Benefits from the Early Initiation of Macitentan for Pulmonary Arterial Hypertension

No abstract available.

Clinical Presentation with High Penetrance in a Korean Family with Pulmonary Arterial Hypertension Associated with a BMPR2 Intron 3 Splice Site Pathogenic Variant

Pathogenic variants of bone morphogenic protein receptor type 2 gene (BMPR2) are related to the majority of cases of heritable pulmonary arterial hypertension (PAH). Over 400 pathogenic variants have been identified. However, clinical characterization of PAH is still incomplete. We present a case of heritable PAH in a Korean family showing serious clinical presentation with high penetrance. Genetic sequencing revealed a known heterozygous BMPR2 pathogenic variant, c.418+5G>A, at a splice site of intron 3. Serious clinical presentation with high penetrance suggested that the interplay of other factors with pathologic variants might be in genotype-phenotype correlation. Further studies are needed to clarify these issues for the development of personalized medicine approaches for PAH.

Echocardiographic, Electrocardiographic Changes and Clinical Outcomes of Patients Who Respond to Cardiac Resynchronization Therapy after One Year

BACKGROUND: Response to cardiac resynchronization therapy (CRT) is commonly assessed after 6 or 12 months. We evaluated subsequent echocardiographic changes, serial QRS duration, and clinical outcomes in patients showing delayed responses to CRT after 12 months. METHODS: Among all patients who received CRT in Seoul St. Mary's Hospital, 36 one-year survivors were enrolled. Indicators of a positive CRT response were ≥ 15% reduction in left ventricular end-systolic volume (LVESV) or ≥ 10% increase in left ventricular ejection fraction (LVEF) on any follow up echocardiogram. We defined the early responders as patients responding before one year, the late responders as patients responding after one year, and the non-responders as patients who did not respond on any follow-up echocardiogram. RESULTS: We identified 17 early responders, 10 late responders, and 9 non-responders. The late responders showed modest improvement in LVESV and LVEF at two years after CRT. QRS duration was shortened the day after CRT in all three groups. Narrowed QRS was maintained for two years in early and late responders, whereas it was continuously prolonged over time in non-responders. Incidence of all-cause death or heart failure hospitalization was comparable between early and late responders, while non-responders showed worst prognosis. CONCLUSION: Patients responding to CRT after one year show modest echocardiographic improvement but clinical outcome is similar to early responders. Shorter baseline QRS duration and long-term maintenance of QRS duration shortening are important features of the late responders to CRT.

Association between left ventricular function and paraprotein type in patients with multiple myeloma

BACKGROUND/AIMS: Multiple myeloma (MM)–associated cardiac damage, particularly according to the type of monoclonal (M) protein has not been elucidated. We sought to investigate relationship between elevated serum M protein levels and echocardiographic indices of cardiac structure and function in patients with MM. METHODS: We evaluated a total of 184 consecutive MM patients who underwent echocardiography for bone marrow pre-transplant screening. Serum levels of intact immunoglobulin M protein and free light chain kappa/lambda (FLC-κ/-λ) were measured. RESULTS: One hundred thirty-nine patients were non-light chain MM (non-LCMM) and 45 patients belonged to LCMM. In patients with non-LCMM, significant correlations were found between serum M protein and left atrial volume index (LAVi; r = 0.720, p < 0.0001), E/e’ (r = 0.511, p < 0.0001), and systolic pulmonary arterial pressure (r = 0.485, p < 0.0001). In patients with LCMM, log-transformed FLC-λ (log-λ) was correlated with left ventricular ejection fraction (LVEF, r = –0.536, p = 0.010), left ventricular (LV) end-systolic dimension (r = 0.500, p = 0.018), and LV end-systolic volume (r = 0.444, p = 0.038). On multivariate analyses, hematocrit and serum M protein were independent predictors of LAVi in patients with non-LCMM. In patient with LCMM, FLC-λ isotype was only found to be an independent determinant of LVEF. CONCLUSIONS: An increase in serum M protein was associated with LV diastolic dysfunction, whereas an increase in serum FLC-λ concentration showed a negative correlation with the echocardiographic parameters of LV systolic function. These findings also suggest that serum M protein has different effects on LV function according to the type of paraproteins in patients with MM.

Association between left ventricular function and paraprotein type in patients with multiple myeloma

BACKGROUND/AIMS: Multiple myeloma (MM)–associated cardiac damage, particularly according to the type of monoclonal (M) protein has not been elucidated. We sought to investigate relationship between elevated serum M protein levels and echocardiographic indices of cardiac structure and function in patients with MM. METHODS: We evaluated a total of 184 consecutive MM patients who underwent echocardiography for bone marrow pre-transplant screening. Serum levels of intact immunoglobulin M protein and free light chain kappa/lambda (FLC-κ/-λ) were measured. RESULTS: One hundred thirty-nine patients were non-light chain MM (non-LCMM) and 45 patients belonged to LCMM. In patients with non-LCMM, significant correlations were found between serum M protein and left atrial volume index (LAVi; r = 0.720, p < 0.0001), E/e’ (r = 0.511, p < 0.0001), and systolic pulmonary arterial pressure (r = 0.485, p < 0.0001). In patients with LCMM, log-transformed FLC-λ (log-λ) was correlated with left ventricular ejection fraction (LVEF, r = –0.536, p = 0.010), left ventricular (LV) end-systolic dimension (r = 0.500, p = 0.018), and LV end-systolic volume (r = 0.444, p = 0.038). On multivariate analyses, hematocrit and serum M protein were independent predictors of LAVi in patients with non-LCMM. In patient with LCMM, FLC-λ isotype was only found to be an independent determinant of LVEF. CONCLUSIONS: An increase in serum M protein was associated with LV diastolic dysfunction, whereas an increase in serum FLC-λ concentration showed a negative correlation with the echocardiographic parameters of LV systolic function. These findings also suggest that serum M protein has different effects on LV function according to the type of paraproteins in patients with MM.

Current Awareness and Use of the Strain Echocardiography in Routine Clinical Practices: Result of a Nationwide Survey in Korea

BACKGROUND: Because conventional echocardiographic parameters have several limitations, strain echocardiography has often been introduced in clinical practice. However, there are also obstacles in using it in clinical practice. Therefore, we wanted to find the current status of awareness on using strain echocardiography in Korea. METHODS: We conducted a nationwide survey to evaluate current use and awareness of strain echocardiography from the members of the Korean Society of Echocardiography. RESULTS: We gathered total 321 questionnaires from 25 cardiology centers in Korea. All participants were able to perform or interpret echocardiographic examinations. All participating institutions performed strain echocardiography. Most of our study participants (97%) were aware of speckle tracking echocardiography and 185 (58%) performed it for clinical and research purposes. Two-dimensional strain echocardiography was the most commonly used modality and left ventricle (LV) was the most commonly used cardiac chamber (99%) for clinical purposes. Most of the participants (89%) did not think LV strain can replace LV ejection fraction (LVEF) in their clinical practice. The common reasons for not performing routine use of strain echocardiography was diversity of strain measurements and lack of normal reference value. Many participants had a favorable view of the future of strain echocardiography. CONCLUSION: Most of our study participants were aware of strain echocardiography, and all institutions performed strain echocardiography for clinical and research purposes. However, they did not think the LV strain values could replace LVEF. The diversity of strain measurements and lack of normal reference values were common reasons for not using strain echocardiography in clinical practice.

Giant Right Coronary Artery with Coronary Artery Fistula Complicated by Infective Endocarditis: Multimodality Imaging Approach

No abstract available.

Normal 2-Dimensional Strain Values of the Left Ventricle: A Substudy of the Normal Echocardiographic Measurements in Korean Population Study

BACKGROUND: It is important to understand the distribution of 2-dimensional strain values in normal population. We performed a multicenter trial to measure normal echocardiographic values in the Korean population. METHODS: This was a substudy of the Normal echOcardiogRaphic Measurements in KoreAn popuLation (NORMAL) study. Echocardiographic specialists measured frequently used echocardiographic indices in healthy people according to a standardized method at 23 different university hospitals. The strain values were analyzed from digitally stored images. RESULTS: Of a total of 1003 healthy participants in NORMAL study, 2-dimensional strain values were measured in 501 subjects (265 females, mean age 47 ± 15 years old) with echocardiographic images only by GE echocardiographic machines. Interventricular septal thickness, left ventricular (LV) posterior wall thickness, systolic and diastolic LV dimensions, and LV ejection fraction were 7.5 ± 1.0 mm, 7.4 ± 1.0 mm, 29.9 ± 2.8 mm, 48.9 ± 3.6 mm, and 62 ± 4%, respectively. LV longitudinal systolic strain (LS) values of apical 4-chamber (A4C) view, apical 3-chamber (A3C) view, apical 2-chamber (A2C) view, and LV global LS (LVGLS) were −20.1 ± 2.3, −19.9 ± 2.7, −21.2 ± 2.6, and −20.4 ± 2.2%, respectively. LV longitudinal systolic strain rate (LVLSR) values of the A4C view, A3C view, A2C view, and LV global LSR (LVGLSR) were −1.18 ± 0.18, −1.20 ± 0.21, −1.25 ± 0.21, and −1.21 ± 0.21(−s), respectively. Females had lower LVGLS (−21.2 ± 2.2% vs. −19.5 ± 1.9%, p < 0.001) and LVGLSR (−1.25 ± 0.18(−s) vs. −1.17 ± 0.15(−s), p < 0.001) values than males. CONCLUSION: We measured LV longitudinal strain and strain rate values in the normal Korean population. Since considerable gender differences were observed, normal echocardiographic cutoff values should be differentially applied based on sex.

Normal Echocardiographic Measurements in a Korean Population Study: Part II. Doppler and Tissue Doppler Imaging

BACKGROUND: Hemodynamic and functional evaluation with Doppler and tissue Doppler study as a part of comprehensive echocardiography is essential but normal reference values have never been reported from Korean normal population especially according to age and sex. METHODS: Using Normal echOcaRdiographic Measurements in a KoreAn popuLation study subjects, we obtained normal reference values for Doppler and tissue Doppler echocardiography including tricuspid annular velocities according to current guidelines and compared values according to gender and age groups. RESULTS: Mitral early diastolic (E) and late diastolic (A) velocity as well as E/A ratio were significantly higher in women compared to those in men. Conversely, mitral peak systolic and late diastolic annular velocity in both septal and lateral mitral annulus were significantly lower in women compared to those in men. However, there were no significant differences in both septal and lateral mitral early diastolic annular (e') velocity between men and women. In both men and women, mitral E velocity and its deceleration time as well as both E/A and E/e' ratio considerably increased with age. There were no significant differences in tricuspid inflow velocities and tricuspid lateral annular velocities between men and women except e' velocity, which was significantly higher in women compared to that in men. However, changes in both tricuspid inflow and lateral annular velocities according to age were similar to those in mitral velocities. CONCLUSION: Since there were significant differences in Doppler and tissue Doppler echocardiographic variables between men and women and changes according to age were even more considerable in both gender groups, normal Doppler echocardiographic values should be differentially applied based on age and sex.

Baseline Characteristics of the Korean Registry of Pulmonary Arterial Hypertension

Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December 2011. A total of 625 patients were enrolled. The patients' mean age was 47.6 +/- 15.7 yr, and 503 (80.5%) were women. The diagnostic methods included right heart catheterization (n = 249, 39.8%) and Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency, were connective tissue disease (CTD), congenital heart disease, and idiopathic PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%) patients received combination therapy. Incident cases during the registry represented 297 patients; therefore, the incidence rate of PAH was 1.9 patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients exhibited similar age, gender, and survival rate compared with western registries, they showed relatively more CTD-PAH in the etiology and also systemic lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and more specialized therapies should be needed to improve the survival of PAH patients.

Reversible Pulmonary Arterial Hypertension Associated with Dasatinib for Chronic Myeloid Leukemia / Journal of the Korean Cancer Association, 대한암학회지

We describe two cases of pulmonary arterial hypertension (PAH) that occurred under dasatinib treatment and were resolved after dasatinib discontinuation. Two patients with chronic phase chronic myeloid leukemia (CML) were switched to dasatinib therapy because of hematological progress while receiving imatinib. These patients had New York Heart Association (NYHA) functional class II dyspnea with elevated right ventricular systolic pressure (RVSP), which progressed under dasatinib treatment. After dasatinib treatment was discontinued, subjective symptoms were improved to NYHA functional class I and the follow-up transthoracic Doppler echocardiography showed improved RVSP. Treatment with an alternate tyrosine kinase inhibitor was initiated and had been continued without development of dyspnea or elevation of RVSP. This report suggests that dasatinib can cause the reversible PAH, therefore, routine cardiopulmonary evaluation before and during treatment with dasatinib may be needed in CML patients with clinical manifestations.

Normal Echocardiographic Measurements in a Korean Population Study: Part I. Cardiac Chamber and Great Artery Evaluation

BACKGROUND: Measurement of the cardiac chamber is essential, and current guidelines recommend measuring and reporting values for both sides of the cardiac chamber during echocardiographic evaluation. Normal echocardiographic reference values have been suggested previously, but detailed information about right-sided chambers and values according to gender was not included. METHODS: This is a prospective multicenter (23 centers) study evaluating normal Korean adult subjects using comprehensive echocardiography. We included normal adult subjects (age; 20-79 years old) who had no significant cardiac disorders or illnesses, such as hypertension or diabetes, which could affect cardiac structure and function. We measured the cardiac chamber including both right and left ventricles as well as atria according to current echocardiography guidelines and compared values according to gender and age groups. RESULTS: A total of 1003 subjects were evaluated and the mean age was 48 +/- 16 years. Left ventricular (LV) dimensions increased, but LV volume decreased in older subjects. Right ventricular (RV) area decreased in women and older subjects, and the RV long-axis dimension showed a similar trend. Left atrial (LA) volume increased in men but there were no differences in LA volume index between men and women. The dimension of great arteries increased in men and older subjects. CONCLUSION: Since there were considerable differences between men and women and in the different age groups, and the trends differed significantly between different echo variables, normal echocardiographic cutoff values should be differentially applied based on age and gender.

A Case of Pulmonary Arterial Hypertension Associated with Congenital Extrahepatic Portocaval Shunt

Congenital extrahepatic portocaval shunt (CEPS) is a rare anomaly of the mesenteric vasculature in which the intestinal and splenic venous drainage bypasses the liver and drains directly into the inferior vena cava, the left hepatic vein or the left renal vein. This uncommon disease is frequently associated with other malformations and mainly affects females. Here we report a case of pulmonary arterial hypertension associated with CEPS (Abernethy type 1b shunt) in a 20-yr-old man who was incidentally diagnosed during evaluation of multiple nodules of the liver. The patient was treated by inhalation of iloprost (40 microg/day) with improved condition and walking test. Physicians should note that congenital portocaval shunt may cause pulmonary hypertension.

Gender Difference in Bone Loss and Vascular Calcification Associated with Age

BACKGROUND AND OBJECTIVES: It is widely known that both bone loss and vascular calcification are age-related processes. The purpose of this study was to investigate the relationship between coronary artery calcium (CAC) score or bone mineral density (BMD) with age and whether there is a gender difference factoring in the two conditions among healthy subjects. SUBJECTS AND METHODS: Between March 2009 and August 2011, participants included 1727 subjects (mean age: 55+/-10 years, M : F=914 : 813) with routine health check-ups. After being categorized into three groups (normal, osteopenia, and osteoporosis) according to the World Health Organization (WHO) diagnostic classification, we estimated BMD by dual energy X-ray absorptiometry (DEXA) and CAC score by dual-source CT (DSCT). RESULTS: There was a significant gender difference among the risk factors, including total-lumbar spine (1.213+/-0.176 g/cm2 : 1.087+/-0.168 g/cm2, p<0.001) and femur (1.024+/-0.131 g/cm2 : 0.910+/-0.127 g/cm2, p<0.001) in BMD by DEXA, and CAC score (68+/-227 : 27+/-116, p<0.001) in coronary artery calcification by DSCT. Age in male [odds ratio (OR): 1.138 {95% confidence interval (CI): 1.088-1.190}, p<0.001] and menopause in female subjects {OR: 12.370 (95% CI: 3.120-49.047), p<0.001} were, respectively, independently associated with osteopenia. CONCLUSION: Although our results do not demonstrate a direct association between CAC score and BMD in both genders, there is a gender difference of CAC score in normal and osteopenia groups according to the WHO diagnostic classification. Additionally, we suggest that more specific therapeutic strategies be considered during any early bone loss period, especially in female subjects.

Asymptomatic Myxoma Originating from the Right Ventricular Outflow Tract

Asymptomatic right ventricular outflow tract (RVOT) myxoma is quite rare. We report an unusual case of asymptomatic myxoma arising from the RVOT which was successfully surgically removed.

C-Type Natriuretic Peptide as a Surrogate Marker in Variant Angina Pectoris

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the value of C-type natriuretic peptide (CNP) as a surrogate marker for detection of coronary artery spasm in variant angina pectoris (VAP). SUBJECTS AND METHODS: Sixty-six patients (mean age: 51+/-11 years, M : F=40 : 26) who underwent coronary angiography on suspicion of angina and who were diagnosed with VAP by the acetylcholine-induced spasm provocation test (SPT) were enrolled and divided into a SPT (-) group (n=23) and a SPT (+) group (n=43). Concentrations of CNP and other markers were determined by immunoassay in both groups. RESULTS: Plasma CNP and creatine kinase myoglobin band (CK-MB) concentrations were significantly increased in the SPT (+) group relative to the SPT (-) group (CNP, 5.268+/-1.800 pg/mL vs. 3.342+/-1.150 pg/mL, p=0.002; CK-MB, 2.54+/-1.03 ng/dL vs. 1.86+/-0.96 ng/dL, p=0.019, respectively) while plasma high sensitivity C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT pro-BNP) concentrations were not significantly different between the SPT (-) group and SPT (+) group (hs-CRP, 2.76+/-4.99 mg/L vs. 3.13+/-4.88 mg/L, p=0.789; NT pro-BNP, 49+/-47 pg/mL vs. 57+/-63 pg/mL, p=0.818, respectively). Plasma CNP concentration was independently associated with the VAP via SPT {odds ratio: 2.014 (95% confidence interval: 1.016-3.992), p=0.045}. A CNP cut-off value of 4.096 pg/mL was found to have a sensitivity of 68.2% and a specificity of 40.0% for predicting the probability of VAP via SPT. CONCLUSION: Increased plasma CNP concentration in patients with VAP may have an impact on the regulation of endothelial function in accordance with the progression of atherosclerosis. Further analysis is warranted to develop clinical applications of this finding.

Anatomic Variants Mimicking Pathology on Echocardiography: Differential Diagnosis

Differentiation of normal from abnormal findings is critical in echocardiography. Anatomic variants occurring in normal cardiac developments often simulate pathologic entities. This review focuses on the differential diagnosis of normal anatomic structures from pathologic ones in echocardiography.

Comparison of Clinical and Imaging Characteristics and Outcomes between Provoked and Unprovoked Acute Pulmonary Embolism in Koreans

This study was performed to compare clinical and imaging parameters and prognosis of unprovoked pulmonary embolism (PE), provoked PE with reversible risk factors (provoked-rRF), and provoked PE with irreversible risk factors (provoked-iRF) in Koreans. Three hundred consecutive patients (mean age, 63.6 +/- 15.0 yr; 42.8% male) diagnosed with acute PE were included. The patients were classified into 3 groups; unprovoked PE, provoked-rRF, and provoked-iRF; 43.7%, 14.7%, and 41.7%, respectively. We followed up the patients for 25.4 +/- 33.7 months. Composite endpoint was all-cause mortality and recurrent PE. The provoked-iRF group had significantly higher all-cause mortality, mortality from PE and recurrent PE than the unprovoked and provoked-rRF groups (P 1.2 mg/dL; P 5 mg/L; P = 0.002; HR, 5.308; 95% CI, 1.824-15.447) and computed tomography (CT) obstruction index (P = 0.034; HR, 1.090; 95% CI, 1.006-1.181). In conclusion, provoked-iRF has a poorer prognosis than unprovoked PE and provoked-rRF. Renal insufficiency, high CRP, and CT obstruction index are poor prognostic factors in unprovoked PE.

Comparison of Clinical and Imaging Characteristics and Outcomes between Provoked and Unprovoked Acute Pulmonary Embolism in Koreans

This study was performed to compare clinical and imaging parameters and prognosis of unprovoked pulmonary embolism (PE), provoked PE with reversible risk factors (provoked-rRF), and provoked PE with irreversible risk factors (provoked-iRF) in Koreans. Three hundred consecutive patients (mean age, 63.6 +/- 15.0 yr; 42.8% male) diagnosed with acute PE were included. The patients were classified into 3 groups; unprovoked PE, provoked-rRF, and provoked-iRF; 43.7%, 14.7%, and 41.7%, respectively. We followed up the patients for 25.4 +/- 33.7 months. Composite endpoint was all-cause mortality and recurrent PE. The provoked-iRF group had significantly higher all-cause mortality, mortality from PE and recurrent PE than the unprovoked and provoked-rRF groups (P 1.2 mg/dL; P 5 mg/L; P = 0.002; HR, 5.308; 95% CI, 1.824-15.447) and computed tomography (CT) obstruction index (P = 0.034; HR, 1.090; 95% CI, 1.006-1.181). In conclusion, provoked-iRF has a poorer prognosis than unprovoked PE and provoked-rRF. Renal insufficiency, high CRP, and CT obstruction index are poor prognostic factors in unprovoked PE.

Blood Cyst of Subvalvular Apparatus of the Mitral Valve in an Adult

Blood cysts of the heart are rare benign tumors, usually involving the cardiac valves. They are found mainly in the first month of life and in children; and are rarely seen in adults. Here, we report a case of a blood cyst on the subvalvular apparatus of the mitral valve, which was incidentally discovered during chest computed tomography in a 47-year-old man. To the best of our knowledge, this is the first reported case of blood cyst of the heart in an adult in Korea.