GDF-15: a novel biomarker of heart failure predicts short-term and long-term heart-failure rehospitalization and short-term mortality in patients with acute heart failure syndrome.

BACKGROUND: Acute heart failure (AHF) is a potentially life-threatening clinical syndrome, usually requiring hospital admission. Growth Differentiation Factor-15 (GDF-15) is a distant member of the transforming growth factor-ß. The increased expression of GDF-15 has been observed during heart failure (HF) and is associated with worse outcomes. However, the relationship between GDF-15 and AHF is not well understood with limited evidence among Thai patients. PURPOSE: Investigate the correlation between biomarker levels (measured upon admission and discharge) and short- and long-term adverse outcomes, encompassing all-cause mortality and heart-failure (HF) rehospitalization (at 30, 90, and 180 days, as well as throughout the entire follow-up duration) in individuals experiencing acute HF. METHODS: This is a prospective single-center investigation involving patients admitted for AHF. Biomarkers, including GDF-15, high-sensitivity troponin T (hsTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were assessed upon admission and discharge. Outcomes, including all-cause mortality and HF rehospitalization, were examined. Logarithmic transformations were applied to the biomarker variables for subsequent analysis. Univariate and multivariate analyses of cause-specific hazards were conducted using the Cox proportional hazards regression model, while subdistribution hazards were assessed using the Fine-Gray regression model to evaluate outcomes. RESULTS: A total of 84 patients were enrolled (mean age of 69 years, 52% females). The GDF-15 level significantly decreased during admission (median at the time of admission 6,346 pg/mL, median at the time of discharge 5,711 pg/mL; p < 0.01). All-cause mortality at 30 days and 180 days were 6.0% and 16.7%, respectively. HF rehospitalization at 30 days and 180 days were 15.5% and 28.6%, respectively. Univariate analysis showed that total orthoedema congestion score (p = 0.02) and admission GDF-15 level (p = 0.01) were associated with 30-day all-cause mortality, whereas hsTnT or NT-proBNP levels did not show significant associations. However, higher levels of NT-proBNP upon admission were associated with all-cause mortality when considering the entire follow-up period (p < 0.01). Both univariate and multivariate analyses demonstrated that lower discharge GDF-15 levels and a greater reduction in GDF-15 levels from admission to discharge were associated with a lower risk of 30-day rehospitalization. Similarly, univariate analysis revealed that a greater reduction in NT-proBNP levels from admission to discharge was associated with lower 30-day rehospitalization rates. At 180 days, a greater reduction in GDF-15 levels remained associated with lower hazards and incidence of rehospitalization. CONCLUSION: The significant decrease in Growth Differentiation Factor-15 (GDF-15) levels during hospitalization suggests its potential as a dynamic marker reflecting the course of AHF. Importantly, higher GDF-15 levels at admission were associated with an increased risk of 30-day all-cause mortality, highlighting its prognostic value in this patient population. Moreover, lower discharge GDF-15 levels, reductions in GDF-15 from admission to discharge, and decreases in NT-proBNP from admission to discharge were associated with a reduced risk of 30-day rehospitalization.

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).

Cardiac donors with renal impairment: Usage and outcomes after heart transplant.

INTRODUCTION: Utilization of hearts from donors with significant renal dysfunction and the impact of donor renal function on outcomes following heart transplant (HT) is unknown. We sought to investigate the trends, characteristics and outcomes associated with these donor hearts and the impact of donor renal function on survival and graft failure in adult HT recipients. METHODS: We reviewed the Scientific Registry of Transplant Recipients (SRTR) and summarized trends, characteristics and outcomes of hearts from adult donors by renal impairment. Single-organ HTs were evaluated and stratified by donors with estimated glomerular filtration rate (eGFRs) < and ≥30 ml/min. We constructed Cox proportional hazards regression models to compare time-to-mortality over 30-day, 1-, 3-, and 5-year time-horizons between groups, and the association of donor eGFR group with graft failure. RESULTS: A total of 162,586 adults were evaluated for cardiac donation, of which, 22,780 (14%) had an eGFR ≤ 30 ml/min. Donors with an eGFR ≤ 30 ml/min increased over time, from 7.2% (358/4966) in 2000 to a high of 19.5% (2283/11,728) in 2020. Such donors were significantly more likely discarded (not offered (7.9% vs. 9.8%, p < .001) or accepted (62.6% vs. 72.2%, p < .001), and less likely to be transplanted (18.0 % vs. 29.5%; p < .001). Of 41,044 HT recipients, 3906 (9.5%) had hearts from such donors. Primary graft failure was similar between groups (OR 1.20, 95% CI .91-1.58; p = .1) while adjusted mortality was lower for recipients from donors with eGFR ≤ 30 ml/min. CONCLUSIONS: More than two-third of hearts from donors with renal dysfunction are discarded. Recipients from donors with renal dysfunction sustained lower mortality post HT during the study period. Increased evaluation and utilization of donors with renal dysfunction has the potential to expand the critically low donor pool.

Primary isolated right ventricular failure after heart transplantation: prevalence, right ventricular characteristics, and outcomes.

To determine the prevalence, right ventricular (RV) characteristics, and outcomes of primary isolated RV failure (PI-RVF) after heart transplant (HTX). PI-RVF was defined as (1) the need for mechanical circulatory support post-transplant, or (2) evidence of RVF post-transplant as measured by right atrial pressure (RAP) > 15 mmHg, cardiac index of < 2.0 L/min/m2 or inotrope support for < 72 h, pulmonary capillary wedge pressure < 18 mmHg, and transpulmonary gradient < 15 mmHg with pulmonary systolic pressure < 50 mmHg. PI-RVF can be diagnosed from the first 24-72 h after completion of heart transplantation. A total of 122 consecutive patients who underwent HTX were reviewed. Of these, 11 were excluded because of secondary causes of graft dysfunction (GD). PI-RVF was present in 65 of 111 patients (59%) and 31 (48%) met the criteria for PGD-RV. Severity of patients with PI-RVF included 41(37%) mild, 14 (13%) moderate, and 10 (9%) severe. The median onset of PI-RVF was 14 (0-49) h and RV recovery occurred 5 (3-14) days after HTX. Severe RV failure was a predictor of 30-day mortality (HR 13.2, 95% CI 1.6-124.5%, p < 0.001) and post-transplant dialysis (HR 6.9, 95% CI 2.0-257.4%, p = 0.001). Patients with moderate PI-RVF had a higher rate of 30-day mortality (14% vs. 0%, p = 0.014) and post-operative dialysis (21% vs. 2%, p = 0.016) than those with mild PI-RVF. Among patients with mild and moderate PI-RVF, patients who did not meet the criteria of PGD-RV had worsening BUN/creatinine than those who met the PGD-RV criteria (p < 0.05 for all). PI-RVF was common and can occur after 24 h post-HTX. The median RV recovery time was 5 (2-14) days after HTX. Severe PI-RVF was associated with increased rates of 30-day mortality and post-operative dialysis. Moderate PI-RVF was also associated with post-operative dialysis. A revised definition of PGD-RV may be needed since patients who had adverse outcomes did not meet the criteria of PGD-RV.

Thyrotoxicosis-Induced Cardiomyopathy Complicated by Refractory Cardiogenic Shock Rescued by Extracorporeal Membrane Oxygenation.

BACKGROUND Thyrotoxicosis-induced cardiomyopathy is a rare but potentially life-threatening condition that occurs in less than 1% of thyrotoxic individuals. Severely impaired left ventricular systolic function can lead to an overt cardiogenic shock requiring mechanical circulatory support. Abnormal cardiac structure and function are potentially reversible after achievement of euthyroid state. CASE REPORT We present a case of a 53-year-old patient with a diagnosis of thyrotoxicosis-induced acute heart failure. Transthoracic echocardiography revealed a mildly dilated left ventricle and severely reduced systolic function with ejection fraction of 20%. Subsequently, the patient developed refractory cardiogenic shock, which was treated with the use of extracorporeal membrane oxygenation (ECMO). After early intensive treatments to achieve euthyroid state, the clinical status significantly improved. Echocardiography prior to discharge showed improvement of left ventricular ejection fraction to 40%. The anti-TSH receptor was positive and Grave's disease was diagnosed. The patient eventually returned to baseline functional status and could return to basic activities of daily living without limitations. CONCLUSIONS Early diagnosis of cardiac involvement in patients with thyrotoxicosis is critical. Promptly delivered intensive treatment with rapid achievement of euthyroid state can reverse cardiac dysfunction and improve patient outcomes. The use of ECMO can be considered as a "bridge" to recovery of cardiac function after restoration of euthyroid state.

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.

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.

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.

The impact of the coronavirus disease and Tele-Heart Failure Clinic on cardiovascular mortality and heart failure hospitalization in ambulatory patients with heart failure.

BACKGROUND: We sought to investigate the impact of the COVID-19 pandemic and the Tele-HF Clinic (Tele-HFC) program on cardiovascular death, heart failure (HF) rehospitalization, and heart transplantation rates in a cohort of ambulatory HF patients during and after the peak of the pandemic. METHODS: Using the HF clinic database, we compared data of patients with HF before, during, and after the peak of the pandemic (January 1 to March 17 [pre-COVID], March 17 to May 31 [peak-COVID], and June 1 to October 1 [post-COVID]). During peak-COVID, all patients were managed by Tele-HFC or hospitalization. After June 1, patients chose either a face-to-face clinic visit or a continuous tele-clinic visit. RESULTS: Cardiovascular death and medical titration rates were similar in peak-COVID compared with all other periods. HF readmission rates were significantly lower in peak-COVID (8.7% vs. 2.5%, p<0.001) and slightly increased (3.5%) post-COVID. Heart transplant rates were substantially increased in post-COVID (4.5% vs. peak-COVID [0%], p = 0.002). After June 1, 38% of patients continued with the Tele-HFC program. Patients managed by the Tele-HFC program for <6 months were less likely to have HF with reduced ejection fraction (73% vs. 54%, p = 0.005) and stage-D HF (33% vs. 14%, p = 0.001), and more likely to achieve the target neurohormonal blockade dose (p<0.01), compared with the ≥6-month Tele-HFC group. CONCLUSIONS: HF rehospitalization and transplant rates significantly declined during the pandemic in ambulatory care of HF. However, reduction in these rates did not affect subsequent 5-month hospitalization and cardiovascular mortality in the setting of Tele-HFC program and continuum of advanced HF therapies.

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.