Increased frequency of CD4+CD57+ senescent T cells in patients with newly diagnosed acute heart failure: exploring new pathogenic mechanisms with clinical relevance.

Recent animal studies showed T cells have a direct pathogenic role in the development of heart failure (HF). However, which subsets of T cells contribute to human HF pathogenesis and progression remains unclear. We characterized immunologic properties of various subsets of T cells and their clinical implications in human HF. Thirty-eight consecutive patients with newly diagnosed acute HF (21 males, mean age 66 ± 16 years) and 38 healthy control subjects (21 males, mean age 62 ± 12 years) were enrolled. We found that pro-inflammatory mediators, including CRP, IL-6 and IP-10 and the frequencies of CD57+ T cells in the CD4+ T cell population were significantly elevated in patients with acute HF compared to control subjects. A functional analysis of T cells from patients with acute HF revealed that the CD4+CD57+ T cell population exhibited a higher frequency of IFN-γ- and TNF-α- producing cells compared to the CD4+CD57- T cell population. Furthermore, the frequency of CD4+CD57+ T cells at baseline and its elevation at the six-month follow-up were significantly related with the development of cardiovascular (CV) events, which were defined as CV mortality, cardiac transplantation, or rehospitalization due to HF exacerbation. In conclusion, CD4+CD57+ senescent T cells showed more inflammatory features and polyfunctionality and were associated with clinical outcome in patients with acute HF. More detailed study for senescent T cells might offer new opportunities for the prevention and treatment of human HF.

Analysis of cytomegalovirus-specific T-cell responses in patients with hypertension: comparison of assay methods and antigens.

BACKGROUND: Recent studies suggest an association between cytomegalovirus (CMV) infection and hypertension. In the present study, we used a variety of antigens and different assay methods to investigate the relationship between CMV-specific T-cell responses and arterial stiffness in patients with hypertension. METHODS: To evaluate arterial stiffness, pulse wave velocity (PWV) was measured in 207 hypertensive patients (average age, 63 ± 8 years). To measure CMV pp65 and IE-1-specific T-cell responses, we performed intracellular cytokine staining (ICS) and enzyme-linked immunospot (ELISPOT) assays. We also analyzed CMV-specific T-cell responses against 10 different CMV antigens using ELISPOT assays. RESULTS: In patients with hypertension, senescent CD8+ T-cell frequencies were significantly correlated with arterial stiffness. Moreover, arterial stiffness was independently associated with CMV pp65-specific CD8+ T-cell responses as measured by ICS. CMV-specific CD8+ T-cell responses measured by ICS and ELISPOT assays showed good agreement and significant correlation with each other. ELISPOT analyses against 10 different CMV antigens revealed a consistent response pattern irrespective of age, gender, and diabetes. CONCLUSIONS: CMV pp65-specific CD8+ T-cell responses were independently correlated with arterial stiffness in patients with hypertension. Additionally, the results of ICS and ELISPOT assays showed a significant correlation and good agreement with each other. These findings are important for guiding choices regarding the broad clinical application of CMV-specific T-cell response assays in this patient population.

Temporal Trends of De Novo Malignancy Development After Heart Transplantation.

BACKGROUND: Malignancy is a concern in cardiac transplant recipients, but the temporal trends of de novo malignancy development are unknown. OBJECTIVES: The goal of this study was to describe the temporal trends of the incidence, types, and predictors of de novo malignancy in cardiac transplant recipients. METHODS: The authors analyzed the temporal trends of post-transplant incidence, types, and predictors of malignancy using 17,587 primary adult heart-only transplant recipients from the International Society for Heart and Lung Transplantation registry. The main study outcomes included the incidence of, types of, and time to de novo malignancy. RESULTS: The risk of any de novo solid malignancy between years 1 and 5 after transplantation was 10.7%. The cumulative incidence by malignancy type was: skin cancer (7.0%), non-skin solid cancer (4.0%), and lymphoproliferative disorders (0.9%). There was no temporal difference in the time to development according to malignancy type. However, the cumulative incidence of de novo solid malignancy increased from 2000 to 2005 vs. 2006 to 2011 (10.0% vs. 12.4%; p < 0.0001). Survival in patients after de novo malignancy was markedly lower than in patients without malignancy (p < 0.0001). Older recipients and patients who underwent transplantation in the recent era had a higher risk of de novo malignancy. CONCLUSIONS: More than 10% of adult heart transplant recipients developed de novo malignancy between years 1 and 5 after transplantation, and this outcome was associated with increased mortality. The incidence of post-transplant de novo solid malignancy increased temporally, with the largest increase in skin cancer. Individualized immunosuppression strategies and enhanced cancer screening should be studied to determine whether they can reduce the adverse outcomes of post-transplantation malignancy.

Surgical Removal of a Left Ventricular Thrombus Which Showed Morphologic Changes Over Time in a Patient with Stress-Induced Cardiomyopathy.

Although stress-induced cardiomyopathy (SCMP) is a reversible disease and the prognosis is usually excellent, several complications can occur and can result in fatal adverse events. The formation of left ventricular (LV) thrombus is one of these critical complications of SCMP. This report describes a case of SCMP complicated by formation of a LV thrombus that became increasingly mobile as LV contractility recovered, and for which surgical removal was performed. Here, we report a case of SCMP complicated by LV thrombus and review the literature regarding this topic.

Absolute change in fasting plasma glucose over 12 months is associated with 2-year and 5-year major adverse cardiovascular events in patients with drug-eluting stent implants.

BACKGROUND: Major adverse cardiovascular events (MACEs) in patients with or without cardiovascular disease (CVD) are greatly affected by various factors associated with metabolism and inflammation. OBJECTIVE: To determine which clinical parameters at treatment are associated with the development of 2-year and 5-year MACEs in high-risk patients with CVD who have undergone drug-eluting stent (DES) implantation. METHOD: The present study involved a total of 432 patients who underwent percutaneous coronary intervention with DES. Variables representing the average and absolute amount of change in clinical parameters over the 12-month follow-up were assessed for association with 2-year and 5-year development of MACE. The study population was divided into quartiles for the variable showing the highest correlation to MACE development. Estimated incidence of 2-year and 5-year MACEs for each of the quartiles was determined by survival curve analysis, and subgroup analysis was performed for patients with diabetes and statin users. RESULTS: Absolute change in fasting plasma glucose (FPG) over 12 months showed the highest correlation with 2-year and 5-year MACE development. The estimated incidence of MACE increased with increasing quartiles for absolute change in FPG. The association between absolute change in FPG and MACE development exhibited a stronger relationship for the specific subgroups of patients with diabetes and statin users. Increases and decreases in FPG had a comparable contribution to MACE development. CONCLUSION: A greater absolute change in FPG over 12 months post-PCI is an independent risk factor for 2-year and 5-year MACE development in DES-implanted patients, especially in the diabetes and statin users.

Three-dimensional angiography-guided percutaneous transluminal angioplasty for distal aorta and bi-iliac chronic total occlusion.

Percutaneous recanalization of chronic total occlusions (CTOs) in peripheral arteries, especially TASC D classification including the distal aorta and both iliac arteries is still technically challenging. The conventional technique using standard guidewires and catheters guided by computed tomography and angiography can achieve a limited initial success, depending on lesion characteristics and operator's experience. A special imaging technique using 3-dimensional rotational angiography and spatio-temporal reconstruction with endoview for a better examination of the proximal stump, exact obstruction location, and distal stump direction in a stumpless lesion can be indispensable for successful intervention. We report a successful revascularization case of stumpless distal aorta and bi-iliac CTO guided by this specialized imaging technique.