the patterns of allergic diseases.

Body fluid status assessment by bio-impedance analysis in patients presenting to the emergency department with dyspnea

BACKGROUND/AIMS: Fluid retention occurs in patients with heart failure, accounting for dyspnea. We investigated the diagnostic implication of body fluid status, assessed by bio-impedance analysis (BIA), in acute heart failure (AHF) among patients who presented with dyspnea. METHODS: A total of 100 patients who presented with dyspnea and suspected with AHF were analyzed in this study. We enrolled 50 AHF and 50 non-AHF patients discriminated through echocardiographic analysis and Framingham criteria and were matched by age and sex. Body composition was analyzed using a multifrequency BIA. RESULTS: AHF patients demonstrated higher extracellular water (ECW)/total body water (TBW) compared with non-AHF patients (0.412 ± 0.017 vs. 0.388 ± 0.023, p 0.412 at lower extremities with sensitivity and specificity of 0.780 and 0.960. The ECW/TBW of the lower extremities (ECW/TBWL) was correlated with log B-type natriuretic peptide (BNP) levels (r = 0.603, p 0.412 had an independent association with AHF patients (p = 0.011). CONCLUSIONS: The ECW/TBWL was higher in patients with dyspnea caused by AHF than their counterparts and demonstrated an independent diagnostic implication. It may be a promising marker to diagnose AHF at bedside.

Relation of Renal Function with Left Ventricular Systolic Function and NT-proBNP Level and Its Prognostic Implication in Heart Failure with Preserved versus Reduced Ejection Fraction: an analysis from the Korean Heart Failure (KorHF) Registry

BACKGROUND AND OBJECTIVES: The relationship between ejection fraction (EF), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and renal function is unknown as stratified by heart failure (HF) type. We investigated their relation and the prognostic value of renal function in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction (HFrEF). MATERIALS AND METHODS: NT-proBNP, glomerular filtration rate (GFR), and EF were obtained in 1,932 acute heart failure (AHF) patients. HFrEF was defined as EF<50%, and renal dysfunction as GFR<60 mL/min/1.73 m² (mild renal dysfunction: 30≤GFR<60 mL/min/1.73 m²; severe renal dysfunction: GFR<30 mL/min/1.73 m²). The primary outcome was 12-month all-cause death. RESULTS: There was an inverse correlation between GFR and log NT-proBNP level (r=−0.298, p<0.001), and between EF and log NT-proBNP (r=−0.238, p<0.001), but no correlation between EF and GFR (r=0.017, p=0.458). Interestingly, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF (49% vs. 52%, p=0.210). Patients with renal dysfunction had higher 12-month mortality in both HFpEF (7.9% vs. 15.2%, log-rank p=0.008) and HFrEF (8.6% vs. 16.8%, log-rank p<0.001). Multivariate analysis showed severe renal dysfunction was an independent predictor of 12-month mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.40–3.11). When stratified according to EF: the prognostic value of severe renal dysfunction was attenuated in HFpEF patients (HR, 1.46; 95% CI, 0.66–3.21) contrary to HFrEF patients (HR, 2.43; 95% CI, 1.52–3.89). CONCLUSION: In AHF patients, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF patients. However, the prognostic value of renal dysfunction was attenuated in HFpEF patients.

Prognostic Implication of the QRS Axis and its Association with Myocardial Scarring in Patients with Left Bundle Branch Block

BACKGROUND AND OBJECTIVES: Left bundle branch block (LBBB) with left axis deviation (LAD) has a worse prognosis than LBBB with a normal axis, and myocardial dysfunction has been suggested as a cause of left axis deviation. This study investigated the prognostic significance of the QRS axis in patients with LBBB and analyzed its relationship with the amount of myocardial scarring. SUBJECTS AND METHODS: A total of 829 patients were diagnosed with LBBB at Seoul National University Hospital from October 2004 to June 2014. Of these, 314 who were asymptomatic and had no previous history of cardiac disease were included in the present study. Myocardial scarring was calculated using the Selvester QRS scoring system, and LAD was defined as a QRS axis between -180° and -30°. RESULTS: Of the total patients, 91 (29%) had LAD, and patients were followed for a median of 30 months. During follow-up, two patients were hospitalized for de novo heart failure, four had pacemaker implants, and 10 died. There was a significant inverse correlation between myocardial scar score and the QRS axis (r=-0.356, p<0.001). Patients with concomitant LAD had a higher rate of major cardiac adverse events compared with patients with a normal axis (5.5% vs. 1.3%, log-rank p=0.010); the prognostic value was attenuated in multivariable analysis (hazard ratio 4.117; 95% confidence interval 0.955-17.743; p=0.058). CONCLUSION: Concomitant LAD is an indicator of poor prognosis for patients with LBBB and may be associated with greater myocardial scarring.

Guidelines for the Antibiotic Use in Adults with Acute Upper Respiratory Tract Infections

These guidelines were developed as part of the 2016 Policy Research Servicing Project by the Korea Centers for Disease Control and Prevention. A multidisciplinary approach was taken to formulate this guideline to provide practical information about the diagnosis and treatment of adults with acute upper respiratory tract infection, with the ultimate aim to promote the appropriate use of antibiotics. The formulation of this guideline was based on a systematic literature review and analysis of the latest research findings to facilitate evidence-based practice, and focused on key questions to help clinicians obtain solutions to clinical questions that may arise during the care of a patient. These guidelines mainly cover the subjects on the assessment of antibiotic indications and appropriate selection of antibiotics for adult patients with acute pharyngotonsillitis or acute sinusitis.

Congenital Absence of Superior Vena Cava with no Manifestation of Superior Vena Cava Syndrome

Total absence of superior vena cava (SVC) is a very rare anomaly, and the patient usually suffers from SVC syndrome or conduction disturbances. We report an asymptomatic 27 year-old male, with complete absence of SVC. Transthoracic echocardiography and computed tomography demonstrated the absence of SVC and other congenital cardiac anomalies, but the presence of prominent collateral vessels that allow a sufficient venous return.

Huge Left Ventricular Thrombus and Apical Ballooning associated with Recurrent Massive Strokes in a Septic Shock Patient / 대한구급학회지

The most feared complication of left ventricular thrombus (LVT) is the occurrence of systemic thromboembolic events, especially in the brain. Herein, we report a patient with severe sepsis who suffered recurrent devastating embolic stroke. Transthoracic echocardiography revealed apical ballooning of the left ventricle with a huge LVT, which had not been observed in chest computed tomography before the stroke. This case emphasizes the importance of serial cardiac evaluation in patients with stroke and severe medical illness.

The Association between Parameters of Socioeconomic Status and Hypertension in Korea: the Korean Genome and Epidemiology Study

We investigated the association between socioeconomic status and hypertension in Korea, a country that has experienced a dynamic socioeconomic transition. We analyzed participants of a prospective cohort study—the Korean Genome and Epidemiology Study—enrolled between 2001 and 2003. We recruited 7,089 subjects who underwent a 4-year follow up till 2007. Education and income levels, which are important parameters for socioeconomic status, were stratified into 4 groups. Education level was defined as short (≤ 6 years), mid-short (7–9 years), mid-long (10–12 years), and long (≥ 12 years). Monthly income level was stratified as low (< 500,000 KRW), mid-low (500,000–1,499,999 KRW), mid-high (1,500,000–2,999,999 KRW) or high (≥ 3,000,000 KRW). At baseline, 2,805 subjects (39.5%) were diagnosed with hypertension. Education and income levels were inversely associated with the prevalence and incidence of hypertension (P < 0.001). In multivariate analysis, a shorter duration of education was significantly associated with a higher prevalence of hypertension (P < 0.001), but income level was not (P = 0.305). During the follow-up, 605 subjects (14.2%) were newly diagnosed with hypertension. In multivariate adjusted analysis, the hazard ratios (95% confidence interval) for incident hypertension across the longer education groups were 0.749 (0.544–1.032), 0.639 (0.462–0.884), and 0.583 (0.387–0.879), compared with the shortest education group. There was no significant association between incident hypertension and income across higher income groups: 0.988 (0.714–1.366), 0.780 (0.542–1.121), and 0.693 (0.454–1.056), compared with the lowest income group. In conclusion, education and income levels are associated with the prevalence and incidence of hypertension, but only education is an independent prognostic factor in Korea.

Huge Left Ventricular Thrombus and Apical Ballooning associated with Recurrent Massive Strokes in a Septic Shock Patient / 대한중환자의학회지

The most feared complication of left ventricular thrombus (LVT) is the occurrence of systemic thromboembolic events, especially in the brain. Herein, we report a patient with severe sepsis who suffered recurrent devastating embolic stroke. Transthoracic echocardiography revealed apical ballooning of the left ventricle with a huge LVT, which had not been observed in chest computed tomography before the stroke. This case emphasizes the importance of serial cardiac evaluation in patients with stroke and severe medical illness.

Correlation Between Salivary Alpha-Amylase Level and Heart Rate Variability in Pediatric Subjects with Sleep-Disordered Breathing

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the relationship between salivary alpha-amylase (sAA) and heart rate variability (HRV) indices in SDB children based on objective parameters of polysomnography (PSG). MATERIALS AND METHOD: This prospective study enrolled 67 children who underwent a physical examination and full-attended in-lab PSG with continuous electrocardiographic signal. The sAA were measured at night before PSG and in the early morning after PSG. RESULTS: The subjects were divided into control [n=26, apnea-hypopnea index (AHI)≤1] and obstructive sleep apnea syndrome (OSAS, n=41, AHI>1) groups; the OSAS group was subdivided into mild (1

Acute Myocardial Infarction Occurring at a Preexisting Intermediate Coronary Artery Stenosis / 대한내과학회지

Acute myocardial infarction often evolves from a mild coronary lesion. Therefore, the evaluation and management of intermediate coronary stenosis are important to prevent cardiac events. However, the decision on how to treat these lesions is challenging. Here, we report acute myocardial infarction occurring at a preexisting intermediate coronary stenosis based on invasive coronary angiography performed 10 days before the event.

Anatomical Analysis of Intraorbital Structures Regarding Sinus Surgery Using Multiplanar Reconstruction of Computed Tomography Scans

OBJECTIVES: This study aimed to investigate the anatomy of the intraorbital structures regarding to endoscopic sinus surgery and external frontal sinus surgery analyzing computer tomography (CT) scans. METHODS: The CT scans of 100 patients were retrospectively evaluated. The anatomic relationships between the intraorbital structures and paranasal structures were measured using multiplanar reconstruction of the CT scan. RESULTS: The mean distances from the medial orbital floor (MOF) to the intraorbital structures were measured at the depth of the anterior ethmoid (AE), basal lamella (BL), and midportion of posterior ethmoid (PE) in the coronal planes respectively. The mean distances from the MOF to the medial rectus muscle and inferior rectus muscle at the depth of AE were approximately 8 mm and those distances in the BL and PE decreased rapidly. The mean distances from the MOF to the infraorbital nerve at the depth of the AE and BL were approximately more than 10 mm. The mean distances from the vertical axis, which passed through the MOF, to the superior oblique muscle and optic nerve at the depth of the PE were approximately 5 mm medially and 1 mm laterally. In addition, the mean distance from the midline to the trochlea of the superior oblique muscle was approximately 15 mm. CONCLUSIONS: Those measurements provide spatial information on the placements of the extraocular muscles within the orbit. The measurements will contribute to the avoidance of orbital complications during sinus surgery.