Development and Feasibility Evaluation of Smart Cancer Care 2.0 Based on Patient-Reported Outcomes for Post-Discharge Management of Patients with Cancer.

Purpose: A "Smart Cancer Care" platform that integrates patient-reported outcomes (PROs) with management has been established in Korea. This study focused on improving health behaviors and connecting patients to welfare services by introducing and assessing the feasibility of "Smart Cancer Care 2.0," an enhanced version designed for monitoring complications post-cancer treatment. Materials and Methods: Smart Cancer Care 2.0 was developed by conducting a literature review and consulting with expert panels to identify symptoms or variables requiring monitoring and management guidelines based on the treatment type. Qualitative and quantitative surveys were conducted to assess the feasibility of the app and web system based on the experiences of patients with cancer and healthcare workers. Results: A total of 81 symptoms or variables (chemotherapy-, surgery-, radiotherapy-, rehabilitation-, and health management-related) were selected for management in Smart Cancer Care 2.0. PROs for these symptoms were basically categorized into three severity grades: (1) preventive management, (2) self-treatment, and (3) consultation with a healthcare worker or visit to a healthcare institution. The overall mean scores in the feasibility evaluation by patients and healthcare workers were 3.83 and 3.90 points, respectively, indicating high usefulness. Conclusion: Smart Cancer Care 2.0 leverages the existing ICT-based platform, Smart Cancer Care, and further includes health behaviors and welfare services. Smart Cancer Care 2.0 may play a crucial role in establishing a comprehensive post-discharge management system for patients with cancer as it provides suitable interventions based on patients' responses and allows the regularly collected PROs to be easily viewed for streamlined care.

Historical Review and Future of Cardiac Xenotransplantation.

Along with the development of immunosuppressive drugs, major advances on xenotransplantation were achieved by understanding the immunobiology of xenograft rejection. Most importantly, three predominant carbohydrate antigens on porcine endothelial cells were key elements provoking hyperacute rejection: α1,3-galactose, SDa blood group antigen, and N-glycolylneuraminic acid. Preformed antibodies binding to the porcine major xenoantigen causes complement activation and endothelial cell activation, leading to xenograft injury and intravascular thrombosis. Recent advances in genetic engineering enabled knock-outs of these major xenoantigens, thus producing xenografts with less hyperacute rejection rates. Another milestone in the history of xenotransplantation was the development of co-stimulation blockaded strategy. Unlike allotransplantation, xenotransplantation requires blockade of CD40-CD40L pathway to prevent T-cell dependent B-cell activation and antibody production. In 2010s, advanced genetic engineering of xenograft by inducing the expression of multiple human transgenes became available. So-called 'multi-gene' xenografts expressing human transgenes such as thrombomodulin and endothelial protein C receptor were introduced, which resulted in the reduction of thrombotic events and improvement of xenograft survival. Still, there are many limitations to clinical translation of cardiac xenotransplantation. Along with technical challenges, zoonotic infection and physiological discordances are major obstacles. Social barriers including healthcare costs also need to be addressed. Although there are several remaining obstacles to overcome, xenotransplantation would surely become the novel option for millions of patients with end-stage heart failure who have limited options to traditional therapeutics.

Erratum: Correction of Authors in the Article "Relevance Index Regional Variation by Each Disease and Its Essential Medical Field: A Retrospective Data Analysis From 2016-2020 in Korea".

This corrects the article on p. e130 in vol. 38, PMID: 37096313.

Relevance Index Regional Variation by Each Disease and Its Essential Medical Field: A Retrospective Data Analysis From 2016-2020 in Korea.

BACKGROUND: To precisely build a healthcare delivery system at regional levels, local patients' healthcare service utilization patterns must be examined. Hence, this study utilized trend analysis of the relevance index of each disease of each essential medical service field at the municipal and provincial levels. METHODS: This study analyzed customized databases released by the National Health Insurance Service from 2016-2020. Diseases defined in the Korean National Burden of Disease (KNBD) study were categorized into the following essential medical service fields: trauma care, cardiocerebrovascular, maternal and neonatal, mental health, infection, cancer, older adults' care and rehabilitation, and others. Relevance index, the percentage of medical service utilization in a region by the residents of that region relative to their total medical service utilization, was examined by region (17 municipal and provincial regions) and disease area. The relevance index was determined based on the number of patients and the total out-of-pocket expenses. RESULT: Eight of the 17 regions showed over a 90.0% relevance index in the infection area. In the cancer area, 14 regions (not including Seoul, Daegu, and Busan) had a relevance index lower than 75.0%. Throughout the analysis period (2016-2020), there were no significant variations in the relevance index. Diseases such as bone and connective tissue cancer (39.0%), neural tube defects (16.7%), and autism (57.1%) had low relevance index in the essential medical service fields. In all 17 regions, the relevance index of inpatients was lower than that of outpatients, and that for out-of-pocket expenses was lower than that based on the number of patients. CONCLUSION: The relevance index of major diseases of each essential medical service field calculated in this study can provide good indicators for monitoring the level of an independent regional healthcare delivery system.

Challenge exposure to whole cigarette smoke condensate upregulates locomotor sensitization by stimulating α4ß2 nicotinic acetylcholine receptors in the nucleus accumbens of rats.

Nicotine, the primary addictive substance in tobacco, produces the psychomotor, rewarding, and reinforcing effects of tobacco dependence by stimulating nicotinic acetylcholine receptors (nAChRs) in the brain. The present study determined that α4ß2 nAChRs regulate locomotor sensitization by altering dopamine concentration in the nucleus accumbens (NAc) after systemic challenge exposure to whole cigarette smoke condensate (WCSC). Rats were administered subcutaneous injection of WCSC (0.2 mg/kg nicotine/day) for 7 consecutive days and then re-exposed to WCSC after 3 days of withdrawal. Challenge exposure to WCSC significantly increased locomotor activity. This increase was decreased by the subcutaneous injection of the α4ß2 nAChR antagonist, DHßE (3 mg/kg), but not by the intraperitoneal injection of the α7 nAChR antagonist, MLA (5 mg/kg). In parallel with a decrease in locomotor activity, blockade of α4ß2 nAChRs with DHßE decreased dopamine concentration in the NAc which was elevated by challenge exposure to WCSC. These findings suggest that challenge WCSC leads to the expression of locomotor sensitization by elevating dopamine concentration via stimulation of α4ß2 nAChRs expressed in neurons of the NAc in rats.

Surgical and Electrical Anatomy of the Inter-Nodal and Intra-Atrial Conduction System in the Heart.

An anatomical understanding of the atrial myocardium is crucial for surgeons and interventionists who treat atrial arrhythmias. We reviewed the anatomy of the inter-nodal and intra-atrial conduction systems. The anterior inter-nodal route (#1) arises from the sinus node and runs through the ventral wall of the atrial chambers. The major branch of route #1 approaches the atrioventricular node from the anterior aspect. Other branches of route #1 are Bachmann's bundle and a vestibular branch around the tricuspid valve. The middle inter-nodal route (#2) begins with a broad span of fibers at the sinus venarum and extends to the superior limbus of the oval fossa. The major branch of route #2 joins with the branch of route #1 at the anterior part of the atrioventricular node. The posterior inter-nodal route (#3) is at the terminal crest and gives rise to many branches at the pectinate muscles of the right atrium and then approaches the posterior atrioventricular node after joining with the vestibular branch of route #1. The branches of the left part of Bachmann's bundle and the branches of the second inter-nodal route form a thin myocardial network at the posterior wall of the left atrium. These anatomical structures could be categorized into major routes and side branches. There are 9 or more anatomical circles in the atrial chambers that could be structural sites for macro re-entry. The implications of normal and abnormal structures of the myocardium for the pathogenesis and treatment of atrial arrhythmias are discussed.

Serial ultrastructural evaluation of myocardial ischemic injury after infusion of del Nido cardioplegia in the human heart.

OBJECTIVES: The safe ischemic time after a single-dose del Nido cardioplegia (DNC) infusion has not yet been established. This study evaluated the progression of myocardial ischemic injury to establish the safe ischemic time after a single-dose DNC infusion in the human heart using a transmission electron microscope. METHODS: Seven hearts extracted from heart transplant recipients after infusion of 1000 mL single-dose DNC were evaluated. Serial left ventricular myocardial tissue samples were collected every 30 minutes for 180 minutes. Ischemic injuries in the mitochondria and nuclei were scored from 0 to 3 (0 = normal, 0.5 = slight, 1 = moderate, 2 = severe, and 3 = irreversible). RESULTS: At the time of extraction, 83.5% of the mitochondria were normal. The proportion of mitochondria with moderate ischemic injury increased gradually from 1.4% at extraction to 52.5% at 180 minutes. From 90 minutes to 180 minutes, the proportion of mitochondria with severe and irreversible injury increased from 0.8% to 4.4% and 0.3% to 1.3%, respectively. A significant linear correlation was identified between the average ischemic injury score of mitochondria and ischemic time (P < .001). Most nuclei showed moderate to severe ischemic injury at every time point (61.0%-85.2%). A significant linear correlation was also found between the average ischemic injury score of nuclei and ischemic time (P < .001). CONCLUSIONS: Myocardial ischemic injury progresses gradually, and irreversible ischemic injury begins to occur 90 minutes after initial DNC infusion in the adult human heart. Therefore, redosing of DNC may be required after 90 minutes of aortic crossclamp time during adult cardiac surgery.

Environmental health survey for children residing near mining areas in South Gobi, Mongolia.

BACKGROUND: We evaluated the level and factors of heavy metal exposure to children residing in the Togttsetsii, Khanbogd, and Bayandalai soums of South Gobi province, Mongolia. METHODS: A total of 118 children aged 9-12 years were surveyed, and the level of heavy metal exposure in their bodies was investigated. Exposure was investigated by measuring concentrations of heavy metals such as cadmium, lead, and mercury in the blood; mercury concentration in the hair; and total arsenic in the urine. RESULTS: Blood cadmium concentration had geometric averages of 0.16 µg/L in the children from Bayandalai, 0.15 µg/L Tsogttsetsii, and 0.16 µg/L Khanbogd. Blood lead concentration showed a relatively higher geometric average of 7.42 µg/dL in the children from Bayandalai compared to 4.78 µg/dL and 5.15 µg/dL in those from Tsogttsetsii and Khanbogd, respectively. While blood mercury concentration was the highest in the children from Bayandalai, with a value of 0.38 µg/L, those from Tsogttsetsii and Khanbogd had similar concentrations of 0.29 µg/L and 0.29 µg/L, respectively. Hair mercury concentration was the highest in the children from Bayandalai, with a value of 78 µg/g, a particularly significant difference, with a concentration of 0.50 µg/g in those from Khanbogd. Urine arsenic concentration was the highest in the children from Khanbogd, with a value of 36.93 µg/L; it was 26.11 µg/L in those from Bayandalai and 23.89 µg/L in those from Tsogttsetsii. CONCLUSIONS: The high blood lead concentration of children in Bayandalai was judged to be due to other factors in addition to mine exposure; the reason why blood and hair mercury concentration was higher in children from Bayandalai may have been due to exposure to many small-scale gold mines in the area. In the case of Khanbogd, it was estimated that the high arsenic level in urine was caused by the effect of mines.

Myocarditis-induced Sudden Death after BNT162b2 mRNA COVID-19 Vaccination in Korea: Case Report Focusing on Histopathological Findings.

We present autopsy findings of a 22-year-old man who developed chest pain 5 days after the first dose of the BNT162b2 mRNA vaccine and died 7 hours later. Histological examination of the heart revealed isolated atrial myocarditis, with neutrophil and histiocyte predominance. Immunohistochemical C4d staining revealed scattered single-cell necrosis of myocytes which was not accompanied by inflammatory infiltrates. Extensive contraction band necrosis was observed in the atria and ventricles. There was no evidence of microthrombosis or infection in the heart and other organs. The primary cause of death was determined to be myocarditis, causally-associated with the BNT162b2 vaccine.

Cardiac toxicity from bisphenol A exposure in human-induced pluripotent stem cell-derived cardiomyocytes.

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical that is widely used in a variety of products, including plastics, medical equipment and receipts. Hence, most people are exposed to BPA through the skin, via inhalation and via the digestive system, and such exposure has been linked to cardiovascular diseases including coronary artery disease, hypertension, atherosclerosis, and myocardial infarction. However, the underlying mechanisms of cardiac dysfunction caused by BPA remain poorly understood. In this study, we found that BPA exposure altered cardiac function in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Acute BPA exposure in hiPSC-CMs resulted in reduced field potential, as measured by multielectrode array (MEA). Furthermore, we observed that BPA dose-dependently inhibited ICa, INa or IKr channels. In addition, BPA exposure dose-dependently inhibited calcium transients and contraction in hiPSC-CMs. Our findings suggest that BPA exposure leads to cardiac dysfunction and cardiac risk factors such as arrhythmia.

Necessity of Assessing Biological Exposure to Arsenic Species by Two Representative Analytical Methods.

Arsenic (As) exists as highly toxic chemical species. Chronic exposure to its inorganic form can cause multiple organ failure and skin cancer in humans, warranting the need to determine the toxicity of each chemical species. This study evaluated the proportions of exposure to four chemical species of As (cAs), namely arsenite (AsIII), arsenate (AsV), monomethylarsinic acid (MMA), and dimethylarsenic acid (DMA), and it confirmed the necessity of evaluating biological exposure to cAs. Urine samples were collected from 457 subjects residing near 103 abandoned metal mines. Hydride generation atomic absorption spectroscopy (HG-AAS) was performed to measure the combined concentration of four cAs (hAsAAS). High-performance liquid chromatography and inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) were performed to determine the concentrations of the individual cAs and the sum of the four cAs (hAsICP). The proportions of AsV and MMA were relatively higher in the low-hAsICP concentration section. These findings suggest that hAsAAS, which is mainly used for its cost-efficiency, is limited for evaluating exposure. Though hAsAAS was found to exist in a low concentration, highly toxic AsV and MMA could be observed in high concentrations. Therefore, HPLC-ICP-MS is recommended for assessing cAs in environmentally vulnerable areas such as abandoned metal mines.

Assessment of Lead and Mercury Exposure Levels in the General Population of Korea Using Integrated National Biomonitoring Data.

In Korea, the estimated values of blood lead (Pb) and mercury (Hg) levels differ between two national-level biomonitors, namely the Korean National Environmental Health Survey and the Korea National Health and Nutrition Examination Survey. The present study used integrated data from these surveys to estimate the representative values of the change in concentration and recent distribution characteristics. The yearly trend of age-standardized exposure levels in regular adults was identified, and the geometric mean (GM) adjusted according to demographic characteristics was presented. Age-standardized GM for blood Pb and Hg in the integrated data was 2.06 and 3.64 µg/L in 2008, respectively, which decreased to 1.55 and 2.92 µg/L, respectively, by 2017. Adjusted GMs from most recently conducted surveys (2015-2017) were 1.61 and 2.98 µg/L for blood Pb and Hg, respectively. In particular, the adjusted percentage of blood Hg exceeding the reference value of 5 µg/L was 20.79%. While the blood Pb and Hg exposure levels are decreasing in Korea, the levels remain high relative to those in other countries. The Hg levels exceeded the reference value in many individuals. Therefore, continued biomonitoring must be conducted, and a reduction plan and exposure management are needed for harmful metals, including Hg.

Feasibility study on stereotactic radiotherapy for total pulmonary vein isolation in a canine model.

We tested the feasibility of pulmonary vein (PV) and left atrial (LA) posterior wall isolation using non-invasive stereotactic ablative body radiotherapy (SABR) and investigated pathological changes in irradiated lesions in a canine model. Seven male Mongrel dogs received single-fraction 33 Gy SABR. We designed the en-bloc circular target of total PVs and LA posterior wall to avoid the esophagus. The circular box lesion included the LA roof and ridge, low posterior wall, and posterior interatrial septum. At 6 weeks or 4 months post-SABR, electrical isolation of the SABR lesion was confirmed using LA posterior wall pacing, and histopathological review was performed. Electrical isolation of all PVs and the LA posterior wall was achieved in three of five dogs in the 4-month group. There was one target failure and one sudden death at 15 weeks. Although two dogs in the 6-week group failed to achieve electrical lesion isolation, the irradiated atrial myocardium showed diffuse hemorrhage with inflammatory cell infiltration. In successfully isolated 4-month model dogs, we observed transmural fibrotic scarring with extensive fibrosis on irradiated atrial tissue. The findings suggest that this novel circular box-design radiotherapy technique using SABR could be applied to humans after further studies are conducted to confirm safety.

Early Changes in Rat Heart After High-Dose Irradiation: Implications for Antiarrhythmic Effects of Cardiac Radioablation.

Background Noninvasive cardiac radioablation is employed to treat ventricular arrhythmia. However, myocardial changes leading to early-period antiarrhythmic effects induced by high-dose irradiation are unknown. This study investigated dose-responsive histologic, ultrastructural, and functional changes within 1 month after irradiation in rat heart. Methods and Results Whole hearts of wild-type Lewis rats (N=95) were irradiated with single fraction 20, 25, 30, 40, or 50 Gy and explanted at 1 day or 1, 2, 3, or 4 weeks' postirradiation. Microscopic pathologic changes of cardiac structures by light microscope with immunohistopathologic staining, ultrastructure by electron microscopy, and functional evaluation by ECG and echocardiography were studied. Despite high-dose irradiation, no myocardial necrosis and apoptosis were observed. Intercalated discs were widened and disrupted, forming uneven and twisted junctions between adjacent myocytes. Diffuse vacuolization peaked at 3 weeks, suggesting irradiation dose-responsiveness, which was correlated with interstitial and intracellular edema. CD68 immunostaining accompanying vacuolization suggested mononuclear cell infiltration. These changes were prominent in working myocardium but not cardiac conduction tissue. Intracardiac conduction represented by PR and QTc intervals on ECG was delayed compared with baseline measurements. ST segment was initially depressed and gradually elevated. Ventricular chamber dimensions and function remained intact without pericardial effusion. Conclusions Mononuclear cell-related intracellular and extracellular edema with diffuse vacuolization and intercalated disc widening were observed within 1 month after high-dose irradiation. ECG indicated intracardiac conduction delay with prominent ST-segment changes. These observations suggest that early antiarrhythmic effects after cardiac radioablation result from conduction disturbances and membrane potential alterations without necrosis.

Effects of Exposure to Lead and Cadmium on Health of Inhabitants of Abandoned Metal Mine Area in Korea.

People living near abandoned mines are at increased risk of exposure to toxic metals. We surveyed 4500 inhabitants with the mean age of 68.5 years old (male: 1768, female: 2732) living near 104 abandoned metal mines from 2013 to 2017 (the 2nd phase health survey in Korea). We conducted personal interviews, blood and urine sampling, and analyzed the concentrations of lead (Pb) and cadmium (Cd) in whole blood and Cd in urine using a graphite furnace atomic absorption spectrometer. The geometric means of blood Pb, blood Cd, and urine Cd were 2.27 µg/dL, 1.42 µg/L, and 1.66 µg/g creatinine, respectively. The level of metal exposure was lower than that reported from the first phase health survey in Korea (2008‒2011) but was higher than in the general population of Korea. Blood Pb was higher in males while blood Cd and urine Cd were significantly higher in females. Blood Pb was highest in the 40‒59 age group, while blood and urine Cd levels continuously increased until age 80 or older. The Cd levels in blood and urine were affected by consumption of locally produced rice and duration of residence near abandoned mines. Furthermore, negative correlations were observed between blood Pb and blood and urine Cd levels. Additionally, 252 of the 4500 subjects exceeded the thresholds of blood Cd or urine Cd levels. Together, these findings suggest that Cd has more sustainable and adverse health effects on the abandoned mine inhabitants, who are mostly aged. Therefore, continuous biomonitoring and risk assessment to environmental health risks are necessary for environmental pollution control and health promotion.

Comparative Evaluation of Heavy Metal Concentrations in Residents of Abandoned Metal Mines.

This study compares the heavy metal exposure levels of the population of abandoned metal mines, with high risks of environmental pollution and health effects. We used data from a two-stage abandoned metal mines survey (AMS, n = 4467). The Korea National Health and Nutrition Examination Survey (KNHANES) and the Korea National Environmental Health Survey (KNEHS) were used as general population data. Based on the sex and age distribution in the AMS, a simple random sampling was performed, so that the two datasets had the same distribution (KNHANES n = 1815, KNEHS n = 2328). Blood lead concentrations were slightly higher in the AMS than in KNEHS. Blood cadmium concentrations were similar between the two groups. However, the difference in urine cadmium concentrations was pronounced and statistically significant. Moreover, 30.6% of the AMS data for urine cadmium concentration exceeded the 95th percentile of the KNEHS data. The concentration of lead and cadmium in the residents of the abandoned metal mines, i.e., the vulnerable regions, was higher than that in the general population. It is necessary to monitor and manage the vulnerable regions via a more active and extensive survey system.

Indirect pathological indicators for cardiac sarcoidosis on endomyocardial biopsy.

BACKGROUND: The definitive pathologic diagnosis of cardiac sarcoidosis requires observation of a granuloma in the myocardial tissue. It is common, however, to receive a "negative" report for a clinically probable case. We would like to advise pathologists and clinicians on how to interpret "negative" biopsies. METHODS: Our study samples were 27 endomyocardial biopsies from 25 patients, three cardiac transplantation and an autopsied heart with suspected cardiac sarcoidosis. Pathologic, radiologic, and clinical features were compared. RESULTS: The presence of micro-granulomas or increased histiocytic infiltration was always (6/6 or 100%) associated with fatty infiltration and confluent fibrosis, and they showed radiological features of sarcoidosis. Three of five cases (60%) with fatty change and confluent fibrosis were probable for cardiac sarcoidosis on radiology. When either confluent fibrosis or fatty change was present, one-third (3/9) were radiologically probable for cardiac sarcoidosis. We interpreted cases with micro-granuloma as positive for cardiac sarcoidosis (five of 25, 20%). Cases with both confluent fibrosis and fatty change were interpreted as probable for cardiac sarcoidosis (seven of 25, 28%). Another 13 cases, including eight cases with either confluent fibrosis or fatty change, were interpreted as low probability based on endomyocardial biopsy. CONCLUSIONS: The presence of micro-granuloma could be an evidence for positive diagnosis of cardiac sarcoidosis. Presence of both confluent fibrosis and fatty change is necessary for probable cardiac sarcoidosis in the absence of granuloma. Either of confluent fibrosis or fatty change may be an indirect pathological evidence but they are interpreted as nonspecific findings.

Surface-Plasmonic-Field-Induced Photoredox Catalysis and Mediated Electron Transfer for Washing-Free DNA Detection.

Distance-dependent electromagnetic radiation and electron transfer have been commonly employed in washing-free fluorescence and electrochemical bioassays, respectively. In this study, we combined the two distance-dependent phenomena for sensitive washing-free DNA detection. A distance-dependent surface plasmonic field induces rapid photoredox catalysis of surface-bound catalytic labels, and distance-dependent mediated electron transfer allows for rapid electron transfer from the surface-bound labels to the electrode. An optimal system consists of a chemically reversible acceptor (Ru(NH3 )63+ ), a chemically reversible photoredox catalyst (eosin Y), and a chemically irreversible donor (triethanolamine). Side reactions with O2 do not significantly decrease the efficiency of photoredox catalysis. Energy transfer quenching between the electrode and the label can be lowered by increasing the distance between them. Washing-free DNA detection had a detection limit of approximately 0.3 nm in buffer and 0.4 nm in serum without a washing step.

The Relationship between Mercury Exposure Indices and Dietary Intake of Fish and Shellfish in Women of Childbearing Age.

Women of childbearing age who are susceptible to mercury exposure were studied to understand the relation between mercury intake through fish and shellfish consumption and mercury exposure indices from blood, hair, and urine samples. A total of 711 women of childbearing age from coastal areas with a high concentration of mercury exposure in Korea were studied. Data were collected on demographic characteristics, dietary intake of fish and shellfish using the simple Food Frequency Questionnaire. Mercury concentration was estimated from the collected samples of blood, hair, and urine. The geometric mean of blood methyl mercury concentration of mercury exposure through seafood was 3.06 µg/L for the low tertile, 3.12 µg/L for the middle tertile, and 3.60 µg/L for the high tertile, indicating a clear tendency of blood methyl mercury to increase as the mercury exposure by fish and shellfish intake ascended. For total blood mercury and hair mercury, the middle and high tertiles had higher values than the low. Mercury exposure through fish and shellfish intake is a main factor for an increase of blood methyl mercury concentration in women of childbearing age. More attention needs to be paid to mercury exposure through seafood intake, considering the serious effect mercury concentration has on women of childbearing age.

Pittsburgh B Compound Positron Emission Tomography in Patients With AL Cardiac Amyloidosis.

BACKGROUND: It remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis. OBJECTIVES: The purpose of this study was to demonstrate that 11C-Pittsburgh B compound positron emission tomography (11C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition. METHODS: This study consecutively enrolled 41 chemotherapy-naïve AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial 11C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure. RESULTS: The degree of myocardial 11C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R2 = 0.343, p < 0.001). During follow-up (median: 423 days, interquartile range: 93 to 1,222 days), 24 patients experienced the primary endpoint. When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial 11C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p = 0.014). The degree of myocardial PiB PET uptake was a significant predictor of clinical outcome on multivariate Cox regression analysis (adjusted hazard ratio: 1.185; 95% confidence interval: 1.054 to 1.332; p = 0.005). CONCLUSIONS: These proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by 11C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients.