METHODS: Eight patients awaiting heart transplantation due to end-stage coronary heart disease underwent coronary CT angiography (CCTA) spectroscopy prior to heart transplantation; coronary artery pathological analysis was performed for all patients. Lipid-core plaques were defined pathologically as manifesting a lipid core diameter > 200 µm, a circumference > 60 degrees, and a cap thickness < 450 µm. The percentage distributions of CT pixel attenuation ≤ 20, 30, 40, and 50 HU were calculated using quantitative histogram analysis.RESULTS: A total of 271 transverse sections were co-registered between CCTA and pathological analysis. Overall, 26 lipid cores and 16 fibrous plaques were identified by pathological analysis. There was no significant difference in median CT attenuation between the lipid and fibrous plaques (51 HU [interquartile range, 46–63] vs. 57 HU [interquartile range, 50–64], p = 0.659). The median percentage of CT pixel attenuation ≤ 30 HU accounted for 11% (5–17) of lipid-core plaques and 0% (0–2) of fibrous plaques (p < 0.001). The sensitivity and specificity of the method for diagnosing lipid plaques by the average CT pixel attenuation ≤ 30 HU were 80.8% and 87.5%, respectively. The area under the receiver operator characteristics curve was 0.898 (95% confidence interval: 0.765–0.970; 3.0% was the best cut-off value). The diagnostic performance was significantly higher than those of the average pixel CT attenuation percentages ≤ 20, 40, and 50 HU and the mean CT attenuation (p < 0.05).CONCLUSION: In in vivo conditions, with the pathological lipid core as the gold standard, quantification of the percentage of average CT pixel attenuation ≤ 30 HU in the histogram can be useful for accurate identification of lipid plaques.]]>
Angiography ; Coronary Disease ; Coronary Vessels ; Diagnosis ; Heart Transplantation ; Humans ; Methods ; Sensitivity and Specificity ; Spectrum Analysis

Oxidative stress and apoptosis are the key factors that limit the hypothermic preservation time of donor hearts to within 4-6 h. The aim of this study was to investigate whether the histone deacetylase 3 (HDAC3) inhibitor RGFP966 could protect against cardiac injury induced by prolonged hypothermic preservation. Rat hearts were hypothermically preserved in Celsior solution with or without RGFP966 for 12 h followed by 60 min of reperfusion. Hemodynamic parameters during reperfusion were evaluated. The expression and phosphorylation levels of mammalian STE20-like kinase-1 (Mst1) and Yes-associated protein (YAP) were determined by western blotting. Cell apoptosis was measured by the terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Addition of RGFP966 in Celsior solution significantly inhibited cardiac dysfunction induced by hypothermic preservation. RGFP966 inhibited the hypothermic preservation-induced increase of the phosphorylated (p)-Mst1/Mst1 and p-YAP/YAP ratios, prevented a reduction in total YAP protein expression, and increased the nuclear YAP protein level. Verteporfin (VP), a small molecular inhibitor of YAP-transcriptional enhanced associate domain (TEAD) interaction, partially abolished the protective effect of RGFP966 on cardiac function, and reduced lactate dehydrogenase activity and malondialdehyde content. RGFP966 increased superoxide dismutase, catalase, and glutathione peroxidase gene and protein expression, which was abolished by VP. RGFP966 inhibited hypothermic preservation-induced overexpression of B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and cleaved caspase-3, increased Bcl-2 mRNA and protein expression, and reduced cardiomyocyte apoptosis. The antioxidant and anti-apoptotic effects of RGFP966 were cancelled by VP. The results suggest that supplementation of Celsior solution with RGFP966 attenuated prolonged hypothermic preservation-induced cardiac dysfunction. The mechanism may involve inhibition of oxidative stress and apoptosis via inactivation of the YAP pathway.
Acrylamides/pharmacology* ; Animals ; Apoptosis/drug effects* ; Cryopreservation ; Disaccharides/pharmacology* ; Electrolytes/pharmacology* ; Glutamates/pharmacology* ; Glutathione/pharmacology* ; Heart/physiology* ; Heart Transplantation/methods* ; Hepatocyte Growth Factor/antagonists & inhibitors* ; Histidine/pharmacology* ; Histone Deacetylase Inhibitors/pharmacology* ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors* ; Male ; Mannitol/pharmacology* ; Oxidative Stress/drug effects* ; Phenylenediamines/pharmacology* ; Proto-Oncogene Proteins/antagonists & inhibitors* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; YAP-Signaling Proteins

PURPOSE: The purpose of this study was to describe the lived experience of patients with heart transplantation in Korea. METHODS: Individual indepth interviews and a focus group interview were used to collect the data from nine patients who had heart transplantations in 2015. All interviews were audio-taped and verbatim transcripts were made for the analysis. Data were analyzed using Colaizzi's phenomenological method. RESULTS: Among the nine participants, eight were men. Mean age was 57.30 years. Six theme clusters emerged from the analysis. ‘Joy of rebirth obtained by good luck’ describes the pleasure and expectation of new life after narrow survival. ‘Suffering from adverse drug effects’ illustrates various psychosocial difficulties, such as low self-esteem, helplessness, alienation, and burnout, arising from the side effects of medications. ‘Body and mind of being bewildered’ illustrates disintegrated health and haunting fear of death. ‘Alienation disconnected with society’ describes isolated feeling of existence due to misunderstandings from society. ‘Suffering overcome with gratitude and responsibility’ includes overcoming experience through various social supports and suitable jobs. Finally, ‘acceptance of suffering accompanied with new heart’ illustrate changed perspective of life itself. CONCLUSION: The findings in this study provide deep understanding and insights of the lived experience of heart related illness for these patients and should help in the development of tailored-interventions for patients with heart transplantation.
Emigrants and Immigrants ; Focus Groups ; Heart Transplantation* ; Heart* ; Humans ; Korea ; Life Change Events ; Male ; Methods ; Organ Transplantation ; Pleasure ; Qualitative Research

OBJECTIVE: To explore the feasibility of cardiopulmonary exercise test (CPET) in leukemia patients after chemotherapy. METHODS: Leukemia patients with histologically confirmed hematologic malignancies were reviewed. We evaluated for CPET, between receiving chemotherapy and undergoing stem cell transplantation after 2 weeks. We recorded exercise testing and physiologic parameters during CPET between January 2013 to May 2015. All patients were subjected to symptoms limited to exercise testing, according to the Modified Bruce Protocol. We considered that if respiratory exchange ratio achieved was over 1.10, participants had successfully completed CPET. We dichotomized all participants into two groups (normal group, normal range of resting heart rate; higher group, over 100 per minute of heart rate). RESULTS: 30 patients were finally enrolled. All participants had no adverse effects during the exercise test. Mean peak double product was 26,998.60 mmHg·beats/min (range, 15,481–41,004), and mean peak oxygen consumption (VO₂ peak) was 22.52±4.56 mL/kg/min. Significant differences were observed in the normal group with VO₂ peak (mean, 24.21 mL/kg/min; p=0.027) and number of prior intensive chemotherapy, compared to the higher group (mean, 1.95; p=0.006). CONCLUSION: Our results indicate that CPET in leukemia patients before stem cell transplantation was very safe, and is an efficient method to screen for patients with poor cardiac functions. As CPET presents the parameters which reveal the cardiopulmonary functions, including VO₂ peak, double product and exercise capacity, this exercise test would help to predict the physical performance or general condition of the leukemia patients.
Drug Therapy* ; Exercise Test* ; Feasibility Studies* ; Heart ; Heart Rate ; Hematologic Neoplasms ; Humans ; Leukemia* ; Methods ; Oxygen Consumption ; Reference Values ; Rehabilitation ; Stem Cell Transplantation ; Tachycardia

BACKGROUND: The shortage of human hearts for allotransplantation makes xenotransplantation a possible option for controllable organ providers. To detect acute xenograft rejection, invasive biopsy seems inevitable; however, this occasionally results in poor incision wound healing or infection. To date, no method of noninvasive imaging for early detection of xenograft rejection has been established. We hypothesized that ultrasound speckle tracking would better detect xenograft failure than routine left ventricular ejection fractions (EF). METHODS: From August 2013 to July 2015, a total of six cardiac heterotopic xenotransplants (α 1, 3-galactosyltransferase gene-knockout porcine heart) into cynomolgus monkeys were monitored with echocardiography every 3 to 7 days. M-mode and two-dimensional (2D)-EF measurements and myocardial strain analyses were performed. Cardiac xenograft pathology was reviewed from the immediate postoperative biopsy, as well as the necropsy. RESULTS: Myocardial speckle tracking analysis was feasible in all six cases. The longest survival was 43 days. Only one pathology-proven immunologic rejection occurred. Cardiac xenograft failure appeared as two types: a dilated pattern with decreased EF or a myocardial-thickening pattern with preserved EF. Both antibody-mediated rejection (n=1) and sepsis-induced myocardial dysfunction (n=2) revealed decreased radial or circumferential strains, but normal-range EF. Xenograft functional decline was significant with respect to radial or circumferential strain (P=0.028), but not to conventional M-mode or 2D-EFs (P=0.600, P=0.340, respectively). CONCLUSIONS: Radial and circumferential strains were significantly decreased in both types of xenograft failure, regardless of EF. Further studies are warranted to correlate the strain analysis and immunopathological details.
Biopsy ; Echocardiography ; Heart ; Heart Transplantation ; Heterografts ; Humans ; Macaca fascicularis ; Methods ; Pathology ; Stroke Volume ; Transplantation, Heterologous* ; Transplants* ; Ultrasonography ; Wound Healing

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been successfully used as a method for the interhospital transportation of critically ill patients. In South Korea, a well-established ECMO interhospital transport system is lacking due to limited resources. We developed a simplified ECMO transport system without mechanical ventilation for use by public emergency medical services. METHODS: Eighteen patients utilized our ECMO transport system from December 2011 to September 2015. We retrospectively analyzed the indications for ECMO, the patient status during transport, and the patient outcomes. RESULTS: All transport was conducted on the ground by ambulance. The distances covered ranged from 26 to 408 km (mean, 65.9±88.1 km) and the average transport time was 56.1±57.3 minutes (range, 30 to 280 minutes). All patients were transported without adverse events. After transport, 4 patients (22.2%) underwent lung transplantation because of interstitial lung disease. Eight patients who had severe acute respiratory distress syndrome showed recovery of heart and lung function after ECMO therapy. A total of 13 patients (70.6%) were successfully taken off ECMO, and 11 patients (61.1%) survived. CONCLUSION: Our ECMO transport system without mechanical ventilation can be considered a safe and useful method for interhospital transport and could be a good alternative option for ECMO transport in Korean hospitals with limited resources.
Ambulances ; Critical Illness* ; Emergency Medical Services ; Extracorporeal Membrane Oxygenation* ; Heart ; Humans ; Korea ; Lung ; Lung Diseases, Interstitial ; Lung Transplantation ; Methods ; Patient Transfer ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; Retrospective Studies ; Transportation ; Ventilators, Mechanical*

OBJECTIVETo investigate the protective effect of high-pressure carbon monoxide for preservation of ex vivo rabbit heart graft in comparison with the conventional HTK cardioplegic solution preservation.

METHODSHeart grafts isolated from 85 New Zealand rabbits were randomly divided into Naive group (n=5), HTK group (n=40) and CO group (n=40). The grafts underwent no preservation procedures in Naive group, preserved at 4 degrees celsius; in HTK cardioplegic solution in HTK group, and preserved at 4 degrees celsius; in a high-pressure tank (PO2: PCO=3200 hPa: 800 hPa) in CO group with Krebs-Henseleit solution perfusion but without cardioplegic solution. After preservation for 2, 4, 6, 8, 10, 14, 18, and 24 h, 5 grafts from the two preservation groups were perfused for 30 min with a modified Langendorff apparatus and examined for left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), arrhythmia score (AS), myocardial ultrestructure, and cardiac enzyme profiles.

RESULTSAfter preservation for 6 to 24 h, the cardiac enzyme profiles and systolic and diastolic functions were significantly better in CO group than in HTK group, but these differences were not obvious between the two groups after graft preservation for 2 to 4 h. Significant changes in the myocardial ultrastructures occurred in the isolated hearts after a 24-h preservation in both CO and HTK groups, but the myocardial damages were milder in CO group.

CONCLUSIONPreservation using high-pressure carbon monoxide can better protect isolated rabbit heart graft than the conventional HTK preservation approach especially for prolonged graft preservation.

Animals ; Carbon Monoxide ; Cardioplegic Solutions ; Glucose ; Heart ; physiology ; Heart Transplantation ; Myocardium ; ultrastructure ; Rabbits ; Tissue Preservation ; methods ; Tromethamine

Fulminant myocarditis has been defined as the clinical manifestation of cardiac inflammation with rapid-onset heart failure and cardiogenic shock. We report on the case of a 23-yr-old woman with pathology-proven fulminant lymphocytic myocarditis presenting shock with elevated cardiac troponin I and ST segments in V1-2, following sustained ventricular tachycardia and a complete atrioventricular block. About 55 min of intensive cardio-pulmonary resuscitation, with extracorporeal membrane oxygenation support, bridged the patient to orthotopic heart transplantation. The explanted heart revealed diffuse lymphocytic infiltration and myocyte necrosis in all four cardiac chamber walls. Aggressive mechanical circulatory support may be an essential bridge for recovery or even transplantation in patients with fulminant myocarditis with shock.
Combined Modality Therapy/methods ; Extracorporeal Membrane Oxygenation/*methods ; Female ; *Heart Transplantation ; Humans ; Myocarditis/complications/*diagnosis/*therapy ; Shock/*diagnosis/etiology/*prevention & control ; Treatment Outcome ; Young Adult

Donor shortage is a major limitation in organ transplantation. Several studies have reported that extracorporeal membrane oxygenation (ECMO)-assisted organ donation can be successfully completed without inducing warm ischemia in patients with brain death. The present report described clinical experience of three patients (23-yr old man, 32-yr old man, and 41-yr old woman) who underwent ECMO for the evaluation of brain death and organ donation. They donated six kidneys, three livers, and one both lungs without warm ischemia by ECMO. Six kidney recipients successfully recovered normal status without hemodialysis and two liver recipients survived with normal liver functions, but one liver recipient and one lung recipient died 3 and 15 days after transplantation. Our report strongly encourages ECMO-assisted organ donation from brain death patients with refractory cardiopulmonary collapse to achieve improved organ transplantation.
Adult ; *Brain Death/diagnosis ; *Extracorporeal Membrane Oxygenation ; Female ; Heart Arrest ; Humans ; Male ; Middle Aged ; Organ Transplantation ; *Tissue Donors ; Tissue and Organ Harvesting ; Tissue and Organ Procurement/*methods ; Treatment Outcome ; Young Adult

PURPOSE: Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model. MATERIALS AND METHODS: ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBISPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed. RESULTS: Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0+/-10.0 vs. -2.6+/-12.0, p=0.019; LVEF, -8.0+/-15.4 vs. -15.9+/-14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining. CONCLUSION: Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model.
Adipose Tissue/cytology ; Animals ; Bone Marrow Cells/cytology/*metabolism ; Chemokine CXCL12 ; Coronary Vessels ; Female ; Heart/physiopathology ; Heart Ventricles ; *Mesenchymal Stromal Cells ; Myocardial Infarction/physiopathology/radionuclide imaging/*therapy ; *Stem Cell Transplantation ; Swine ; Technetium Tc 99m Sestamibi/*pharmacology ; Tomography, Emission-Computed, Single-Photon/*methods ; Troponin T ; *Ventricular Function, Left