The decline in kidney function after heart transplantation and its impact on survival.

BACKGROUND: Evidence of decline in native renal function after heart transplantation (HTx) in the Asian population is limited. This study determined the incidence and risk factors associated with declining kidney function after HTx and its impact on survival. METHODS: A retrospective study of consecutive adult heart transplant patients was conducted in a single center between 2010 and 2020. The decline in kidney function was defined as the presence of one of the following criteria, including a ≥ 40% decline in eGFR, absolute value <15 mL/min/1.73 m2 (calculated by the CKD-EPI method), doubling of serum creatinine, or dialysis. RESULTS: A total of 79 patients (77% male, mean age 44.5 ± 11.53 years, with a mean eGFR at discharge from the heart transplant admission of 87.9 ± 25.48 mL/min/1.73 m2 ) were included. During the median follow-up of 42 months, the rate of decline in eGFR was 3.9 mL/min/1.73 m2 per year, with a cumulative probability of decline in kidney function of 22% at 1 year and 43% at 5 years. The need for dialysis was 2.5% at 1 year and 5% at 5 years. The decline in kidney function within 1 year after discharge (hazard ratio (HR), 22.24; p = .007) and pre-HTx diabetes mellitus (DM) (HR, 8.99; p = .034) were independently associated with the need for dialysis. Post-HTx dialysis predicted all-cause mortality (HR, 4.47; p = .017). CONCLUSIONS: Approximately 20% of HTx patients developed a decline in kidney function within 1 year after discharge. These individuals and pre-HTx DM patients needed preventive measures to prevent progression to chronic dialysis, which impacted survival. (thaiclinicaltrials.org number, TCTR20230620004).

Association of Phenotypic Aging Marker with comorbidities, frailty and inflammatory markers in people living with HIV.

BACKGROUND: Aging characteristics in people living with HIV (PLWH) are heterogeneous, and the identification of risk factors associated with aging-related comorbidities such as neurocognitive impairment (NCI) and frailty is important. We evaluated predictors of novel aging markers, phenotypic age (PhenoAge) and phenotypic age acceleration (PAA) and their association with comorbidities, frailty, and NCI. METHODS: In a cohort of PLWH and age- and sex-matched HIV-negative controls, we calculated PhenoAge using chronological age and 9 biomarkers from complete blood counts, inflammatory, metabolic-, liver- and kidney-related parameters. PAA was calculated as the difference between chronological age and PhenoAge. Multivariate logistic regression models were used to identify the factors associated with higher (>median) PAA. Area under the receiver operating characteristics curve (AUROC) was used to assess model discrimination for frailty. RESULTS: Among 333 PLWH and 102 HIV-negative controls (38% female), the median phenotypic age (49.4 vs. 48.5 years, p = 0.54) and PAA (- 6.7 vs. -7.5, p = 0.24) was slightly higher and PAA slightly less in PLWH although this did not reach statistical significance. In multivariate analysis, male sex (adjusted odds ratio = 1.68 [95%CI = 1.03-2.73]), current smoking (2.74 [1.30-5.79]), diabetes mellitus (2.97 [1.48-5.99]), hypertension (1.67 [1.02-2.72]), frailty (3.82 [1.33-10.93]), and higher IL-6 levels (1.09 [1.04-1.15]), but not HIV status and NCI, were independently associated with higher PAA. PhenoAge marker discriminated frailty better than chronological age alone (AUROC: 0.75 [0.66-0.85] vs. 0.65 [0.55-0.77], p = 0.04). In the analysis restricted to PLWH, PhenoAge alone predicted frailty better than chronological age alone (AUROC: 0.7412 vs. 0.6499, P = 0.09) and VACS index (AUROC: 0.7412 vs. 0.6811, P = 0.34) despite not statistically significant. CONCLUSIONS: While PLWH did not appear to have accelerated aging in our cohort, the phenotypic aging marker was significantly associated with systemic inflammation, frailty, and cardiovascular disease risk factors. This simple aging marker could be useful to identify high-risk PLWH within a similar chronological age group.

Outcomes and predictors of one-year mortality in patients hospitalized with Acute Heart Failure.

Background: Registries of patients hospitalized with acute heart failure (AHF) provided useful description of characteristics and outcomes. However, a contemporary registry which provides sufficient evidence on outcomes after discharge is needed. Objective: The study aims to identify 1-year clinical outcomes and prognostic predictors of patients hospitalized with AHF. Method: This is a retrospective registry which enrolled patients who were hospitalized due to a principal diagnosis of AHF in a tertiary care center in Thailand between July 2017 and June 2019. Baseline characteristics and hospital courses between the deceased patients and the survivors at 1 year were compared. Prognostic predictors for 1-year mortality were analyzed using Cox regression model. Results: A total of 759 patients were enrolled (mean age of 68.9 ± 15 years, 49.8% men, mean ejection fraction of 47.1 ± 19.2%, 55.7% heart failure reduced ejection fraction (HFrEF)). Among these, 40.7% had no history of heart failure. The in-hospital and 1-year mortality was 5.8% and 21.5%, respectively. Patients with HFrEF had lower 1-year mortality compared to those without (HR = 0.57, p = 0.04). Age ≥ 70 years, the history of heart failure, prior heart failure hospitalization, cerebrovascular accident (CVA), reactive airway disease, cancer, length of stay > 10 days and NT-proBNP ≥ 10,000 pg/mL were associated with higher 1-year mortality (p < 0.05). The multivariate analysis showed age, CVA and NT-proBNP were independent predictors. Conclusion: Patients with AHF had high mortality after discharge. Patients with poor prognostic predictors, such as elderly, may benefit from continuous care. The study is the most recent registry of patients with AHF in Thailand.

Circulating growth differentiation factor-15 as a novel biomarker in heart transplant.

AIMS: This study aimed to examine (i) whether circulating growth differentiation factor-15 (GDF-15) is associated with acute cellular cardiac allograft rejection (ACR); (ii) a longitudinal trend of GDF-15 after heart transplantation; and (iii) the prognostic value of GDF-15 in predicting a composite outcome of severe primary graft dysfunction (PGD) and 30 day mortality post-transplant. METHODS AND RESULTS: Serum samples were collected before heart transplantation and at every endomyocardial biopsy (EMB) post-heart transplantation in de novo transplant patients. A total of 60 post-transplant serum samples were matched to the corresponding EMBs. Seven (12%) were considered International Society for Heart Lung Transplantation Grade 1R ACR, and one (2%) was identified as Grade 2R ACR. GDF-15 levels in patients with ACR were not different from those in the non-rejection group (6230 vs. 6125 pg/mL, P = 0.27). GDF-15 concentration gradually decreased from 8757 pg/mL pre-transplant to 5203 pg/mL at 4 weeks post-transplant. The composite adverse outcome of PGD and 30 day mortality was significantly associated with increased post-operative GDF-15 (odds ratio: 40; 95% confidence interval: 2.01-794.27; P = 0.005) and high inotrope score post-transplant (odds ratio: 18; 95% confidence interval: 1.22-250.35; P = 0.01). CONCLUSIONS: Circulating GDF-15 concentration was markedly elevated in patients with end-stage heart failure and decreased after heart transplantation. GDF-15 was significantly associated with post-transplant PGD and mortality. A lack of association between ACR and GDF-15 did not support routine use of GDF-15 as a biomarker to detect ACR. However, GDF-15 may be potentially useful to determine heart transplant recipients at high risk for adverse post-transplant outcomes. We suggest that GDF-15 levels in recipient serum can provide risk stratification for severe PGD including death during post-operative period. This novel biomarker may serve to inform and guide timely interventions against severe PGD and adverse outcomes during the first 4 weeks after transplantation. Further studies to support the utility of GDF-15 in heart transplantation are required.

Endomyocardial Biopsy and Prevalence of Acute Cellular Rejection in Heart Transplantation.

BACKGROUND: Percutaneous endomyocardial biopsy (EMB) remains the criterion standard method for surveillance of allograft rejection after heart transplant (HT). However, data regarding utility of EMBs and prevalence of acute cellular rejection (ACR) in Asian populations are still limited. We aimed to report our experience in the use of EMBs and prevalence of ACR in HT recipients. METHODS: We retrospectively evaluated all EMBs from consecutive HT recipients between January 2008 and December 2018. EMB pathology results were according to International Society for Heart and Lung Transplantation 2004 revision of biopsy grading. We also divided patients into previous era and current era group (underwent HT before and after 2015) to compare prevalence of ACR and survival outcome. RESULTS: A total of 832 EMBs from 81 HT recipients were included. Pathologic reports revealed ACR grade 1R 22.8%, 2R 4.2%, and 3R 0.6%. At patient level, at least 1 episode of ACR grade 1R, 2R, and 3R were found in 70.6%, 24.7%, and 3.5% of the patients, respectively. When compared between era, frequency of EMB during the first year after HT in current era was significantly higher (9.74 ± 3.38 vs 4.93 ± 3.29, P < .001), but lower frequency of rejection grade ≥ 2R were found (2.3% vs 8.1%, P < .001). However, 1-year survival was not statistically different (76% in previous era vs 80% in current era, P = .37). CONCLUSIONS: From our study, prevalence of grade ≥ 2R rejection was approximately 5%, which is comparable with previous studies. Further studies are needed to evaluate proper interval and number of EMBs in HT recipients.

Incident Liver Cirrhosis, Associated Factors, and Cardiovascular Disease Risks Among People Living With HIV: A Longitudinal Study.

OBJECTIVES: We investigated the incidence and associated factors of liver cirrhosis and cardiovascular disease risks among people living with HIV (PLHIV) in a Thai cohort. DESIGN: A prospective cohort analysis. METHODS: Participants with at least one reliable transient elastography measurement during follow-up, who had pretreatment alanine transaminase, AST, and platelet count at HIV treatment initiation were included. Liver cirrhosis was defined as AST to Platelet Ratio Index >1.5 or fibrosis-4 (FIB-4) >3.25 or liver stiffness by transient elastography >12.5 kPa and confirmed by imaging or liver biopsy. Competing-risk regression was used to identify factors associated with liver cirrhosis. Time-updated 10-year atherosclerotic CVD (ASCVD) risks were compared between PLHIV with or without liver cirrhosis. RESULTS: A total of 1069 participants (33% women, 9% hepatitis C virus, and 16% hepatitis B virus) with the median age and CD4 at cART initiation of 32 years and 240 cells/mm3 were included. During 8232 person-years, 124 (12%) developed liver cirrhosis after a median of 6.9 (2.4-13.7) follow-up years [incidence, 1.5 (95% confidence interval: 1.3 to 1.8) per 100 person-years]. In multivariable analysis, the factors independently associated with liver cirrhosis were time-updated HIV viremia, hepatitis B virus, and hepatitis C virus coinfection, diabetes mellitus, high-density lipoproteins <40 mg/mL, and d4T exposure. The median time-updated 10-year ASCVD risk score was statistically higher among cirrhotic PLHIV vs. noncirrhosis [4.9% (interquartile range, 2.3-9.7) vs. 2.4% (interquartile range, 1.3-4.9), P < 0.001]. CONCLUSION: PLHIV with metabolic diseases were more likely to develop liver cirrhosis, independent of hepatitis coinfections, and ASCVD risks were higher among cirrhotic individuals.

Recurrent Cardiac Myxoma Treated by Orthotopic Heart Transplantation: A Case Report and Literature Review of Heart Transplantation for Primary Cardiac Tumor.

Primary cardiac myxoma is the most common primary cardiac tumor. Tumor resection is the treatment of choice and overall long-term prognosis is good and recurrence is rare. This report presents a case of a young girl who presented with multiple recurrent cardiac myxoma. She underwent 3 sternotomy surgeries of 3 separated episodes of cardiac myxoma resection. On the fourth recurrence, the patient underwent orthotopic heart transplant. The patient tolerated the procedure well and is alive 6 months after the procedure with NYHA class I. We reviewed evidences and summarized reported cases of orthotopic heart transplant operation for primary cardiac tumor in the literature.

Cardiovascular Disease and Cardiovascular Disease Risk in HIV-Positive Populations in the Asian Region.

INTRODUCTION: Cardiovascular diseases (CVD) are becoming more prevalent in HIV-infected populations as they age largely due to improved treatment outcomes. Assessment of CVD risk and CVD risk factors in HIV-positive populations has focused on high income settings, while there are limited studies evaluating CVD in HIV-positive populations in the Asian region. MATERIALS AND METHODS: We provided an overview of the prevalence and incidence of CVD and its risk factors in adult HIV-positive populations, and of the strategies currently in place for CVD management in the Asian region. RESULTS: Studies from the Asian region showed that CVD and CVD risk factors, such as dyslipidaemia, elevated blood glucose, obesity and smoking, are highly prevalent in HIV-positive populations. A number of studies suggested that HIV infection and antiretroviral therapy may contribute to increased CVD risk. National HIV treatment guidelines provide some directions regarding CVD risk prevention and management in the HIV-infected population, however, they are limited in number and scope. CONCLUSION: Development and consolidation of guidelines for integrated CVD and HIV care are essential to control the burden of CVD in HIV-positive populations. To inform guidelines, policies and practice in the Asian region, research should focus on exploring appropriate CVD risk screening strategies and estimating current and future CVD mortality and morbidity rates.