Joseph E. Murray's Struggle to Transplant Kidneys: Failure, Individuality, and Plastic Surgery, 1950-1965.

This paper offers a historical analysis of the American plastic surgeon and Nobel laureate Joseph E. Murray's kidney transplantation. After succeeding in the first kidney transplantation between monozygotic twins in 1954, he transplanted kidneys between genetically distinct people after X-radiation and immunosuppressants. Amid these achievements, however, Murray encountered numerous failures, which he thought were closely intertwined with each patient's physiological and pathological individuality. As he appropriated his expertise in plastic surgery for kidney transplantation, this individuality became a major issue that he had to cope with in his efforts to avoid failures. To him, kidney transplantation could fail because of each individual's immunological barrier or constitutional singularity that could engender unexpected complications. Although he could neither explain nor control many of these failures, I argue that his unsuccessful work and patient individuality played multiple roles in shaping his operations as a plastic surgeon. They structured the path of his surgical research, made sense of it, defended him from criticism, and formed the way that he presented the results of his work with an immunological implication. Consequently, Murray, with little scientific training, articulated an important dimension of immunological tolerance relevant to clinical settings.

Identification of concealed cardiomyopathy using next-generation sequencing-based genetic testing in Korean patients initially diagnosed with idiopathic ventricular fibrillation.

AIMS: Idiopathic ventricular fibrillation (IVF) is a disease in which the cause of ventricular fibrillation cannot be identified despite comprehensive clinical evaluation. This study aimed to investigate the clinical yield and implications of genetic testing for IVF. METHODS AND RESULTS: This study was based on the multi-centre inherited arrhythmia syndrome registry in South Korea from 2014 to 2017. Next-generation sequencing-based genetic testing was performed that included 174 genes previously linked to cardiovascular disease. A total of 96 patients were clinically diagnosed with IVF. The mean age of the onset was 41.2 ± 12.7 years, and 79 patients were males (82.3%). Of these, 74 underwent genetic testing and four (5.4%) of the IVF probands had pathogenic or likely pathogenic variants (each having one of MYBPC3, MYH7, DSP, and TNNI3). All pathogenic or likely pathogenic variants were located in genes with definite evidence of a cardiomyopathy phenotype, either hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. CONCLUSION: Next-generation sequencing-based genetic testing identified pathogenic or likely pathogenic variants in 5.4% of patients initially diagnosed with IVF, suggesting that genetic testing with definite evidence genes of cardiomyopathy may enable molecular diagnosis in a minority of patients with IVF. Further clinical evaluation and follow-up of patients with IVF with positive genotypes are needed to unveil concealed phenotypes, such as the pre-clinical phase of cardiomyopathy.

Comparative Bleeding Risk in Patients with Atrial Fibrillation with Cancer versus Without Cancer from Nationwide Prospective Cohort.

Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.

Clinical utility and prognostic implications of the 4S-AF scheme: Report from Asia Pacific Heart Rhythm Society Atrial Fibrillation Registry.

BACKGROUND: The 4S-AF classification scheme comprises of four domains (stroke risk [St], symptoms [Sy], severity of atrial fibrillation (AF) burden [Sb] and substrate [Su]), which has been recommended in the 2020 ESC guidelines to characterize and evaluate patients with AF. OBJECTIVES: We aimed to determine whether the 4S-AF scheme would be useful for AF characterization and provides prognostic information in a large contemporary prospective Asian registry conducted by the Asia Pacific Heart Rhythm Society (APHRS). METHODS: Among 4666 patients enrolled in APHRS registry, 3586 of them whose data about left atrial (LA) dimension and European Heart Rhythm Association (EHRA) symptom score were available have constituted as the study population. The 4S-AF score was calculated as the sum of each domain with a maximum score of 9. The clinical endpoint was defined as the 1-year composite risk of any thromboembolic event, ischaemic stroke, heart failure, acute coronary syndrome, significant coronary artery disease requiring coronary intervention and all-cause mortality. RESULTS: Based on the 4S-AF domains, 86.7% were 'non-low risk' for stroke; 94.3% had EHRA Class I-II, 48.5% were newly diagnosed or paroxysmal AF; and only 8.4% had no cardiovascular risk factors or LA enlargement. The risk of clinical events was higher in patients who were 'non-low risk' for stroke (aOR 2.175, 95% CI 1.060-4.461), with permanent AF (aOR 1.579, 95% CI 1.106-2.225) and increasing points for substrate (aORs 2.376-4.968 from score 2 to 4). When compared to the first tertile of 4S-AF score (0-3 points), patients in the second tertile (4-5 points) had approximately 2.5-fold increase in adverse events (OR 2.478, 95% CI 1.678-3.661, p < .001), while those in the third tertile (6-9 points), had a 3.5-fold increase (OR 3.484, 95% CI 2.322-5.226, p < .001), both without significant differences between the 5 participating countries (p for interaction > .05). If all 4S-AF domains were appropriately treated, this was associated with a lower risk of composite clinical outcomes (aOR 0.384, p < .001; p for interaction for different countries = .234). CONCLUSIONS: Categorization according to the 4S-AF scheme can be related to the risk of the composite adverse event rate in Asian AF patients, and appropriate treatments based on the 4S-AF scheme resulted in better clinical outcomes. These observations support the characterization and management according to the 4S-AF scheme in Asian patients.

Prognosis and treatment of atrial fibrillation in Asian cities: 1-year review of the Asia-Pacific Heart Rhythm Society Atrial Fibrillation Registry.

AIMS: The aim of this study is to describe the implementation of the current guidance for stroke prevention and treatment option in atrial fibrillation (AF) and to evaluate mortality and morbidity in relation to therapeutic decisions, including persistence with treatment at 1 year in Asia-Pacific regions. METHODS AND RESULTS: We recruited 4664 patients consecutive in- and outpatients with AF who presented to cardiologists in five countries under the Asia-Pacific Heart Rhythm Society (APHRS) in whom 1-year follow-up was completed for 4003 (65.5% male; mean age 68.5 years). Oral anticoagulant (OAC) use remained high, 77% at follow-up, including 17% prescribed a vitamin K antagonist (VKA) and 60% a non-VKA oral anticoagulant (NOAC). At 1-year follow-up, 93% and 88% remained on a VKA or NOAC, respectively. With good adherence to OAC therapy, 1-year mortality was only 2.7%. Most deaths were non-cardiovascular (72.3%) and the 1-year incidence of stroke/transient ischaemic events (TIA) was low (<1%). Hospital readmissions were common for non-cardiovascular cases and atrial tachyarrhythmias. On multivariate analysis, independent baseline predictors of mortality and/or stroke/TIA/peripheral embolism were age, previous heart failure for >12 months, and malignancy. Independent predictors of mortality were age, chronic obstructive pulmonary disease, malignancy, and diuretic use. AF as a primary presentation was predictive of lower mortality and/or stroke/TIA/peripheral embolism as well as mortality. CONCLUSION: In this 1-year analysis of the APHRS-AF registry, overall OAC use and persistence were high and were associated with low 1-year cardiovascular mortality and morbidity, but mortality and morbidity related to non-cardiovascular causes were high in AF patients, particularly from malignancy and pneumonia.

Effect of alcohol consumption on the risk of adverse events in atrial fibrillation: from the COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry.

AIMS: The aim of this study is to determine the relationship between alcohol consumption and atrial fibrillation (AF)-related adverse events in the AF population. METHODS AND RESULTS: A total of 9411 patients with nonvalvular AF in a prospective observational registry were categorized into four groups according to the amount of alcohol consumption-abstainer-rare, light (<100 g/week), moderate (100-200 g/week), and heavy (≥200 g/week). Data on adverse events (ischaemic stroke, transient ischaemic attack, systemic embolic event, or AF hospitalization including for AF rate or rhythm control and heart failure management) were collected for 17.4 ± 7.3 months. A Cox proportional hazard models was performed to calculate hazard ratios (HRs), and propensity score matching was conducted to validate the results. The heavy alcohol consumption group showed an increased risk of composite adverse outcomes [adjusted hazard ratio (aHR) 1.32, 95% confidence interval (CI) 1.06-1.66] compared with the reference group (abstainer-rare group). However, no significant increased risk for adverse outcomes was observed in the light (aHR 0.88, 95% CI 0.68-1.13) and moderate (aHR 0.91, 95% CI 0.63-1.33) groups. In subgroup analyses, adverse effect of heavy alcohol consumption was significant, especially among patients with low CHA2DS2-VASc score, without hypertension, and in whom ß-blocker were not prescribed. CONCLUSION: Our findings suggest that heavy alcohol consumption increases the risk of adverse events in patients with AF, whereas light or moderate alcohol consumption does not.

Right Ventricular Longitudinal Conduction Delay in Patients with Brugada Syndrome.

BACKGROUND: The mechanism of Brugada syndrome (BrS) is still unclear, with different researchers favoring either the repolarization or depolarization hypothesis. Prolonged longitudinal activation time has been verified in only a small number of human right ventricles (RVs). The purpose of the present study was to demonstrate RV conduction delays in BrS. METHODS: The RV outflow tract (RVOT)-to-RV apex (RVA) and RVA-to-RVOT conduction times were measured by endocardial stimulation and mapping in 7 patients with BrS and 14 controls. RESULTS: Patients with BrS had a longer PR interval (180 ± 12.6 vs. 142 ± 6.7 ms, P = 0.016). The RVA-to-RVOT conduction time was longer in the patients with BrS than in controls (stimulation at 600 ms, 107 ± 9.9 vs. 73 ± 3.4 ms, P = 0.001; stimulation at 500 ms, 104 ± 12.3 vs. 74 ± 4.2 ms, P = 0.037; stimulation at 400 ms, 107 ±12.2 vs. 73 ± 5.1 ms, P = 0.014). The RVOT-to-RVA conduction time was longer in the patients with BrS than in controls (stimulation at 500 ms, 95 ± 10.3 vs. 62 ± 4.1 ms, P = 0.007; stimulation at 400 ms, 94 ±11.2 vs. 64 ± 4.6 ms, P = 0.027). The difference in longitudinal conduction time was not significant when isoproterenol was administered. CONCLUSION: The patients with BrS showed an RV longitudinal conduction delay obviously. These findings suggest that RV conduction delay might contribute to generate the BrS phenotype.

Radiofrequency catheter ablation without radiation exposure in a 13th week pregnant woman with Wolff-Parkinson-White syndrome.

A 36-year-old woman with 12-week gestation visited the emergency department, complaining of palpitations. Her electrocardiography (ECG) demonstrated ventricular pre-excitation combined with atrial fibrillation. The polarity of the delta waves in leads V5, V6, I, and aVL were positive and negative in leads V1, III, and aVF, suggesting that the accessory pathway (AP) was located on the right posterior free wall. She did not want to take any medicine to prevent the tachycardia. Moreover, the shortest pre-excited RR interval during the atrial fibrillation was 200 ms, so we decided to ablate the AP without fluoroscopy. An electrophysiology study was performed with guidance of a 3-dimension (3D) navigation system and intracardiac echocardiography (ICE). We ablated the right free wall AP without fluoroscopy. A follow-up ECG no longer exhibited any delta waves. Even in the early period of pregnancy, catheter ablation might be performed safely using ICE and a 3D navigation system without fluoroscopy. Therefore, it could more often be considered as a therapeutic option in pregnant women without concern for radiation exposure.

Positive chronotropic effects of theophylline and cilostazol in patients with symptomatic sick sinus syndrome who have declined permanent pacing.

Pacemakers are more commonly recommended than theophylline for sick sinus syndrome (SSS) treatment. The positive effects of cilostazol on bradyarrhythmias also have been reported. However, no comparison of cilostazol and theophylline has been previously reported found. We retrospectively enrolled SSS patients, who refused a pacemaker implantation. Theophylline or cilostazol was administered, and the heart rate (HR) was evaluated in 4-8 weeks using a digital sphygmomanometer and the electrocardiogram (ECG). A 200-400 mg of theophylline or 100-200 mg of cilostazol were administered per day in 50 and 30 patients, respectively. The baseline HR was 54.8 ± 13.5 beats per minute (bpm) on using sphygmomanometry and 51.9 ± 11.8 bpm using the ECG. In the theophylline group, the HR increased by 12.0 ± 16.3 bpm by sphygmomanometry (P < 0.001) and 8.4 ± 12.0 bpm by the ECG (P < 0.001). In the cilostazol group, the HR increased by 16.8 ± 13.9 bpm by sphygmomanometry (P < 0.001) and 12.4 ± 13.4 bpm using the ECG (P < 0.001). In 15 of the 50 theophylline patients, the medication was switched to cilostazol. The HR increased from 61.4 ± 13.8 bpm to 64.0 ± 12.6 bpm (P = 0.338). Symptoms such as dyspnea, chest discomfort, dizziness, and syncope significantly improved after the administration of the medications. There were no significant differences in the improvement in the symptoms except for dizziness between the two agents. Cilostazol was as effective as theophylline for increasing the HR in SSS patients.

Left atrial longitudinal strain as a predictor of Cancer therapeutics-related cardiac dysfunction in patients with breast Cancer.

BACKGROUND: We investigated the usefulness of the left atrial (LA) strain measurement on the prediction of upcoming cancer therapeutics-related cardiac dysfunction (CTRCD) after trastuzumab therapy in patients with breast cancer who did not develop CTRCD after chemotherapy. METHODS: A total of 72 females with breast cancer who did not develop CTRCD after chemotherapy and underwent additional trastuzumab therapy were divided into CTRCD (n = 13) and no CTRCD group (n = 59). Echocardiographic measurements including left ventricular global longitudinal strain (LVGLS) and peak atrial longitudinal strain (PALS) decline were compared. RESULTS: CTRCD was identified in 13 patients (18.1%) after additional trastuzumab therapy. Baseline echocardiographic findings were not different. After the completion of chemotherapy, conventional echocardiographic parameters were not different, but PALS decline (15.0 ± 4.7 vs. 8.9 ± 3.2%, p < 0.001) and LVGLS decline (10.5 ± 1.3 vs. 9.1 ± 1.1%, p = 0.002) were significantly greater in CTRCD than in no CTRCD group. PALS decline at the time of chemotherapy completion could predict future CTRCD after trastuzumab therapy with better sensitivity and specificity (cutoff value 11.79%, sensitivity 76.9% and specificity 81.4%) than LVGLS decline (cutoff value 9.9%, sensitivity 69.2% and specificity 78.0%). CONCLUSIONS: PALS or LVGLS decline developed before developing overt CTRCD after chemotherapy for breast cancer, and PALS decline showed better sensitivity and specificity in predicting future CTRCD than LVGLS decline. Serial measurement of PALS can be used as a useful parameter in the prediction of future CTRCD.

Experimental verification of the value of the Tpeak -Tend interval in ventricular arrhythmia inducibility in an early repolarization syndrome model.

INTRODUCTION: In patients with early repolarization patterns on ECG, many researchers have studied to find predictors of fatal arrhythmia. However, there are no satisfying clinical predictors. We evaluated the value of the Tpeak -Tend interval on pseudo-ECG in canine myocardial wedge preparation models of early repolarization syndrome. METHODS AND RESULTS: Transmural pseudo-ECG and endocardial/epicardial action potentials were recorded from coronary-perfused canine left ventricular wedge preparations (n = 34). The Ito agonist NS5806 (8-10 µM), the calcium channel blocker verapamil (3 µM) and acetylcholine (2-3 µM) were used to mimic the disease model. A ventricular arrhythmia induction test was performed. QTpeak , QTend , Tpeak -Tend , and Tpeak -Tend /QTend were measured at 15 to 20 minutes after the provocative agent infusion. Polymorphic ventricular tachycardias (pVT) developed in 23 of the 34 preparations (67%). The maximal values of Tpeak -Tend and Tpeak -Tend /QTend were recorded just before pVT induction. At baseline, without the provocative agents, Tpeak -Tend and Tpeak -Tend /QTend were not different between pVT-induced and pVT-noninduced preparations. The Tpeak -Tend of the pVT-induced preparations was longer than that of non-induced preparations (58 ± 26.8 msec vs 33 ± 6.8 msec, P < .001). The Tpeak -Tend /QTend of pVT- induced preparations was larger than that of noninduced preparations (0.220 ± 0.1017 vs 0.128 ± 0.0312, P < .001). The transmural and epicardial dispersion of repolarization of pVT-induced preparations were larger than those of pVT-noninduced preparations. The transmural dispersion of repolarization showed a positive correlation with Tpeak -Tend . CONCLUSION: Tpeak -Tend predicted malignant ventricular arrhythmias in early repolarization syndrome models. Tpeak -Tend reflects the repolarization heterogeneity of ventricular myocardium.

Woven Kevlar Fiber/Polydimethylsiloxane/Reduced Graphene Oxide Composite-Based Personal Thermal Management with Freestanding Cu-Ni Core-Shell Nanowires.

Thermotherapy is a widespread technique that provides relief for muscle spasms and joint injuries. A great deal of energy is used to heat the surrounding environment, and heat emitted by the human body is wasted on our surroundings. Herein, a woven Kevlar fiber (WKF)-based personal thermal management device was fabricated by directly growing vertical copper-nickel (Cu-Ni) nanowires (NWs) on the WKF surface using a hydrothermal method. The treated WKF was combined with reduced graphene oxide (rGO) dispersed in polydimethylsiloxane (PDMS) to form composites using vacuum-assisted resin transfer molding (VARTM). This WKF-based personal thermal management system contained a conductive network of metallic NWs and rGO that promoted effective Joule heating and reflected back the infrared (IR) radiation emitted by the human body. It thus behaved as a type of thermal insulation. The Cu-Ni NWs were synthesized with a tunable Ni layer on Cu core NWs to enhance the oxidation resistance of the Cu NWs. The combined effect of the NW networks and rGO enabled a surface temperature of 70 °C to be attained on application of 1.5 V to the composites. The Cu3Ni1-WKF/PDMS provided 43% more thermal insulation and higher IR reflectance than bare WKF/PDMS. The absorbed impact energy and tensile strength was highest for the Cu1Ni3- and rGO-integrated WKF/PDMS samples. Those Cu-Ni NWs having higher Ni contents displayed better mechanical properties and those with higher Cu contents showed higher Joule heating performance and IR reflectivity at a given rGO loading. The composite shows sufficient breathability and very high durability. The high flexibility of the composites and their ability to generate sufficient heat during various human motions ensures their suitability for wearable applications.

Hybrid Architectures of Heterogeneous Carbon Nanotube Composite Microstructures Enable Multiaxial Strain Perception with High Sensitivity and Ultrabroad Sensing Range.

Low-dimensional nanomaterials are widely adopted as active sensing elements for electronic skins. When the nanomaterials are integrated with microscale architectures, the performance of the electronic skin is significantly altered. Here, it is shown that a high-performance flexible and stretchable electronic skin can be produced by incorporating a piezoresistive carbon nanotube composite into a hierarchical topography of micropillar-wrinkle hybrid architectures that mimic wrinkles and folds in human skin. Owing to the unique hierarchical topography of the hybrid architectures, the hybrid electronic skin exhibits versatile and superior sensing performance, which includes multiaxial force detection (normal, bending, and tensile stresses), remarkable sensitivity (20.9 kPa-1 , 17.7 mm-1 , and gauge factor of 707 each for normal, bending, and tensile stresses), ultrabroad sensing range (normal stress = 0-270 kPa, bending radius of curvature = 1-6.5 mm, and tensile strain = 0-50%), sensing tunability, fast response time (24 ms), and high durability (>10 000 cycles). Measurements of spatial distributions of diverse mechanical stimuli are also demonstrated with the multipixel electronic skin. The stress-strain behavior of the hybrid structure is investigated by finite element analysis to elucidate the underlying principle of the superior sensing performance of the electronic skin.

Impacts of Predischarge Diastolic Functional Recovery on Clinical Outcomes in Patients With Hypertensive Heart Failure.

BACKGROUND: Diastolic function is an independent predictor of death in heart failure (HF), but the effect of a change in diastolic function during hospitalization on clinical outcomes in patients with hypertensive HF (HHF) has been poorly studied. Therefore, the aim of this study was to investigate the effect of predischarge diastolic functional recovery (DFR) on future clinical outcomes in hospitalized patients with a first diagnosis of HHF.Methods and Results:A total of 175 hospitalized patients with HHF were divided into 2 groups according to the change in diastolic function on predischarge echocardiography in comparison with baseline echocardiography: DFR group (n=74, 54.2±17.1 years, 55 males) vs. no DFR group (n=101, 59.1±16.8 years, 72 males). During 66.5±37 months of clinical follow-up, major adverse cardiac events (MACE) occurred in 89 patients: 85 HF rehospitalizations, 4 deaths, no MI. The number of MACE were significantly higher in the no DFR group than in the DFR group (61.6% vs. 32.4%, P<0.001). Predischarge systolic functional recovery was not a predictor of MACE, but impaired DFR was an independent predictor of MACE (RR=2.952, P=0.010, confidence interval, 1.878-6.955). CONCLUSIONS: Impaired predischarge DFR, regardless of the type of HF or predischarge systolic functional recovery, is an independent predictor of future MACE in HHF. Changes in diastolic function should be carefully monitored and would be useful in risk stratification of HHF.

Quality of Anticoagulation and Treatment Satisfaction in Patients with Non-Valvular Atrial Fibrillation Treated with Vitamin K Antagonist: Result from the KORean Atrial Fibrillation Investigation II.

BACKGROUND: Vitamin K antagonist (VKA) to prevent thromboembolism in non-valvular atrial fibrillation (NVAF) patients has limitations such as drug interaction. This study investigated the clinical characteristics of Korean patients treated with VKA for stroke prevention and assessed quality of VKA therapy and treatment satisfaction. METHODS: We conducted a multicenter, prospective, non-interventional study. Patients with CHADS2 ≥ 1 and treated with VKA (started within the last 3 months) were enrolled from April 2013 to March 2014. Demographic and clinical features including risk factors of stroke and VKA treatment information was collected at baseline. Treatment patterns and international normalized ratio (INR) level were evaluated during follow-up. Time in therapeutic range (TTR) > 60% indicated well-controlled INR. Treatment satisfaction on the VKA use was measured by Treatment Satisfaction Questionnaire for Medication (TSQM) after 3 months of follow-up. RESULTS: A total of 877 patients (age, 67; male, 60%) were enrolled and followed up for one year. More than half of patients (56%) had CHADS2 ≥ 2 and 83.6% had CHA2DS2-VASc ≥ 2. A total of 852 patients had one or more INR measurement during their follow-up period. Among those patients, 25.5% discontinued VKA treatment during follow-up. Of all patients, 626 patients (73%) had poor-controlled INR (TTR < 60%) measure. Patients' treatment satisfaction measured with TSQM was 55.6 in global satisfaction domain. CONCLUSION: INR was poorly controlled in Korean NVAF patients treated with VKA. VKA users also showed low treatment satisfaction.

Predictors of Left Ventricular Functional Recovery and Their Impact on Clinical Outcomes in Patients With Newly Diagnosed Dilated Cardiomyopathy and Heart Failure.

BACKGROUND: To identify the predictors of left ventricular functional recovery (LVFR) and its impacts on clinical outcomes in acute heart failure (AHF) patients with newly diagnosed dilated cardiomyopathy (DCM). METHODS: A total of 175 consecutive patients with newly diagnosed DCM and AHF were divided into two groups according to LVFR on FU echocardiography; the recovered group (n=54, 54.3±18.5years, 31 males) vs. the non-recovered group (n=121, 60.5±15.1years, 79 males). Clinical, laboratory, and echocardiographic findings were compared, and major adverse cardiac and cerebrovascular events (MACCE) including death, rehospitalisation, and stroke were analysed. RESULTS: Left ventricular function (LV) was normalised in 54 patients (30.8%) on follow-up echocardiography. The change in the level of N-terminal pro-B-type natriuretic peptide (ΔNT-proBNP) between initial presentation and discharge >1633.5pg/mL was an independent predictor of LVFR, whereas diabetes and LV end-systolic diameter >50mm were negative predictors of LVFR on multivariate analysis. During five years of clinical follow-up, MACCE developed in 91 patients: 58 deaths, 29 rehospitalisations, and 4 strokes. On multivariate analysis, baseline LVEF <30% and no LVFR were independent predictors of MACCE. CONCLUSION: Left ventricular functional recovery was not uncommon in newly diagnosed DCM with AHF. The changes in NT-proBNP level during hospitalisation, diabetes, and larger initial LV size were independent predictors of LVFR, and LVFR was an independent predictor of future MACCE. Serial monitoring of NT-proBNP and LV function would be useful in the risk stratification of newly diagnosed DCM with AHF.

Managing failure: Sir Peter Brian Medawar's transplantation research.

Sir Peter Medawar experimentally demonstrated immunological tolerance through his tissue transplantation experiment in the early and mid-1950s. He made a central contribution to modern biomedicine by showing that genetically distinct cells introduced into a body during its foetal phase could not only be permanently tolerated but also make the host accept any subsequent skin grafts from the original cell donors. However, this discovery had only a limited clinical applicability. None could practise Medawar's method on human foetuses in preparation for their future need for organ or skin transplantation. I analyse this problem by focusing on his management of 'failures' during the tissue transplantation experiments. Through statistical, material, theoretical and rhetorical strategies, he managed unsatisfactory findings of his research, including unexpected skin infection, sudden animal death and irregularities in homograft survival times. I argue that these strategies and their inherent ambiguities constituted the course of Medawar's research, enabling him to delineate the temporal dimensions of tolerance and a clinical relevance, which were mutually contradictory. This paper thus illustrates the multiple roles that failures play in scientific research as well as the conflicting outcomes of investigators' efforts to manage them.

Optimal dose of dabigatran for the prevention of thromboembolism with minimal bleeding risk in Korean patients with atrial fibrillation.

AIMS: We aim to determine the optimal dose of dabigatran in Korean patients with atrial fibrillation (AF). METHODS AND RESULTS: We analysed 1834 patients with non-valvular AF, classified into a warfarin group (n = 990), dabigatran 150 mg group (D150, n = 294), and 110 mg group (D110, n = 550). The D110 group was further classified into patients concordant (co-D110, n = 367) and patients discordant (di-D110, n = 183) with guidelines to dose reduction. Propensity-matched 1-year clinical outcomes were then compared. Efficacy outcomes were defined as thromboembolism composed of new-onset stroke or systemic embolism. Safety outcomes were major bleeding. Both D150 and D110 had comparable efficacies as warfarin. However, only D110 significantly lowered the risk of major bleeding [hazard ratio (HR) 0.19, 95% confidence interval (CI) 0.07-0.55, P = 0.002]. In a subgroup analysis according to guideline-concordant indications for dose reduction, both co-D110 and di-D110 displayed a comparable efficacy as warfarin. Both co-D110 (HR 0.22, 95% CI 0.06-0.76, P = 0.017) and di-D110 (HR 0.11, 95% CI 0.02-0.81, P = 0.030) significantly lowered incidences of major bleeding. There were no differences in the efficacy and safety between di-D110 and D150, and net clinical outcomes were similar. CONCLUSION: Although D150 and D110 had a comparable efficacy, only D110 lowered the risk of major bleeding in Korean AF patients compared with warfarin. Even the guideline-discordant use of dabigatran 110 mg demonstrated a similar efficacy and safety compared with D150. However, further prospective randomized trials are needed in order to comprehensively evaluate whether D150 or D110 is the optimal dosage in Asian patients with AF.

Tpeak-Tend interval during therapeutic hypothermia can predict upcoming ventricular fibrillation in subjects with aborted arrhythmic sudden cardiac death: 3-years follow-up results.

AIMS: Prolonged Tpeak-Tend interval has been shown to be markers of arrhythmogenesis in various cardiac disorders. However, its dynamicity is one of the obstacles to predict fatal ventricular arrhythmia. This study investigated whether Tpeak-Tend interval during therapeutic hypothermia (TH) is associated with ventricular fibrillation (VF) inducibility and clinical arrhythmia in subjects with aborted arrhythmic sudden cardiac death (SCD). METHODS AND RESULTS: The study group included 31 patients (24 males, age 39.1 ± 17.6 years) presenting with arrhythmic SCD in whom Tpeak-Tend interval and J-wave amplitude were measured in electrocardiogram (ECG) of the earliest medical contact and during TH; these patients underwent programmed ventricular stimulation. The summation of J-wave amplitude and QTc interval increased during TH. However, it was not associated with VF inducibility. Patients with inducible VF showed a small Tpeak-Tend interval dispersion in the baseline 12-lead ECG (68.8 ± 24.7 vs. 94.0 ± 55.6 ms, P = 0.044) and a marked increase of the dispersion during the TH (36.2 ± 51.2 vs. -6.1 ± 45.5 ms, P = 0.039). Twenty-four patients underwent implantable cardioverter defibrillator (ICD) implantation. Among them, the patients with long QTc, Tpeak-Tend, and precordial Tpeak-Tend during the TH developed VF more frequently (QTc, 511.9 ± 53.71 ms vs. 566.5 ± 56.08 ms, P = 0.038; Tpeak-Tend interval, 145.6 ± 38.4 ms vs. 185.7 ± 49.95 ms, P = 0.048; precordial Tpeak-Tend interval, 139.3 ± 35.11 ms vs. 185.7 ± 49.95 ms, P = 0.018). The initial VF inducibility was not related with the VF development in follow-up. CONCLUSION: In patients with aborted arrhythmic SCD, long Tpeak-Tend interval and QTc interval during TH could predict VF development in their follow-up.

Carotid plaque rather than intima-media thickness as a predictor of recurrent vascular events in patients with acute ischemic stroke.

BACKGROUND: To investigate the impacts of carotid plaque and intima-media thickness (IMT) on future vascular events (VEs) in the patients with acute ischemic stroke. METHODS: A total of 479 consecutive Korean patients with acute ischemic stroke were divided into 2 groups according to development of VEs; VE group (65.4 ± 10.9 years) vs no VE group (62.8 ± 13.2 years). VEs were defined as the development of recurrent stroke, coronary events, peripheral arterial disease, and death. Clinical, laboratory, and imaging findings were compared between the groups. RESULTS: During 105.5 ± 29.0 months of follow up, VEs were developed in 142 patients (29.6%). In univariate analysis, VEs were significantly associated with age, gender, diabetes, renal function, lipid levels, left ventricular function, carotid plaque or IMT. In multivariate analysis, the presence of carotid plaque, diabetes, renal function and male gender were independent predictors of future VEs in the patients with ischemic stroke, but carotid IMT was not a predictor of future VEs. Event free survival was significantly lower in patients with carotid plaque than without carotid plaque on Kaplan-Meier analysis (log rank p < 0.001). CONCLUSION: The present study demonstrated that diabetes, impaired renal function, male gender, and the presence of carotid plaque rather than IMT were independent predictors of future VEs in Korean patients with acute ischemic stroke. Active medical management and careful monitoring for the development of recurrent VEs are strongly recommended in patients with acute ischemic stroke and carotid plaque.