The Impact of Frailty Components and Preoperative Mechanical Cardiac Support Changes with Time after Heart Transplantation.

BACKGROUND: Frailty has been proven to be associated with mortality after orthotopic heart transplantation (OHT). The aim of our study was to determine the impact of frailty on mortality in the current era using pretransplant mechanical cardiac support (MCS). METHODS: We retrospectively calculated the frailty scores of 471 patients undergoing OHT in a single institution between January 2012 and August 2022. The outcome was all-cause mortality. RESULTS: The median survival time was 1987 days (IQR: 1487 days) for all patients. In total, 266 (56.5%) patients were categorized as nonfrail, 179 (38.0%) as prefrail, and 26 (5.5%) as frail. The survival rates were 0.73, 0.54, and 0.28 for nonfrail, prefrail, and frail patients, respectively. The frailty score was associated with mortality [HR: 1.34 (95% CI: 1.22-1.47, p < 0.001)]. Among the components of the frailty score, age above 50 years, creatinine ≥ 3.0 mg/dL or prior dialysis, and hospitalization before OHT were independently associated with mortality. Continuous-flow left ventricular assist devices (CF-LVAD) were associated with an increased risk for all-cause mortality [AHR: 1.80 (95% CI: 1.01-3.24, p = 0.047)]. CONCLUSIONS: The components of the frailty score were not equally associated with mortality. Frailty and pretransplant MCS should be included in the risk estimation.

The Perioperative Period of Heart Transplantation Is Affected by Thyroid Hormone Status.

Background: Orthotopic heart transplantation (HTx) is a long-term surgical therapeutic approach for patients with end-stage heart failure. The objective of the present study was to uncover associations between altered thyroid hormone (TH) status and adverse outcomes after HTx. Methods: In this prospective, single-center cohort study, 283 patients underwent HTx between 2013 and 2020 at the Heart and Vascular Center of Semmelweis University in Hungary. We measured serum free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) pre- and postoperatively. TaqMan qPCR was used to measure type 2 deiodinase and type 3 deiodinase mRNA (Dio2 and Dio3, respectively) levels from the diseased heart bioptates. To assess the local TH action of the heart, mRNA levels of Hcn2 and Myh7 were measured in a subgroup of patients receiving extracorporeal membrane oxygenation (ECMO) postoperatively. Groups were compared using nonparametric tests. Cox regression analysis and logistic regression test were used to investigate the outcomes. The connection between serum TH parameters and cardiac gene expressions was assessed using linear regression. Results: Serum TSH (p = 0.009), fT3 (p < 0.001), and fT4 (p < 0.001) levels were lower after HTx than preoperatively. Levothyroxine (LT4) administered to donors was associated with better survival after 30 days (p = 0.049). LT4 replacement given to recipients after HTx was associated with better survival after 30 days (p = 0.018), 1 year (p = 0.002), and 2 years (p = 0.001). Dio3 mRNA level was significantly increased in patients who were treated with ECMO (p = 0.026), left ventricular assist device (LVAD) (p = 0.008), and biventricular assist device (BiVAD) (p = 0.013) preoperatively, and ECMO (p = 0.042) postoperatively, compared with those who did not require any type of mechanical circulatory support (MCS). We found no significant difference in the expression of the Hcn2 and Myh7 marker genes between patients on postoperative ECMO and those without MCS, and neither did they correlate with serum hormone levels (p = 0.519 and p = 0.056, respectively). Conclusions: We conclude that TH status plays an important role in HTx patients, and monitoring of TH status in the perioperative period may contribute to improved treatment outcomes. Our findings require independent confirmation in a randomized controlled clinical trial.

Recipient Pericardial Apolipoprotein Levels Might Be an Indicator of Worse Outcomes after Orthotopic Heart Transplantation.

BACKGROUND: End-stage heart failure (ESHF) leads to hypoperfusion and edema formation throughout the body and is accompanied by neurohormonal and immunological alterations. Orthotopic heart transplantation (HTX) has been used as a beneficial option for ESHF. Due to the shortage of donor hearts, the ideal matching and timing of donors and recipients has become more important. PURPOSE: In this study, our aim was to explore the relationship between the clinical outcomes of HTX and the cytokine and apolipoprotein profiles of the recipient pericardial fluid obtained at heart transplantation after opening the pericardial sac. MATERIALS AND METHODS: The clinical data and the interleukin, adipokine, and lipoprotein levels in the pericardial fluid of twenty HTX recipients were investigated. Outcome variables included primer graft dysfunction (PGD), the need for post-transplantation mechanical cardiac support (MCS), International Society for Heart and Lung Transplantation grade ≥2R rejection, and mortality. Recipient risk scores were also investigated. RESULTS: Leptin levels were significantly lower in patients with PGD than in those without PGD (median: 6.36 (IQR: 5.55-6.62) versus 7.54 (IQR = 6.71-10.44); p = 0.029). Higher ApoCII levels (median: 14.91 (IQR: 11.55-21.30) versus 10.31 (IQR = 10.02-13.07); p = 0.042) and ApoCIII levels (median: 60.32 (IQR: 43.00-81.66) versus 22.84 (IQR = 15.84-33.39); p = 0.005) were found in patients (n = 5) who died in the first 5 years after HTX. In patients who exhibited rejection (n = 4) in the first month after transplantation, the levels of adiponectin (median: 74.48 (IQR: 35.51-131.70) versus 29.96 (IQR: 19.86-42.28); p = 0.039), ApoCII (median: 20.11 (IQR: 13.06-23.54) versus 10.32 (IQR: 10.02-12.84); p = 0.007), and ApoCIII (median: 70.97 (IQR: 34.72-82.22) versus 26.33 (IQR: 17.18-40.17); p = 0.029) were higher than in the nonrejection group. Moreover, the pericardial thyroxine (T4) levels (median: 3.96 (IQR: 3.49-4.46) versus 4.69 (IQR: 4.23-5.77); p = 0.022) were lower in patients with rejection than in patients who did not develop rejection. CONCLUSION: Our results indicate that apolipoproteins can facilitate the monitoring of rejection and could be a useful tool in the forecasting of early and late complications.

Hormonal changes in the first 24 postoperative hours after cardiac surgical procedures.

Background: Hormone level changes after heart surgeries are a widely observed phenomenon due to neurohormonal feedback mechanisms that may affect postoperative morbidity and mortality. The current study aimed to analyze the changes in thyroid and sex hormones in the first 24 postoperative hours after heart surgery. Methods: This prospective, observational study (registered on ClinicalTrials.gov: NCT03736499; 09/11/2018) included 49 patients who underwent elective cardiac surgical procedures at a tertiary heart center between March 2019 and December 2019. Thyroid hormones, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), and sex hormones, including prolactin (PRL) and total testosterone, were measured preoperatively and at 24 h postoperatively. Results: Significant decreases in serum TSH (P < 0.001), T3 (P < 0.001) and total testosterone (P < 0.001) levels were noted, whereas T4 (P = 0.554) and PRL (P = 0.616) did not significantly change. Intensive care unit (ICU) hours (P < 0.001), mechanical ventilation (P < 0.001) and Vasoactive-Inotropic Score (VIS) (P = 0.006) were associated with postoperative T3 level. ICU hours were associated with postoperative T4 level (P = 0.028). Postoperative and delta testosterone levels were in connection with lengths of stay in ICU (P = 0.032, P = 0.010 respectively). Model for End-Stage Liver Disease (MELD) scores were associated with thyroid hormone levels and serum testosterone. Conclusions: T3 may represent a marker of nonthyroidal illness syndrome and testosterone may reflect hepatic dysfunction. In addition, PRL may act as a stress hormone in female patients.

Comprehensive frailty assessment with multidimensional frailty domains as a predictor of mortality among vascular and cardiac surgical patients.

Purpose: The frailty concept has become a fundamental part of daily clinical practice. In this study our purpose was to create a risk estimation method with a comprehensive aspect of patients' preoperative frailty. Patients and methods: In our prospective, observational study, patients were enrolled between September 2014 and August 2017 in the Department of Cardiac Surgery and Department of Vascular Surgery at Semmelweis University, Budapest, Hungary. A comprehensive frailty score was built from four main domains: biological, functional-nutritional, cognitive-psychological and sociological. Each domain contained numerous indicators. In addition, the EUROSCORE for cardiac patients and the Vascular POSSUM for vascular patients were calculated and adjusted for mortality. Results: Data from 228 participants were included for statistical analysis. A total of 161 patients underwent vascular surgery, and 67 underwent cardiac surgery. The preoperatively estimated mortality was not significantly different (median: 2.700, IQR (interquartile range): 2.000-4.900 vs. 3.000, IQR: 1.140-6.000, P = 0.266). The comprehensive frailty index was significantly different (0.400 (0.358-0.467) vs. 0.348 (0.303-0.460), P = 0.001). In deceased patients had elevated comprehensive frailty index (0.371 (0.316-0.445) vs. 0.423 (0.365-0.500), P < 0.001). In the multivariate Cox model an increased risk for mortality in quartiles 2, 3 and 4 compared with quartile 1 as a reference was found (AHR (95% CI): 1.974 (0.982-3.969), 2.306 (1.155-4.603), and 3.058 (1.556-6.010), respectively). Conclusion: The comprehensive frailty index developed in this study could be an important predictor of long-term mortality after vascular or cardiac surgery. Accurate frailty estimation could make the traditional risk scoring systems more accurate and reliable.

Donor Pericardial Interleukin and Apolipoprotein Levels May Predict the Outcome after Human Orthotopic Heart Transplantation.

The proinflammatory cascade that is activated at the time of brain death plays a crucial role in organ procurement. Our aim of this study was to explore the relationship between the clinical outcome of orthotopic heart transplantation, as well as cytokine and apolipoprotein profiles of the pericardial fluid obtained at donation. Interleukin, adipokine and lipoprotein levels in the pericardial fluid, as well as clinical data of twenty donors after brain death, were investigated. Outcome variables included primary graft dysfunction, the need for posttransplantation mechanical cardiac support and International Society for Heart and Lung Transplantation grade ≥ 2R rejection. Hormone management and donor risk scores were also investigated. Lower levels of IL-6 were observed in primary graft dysfunction (median: 36.72 [IQR: 19.47-62.90] versus 183.67 [41.21-452.56]; p = 0.029) and in the need for mechanical cardiac support (44.12 [20.12-85.70] versus 247.13 [38.51-510.38]; p = 0.043). Rejection was associated with lower ApoAII (p = 0.021), ApoB100 (p = 0.032) and ApoM levels (p = 0.025). Lower adipsin levels were detected in those patients receiving desmopressin (p = 0.037); moreover, lower leptin levels were found in those patients receiving glucocorticoid therapy (p = 0.045), and higher T3 levels were found in those patients treated with L-thyroxine (p = 0.047) compared to those patients not receiving these hormone replacement therapies. IL-5 levels were significantly associated with UNOS-D score (p = 0.004), Heart Donor Score (HDS) and Adapted HDS (p < 0.001). The monitoring of immunological and metabolic changes in donors after brain death may help in the prediction of potential complications after heart transplantation, thus potentially optimizing donor heart allocation.

Association between Hepatic Venous Congestion and Adverse Outcomes after Cardiac Surgery.

INTRODUCTION: Hepatic venous flow patterns reflect pressure changes in the right ventricle and are also markers of systemic venous congestion. Fluid management is crucial in patients undergoing cardiac surgery. METHODS: Our goal was to determine which factors are associated with the increased congestion of the liver as measured by Doppler ultrasound in patients undergoing cardiac surgery. This prospective, observational study included 41 patients without preexisting liver disease who underwent cardiac surgery between 1 January 2021 and 30 September 2021 at a tertiary heart center. In addition to routine echocardiographic examination, we recorded the maximal velocity and velocity time integral (VTI) of the standard four waves seen in the common hepatic vein (flow profile) using Doppler ultrasound preoperatively and at the 20-24th hour of the postoperative period. The ratios of the retrograde and anterograde hepatic venous waves were calculated, and the waveforms were compared to the baseline value and expressed as a delta ratio. Demographic data, pre- and postoperative echocardiographic parameters, intraoperative variables (procedure, cardiopulmonary bypass time), postoperative factors (fluid balance, vasoactive medication requirement, ventilation time and parameters) and perioperative laboratory parameters (liver and kidney function tests, albumin) were used in the analysis. RESULTS: Of the 41 patients, 20 (48.7%) were males, and the median age of the patients was 65.9 years (IQR: 59.8-69.9 years). Retrograde VTI growth showed a correlation with positive fluid balance (0.89 (95% CI 0.785-0.995) c-index. After comparing the postoperative echocardiographic parameters of the two subgroups, right ventricular and atrial diameters were significantly greater in the "retrograde VTI growth" group. The ejection fraction and decrement in ejection fraction to preoperative parameters were significantly different between the two groups. (p = 0.001 and 0.003). Ventilation times were longer in the retrograde VTI group. The postoperative vs. baseline delta VTI ratio of the hepatic vein correlated with positive fluid balance, maximum central venous pressure, and ejection fraction. (B = -0.099, 95% CI = -0.022-0.002, p = 0.022, B = 0.011, 95% CI = 0.001-0.021, p = 0.022, B = 0.091, 95% CI = 0.052-0.213, p = 0.002, respectively.) Conclusion: The increase of the retrograde hepatic flow during the first 24 h following cardiac surgery was associated with positive fluid balance and the decrease of the right ventricular function. Measurement of venous congestion or venous abdominal insufficiency seems to be a useful tool in guiding fluid therapy and hemodynamic management.

Endocrine Management and Hormone Replacement Therapy in Cardiac Donor Management: A Retrospective Observational Study.

BACKGROUND: Pituitary dysfunction after brainstem death can cause various hormone deficiencies in potential heart donors. The aim of this study was to evaluate the relationship between hormone replacement therapy (HRT; including antidiuretic hormone analog, thyroid hormone, and methylprednisolone) in heart donors and the recipients' outcomes after heart transplantation (HTx). METHODS: We retrospectively analyzed HTxs performed between January 2012 and October 2018. Donor and recipient characteristics were retrieved with a focus on endocrine parameters and HRT. The primary outcome was primary graft dysfunction (PGD). Secondary outcomes were the 30-day and 2-year mortality of the recipients. Univariate and multivariate Cox regression analyses were applied. RESULTS: The study included 297 HTxs. PGD occurred in 56 recipients (18.9%). In the multivariable Cox analysis, methylprednisolone and thyroxine treatment in donors were associated with a lower odds for PGD (odds ratio [OR], 0.43; 95% CI, 0.19-1.01; P = .052; and OR,: 0.34; 95% CI, 0.15-0.76; P = .009, respectively). In multivariate analysis, thyroxine treatment in donors was associated with a lower odds of PGD (OR, 0.38; 95% CI, 0.17-0.86; P = .020). Donor thyroxine supplementation also had a beneficial effect on recipients' 2-year survival (OR, 0.53; 95% CI, 0.29-0.96; P = .036). CONCLUSIONS: Combined thyroxine and methylprednisolone treatment could be a protective factor against PGD. Thyroxine administration was associated with better 2-year survival in recipients.

Preoperative nutritional state is associated with mid- and long-term mortality after cardiac surgery.

BACKGROUND: The frailty score has been developed to determine physiological functioning capacity. The aim of our research was to explore the relationship between frailty factors and mortality in cardiac surgery patients. METHODS: Our research is an observational, single-center, prospective cohort study (registered on ClinicalTrials.gov: NCT02224222), and we studied 69 patients who underwent elective cardiac surgery between 2014 and 2017. Thirty days before the surgery, they completed a questionnaire that contained questions related to social support, self-reported life quality-happiness, cognitive functions, anxiety and depression. Demographic, anthropometric and medical data were widely collected. The Geriatric Nutritional Risk Index (GNRI) and the Comprehensive Geriatric Assessment (CGA)-based frailty index were calculated as a sum and the domains, respectively. Cox regression and the Kaplan-Meier tests were applied to analyze survival and relative risk. The primary outcome was mid-term mortality. RESULTS: The patients' mean age was 65.43 years [standard deviation (SD): 9.81 years]. The median follow-up was 1,656 days of survival [interquartile range (IQR), 1,336-2,081 years], during this period 14 patients died. The median of EuroSCORE II was 1.56 (1.00-2.58) points. The median preoperative albumin level was 32.80 g/L (IQR, 29.9-35.8 g/L). Major adverse cardiovascular and cerebral events (MACCEs) occurred 7 times during follow-up. The nutrition score of the CGA was significantly associated with worse long-term survival [score; hazard ratio (HR): 5.35; 95% CI: 1.10-25.91, P=0.037]. After adjustment for EuroSCORE II and postoperative complications the noncardiovascular CGA score was associated with overall mortality [adjusted hazard ratio (AHR): 1.44, 95% CI: 1.02-2.04, P=0.036]. In the multivariable Cox regression, GNRI <91 showed an increased risk for mortality (AHR: 4.76, 95% CI: 1.52-14.92, P=0.007). CONCLUSIONS: The CGA-based noncardiovascular score and nutritional status should be assessed before cardiac surgery prehabilitation and may help decrease long-term mortality.

Effect of Preoperative Chronic Opioid Use on Mortality and Morbidity in Vascular Surgical Patients.

Introduction Opioid derivates are an essential part of everyday clinical pain management practice. They have excellent analgesic, sedative, and sympatholytic effects and are widely used in various conditions. Beyond advantageous aspects, there are numerous problems with the chronic use of these agents. Dependency and life-threatening complications are the biggest problems with both illegal and prescribed opioid derivates. In our current study, effects of chronic opioid use were observed on mortality and life quality in the case of vascular surgery. Methods This prospective, observational study was conducted between 2014 and 2017. After obtaining informed consent, all participants were asked to fill a questionnaire containing different psychological tests. Perioperative data, chronic medical therapy, and anthropometric data were also collected. Opioid user and non-user patients' psychological results were compared with non-parametrical tests. The effect of chronic opioid administration was investigated with logistic regression method with bootstrapping. Results Finally, the data of 164 patients were analyzed. 64.0% of participants were male, the mean age was 67.05 years, and the standard deviation was 9.48 years. The median follow-up time was 1312 days [interquartile range (IQR): 930-1582 days]. During the follow-up time, 42 patients died (25.6%). In the examined patient cohort, the frequency of opioid derivate use was 3.7% (only six patients). In the non-survived group, opioid use was significantly higher (1.6% vs. 9.5%, p=0.019). Significant differences were found in the aspect of cognitive performance measured by Mini-Mental State Examination (MMSE), opioid users have had lower points [25.5 (IQR: 24.5-26.0) vs. 28.0 (IQR: 27.0-29.0) p=0.008]. Opioid users have showed higher score on Beck Depression Inventory (BDI) [15.5 (IQR: 10.0-18.0) vs. 6.0 (IQR: 3.0-11.0), p=0.030). In a multivariate Cox regression model built up from registered preoperative medical treatment, opioids were found as a risk factor for all-cause mortality [adjusted hazard ratio (AHR): 4.31, 95% CI: 1.77-10.55, p=0.001]. Conclusion Our current findings suggest that chronic, preoperative use of opioids could associate with increased mortality. Furthermore, both decrease in cognitive performance and increased depression symptoms were found in the opioid user cohorts which emphasize the importance of further risk stratification of these patients.

Perioperative Low Tetraiodothyronine Levels and Adverse Outcomes After Heart Transplantation: A Retrospective, Observational Study.

OBJECTIVES: Thyroid dysfunction has been shown to be associated with increased all-cause mortality and severity of chronic heart failure in critical illness and severe cardiac diseases. The present study was conducted to ascertain the relationship between perioperative free triiodothyronine and free tetraiodothyronine (fT4) levels and postoperative adverse outcomes after heart transplantation (HTX). DESIGN: Retrospective, observational study. SETTING: Single-center study in a quaternary care university clinical center. PARTICIPANTS: The study comprised adult patients who underwent HTX between 2015 and 2019 and had at least 1 perioperative thyroid hormone laboratory test on the day of surgery or in the 24 hours before/after the procedure (free triiodothyronine, fT4, and thyroid-stimulating hormone). INTERVENTIONS: No interventions were applied. MEASUREMENTS AND MAIN RESULTS: The primary outcome was primary graft dysfunction (PGD), defined by the consensus conference of the International Society for Heart and Lung Transplantation. A total of 151 patients were included in the final analyses. Twenty-nine (19.2%) patients had PGD. Fourteen (9.3%) patients had low fT4 levels. An independent association was found between fT4 and PGD (odds ratio 6.49; 95% confidence interval 2.26-18.61; p = 0.001), with adjusted multivariate Cox regression models. CONCLUSION: The perioperative fT4 level could be a prognostic marker of adverse outcomes in HTX. The authors suggest appropriate perioperative monitoring of fT4 levels. Additional research is warranted to examine the optimal timing, dosage, and method of replacement.