Urgent Transplantation Research Articles

Growth Differentiation Factor-15 IsAssociated With Congestion-Related Anorexia and Weight Loss in AdvancedHeartFailure.

Growth differentiation factor (GDF)-15 is a pleiotropic cytokine that is associated with appetite-suppressing effects and weight loss in patients with malignancy. This study aims to investigate the relationships between GDF-15 levels, anorexia, cachexia, and clinical outcomes in patients with advanced heart failure with reduced ejection fraction (HFrEF). In this observational, retrospective analysis, a total of 344 patients with advanced HFrEF (age 58 ± 10 years, 85% male, 67% NYHA functional class III), underwent clinical and echocardiographic examination, body composition evaluation by skinfolds and dual-energy x-ray absorptiometry, circulating metabolite assessment, Minnesota Living with HeartFailure Questionnaire, and right heart catheterization. The median GDF-15 level was 1,503ng/L (Q1-Q3: 955-2,332ng/L) (reference range:<1,200ng/L). Higher GDF-15 levels were associated with more prevalent anorexia and cachexia. Patients with higher GDF-15 had increased circulating free fatty acids and beta-hydroxybutyrate, lower albumin, cholesterol, and insulin/glucagon ratio, consistent with a catabolic state. Patients with higher GDF-15 had worse congestion and more severe right ventricular dysfunction. In multivariable Cox analysis, elevated GDF-15 was independently associated with risk of the combined endpoint of death, urgent transplantation, or left ventricular assist device implantation, even after adjusting for coexisting anorexia and cachexia (T3 vs T1 HR: 2.31 [95%CI: 1.47-3.66]; P< 0.001). In patients with advanced HFrEF, elevated circulating GDF-15 levels are associated with a higher prevalence of anorexia and cachexia, right ventricular dysfunction, and congestion, as well as an independently increased risk of adverse events. Further studies are warranted to determine whether therapies altering GDF-15 signaling pathways can affect metabolic status and clinical outcomes in advanced HFrEF.

MELD score predicts outcomes in patients with advanced heart failure: A longitudinal evaluation.

Advanced heart failure (AHF) is characterized by recurrent episodes of haemodynamic instability and frequent hospitalizations, leading to a progressive decline in quality of life and high mortality rates. The objectives of this study were to evaluate the effect of the model for end-stage liver disease (MELD) score and its variations in predicting adverse outcomes [death, urgent heart transplant, and left ventricular assist device (LVAD) implant] among patients with AHF to assess the clinical associations of the MELD score in this population and to compare the efficacy of this tool with other prognostic scores in AHF. In this longitudinal prospective study, 162 patients with advanced heart failure (AHF) were enrolled; all patients included in the study were receiving the maximum tolerated medical therapy according to guidelines. The MELD score was measured at baseline and every 6months during follow-up. All patients underwent echocardiographic assessment and cardiopulmonary testing, which included the evaluation of maximal oxygen uptake (VO2max) and the minute ventilation/carbon dioxide production (VE/VCO2) slope. The mean age of the study group was 57.7±11.6years. There were 26 deaths, 5 urgent transplants, and 1 LVAD implantation during a follow-up period of 31.4±15.6months. The mean New York Heart Association (NYHA) class was 2.8±0.5, ejection fraction (EF) was 26.3±6.5%, the mean VO2max was 11.7±3.5mL/kg/min. Multiple regression analysis revealed a positive correlation between the MELD score and NT-proBNP (β=0.215; P=0.041) and furosemide dosage (β=0.187; P=0.040). Conversely, a negative correlation was observed between the MELD score and TAPSE (β=-0.204; P=0.047). Multivariate Cox regression on combined outcome shows a HR of 1.094 (95% CI 1.003-1.196) for unit increase in MELD considered as a continuous variable. The predictive role is independent by the effect of covariates considered in the analysis such as age, sex, NYHA class, EF, TAPSE, PASP, VO2max, NT-proBNP, MELD score worsening, and NT-proBNP increase. Changes in MELD score percentage, considered as a dichotomous variable (≤100% and >100%), were found to be predictors of mortality, urgent heart transplant and LVAD implant. Receiver operating characteristic (ROC) curves showed an area under the curve (AUC) of 0.887 for MELD score and composite outcome of death, urgent transplant, and need for LVAD. The predictive performance of MELD was even superior compared with MELD-Na, MELD-XI, MAGGIC risk score, and MECKI. The MELD score and its longitudinal changes are effective predictors of adverse outcomes in AHF.

First consensus document of waiting list prioritization for liver transplantation by the Spanish Society of Liver Transplantation (SETH).

Spain is worldwide leader in deceased donation rates per million habitants and count on a strong network of twenty-five liver transplant institutions. Although the access to liver transplantation is higher than in other countries, approximately 10% of patients qualifying for liver transplantation in Spain will die in the waiting list or would be excluded due to clinical deterioration. A robust waiting list prioritization system is paramount to grant the sickest patients with the first positions in the waiting list for an earlier access to transplant. In addition, the allocation policy may not create or perpetuate inequities, particularly in a public and universal healthcare system. Hitherto, Spain lacks a unique national allocation system for elective liver transplantation. Most institutions establish their own rules for liver allocation and only two autonomous regions, namely Andalucía and Cataluña, share part of their waiting list within their territory to provide regional priority to patients requiring more urgent transplantation. This heterogeneity is further aggravated by the recently described sex-based disparities for accessing liver transplantation in Spain, and by the expansion of liver transplant indications, mainly for oncological indications, in absence of clear guidance on the optimal prioritization policy. The present document contains the recommendations from the first consensus of waiting list prioritization for liver transplantation issued by the Spanish Society of Liver Transplantation (SETH). The document was supported by all liver transplant institutions in Spain and by the Organización Nacional de Trasplantes (ONT). Its implementation will allow to homogenize practices and to improve equity and outcomes among patients with end-stage liver disease.

Mitral Transcatheter Edge-to-Edge Repair in INTERMACS 3-4 Profile Patients with Severe Mitral Regurgitation.

Heart transplantation and left ventricular assist device (LVAD) implementation are effective treatments for advanced heart failure (HF), although their use is limited by organ availability and the high incidence of adverse events. The efficacy of mitral transcatheter edge-to-edge repair (TEER) as a bridge to transplantation or as a destination therapy in advanced HF is still debated. A total of 63 patients with INTERMACS class 3 or 4 with contraindications for LVAD and severe functional mitral regurgitation (FMR) were evaluated for TEER implantation eligibility. The primary endpoint was a composite of death, urgent heart transplantation and LVAD implantation at 12 months. A total of 36 patients underwent TEER, while 27 patients received optimal medical therapy (MT) alone. In the intervention group, 35 patients (97%) were discharged alive. In the MT group, two in-hospital deaths occurred, two patients underwent urgent heart transplantation, and three patients were discharged on inotropes. At the 12-month follow-up, the incidence of the primary endpoint occurring was lower in the TEER group (25% vs. 70%, HR 0.25, 95% CI 0.11-0.60, p < 0.01) and the tolerance to neurohormonal therapy was higher (53% vs. 30%, p = 0.03). In advanced HF patients with INTERMACS profile 3 or 4 and severe FMR, TEER on top of optimal MT was associated with a lower incidence of death, urgent heart transplantation or LVAD implantation at 12 months compared to optimal MT alone.

Abstract 4143270: PREDICTIVE MODELS AID PHYSICIAN PROGNOSTICATION: A SECONDARY ANALYSIS EVALUATING INTEGRATED MODEL AND PHYSICIAN PROGNOSTIC ESTIMATES IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION

Background: In recent studies from a multicenter Canadian cohort of outpatients with heart failure (HF), we found that model predictions were significantly more accurate than HF cardiologists. In this study, trying to mimic practice, we evaluated the additional predictive value and clinical impact of model predictions to refine physician estimated risk of 1-year mortality by combining model and physician estimates. Methods: We included consented consecutive HF outpatients (LVEF &lt;40%) followed at 11 HF clinics in Canada. HF cardiologists estimated patient 1-year mortality using their clinical judgment. We calculated model predicted mortality using the Seattle HF Model (SHFM). We followed patients for at least a year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using random forest survival model and cross-validation, we compared the performance SHFM and the HF cardiologist alone, and the integrated HF cardiologist and the SHFM predictions by evaluating model discrimination (c-statistic), calibration (observed vs predicted event rate), risk reclassification and clinical net benefit analyses. Results: Among 1,643 HF patients, 1-year event rate was 9% (95%CI 8%-11%). The SHFM had the adequate discrimination (c-statistic 0.76) and excellent calibration while cardiologists showed adequate discrimination (c-statistic 0.75) and poor calibration with significant risk overestimation ( Figure 1 ). When the SHFM estimates were added physician predictions, discrimination significantly improved (0.82, 95%CI 0.78-0.86) with excellent calibration. By risk reclassification analysis, among patients with events, HF cardiologist better reclassified 44% than the SHFM or the integrated model. Among patients without event, however, HF cardiologists worse risk-classified 52% in comparison to SHFM and 71% to the integrated model. By net clinical benefit analysis ( Figure 2 ), when the decision to treat involves patients with 1-year mortality of &gt;5%, SHFM predictions would lead to higher benefit than guiding care by physician judgement. Integrating model and HF cardiologist predictions led to minimally increased benefit in comparison to SHFM alone. Conclusions: Integrating prediction from the SHFM to physician judgment or using the SHFM alone showed superior accuracy than HF cardiologist predictions, proving that model-informed care may provide more accurate prognostic information to tailor clinical decision making.

Acute heart failure with urgent heart transplantation: a case report

Acute heart failure with urgent heart transplantation: a case report

What is the true normal: comparison of different equations for estimating peak oxygen uptake for outcome prediction in heart failure

Abstract Background and Objectives One of the strongest prognostic parameters obtained during Cardiopulmonary exercise testing (CPET) in patients with heart failure (HF) is the peak oxygen uptake (pVO2), as a standalone or as a percentage of the predicted peak oxygen uptake (ppVO2) reached. However, traditional standards by which ppVO2 is calculated have limitations, having been derived from small cohorts, lacking portability and poorly represented by women. Thus, we aim to compare the FRIEND Registry equation to previously used methods of calculating ppVO2 as it relates to prognostic value imparted by the percentage of ppVO2 (%ppVO2) reached during CPET and portability to the Portuguese HF population. Methods Single centre retrospective study of patients with HF with LVEF &amp;lt; 50% who underwent CPET between 2015-2021. Patients who did not reach RER≥ 1.05 were excluded from our analysis. All tests were evaluated and ventilatory thresholds determined by 3 independent, experienced operators. ppVO2 was calculated according to 1) the Wasserman equation; 2) the Wasserman equation using ideal body weight; 3) the Neder equation, 4) the SHIP equation and 5) the FRIEND equation. Our primary endpoint was a composite of CV death, urgent transplant or left ventricular assist device implantation and HF hospitalization. Results We included 238 patients (mean age 59 ± 11 years, 83% males). The HF aetiology was mostly ischemic in nature (68%), with LVEF of 34 ± 9% and median NTproBNP of 776 (2566 – 2342) pg/mL. Most patients (67%) were in class NYHA I-II and with high prevalence of GDMT (93% ACEi/ARB; 97% beta-blockers and 64% on MRA). Mean BMI in this group was 27.3 ± 4.7 kg/min. Patients performed CPET on a treadmill with a protocol adjusted to their predicted exercise capacity. Mean pVO2 was 18.1 ± 6.2mL/kg/min, corresponding to a median %ppVO2 that ranges from 51 ± 16% to 71 ± 22%, depending on the equation that is used. Mean VE/VCO2 Slope was 42 ± 13 and 48 % (n = 98) of patients showed exercise oscillatory ventilation (EOV). Mean ppVO2 as per the FRIEND and Wasserman equations was 18.9 ± 6.6 and 21.2 ± 4.5 mL/kg/min, with no statistically significant difference between both. %ppVO2 as calculated through all equations was an independent predictor of prognosis on multivariate analysis adjusted for LVEF, NTproBNP and VE/VCO2 Slope (p &amp;lt; 0.001 for values derived from all equations). However, the FRIEND and Wasserman equations showed a slight advantage over the remaining 2 equations, with higher AUC on ROC curve analysis (see figure). Conclusions In our population of Portuguese patients with HF, both the FRIEND registry and Wasserman equations for predicting pVO2 yielded strong prognostic power. However, these equations provide different absolute predicted VO2 values for the same patients and thus should not be used interchangeably. Standardisation of the type ppVO2 equation used should be recommended by local scientific societies.

Prognostic value of baseline and follow-up ECG in patients with biopsy-proven fulminant myocarditis

Abstract Background Fulminant myocarditis represents a life-threatening condition with poor outcomes characterized by increased short- and long-term mortality and need for heart transplant. Treatment largely relies on mechanical support and immunosuppressive therapy guided by histologic and virology findings but reliable short-term prognostic markers guiding therapy and management are still lacking. We hypothesised that baseline and short-term ECG evolution may provide relevant easily accessible prognostic information in these patients. Purpose We sought to assess the prognostic value of baseline and short-term follow-up ECG in patients affected by fulminant myocarditis. Methods We retrospectively enrolled patients with biopsy-proven fulminant myocarditis according to current diagnostic criteria. We evaluated baseline and follow-up ECG (performed 3 to 7 days after admission) together with clinical, laboratory and histologic data. The primary endpoint was a composite of in-hospital mortality or need for urgent heart transplantation. Results We enrolled 39 patients (22/39 M, 56.4%) and a mean age of 38 years. Histology demonstrated lymphocytic myocarditis in 35/39 cases, 2 eosinophilic and 1 giant cell myocarditis, 1 sarcoidosis. All patients received vasopressor and/or inotrope therapy with 19/39 requiring mechanical circulatory support. Follow-up ECGs were performed after 4.8±1.3 days from admission. The primary endpoint was reached in 7/39 patients (17.9%) with 5 deaths and 2 urgent cardiac transplants. These patients more commonly required mechanical (85.7% vs 40.6%, p=0.044) or extracorporeal membrane oxygenator (85.7% vs 12.5%, p&amp;lt;0.001) support and showed higher lactate levels on admission (11.0±7.3 vs 4.2±3.1 mmol/L, p=0.001). They also more frequently had cardiac arrest as first clinical presentation (50. 0% vs 9.7%, p=0.022) and sustained ventricular tachycardia (71.4% vs 15.6%, p=0.007) in the acute phase. Patients with a worse outcome showed persistence of low voltages (&amp;lt; 5 mm in all peripheral leads) at follow-up ECG (100.0% vs 37.5%, p=0.003) with lower R wave amplitude in lead II (1.1±0.9 vs 4.0±2.6 mm, p=0.004), III (0.7±0.5 vs 2.5±2.2 mm, p=0.043), aVF (0.9±0.7 vs 3.0±2.0 mm, p=0.01) and V6 (3.0±2.8 vs 7.5±4.2 mm, p=0.011) and reduced S wave amplitude in V1 (2.6±3.9 vs 6.4±4.4 mm, p=0.047), V2 (3.9±3.9 vs 10.2±6.7 mm, p=0.035), V3 (3.3±3.2 vs 10.7±6.7 mm, p=0.007) leads. Low QRS voltages at baseline ECG were not associated with worse prognosis (71.4% vs 46.9%, p=0.407). No significant difference in terms of steroid (85.7% vs 78.1%, p=0.929) or other immunosuppressive (14.3% vs 31.2%, p=0.366) therapy was observed between the groups. Conclusions In patients with fulminant myocarditis, persistence of low QRS voltages at 5-day follow-up ECG is associated with adverse in-hospital outcomes. Short-term ECG evolution can identify high-risk patients requiring earlier and more intensive mechanical and pharmacological treatment.

O2 consumption overshoot in patients with heart failure: crossing the line

Abstract Background Cardiopulmonary exercise testing (CPET) is among the most valuable clinical tools for evaluating disease severity and physical activity limitations in heart failure (HF) patients. Peak oxygen uptake (pVO2) reflects maximal cardiac output during exercise, and it is considered a major parameter in selecting candidates for cardiac transplantation. VO2 overshoot, a transient increase in VO2 during recovery from maximal exercise, has been frequently observed in HF patients and is attributed to the transient increase in cardiac output caused by the mismatch between cardiac contractility and afterload reduction. However, the prognostic significance of this phenomenon remains to be fully established. Purpose This study aimed to characterize the prognostic significance of VO2 overshoot following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (&amp;gt;3 months) and stable HF, with left ventricular ejection fraction (LVEF) &amp;lt;50%, who underwent CPET between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sitting passively for 2 minutes). VO2 overshoot kinetics during recovery were measured and described as the time until post-exercise VO2 fell below pVO2 for at least 15 seconds. Please refer to Figure 1A for an example of normal and prolonged VO2 overshoot. The study endpoint was time to cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) over 1-year follow-up. Results A total of 254 patients were included (mean age 59 ± 12 years; 83% males; mean LVEF 34 ± 9%; 70% with ischemic HF; 77% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean predicted pVO2% 52 ± 16%; mean VE/VCO2 slope 41 ± 13). The VO2 overshoot had a normal distribution (Figure 1B) and lasted on average for 45 ± 33 seconds. There were no differences between patients that had an overshoot higher and below average. Overall, during follow-up, 25 patients met the composite endpoint (12 CV deaths, 9 urgent heart transplants, and 4 LVAD). Univariate analysis showed a significant relationship between VO2 overshoot and the outcome of interest (HR 1.01, 95% CI 1.00 – 1.02, p=0.027). In multivariate analysis, this association remained significant, even after adjusting for pVO2 and VE/VCO2 slope (HR 1.01, CI 95% 1.00– 1.02, p=0.026). Conclusion This study delves into the intriguing phenomenon of VO2 overshoot in patients with heart failure, shedding light on its potential prognostic significance. The independent association between VO2 overshoot and the composite endpoint suggests that this transient increase in oxygen consumption may carry prognostic value. Further studies should confirm these findings.

Exercise stress testing recovery kinetics: the forgotten phase

Abstract Background Impaired exercise capacity is a cardinal feature of heart failure (HF). Peak oxygen uptake (pVO2) and ventilatory efficiency (VE/VCO2 slope) during exercise are well-consolidated prognostic markers in patients with HF. A previous study suggested that abnormally prolonged VO2 recovery, specifically the failure to decrease VO2 from peak exercise by 10.5 mL/kg/min at 180 seconds of the recovery phase, predicts adverse outcomes in HF. However, it is unknown to what extent the recovery of VEqCO2, a marker of ventilation/perfusion mismatch, adds prognostic value to the already existing parameters. Purpose The aim of this study was to characterize the functional and prognostic significance of VEqCO2 kinetics following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (&amp;gt;3 months) and stable HF with left ventricular ejection fraction (LVEF) &amp;lt;50% who underwent cardiopulmonary exercise testing (CPET) between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sittng passively for 2 minutes). VO2 and VEqCO2 kinetics during recovery, described as the absolute difference to peak VO2 (difVO2) and VEqCO2 (difVEqCO2), were measured at 30, 60, 120, and 180 seconds. Outcomes were assessed as a composite of cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) implantation at 1 year. Results A total of 238 patients were included (mean age 58 ± 12 years; 82% males; mean LVEF 34 ± 10%; 68% with ischemic HF; 75% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean VE/VCO2 slope 41 ± 12). During the 1-year follow-up, 19 patients met the endpoint (8 CV deaths, 8 urgent heart transplants, and 3 LVAD). ROC curve analysis showed that the best correlation between difVEqCO2 and outcomes was apparent at difVEqCO2 of 180 seconds (AUC 0.83) with a cut-off value of 1 (sensitivity 93%, specificity 58%). These patients, who had a decrease in VEqCO2 (difVEqCO2 &amp;gt;1) at 180 seconds, were significantly older (p=0.02), had a lower LVEF (p&amp;lt;0.001), and higher NYHA (p&amp;lt;0.001). They were at an increased risk of cardiovascular events compared to those with an increase in VEqCO2 (difVEqCO2 &amp;lt;1) at 180 seconds (event-free survival at 1 year 86% vs. 98%, log-rank p&amp;lt;0.001). In multivariate analysis, the statistical association between difVEqCO2 and outcomes remained significant, even after adjusting for difVO2 at 180 seconds (HR 4.315, CI95% (1.349-13.804), p=0.014). Conclusion Abnormal VEqCO2 kinetics in the recovery period of CPET is an easily recognizable non-invasively derived measurement that predicts outcomes in HF. VEqCO2 may complement the evaluation of VO2 and other parameters during recovery to further improve prognostic risk stratification in HF.

Third ventilatory threshold in heart failure patients undergoing CPET: a prognostic analysis

Abstract Introduction One crucial element in cardiopulmonary exercise testing (CPET) involves identifying the first and second ventilatory thresholds (VT), VT1 and VT2, which hold known prognostic implications. If the individual can sustain exercise considerably beyond VT2, a third breakpoint (VT3 – Figure A) may emerge, coinciding with heightened hyperventilation to counter metabolic acidosis. Historically, this point has been mainly described among athletes and its meaning is still not entirely clear. We aimed to assess the prognostic value of VT3 in patients with heart failure (HF). Methods Retrospective, single-center study enrolling HF patients undergoing CPET from 2015 to 2021. We evaluated the typical CPET parameters along with the three ventilatory thresholds: VT1, VT2, and the newly introduced VT3. The primary outcome was a composite of cardiovascular death, urgent heart transplant, need for left ventricle assistance device and HF hospitalizations. Results We included 221 patients (82% men, mean age 58±12 years), among whom 69% had ischemic heart failure aetiology. The mean left ventricular ejection fraction (LVEF) was 34±9%, with a mean respiratory exchange ratio 1.15±0.082, mean pVO2 18.5±6.3, and a mean VE/VCO2 slope of 41.3±12.9. VT3 was attained by 43% (n = 94) of the patients. In comparison to those who did not achieve VT3, patients who reached this threshold were younger (56±11 vs 60±12; p = 0.05), had a higher pVO2 (20.5±6.9 vs 17±5.4; p = 0.05), higher RER (1.16±0.86 vs 1.13±0.78; p = 0.05), and lower VE/VCO2 slope (39±10.3 vs 43±14.3; p = 0.05). Regarding the three ventilatory thresholds (VT1, VT2, VT3), 7% (n=17) achieved a maximum of one threshold, 50% (n=110) achieved two thresholds, and 43% (n=94) reached all three thresholds. After a median follow-up of 2,3 years patients with identifiable VT3 had significantly better prognosis (HR 0,434; 95%CI 0,246-0,767; p=0,004) than those without this threshold. Furthermore, the number of identifiable ventilatory thresholds correlated positively with prognosis. In fact, patients with only 2 thresholds have twice the probability of developing an event and those with one or zero identifiable thresholds have a 4-fold increase in the probability of events (Figure C). Conclusion In a cohort of patients with HF, those with identifiable VT3 had a lower incidence of events. This parameter may aid in prognostic stratification in this population. However, this findings warrant further prospective validation.Figure 1

Impact of mitral transcatheter edge-to-edge repair in patients with advanced heart failure evaluated for heart transplantation

Abstract Background Heart transplantation is sometimes the only therapeutic option in patients with advanced heart failure (HF), impaired ventricular function and significant functional or secondary mitral regurgitation (MR). The shortage of organs and the limitations of the recipient make it necessary to consider other therapeutic alternatives in these patients, such as mitral transcatheter edge-to-edge repair (M-TEER). The MitraBridge registry has recently been published in which they analyze the potential effect of M-TEER in patients with advanced HF and moderate-severe MI who are candidates for heart transplantation (mean age 59 years, left ventricular ejection fraction (LVEF) 27%); after a mean follow-up of 24 months, complete in 82.4%, they report an overall survival of 78.5%, a combined event-free survival of 47%, with a 6.5 % need for urgent transplantation and an HF hospitalization rate after M-TEER of 44/100 patient-years. The aim of our study is to assess the impact of M-TEER on mortality and the combined events of death, HF rehospitalization and the need for urgent transplantation or a ventricular assistance device in patients with moderate-severe functional MI and advanced HF who have also been evaluated for cardiac transplantation in our hospital. Methods This is a retrospective analysis of a prospective registry. Of the patients treated by M-TEER for severe MI, we selected those with advanced HF (defined as LVEF≤35%, and/or advanced functional class (NYHA III-IV)) who had also been evaluated as possible candidates for inclusion in the heart transplant list. Results From November 2011 to December 2023, 191 patients were treated by M-TEER, of whom 38 patients met the established criteria (median age 59 years [48-65], 31 (81%) males, mean LVEF was 26 ± 6%). All patients had at least one previous hospitalization for HF and optimal medical treatment according to guidelines; the rest of the baseline clinical characteristics are listed in Table 1. During the follow-up after M-TEER, with a median of 34 months [7-70], the probability of overall survival at 2 years was 75.6%. The combined endpoint of death, need for urgent transplantation or a ventricular assist device, and rehospitalization for heart failure occurred in 26 patients with a 2-year event-free survival probability of 48% (Figure 1). Five patients (13%) were transplanted, one (2.6%) urgently. Prior to M-TEER therapy, the rate of HF hospitalization was 108 hospitalizations/100 patient-years, which was significantly reduced after the procedure to 33 hospitalizations/100 patient-years (rate ratio 0.31 [95% CI 0.21-0.45, p&amp;lt;0.0005]). Conclusions In patients with advanced HF and severe functional MR who are candidates for cardiac transplantation, M-TEER is an effective therapeutic alternative, achieving a survival rate of more than three-quarters of the patients at 2 years of follow-up, a significant reduction in HF hospitalizations, and a low rate of need for cardiac transplantation.

Newest "Co-Members" of the 1000s Club: A Case of Severe Transaminitis Secondary to Epstein-Barr and Dengue Virus Co-Infection in a Returning Traveler.

Timely identification of the etiology of transaminitis is critical in informing subsequent management as strategies can vary from supportive care to urgent transplant assessment. This is especially important in returning travelers as there may be multiple causes of injury that need to be addressed. We present a case of severe transaminitis secondary to non-hepatitis viral co-infections. A 28-year-old south Asian male returning traveler presented with an acute liver injury (aspartate aminotransferase/alanine aminotransaminase levels of ≥4000 IU/l) and marked jaundice. A thorough and expanded work-up of acute hepatitis was negative aside from positive mononucleosis spot testing and positive dengue fever serologies. This atypical presentation of mononucleosis and dengue fever was managed conservatively, and the patient was discharged with outpatient follow-up after an eight-day admission. Usually, non-hepatitis viruses typically do not present with severe transaminitis or hyperbilirubinemia. These viruses, such as infectious mononucleosis and dengue fever, may work synergistically to cause an elevated inflammatory response, resulting in severe transaminitis in returning travelers. In the absence of a classic clinical presentation, clinicians should be aware of co-infections in returning travelers and test for them based on a thorough history and physical examination. The differential diagnosis for severe transaminitis is narrow and commonly includes viral hepatitis (A-E), drug-induced liver injury, vascular and autoimmune causes; however other causes exist, and greater clinical awareness is needed.This case study demonstrates that even in the absence of a classic clinical presentation; in returning travelers, clinicians should have a low index of suspicion to order appropriate screening serologies based on a thorough history and physical examination as they can be sensitive diagnostic tools in detecting the etiology of severe transaminitis.In rare cases, non-hepatitis virus may act synergistically to cause severe transaminitis and should be considered in returning travelers when viral hepatitis serologies are negative.

Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point. A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (N=187) or enalapril (N=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; P=0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02678312.

The chronic heart failure evolutions: Different fates and routes.

Individual prognostic assessment and disease evolution pathways are undefined in chronic heart failure (HF). The application of unsupervised learning methodologies could help to identify patient phenotypes and the progression in each phenotype as well as to assess adverse event risk. From a bulk of 7948 HF patients included in the MECKI registry, we selected patients with a minimum 2-year follow-up. We implemented a topological data analysis (TDA), based on 43 variables derived from clinical, biochemical, cardiac ultrasound, and exercise evaluations, to identify several patients' clusters. Thereafter, we used the trajectory analysis to describe the evolution of HF states, which is able to identify bifurcation points, characterized by different follow-up paths, as well as specific end-stages conditions of the disease. Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant). Findings were validated on internal (n=527) and external (n=777) populations. We analyzed 4876 patients (age=63 [53-71], male gender n=3973 (81.5%), NYHA class I-II n=3576 (73.3%), III-IV n=1300 (26.7%), LVEF=33 [25.5-39.9], atrial fibrillation n=791 (16.2%), peak VO2% pred=54.8 [43.8-67.2]), with a minimum 2-year follow-up. Nineteen patient clusters were identified by TDA. Trajectory analysis revealed a path characterized by 3 bifurcation and 4 end-stage points. Clusters survival rate varied from 44% to 100% at 2years and from 20% to 100% at 5years, respectively. The event frequency at 5-year follow-up for each study cohort cluster was successfully compared with those in the validation cohorts (R=0.94 and R=0.84, P<0.001, for internal and external cohort, respectively). Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant observed in 22% of cases). Each HF phenotype has a specific disease progression and prognosis. These findings allow to individualize HF patient evolutions and to tailor assessment.

Comparative Temporal Analysis of Morbidity and Early Mortality in Heart Transplantation with Extracorporeal Membrane Oxygenation Support: Exploring Trends over Time.

The direct bridge to urgent heart transplant (HT) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support has been associated with high morbidity and mortality. The objective of this study is to analyze the morbidity and mortality of patients transplanted with VA-ECMO and compare the presumed differences between various eras over a 17-year timeline. This is a prospective, observational study on consecutive patients stabilized with VA-ECMO and transplanted with VA-ECMO from July 2007 to December 2023 at a reference center (98 patients). Objective variables were mortality and morbidity from renal failure, venous thromboembolic disease (VTD), primary graft dysfunction (PGD), the need for tracheostomy, severe myopathy, reoperation, post-transplant ECMO, vascular complications, and sepsis/infection. The percentage of patients who reached transplantation without the need for mechanical ventilation has increased over the periods studied. No significant differences were found between the study periods in 30-day mortality (p = 0.822), hospital discharge (p = 0.972), one-year mortality (p = 0.706), or five-year mortality (p = 0.797). Survival rates in these periods were 84%, 75%, 64%, and 61%, respectively. Comorbidities were very frequent, with an average of 3.33 comorbidities per patient. The most frequent were vascular complications (58%), the need for post-transplant ECMO (57%), and myopathy (55%). The development of myopathy and the need for post-transplant ECMO were higher in recent periods (p = 0.004 and p = 0.0001, respectively). VA-ECMO support as a bridge to HT allows hospital discharge for 3 out of 4 transplanted patients. This survival rate has not changed over the years. The comorbidities associated with this device are frequent and significant.

Analysis of the waitlist performance and post-transplant outcomes of lung transplant in elderly recipients in Korea: A nationwide cohort study.

There is a lack of information on the waitlist performance and post-transplant outcomes of lung transplants in elderly recipients in Korea. We retrospectively reviewed and analyzed data from the Korean Network for Organ Sharing database between March 2010 and August 2023. In total, 2574 patients were listed for lung transplantation during the study period, with 511 (19.9%) of them being over 65 years of age. Among these, 188 patients (36.8%) underwent transplantation, while 184 patients (36%) passed away without undergoing transplantation at the time of data extraction. The most prevalent underlying disease on the waitlist was idiopathic pulmonary fibrosis, accounting for 68.1%. The 1-year survival rate was significantly lower in the elderly compared to that in the nonelderly (65.4vs. 75.4%; p=.004). In the multivariate Cox analysis, elderly (hazard ratio [HR], 1.49; 95% CI, 1.14-1.97; p=.004) and a high urgent status at registration (HR, 1.83; 95% CI, 1.40-2.40; p<.001) were significantly associated with post-transplant 1-year mortality. Kaplan-Meier curves demonstrated a significant difference in post-transplant mortality based on the urgency status at enrollment (χ2=8.302, p=.016). Even with the same highly urgent condition at the time of transplantation, different prognoses were observed depending on the condition at listing (χ2=9.056, p=.029). The elderly exhibited worse transplant outcomes than nonelderly adults, with a highly urgent status at registration identified as a significant risk factor. Unprepared, highly urgent transplantation was associated with poor outcomes.

What happens to patients awaiting urgent transplantation for refractory electrical storm when they are not transplanted?

What happens to patients awaiting urgent transplantation for refractory electrical storm when they are not transplanted?

Transplantation, bridging, and support technologies in pulmonary hypertension.

Despite the progress made in medical therapies for treating pulmonary hypertension (PH), a subset of patients remain susceptible to developing a maladaptive right ventricular phenotype. The effective management of end-stage PH presents substantial challenges, necessitating a multidisciplinary approach and early identification of patients prone to acute decompensation. Identifying potential transplant candidates and assessing the feasibility of such a procedure are pivotal tasks that should be undertaken early in the treatment algorithm. Inclusion on the transplant list is contingent upon a comprehensive risk assessment, also considering the specific type of PH and various factors affecting waiting times, all of which should inform the decision-making process. While bilateral lung transplantation is the preferred option, it demands expert intra- and post-operative management to mitigate the heightened risks of pulmonary oedema and primary graft dysfunction in PH patients. Despite the availability of risk assessment tools, the occurrence of acute PH decompensation episodes can be unpredictable, potentially leading to refractory right ventricular failure even with optimal medical intervention, necessitating the use of rescue therapies. Advancements in right ventricular assist techniques and adjustments to graft allocation protocols for the most critically ill patients have significantly enhanced the survival in intensive care, affording the opportunity to endure while awaiting an urgent transplant. Given the breadth of therapeutic options available, specialised centres capable of delivering comprehensive care have become indispensable for optimising patient outcomes. These centres are instrumental in providing holistic support and management tailored to the complex needs of PH patients, ultimately enhancing their chances of a successful transplant and improved long-term prognosis.

Cardiac sarcoidosis in patients with recurrent ventricular arrhythmias refractory to endocardial ablation.

The clinical presentation of cardiac sarcoidosis is diverse. Detection of granuloma in histopathological evaluation proves the diagnosis, but endomyocardial biopsy (EMB) is associated with a high sampling error. However, prompt immunosuppressive therapy may significantly affect patient's prognosis. By analyzing our single center cohort of patients with recurrent ventricular arrhythmias (VA) and nonischemic cardiomyopathy after failure of endocardial ablation, we looked for additional markers supporting the diagnosis of cardiac sarcoidosis. In the last 4years, 135 patients (mean age 49 y, 63% male) were hospitalized for epicardial ventricular arrhythmia (VA) ablation after failure of endocardial ablation. Nineteen patients had either previously received a diagnosis of cardiac sarcoidosis or were newly diagnosed. The mean follow-up time was 4.3years. The ECG criteria, primary manifestation, histological findings in EMB, history of VT ablation, distribution of scars on MRI, electroanatomical mapping (EAM), PET CT findings, presence of atrial tachycardias, valve disease and comorbidities were analyzed. Six of 19 (32%) patients showed right bundle block; 6 of 19 (32%) had AV nodal disease, including 4 patients with AV-block III; and 14 patients (73%) primarily presented with ventricular arrhythmias (including 3 with cardiac arrest). In all 19 patients cardiac EMB revealed elevated CD68 macrophages and CD3 T lymphocytes, and 7 of 19 were positive for granuloma (36,8%). Six of 6 patients (100%) undergoing PET CT showed acute inflammation. By analyzing the scar distribution, the most common locations were basal anteroseptal, basal inferoseptal, mid inferoseptal, mid inferior and the septal RV/RVOT. (septal substrate in 100%). There was a high correlation between the findings on the MRIs and low voltage in the electroanatomical mapping EAM). All patients received an immunosuppressive therapy. No patient died during follow-up, 1 patient had a high urgent heart transplant after withdrawal of steroid therapy. Chronic untreated inflammation may be the underlying pathophysiology for patients with unspecific cardiomyopathy and recurrent VA refractory to endocardial and epicardial ablation. Septal substrate in the EAM/MRI, elevated CD3 lymphocytes in the EBM and inflammation in the PET CT may indicate the possible diagnosis of cardiac sarcoidosis. Initializing immunosuppressive therapy in patients with this dedicated constellation with should be taken into consideration.