Shape phenotype of thigh fat and muscle and risk of major adverse cardiovascular events after fragility hip fracture.

BACKGROUND: Although sarcopenia has been recognized as a predictor of mortality in elderly patients with hip fracture, the association of thigh fat and muscle with cardiovascular (CV) outcome remains unclear. We examined the impact of computed tomography (CT)-derived shape features of thigh fat and muscle on major adverse CV events (MACE) in elderly patients with hip fracture. METHODS: We conducted a retrospective analysis of consecutive patients aged ≥65 years who presented with hip fracture confirmed on pelvic bone CT scan and underwent hip fracture surgery at our institution from April 2019 to December 2021. The cross-sectional area (CSA) and compactness (CM) of both the muscle and fat at the upper-thigh level were calculated from two-dimensional CT images using AVIEW Research (v1.1.38, Coreline Soft, Co. Ltd, Seoul, South Korea). The shape features of thigh fat and muscle were categorized into four groups based on the combination of CSA and CM: fat CSA (fat area [FA])/fat CM (FCM), muscle CSA (muscle area [MA])/muscle CM (MCM), FA/MCM and MA/FCM. In each of them, subjects were categorized into four subgroups: high CSA/high CM, high CSA/low CM, low CSA/high CM and low CSA/low CM. The primary outcome was MACE after 30 days of surgery, defined as a composite of all-cause death, acute myocardial infarction, stroke or hospitalization for heart failure. RESULTS: Of 356 patients enrolled (median age, 82 years; 76.7% females), 72 (20.2%) had MACE over a median follow-up of 13.1 months (ranges 5.9-21.0 months). Patients with MACE had a significantly lower median FA (193.7 vs. 226.2 cm2 , P < 0.0001) and FCM (0.443 vs. 0.513, P = 0.001) compared with those without MACE, but no significant differences were found in MA, MCM and FA-MA ratio between the two groups. In a multivariate Cox regression analysis, low FA (<240.1 cm2 ) (adjusted hazard ratio [HR] 2.99, 95% confidence interval [CI] 1.39-6.44, P = 0.005) and low FCM (<0.477) (adjusted HR 2.00, 95% CI 1.10-3.63, P = 0.023) were associated with an increased risk of MACE. Among the shape phenotypes of thigh fat and muscle, the thigh fat phenotype of low FA/low FCM (adjusted HR 3.13, 95% CI 1.81-5.42, P < 0.0001 [reference, high FA/high FCM]) was found to be an independent predictor of MACE. CONCLUSIONS: In elderly patients with fragility hip fracture, thigh CT-derived measures of FA and FCM may provide useful prognostic information for predicting adverse CV outcomes.

Sodium-Glucose Cotransporter-2 Inhibitors After Acute Myocardial Infarction in Patients With Type 2 Diabetes: A Population-Based Investigation.

Background Whether the early use of sodium-glucose cotransporter-2 (SGLT2) inhibitors have cardioprotective effects following acute myocardial infarction is unknown. Thus, we aimed to evaluate the association between the early initiation of SGLT2 inhibitors and cardiac event rates in patients with diabetes with acute myocardial infarction undergoing percutaneous coronary intervention. Methods and Results Based on the National Health Insurance claims data in South Korea, patients who received percutaneous coronary intervention for acute myocardial infarction between 2014 and 2018 were analyzed. Patients given SGLT2 inhibitors or other glucose-lowering drugs were matched based on a propensity score. The primary end point was a composite of all-cause mortality and hospitalizations for heart failure. Major adverse cardiac events (a composite of all-cause death, nonfatal myocardial infarction, and ischemic stroke) were compared as the secondary end point. After 1:2 propensity score matching, the SGLT2 inhibitors group (938 patients) and the no use of SGLT2 inhibitors group (1876 patients) were compared. During a median follow-up of 2.1 years, the early use of SGLT2 inhibitors was associated with lower risks of both the primary end point (9.8% versus 13.9%; adjusted hazard ratio [HR], 0.68 [95% CI, 0.54-0.87]; P=0.002) and secondary end point (9.1% versus 11.6%; adjusted HR, 0.77 [95% CI, 0.60-0.99]; P=0.04). All-cause mortality and hospitalizations for heart failure were also significantly lower in early users of SGLT2 inhibitors. Conclusions The early use of SGLT2 inhibitors in patients with diabetes treated with percutaneous coronary intervention for acute myocardial infarction was associated with a significantly lower risk of cardiovascular events, including all-cause mortality, hospitalizations for heart failure, and major adverse cardiac events.

Comparative efficacy and safety of fimasartan in patients with hypertension: A network meta-analysis of randomized controlled trials.

Hypertension is a prevalent risk factor for cardiovascular disease. Angiotensin II receptor blockers are widely prescribed to patients with hypertension, while new drugs are continuously developed. However, data on comparative efficacy and safety of novel agents, such as fimasartan, are scarce. Here, we aimed to collect clinical evidence on different angiotensin II receptor blockers using a network meta-analysis. Randomized controlled trials whose follow-up time is within 12 weeks were identified from eight databases via a systematic literature review. Of the 7909 possibly relevant studies, 61 studies with 14,249 adult patients were included in the analysis. These studies were further subjected to quality appraisal using Cochran's Risk of Bias, and sitting systolic blood pressure was considered the primary endpoint. A Bayesian random effect generalized linear model was used for the network meta-analysis, and the treatment rank probability was determined. Olmesartan (standardized mean difference -0.987 [-1.29, -0.729]) and fimasartan (standardized mean difference -0.966 [-1.21, -0.745]) showed the highest rank probabilities (37% and 35%) in the 4-week group, considering the primary endpoint. Furthermore, the odds ratio of adverse events for all agents did not differ significantly from that of the placebo. The treatment rank of angiotensin II receptor blockers varied depending on the outcome type and follow-up period considerably. Fimasartan rapidly lowered blood pressure in 4 weeks, which was further maintained until 12 weeks, indicating its competent efficacy and tolerability. Our findings may help medical practitioners and patients to select the best angiotensin II receptor blocker against hypertension.

Gender Differences in the Impact of New-Onset Atrial Fibrillation on Long-Term Risk of Ischemic Stroke after Acute Myocardial Infarction.

BACKGROUND: Atrial fibrillation (AF) has been identified as a major risk factor for mortality after acute coronary syndrome (ACS). However, the long-term risk of ischemic stroke associated with new-onset atrial fibrillation (NOAF) in ACS remains controversial, and its gender-specific association is unknown. METHODS: We analyzed the data of 10,137 ACS survivors included in a multicenter, prospective registry for Korean patients with acute myocardial infarction (AMI) between January 2004 and August 2014. Subjects were categorized into three groups (non-AF vs. NOAF vs. previous AF) based on medical history and electrocardiographic evidence of AF, either at admission or during hospitalization. RESULTS: Among the total study population (72.3% men), 370 patients (3.6%) had NOAF and 130 (1.3%) had previous AF. During a median follow-up of 61 months (interquartile range, 38.8 to 89.3 months), 245 (2.4%) patients (218 (2.3%) non-AF vs. 15 (4.1%) NOAF vs. 12 (9.2%) previous AF, p < 0.001) experienced ischemic stroke. After adjustment for confounding variables, both NOAF (adjusted hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.09-3.24, p = 0.024) and previous AF (adjusted HR 4.00, 95% CI 2.03-7.87, p < 0.001), along with older age, diabetes, current smoker, and previous stroke were independent risk factors of ischemic stroke. In the gender-stratified analysis, men with previous AF but not NOAF had a significantly higher risk of ischemic stroke (adjusted HR 4.14, 95% CI 1.79-9.55, p = 0.001) than those without AF. In women, NOAF (adjusted HR 2.54, 95% CI 1.21-5.35, p = 0.014) as well as previous AF (adjusted HR 3.72, 95% CI 1.16-11.96, p = 0.028) was a strong predictor of ischemic stroke, and the predictive value was comparable to that of previous AF among patients with a CHA2DS2-VASc score ≥ 2. CONCLUSIONS: Both NOAF and previous AF were associated with ischemic stroke after AMI, but the impact of NOAF as a risk factor of ischemic stroke was significant only in women.

Additive prognostic value of red cell distribution width over late gadolinium enhancement on CMR in patients with non-ischemic dilated cardiomyopathy.

Elevated red cell distribution width (RDW) and late gadolinium enhancement on cardiac magnetic resonance (LGE-CMR) are both poor prognostic factors. This study examined the relationship between RDW and LGE-CMR characteristics in patients with non-ischemic dilated cardiomyopathy (NICM), and investigated whether the additive prognostic value of RDW as an integrative systemic factor over LGE-CMR exists or not. A total of consecutive 378 patients who underwent CMR at two general hospitals in South Korea were retrospectively analyzed. The primary endpoint was a composite of all-cause death, hospitalizations due to worsening heart failure and major arrhythmic events. During a mean follow-up period of 40.8 months, 151 (39.9%) patients experienced primary endpoints. The RDW value was significantly higher in patients with LGE than in those without LGE (13.7 ± 1.5% vs. 13.3 ± 1.4%, p = 0.034), but it was not associated with the extent or distribution patterns of the LGE. Addition of RDW into the model with clinical risk factors and LGE-CMR characteristics led to a significant improvement in the prediction of worse outcomes (χ2 increased from 73 to 82; p = 0.023). RDW could provide incremental predictive value for adverse clinical events beyond LGE-CMR data in NICM patients.

Extracorporeal shock waves protect cardiomyocytes from doxorubicin-induced cardiomyopathy by upregulating survivin via the integrin-ILK-Akt-Sp1/p53 axis.

Doxorubicin (DOX) is a widely used anti-cancer drug; however, it has limited application due to cardiotoxicity. Extracorporeal shock waves (ESW) have been suggested to treat inflammatory and ischemic diseases, but the concrete effect of ESW in DOX-induced cardiomyopathy remain obscure. After H9c2 cells were subjected to ESW (0.04 mJ/cm2), they were treated with 1 µM DOX. As a result, ESW protected cardiomyocytes from DOX-induced cell death. H9c2 cells treated with DOX downregulated p-Akt and survivin expression, whereas the ESW treatment recovered both, suggesting its anti-apoptotic effect. ESW activated integrin αvß3 and αvß5, cardiomyocyte mechanosensors, followed by upregulation of ILK, p-Akt and survivin levels. Further, Sp1 and p53 were determined as key transcriptional factors mediating survivin expression via Akt phosphorylation by ESW. In in vivo acute DOX-induced cardiomyopathy model, the echocardiographic results showed that group subjected to ESW recovered from acute DOX-induced cardiomyopathy; left ventricular function was improved. The immunohistochemical staining results showed increased survivin and Bcl2 expression in ESW + DOX group compared to those in the DOX-injected group. In conclusion, non-invasive shockwaves protect cardiomyocytes from DOX-induced cardiomyopathy by upregulating survivin via integrin-ILK-Akt-Sp1/p53 pathway. In vivo study proposed ESW as a new kind of specific and safe therapy against acute DOX-induced cardiomyopathy.

Prognostic significance of acute hypertensive response in ischemic stroke or transient ischemic attack patients and its relationship with left ventricular myocardial function.

OBJECTIVES: Acute hypertensive response (AHR) in acute stroke is associated with adverse outcomes; however, the underlying pathophysiology of the association is poorly understood and its prognostic impact in ischemic stroke remains unclear. We aimed to investigate the prognostic significance of AHR in patients with ischemic stroke or transient ischemic attack (TIA), and further examined the relationship between AHR and myocardial function, using two-dimensional speckle-tracking echocardiography (2D-STE). METHODS: A total of 244 consecutive patients with acute ischemic stroke (AIS) (n = 192) or TIA (n = 52), who were evaluated with 2D-STE within 7 days from admission, were retrospectively analysed. The primary endpoint was a composite of major adverse cardiovascular and cerebrovascular events (MACCE), including death, myocardial infraction or recurrent ischemic stroke. RESULTS: Among the study population, AHR was observed in 161 (66%) patients. During a mean follow-up of 21.0 ±â€Š12.5 months, 29 patients (11.9%) [25 (15.5%) AHR vs. 4 (4.8%) No AHR, P = 0.014] reached the primary endpoint. A Kaplan-Meier curve revealed that patients with AHR had a significantly higher incidence of MACCE than those without AHR (log-rank P = 0.013). Multivariate Cox regression analysis demonstrated that AHR [adjusted hazard ratio 4.60, 95% confidence interval (95% CI) 1.31-16.15] was a strong predictor of MACCE. In multivariate logistic regression analysis, left ventricular global longitudinal strain (per 1% decrease) showed a significant relationship with AHR (adjusted odds ratio 1.17, 95% CI 1.02-1.35). CONCLUSION: AHR in patients with AIS or TIA may be an important poor prognostic marker related to myocardial dysfunction.

CHA2DS2-VASc score predicts exercise intolerance in young and middle-aged male patients with asymptomatic atrial fibrillation.

Exercise intolerance among the clinical symptoms in patients with atrial fibrillation (AF) has usually been masked by their adjusted life style. We sought to assess the role of CHA2DS2-VASc score to predict exercise intolerance in asymptomatic AF patients, and further examine whether the relationship differs by age and gender. Among the 6,275 participants of the prospective Korean registry of the Comparison study of Drugs for symptom control and complication prevention of Atrial Fibrillation (CODE-AF), 1,080 AF patients who underwent exercise treadmill testing were studied. Exercise intolerance was defined as a peak exercise capacity of 7 metabolic equivalents (METs) or less, and the patients were divided into two groups for the analysis: ≤7 METs (n = 131) and >7 METs (n = 949). Patients with exercise intolerance had a significantly higher CHA2DS2-VASc score than those without (3.1 ± 1.3 vs. 2.0 ± 1.5, p < 0.0001). In the multivariate analysis, a higher CHA2DS2-VASc score (OR 1.54, 95% CI 1.31-1.81, p < 0.0001), corrected QT interval (OR 1.01, 95% CI 1.00-1.02, p = 0.026), and increased left atrial volume index (OR 1.02, 95% CI 1.01-1.03, p = 0.001) were found to be independent predictors of exercise intolerance. The impact of the CHA2DS2-VASc score on exercise intolerance was significant only in male patients aged <65 years (OR 3.30, 95% CI 1.76-6.19, p < 0.0001). The CHA2DS2-VASc score may be a feasible risk assessment tool to predict exercise intolerance, especially in young and middle-aged male patients with asymptomatic AF.

Prognostic implications of late gadolinium enhancement at the right ventricular insertion point in patients with non-ischemic dilated cardiomyopathy: A multicenter retrospective cohort study.

INTRODUCTION: The presence of late gadolinium enhancement (LGE) at the right ventricular insertion point (RVIP) on cardiac magnetic resonance (CMR) is generally believed to be nonspecific, but the clinical implication of this unique LGE pattern in patients with non-ischemic dilated cardiomyopathy (NICM) has not been elucidated. OBJECTIVES: We investigated the prognostic significance of RVIP-LGE in NICM patients. METHODS: A total of 360 consecutive NICM patients referred for CMR (102 with no LGE, 50 with RVIP-LGE, 121 with left ventricular [LV]-LGE, and 87 with both an LV and RVIP-LGE) were studied. The primary endpoint was a composite of the all-cause death, hospitalization due to worsening of heart failure, and major arrhythmic events. RESULTS: During a mean follow-up of 45.2 ± 36.5 months, 149 (41.4%) patients (22 [21.6%] no LGE vs. 16 [32.0%] RVIP-LGE vs. 62 [51.2%] LV-LGE vs. 49 [56.3%] both LV and RVIP-LGE, P < 0.0001) reached the primary endpoint. A Kaplan Meier curve demonstrated that RVIP-LGE patients had an intermediate trend of an event free survival rate for the composite endpoint (log-rank P < 0.0001). In a multivariable Cox regression model, LV-LGE (P = 0.008) and both LV and RVIP-LGE (P = 0.003) were significantly associated with a worse outcome, whereas RVIP-LGE was not (P = 0.101). In addition, RVIP-LGE patients (n = 32) had a more favorable outcome compared to LV-LGE patients (n = 32) even after matching the extent of the LGE (median 3.4% [interquartile range, 3.1-3.8], 8 [25.0%] RVIP-LGE vs. 20 [62.5%] LV-LGE, P = 0.002). CONCLUSIONS: LGE confined to the RVIP among NICM patients did not significantly increase the risk of adverse cardiac events, and also showed a better outcome than the same extent of LGE located in the LV. Identification of this unique LGE distribution may help refine the current risk stratification.

Smoking aggravates ventricular arrhythmic events in non-ischemic dilated cardiomyopathy associated with a late gadolinium enhancement in cardiac MRI.

Smoking is known to increase cardiovascular events, but the association and mechanisms between smoking and ventricular arrhythmic events in dilated cardiomyopathy (DCMP) are unknown. The purpose of this study is to investigate the hypothesis that smoking is associated with sudden cardiac death (SCD) and ventricular arrhythmia in DCMP patients. We enrolled 378 patients who underwent cardiovascular magnetic resonance imaging (cMRI) and were diagnosed with DCMP at two general hospitals in Korea. The clinical data and left ventricular late-gadolinium enhancement (LV-LGE) of all patients were analyzed according to being never-smokers or smokers. Smokers were more likely to be male than never-smokers, but there was no other clinical difference between them. Smokers had a greater LV-LGE ratio, and multi-segment involvement of LV-LGEs. Smoking and a low left ventricular (LV) ejection fraction were significant predictors of the presence of LV-LGEs even after adjusting for optimal medical therapy. In addition, smokers had a higher fatal ventricular arrhythmic (FVA; sustained ventricular tachycardia, and ventricular fibrillation) and FVA + SCD, and ex-smokers had a similar FVA to never-smokers during 44.3 ± 36.4 months of follow-up. Finally, smoking independently increased the FVA + SCD even after adjusting for the clinical variables and LV-LGE. Smoking is associated with a multi-segmental involvement of LV-LGE and increased FVA + SCD in DCMP patients when compared to never-smokers.

Cardiac and Pericardial 18F-FDG Uptake on Oncologic PET/CT: Comparison with Echocardiographic Findings.

BACKGROUND: Interpretation of cardiac uptake on 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is often confounded by intense physiological FDG uptake and numerous benign conditions. The aim of the study was to describe the echocardiographic features in concordance with cardiac and pericardial 18F-FDG uptake on whole-body oncology PET/CT. METHODS: We enrolled 43 consecutive patients (34 solid tumors, 8 lymphomas and 1 leukemia) who were newly diagnosed with non-cardiac malignancy showing incidental cardiac or pericardial 18F-FDG uptake on PET/CT and underwent transthoracic Doppler echocardiography (TTE) within 1 month of PET/CT. The maximum standardized uptake (SUVmax) of all lesions was measured. RESULTS: Fifty-six 18F-FDG uptake lesions (32 pericardium, 7 myocardium, 9 cardiac chambers and 8 great vessels) were found, and pericardial effusion was the most common echocardiographic finding (22/43, 51.2%) among study population. Pericardial FDG uptake was shown as pericardial effusion (68.8%), intrapericardial echogenic materials (31.3%), pericardial thickening (28.1%), hyperechogenicity of myopericardium (18.8%), and restricted sliding movement or constrictive pericarditis (15.6%) on TTE. Lesions with regional wall motion abnormality (p = 0.004) or constrictive pericarditis (p = 0.021) had significantly higher mean SUVmax than those without. Myocardial FDG uptake demonstrated pericardial effusion (57.1%), regional wall motion abnormality (57.1%), and increased myocardial wall thickness (42.9%). All cardiac chamber FDG uptakes showed intracardiac mass on TTE. CONCLUSIONS: Cardiac or pericardial 18F-FDG uptake on oncology PET/CT shows characteristic echocardiographic features according to which heart sites are involved.

Emphysematous endocarditis caused by AmpC beta-lactamase-producing Escherichia coli: A case report.

RATIONALE: Infective endocarditis (IE) is a life-threatening disease, mostly caused by gram-positive bacteria. Gram-negative bacteria were identified as a causative organism in relatively small number of cases. Although, antibiotic-resistant Escherichia coli is common cause of gram-negative endocarditis, AmpC beta-lactamase (BL)-harboring E coli is very rare cause of IE. Furthermore, emphysematous endocarditis is also a very rare manifestation of E coli infection. PATIENT CONCERNS: We report a case of 80-year-old female patient presenting with dizziness, fever, and altered mental status, who was finally diagnosed with emphysematous endocarditis caused by E coli harboring an AmpC BL gene. DIAGNOSIS: Her chest computed tomography revealed air bubbles surrounding the annulus of a mitral valve and a transesophageal echocardiogram revealed a hyperechogenic mass fixed on the posteromedial side of the mitral annulus with 2 eccentric mitral regurgitation jets. Blood cultures grew E coli which harbored the DHA-type AmpC BL. The organism belonged to a B2 phylogenic group, and multilocus sequence typing analyses revealed that the strains were of ST-95. INTERVENTIONS: She was treated with meropenem following the resistant profiles, and surgery was recommended by the healthcare professional, but denied by the patient's guardians. She was transferred to another hospital due to a refusal for further treatment. LESSONS: Emphysematous endocarditis is an uncommon complication of E coli bacteremia. Certain phylogenetic groups may be associated with development of E coli endocarditis.

Clinical implication of an impaired fasting glucose and prehypertension related to new onset atrial fibrillation in a healthy Asian population without underlying disease: a nationwide cohort study in Korea.

AIMS: For healthy populations without comorbidities, whether prehypertension and impaired fasting glucose (IFG) are associated with new onset atrial fibrillation (AF) is not well known. METHODS AND RESULTS: We included 366 507 subjects (age ≥20 years) not diagnosed with non-valvular AF from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) from 2003 to 2008. In total, 139 306 subjects diagnosed with AF-related comorbidities were excluded, and a 227 102 healthy population was followed up until 2013. The body mass index (BMI), blood pressure (BP), and fasting blood glucose (BG) level were acquired during National health check-ups. Subjects with IFG [hazard ratio (HR) 1.16, P = 0.017] had a higher AF risk and the diastolic BP (HR 1.11, P = 0.045) was a stronger indicator for an AF incidence than the systolic BP. After dividing the subjects into two mutually exclusive groups, AF incidence was increased dramatically by the combination effect of both prehypertension and an IFG in BMI <25 kg/m2 group, but, in BMI ≧25 kg/m2 group, did not show this tendency. An IFG related to AF risk was more prominent in the BMI <25 kg/m2 population (HR 1.18, P = 0.025) than those with a BMI ≥25 kg/m2, and subjects with both an IFG and prehypertension had a greater AF risk (HR 1.27, P = 0.016) than those without. CONCLUSION: Even in a healthy Asian populations without comorbidities, prehypertension and IFG were important risk factors of AF. Specifically, when prehypertension, including systolic and diastolic BPs, was finally combined with the IFG, the risk of new onset AF was increased especially in the BMI <25 kg/m2 group.

Hemorheological abnormalities and their associations with coronary blood flow in patients with cardiac syndrome X: a comparison between males and females.

AIM: The role of elevated whole blood viscosity (WBV) in the pathogenesis of atherosclerosis is well known. We sought to investigate the gender differences in the association between WBV, coronary blood flow and tissue oxygen delivery index (TODI) in cardiac syndrome X (CSX). METHODS: Forty-six CSX patients and 14 healthy volunteers were enrolled. The coronary flow parameters were obtained with transthoracic Doppler echocardiography and WBV was measured (at high-shear and low-shear rates of 300s-1 and 5s-1, respectively) using a scanning capillary tube viscometer. TODI was determined from the ratio of hematocrit to WBV measured at a low-shear rate of 5s-1. RESULTS: In male patients, the mean diastolic coronary flow velocity (CFV) and diastolic velocity time integral (VTI) were significantly decreased compared to control group (all p<0.05) and the WBV showed significant negative correlation with peak systolic CFV (r = -0.559 at 300s-1, r = -0.438 at 5s-1), mean systolic CFV (r = -0.577 at 300s-1, r = -0.488 at 5s-1), systolic VTI (r = -0.576 at 300s-1, r = -0.530 at 5s-1) and diastolic VTI (r = -0.553 at 300s-1, r = -0.551 at 5s-1) (all p<0.01). Meanwhile, although female patients showed no significant relationships between WBV and coronary flow parameters, TODI were significantly decreased compared to the control group (3.64 ± 0.34 vs. 4.07 ± 0.38%/centipoises (cP), respectively, p=0.008). CONCLUSION: Our study suggests that there are gender-related differences in the pathogenesis of microvascular angina and gender-specific approaches for CSX patients might be needed.

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.

Contrast Volume/Raw eGFR Ratio for Predicting Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention for Myocardial Infarction.

BACKGROUND: Considering that contrast medium is excreted through the whole kidney in a similar manner to drug excretion, the use of raw estimated glomerular filtration rate (eGFR) rather than body surface area (BSA)-normalized eGFR is thought to be more appropriate for evaluating the risk of contrast-induced acute kidney injury (CI-AKI). METHODS: This study included 2,189 myocardial infarction patients treated with percutaneous coronary intervention. Logistic regression analysis was performed to identify the independent risk factors. We used receiver-operating characteristic (ROC) curves to compare the ratios of contrast volume (CV) to eGFR with and without BSA normalization in predicting CI-AKI. RESULTS: The area under the curve (AUC) of the ROC curve for the model including all the significant variables such as diabetes mellitus, left ventricular ejection fraction, preprocedural glucose, and the CV/raw modification of diet in renal disease (MDRD) eGFR ratio was 0.768 [95% confidence interval (CI), 0.720-0.816; p < 0.001]. When the CV/raw MDRD eGFR ratio was used as a single risk value, the AUC of the ROC curve was 0.650 (95% CI, 0.590-0.711; p < 0.001). When the CV/MDRD eGFR ratio with BSA normalization ratio was used, the AUC of the ROC curve further decreased to 0.635 (95% CI, 0.574-0.696; p < 0.001). The difference between the two AUCs was significant (p = 0.002). CONCLUSIONS: Raw eGFR is a better predictor for CI-AKI than BSA-normalized eGFR.

Reversible Pulmonary Arterial Hypertension Associated with Dasatinib for Chronic Myeloid Leukemia.

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.