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Introduction: Recent advances in nuclear molecular imaging have allowed a more specific, non-invasive approach to the diagnosis and prognostication of cardiac amyloidosis (CA). 11 C-Pittsburgh compound B positron emission tomography/computed tomography (PiB PET/CT) is one of the widely studied nuclear molecular imaging. However, it remains to be verified whether it has any independent additional prognostic value. Hypothesis: 11 C-PiB PET/CT would have independent prognostic value in patients with light chain CA (ALCA). Methods: A prospective cohort study of 58 consecutive patients with ALCA who underwent 11 C-PiB PET/CT, were stratified into 2 groups based on a myocardial 11 C-PiB uptake or not on PET/CT. The primary and secondary outcomes were all-cause death and cardiovascular death, respectively. Results: During a median 13.6 month follow-up, 29 patients died, of which 12 died from cardiovascular events. Patients with positive 11 C-PiB PET uptake had worse event-free survival from all-cause deaths (60.5% vs. 28.7%, P =0.001) and cardiovascular deaths (84.9% vs. 58.5%, P =0.001). A positive myocardial 11 C-PiB PET/CT was an independent predictor for all-cause death (adjusted hazard ratio [aHR] 4.143, 95% confidence interval [95%CI] 1.243-13.816, P =0.021) and cardiovascular death (aHR 5.598, 95%CI 1.060-29.560, P =0.043). When 11 C-PiB PET/CT was combined with troponin I and N-terminal probrain Natriuretic Peptide, the performance of prediction significantly improved by net reclassification index of 0.872 and by integrated discrimination improvement statistics of 0.177. Conclusions: 11 C-PiB PET/CT is a strong independent predictor for all-cause and cardiovascular mortality, and provides incremental prognostic benefits in patients with ALCA. Further investigations are warranted on whether PET/CT should be included in the risk stratification for the ALCA patients

A 35-year-old woman presenting with left-side weakness visited our emergency room. She was previously healthy and did not have any clinical risk factors for cerebral vascular disease. Multiple embolic cerebral infarctions were found in her brain through magnetic resonance imaging (MRI). An ECG showed ST depression and T-wave inversion in all of the precordial leads (Figure 1). An abnormal eosinophil count (2718 per 1 μL) and elevated erythrocyte sedimentation rate (58 mm/h) were reported in her blood test; otherwise, her blood test was normal. Her cardiac enzyme level was within normal limits. Transthoracic echocardiography was performed (Figure 2 and online-only Data Supplement Movies I and II), and apical hypertrophy suggesting apical cardiomyopathy was initially reported. Figure 1. Initial ECG at the emergency room. T-wave inversions were present in all the …

Introduction: Pannus formation is a rare but important complication that can be missed in patients with prosthetic valves. However, currently available methodologies are not sufficient to diagnose subvalvular pannus formation especially in mechanical aortic valves. Hypothesis: In this study, we explored a series of experiences with three-dimensional transesophageal echocardiography (3D-TEE) for the visualization and accurate assessment of subvalvular pannus in patients with mechanical aortic valve. Methods: We enrolled 11 patients (mean age 64±8.6 years, 10 patients with either double or triple valve replacement) who had previously implanted mechanical aortic valve, with transaortic mean pressure gradient >40mmHg or transaortic maximal velocity >4m/sec despite normal occluder motion. All patients underwent 3D-TEE examination to rule out pannus formation and these findings were compared with multi-detector computed tomography (MDCT) images and/or surgical findings. Results: In 10 patients, 3D-TEE allowed good visualization of subaortic pannus formation whereas there was no significant pannus ingrowth in one patient. Through cropping full-volume 3D-TEE images, subaortic pannus formation could be visualized well in en face view, which was confirmed by MDCT images. The 3D-TEE images of the pannus were also matched with intraoperative findings in 7 patients undergoing reoperation of the mechanical aortic valve (Figure). Quantitative measurement of geometric subvalvular area using 3D planimetry was feasible and correlated well with the area measured by MDCT and with transaortic mean pressure gradient on transthoracic echocardiography (Spearman’s ρ=0.761 and -0.726, all p-value Conclusions: Real-time 3D-TEE is a useful diagnostic tool for the anatomical assessment of subvalvular pannus formation in mechanical aortic valves.

Introduction: Patients with rheumatic mitral stenosis (RMS) and atrial fibrillation (AF) have revealed a high incidence of systemic embolism. Current guidelines do not recommend anticoagulation in patient with RMS and sinus rhythm. Hypothesis: The predictors of clinical events may facilitate adverse outcome in RMS patients with sinus rhythm. Methods: A total 1,019 patients who diagnosed with RMS were evaluated retrospectively between March 2003 and June 2013. Of these, patients with past or present AF (n = 447), who used anticoagulants or had prior thromboembolism (n = 154), or who performed mitral valve replacement within 9-month after diagnosis (n = 125) were excluded. A total of 293 patients were included. The clinical events were defined as all cause death and systemic embolism. Results: During the mean follow-up period of 68.2 ± 36.6 months, clinical events were developed in twenty-one patients (7.2%; embolism 12, all cause death 9) with 2.1% of average annual event rate. In the Cox-proportional hazard regression analysis, age was independent predictor of clinical events (HR 1.07 (95% CI 1.01-1.13), p = 0.026) after adjustment of confounding factors. LA dimension ≥ 47 mm showed borderline significance to predict events (HR 2.45 (95% CI 0.98 - 6.15), p = 0.057). Mitral valve area was not associated with events. In middle and old aged group (age ≥ 50), LA dimension ≥ 47 mm was a good prognosticator (HR 2.97 (95% CI 1.05 - 8.36), p = 0.040). During follow-up, sixty patients (20.5%) were developed AF with 3.5% annual event rate. LA dimension ≥ 47 mm was an independent predictor of composite all events including clinical events and development of AF. Conclusions: New onset AF was frequently developed in patients with RMS and sinus rhythm. Because of high risk of embolism of valvular AF, we need careful follow up in these patients group. In middle and old age group, enlarged LA dimension was closely related with all cause death or systemic embolism.

Introduction: Aortic stenosis (AS) typically provokes diffuse myocardial fibrosis (DMF). Methods to evaluate DMF using cardiovascular magnetic resonance (CMR) are yet to be made easier and validated for wide clinical use. Hypothesis: To test whether T1 mapping, without the use of gadolinium contrast, may be useful for assessment of DMF and whether it correlates with subclinical myocardial dysfunction in asymptomatic AS patients. Methods: 80 asymptomatic patients with moderate or severe AS and normal LVEF and 15 sex-matched control subjects were prospectively enrolled. Patients underwent 2D-echocardiography, speckle tracking imaging and CMR in a 3.0T scanner including mapping of T1 relaxation time with modified Look-Locker Inversion-recovery (MOLLI) sequence. Patients were divided into three groups according to the native T1 value. Results: Native T1 values correlated well with the degree of DMF on intraoperative myocardial biopsy specimens (r=0.777, p-value Conclusion: Native T1 value using MOLLI sequence in asymptomatic AS patients enables noninvasive, simple quantification of DMF and correlates well with subclinical LV systolic and diastolic dysfunction.

A 56-year-old man was referred to the outpatient clinic of our cardiology department with a complaint of chest pain and dyspnea on exertion (New York Heart Association functional class II to III). According to his past medical history, he had visited a private hospital and had a diagnosis of idiopathic pulmonary arterial hypertension a few months earlier. He also had an episode of hoarseness due to left vocal cord palsy. On physical examination at our hospital, his blood pressure was 124/86 mm Hg, and his heart rate was 104 bpm. ECG showed sinus tachycardia, right atrial enlargement, and right ventricular hypertrophy (Figure 1). Initial transthoracic echocardiography revealed dilated right-sided chambers and right ventricular hypertrophy without any intracardiac or extracardiac …

Introduction Though the efficacy on traditional lipid parameters of simvastatin/ezetimibe and atorvastatin has been studied extensively, ApoB/ApoA1 ratio which has better predictive value for cardiovascular event has not been compared as a primary endpoint in these two treatment groups before, especially in diabetes. Methods This study was a single center, open label, randomized phase 4 study to compare the efficacy and safety of simvastatin/ezetimibe 20/10mg versus atorvastatin 20mg once daily in subjects with type 2 diabetes. One hundred thirty-two well controlled diabetic patients (HbA1C Results In total, 132 patients (66 for each group; 60 males; mean age, 64.6±7.6 years) were enrolled and 125 patients were included in the full analysis set (62 for simvastatin/ezetimibe; 63 for atorvastatin). Baseline characteristics including lipid profiles were comparable between two groups. After 12 weeks of treatment ApoB/ApoA1 ratio was significantly reduced in both groups, however the differences of % changes between two groups were statistically not significant (-38.1±17.9% vs. -34.2±16.2%, p =0.279) and the changes in conventional lipid profiles including total cholesterol, LDL cholesterol and triglyceride also showed no significant difference. However, HDL cholesterol and ApoA1 levels increased significantly in the simvastatin/ezetimibe group, whereas decreased in the atorvastatin group (HDL cholesterol 4.2±12.7% vs. -0.2±14.8% and ApoA1 2.8±10.0% vs. -1.8±9.8%, p =0.041 and 0.002). In per-protocol analysis, improvement of ApoB/ApoA1 was significantly greater in the simvastatin/ezetimibe group (-42.3±11.9% vs. -36.5±14.1%, p =0.031). The changes of HOMA index and hsCRP were comparable between two groups in full analysis set. But in per-protocol analysis, HOMA index and hsCRP decreased in the simvastatin/ezetimibe group whereas increased in the atorvastatin group although there was no statistic significance. The frequency of adverse reaction was comparable between two groups. Conclusion Based on the results of this randomized controlled trial, simvastatin/ezetimibe 20/10mg might be preferable to atorvastatin 20mg for management of dyslipidemia in the patients with type 2 diabetes.

We thank Drs Raikhelkar and Scurlock for their thoughtful review of our article.1 As pointed out, the pathogenesis of tricuspid regurgitation was functional late after left-sided valve surgery in most of our study subjects, and thus our findings may not be directly applicable in tricuspid regurgitation patients with other organic valve diseases. We agree that this is an important limitation of our study. However, because we prospectively enrolled consecutive patients, we believe our data represent the real patient population in tertiary referral center. Further long-term study is needed to determine predictors of …

Background Assessment of the left ventricular (LV) contractile function is critical for deciding optimal timing of surgery in patients with chronic severe mitral regurgitation (MR). We investigated the LV long-axis and short-axis function in MR. Methods We studied 30 patients (16 men, age: 51 ± 14 years) who had 3+ or 4+ MR with LV ejection fraction (EF) greater than 50%. Comprehensive 2D and Doppler echocardiography was performed. Peak systolic radial (SR R ), circumferential (SR C ), and longitudinal strain rate (SR L ) were measured using speckle tracking imaging. In all patients, peak dP/dt was measured using micromanometer-tipped catheter. Results Mean LVEF was 63.1% and regurgitation fraction was 61.8%. LV end-systolic volume was 78.3 ml. Peak dP/dt ranged from 1019 to 2049 mmHg/sec with the mean value of 1583 mmHg/sec. 16 patients (53.3%) showed latent systolic dysfunction defined by peak dP/dt less than 1300 mmHg/s. SR R and SR C correlated well with peak dP/dt (Fig. A , r=0.74, p< 0.01, r=− 0.54, pL did not correlate with peak dP/dt (r=− 0.58, p=0.76). SR R > 1.94 S −1 showed a sensitivity of 86 % and a specificity of 75 % for predicting latent LV systolic function (Fig. B , AUC=0.87, CI=0.732– 0.991). SR R also correlated with LV end-diastolic and end-systolic sphericity index (r=− 0.54, p Conclusion SR R and SR C , not SR L , correlated well with peak LV dP/dt. These results imply the importance of short-axis function in the presence of chronic severe MR, probably due to the geometrical change in response to chronic volume overload.

Background Growing use of the left ventricular(LV) systolic(LVSIsys) and diastolic synchronicity indexes(LVSIdia) in selecting potential responders to cardiac resynchronization therapy(CRT) has created a need for normative reference values. This study was performed to determine reference ranges for tissue Doppler imaging-derived LVSIsys and LVSIdia, and to assess their relationships to age and conventional parameters reflecting LV systolic and diastolic functions. Methods and Results We recruited 160 completely healthy volunteers (45±13yrs, 104 men) free of any systemic or cardiovascular disease. Maximal difference and SD of time to peak systolic and early diastolic velocities for LVSIsys and LVSIdia were measured using 6- and 12-segment models. Table and Figure represent normal ranges. Aging was not found to significantly change LVSIsys, whereas LVSIdia progressively and consistently increased with age. Significant correlations were observed between LVSIdia and parameters representing LV diastolic function, i.e. early mitral inflow velocity and its deceleration time, and early mitral annulus velocity. A physiologic rise in LV mass/Ht 2.7 showed a weak, but significant correlation with LVSIdia( r = 0.15 to 0.22), but not with LVSIsys. On multivariate analysis, age-dependent increase in LVSIdia was confirmed. Conclusions Age-specific reference ranges for LVSIsys and LVSIdia are presented here. LVSIsys remain stable throughout age groups, whereas LVSIdia progressively increases with age. These data given here will be useful for defining abnormal LV synchronous contraction and relaxation, and help better select patients likely to respond favorably to CRT.

Background Afterload is expected to increase with pneumatic compression of the lower extremities. Therefore, left ventricular (LV) wall stress which is the most important factor determining myocardial oxygen demand will also increase, leading to an increase in sensitivity of dobutamine stress echocardiography (DSE) or shortened time to positive response.The purpose of this study was to evaluate the effect of pneumatic compression of lower extremities on the diagnostic accuracy of DSE. Methods In 40 patients who underwent DSE and were anticipating coronary angiography, DSE was repeated with the pneumatic compression (100mmHg) of lower extremities (DSEcomp) prior to coronary angiography. Sensitivity and specificity of DSE and DSEcomp were determined based on the coronary angiographic finding. Results All patients tolerated pneumatic compression of the lower extremities during the tests. LV end-systolic volume (p=0.042) and end-systolic wall stress (p=0.036) were significantly greater in the DSEcomp than DSE. In 3 patients with false negative results in DSE, DSEcomp showed positive responses, demonstrating a significant increase in sensitivity from 75% to 94% (p=0.045). Only 1 patient with true negative result in DSE was interpreted as showing positive response in DSEcomp, resulting in a decrease in specificity from 88% to 83% (p=NS). In 11 of 13 patients with true positive results both in DSE and DSEcomp, positive responses were seen at least 1 stage earlier in DSEcomp compared to DSE. Conclusions Pneumatic compression of lower extremities increases the sensitivity of DSE and shortens the time to positive response.