Standard Heart Failure Treatment Research Articles

Obstructive sleep apnea and acute decompensated heart failure

Abstract Funding Acknowledgements None. Background Acute decompensated heart failure is a condition with a high frequency of hospitalizations and mortality. Screening and treatment for obstructive sleep apnea can be helpful in these patients. Purpose To determine the frequency of obstructive sleep apnea in patients with acute decompensated heart failure. To add CPAP home therapy to standard medical treatment for heart failure. To follow patients for 1 year. Methods We conducted a single-centre, prospective cohort study form 150 consecutive patients hospitalized for exacerbation heart failure in the cardiology department. 81 patients meet inclusion criteria – Apnea-Hypopnea index (AHI) > 5, Epworth Sleepiness Scale (ESS) > 8, NYHA class II/III and NTproBNP>900 pg/ml. Patients with OSA were offered to purchase a CPAP device for the home. They were divided into two groups with CPAP and no-CPAP. All patients receiving optimal medical treatment. The follow-up period was 1 year. At the end of the period, patients underwent a physical examination, an echocardiography, and ESS. In the non-CPAP group, 29 patients were followed up and 13 patients dropped out due to mortality. In the CPAP group, 16 patients were followed up, with 1 dropped out. Sleep apnea screening was performed with ApneaLinkTM. Echocardiographic assessment of left ventricular ejection fraction (LVEF) and the E/e‘m ratio. Results From 81 with sleep apnea 72.8% (n=59) has obstructive sleep apnea (OSA) and 27.2% (n=22) has central sleep apnea (CSA). Of the 59 patients with OSA, 17 patients (28.8%) purchased a device and continued therapy at home, while 42 patients (71.2%)on optimal drug therapy without CPAP. There is a statistically significant difference in BMI in the group with CPAP compared to the no-CPAP group at the beginning and at the end of the follow-up (CPAP group at the start 36.47±7.3 vs. the end 33.3±5.7, p=0.001 and no-CPAP group at the start 36.35±7.34 vs. the end 35.74±7.46 , p=0.356). A similar relationship is found in systolic blood pressure(SBP) and diastolic blood pressure(DBP). SBP in CPAP group at start 136.2±6.2 mmHg vs. end 123.1±5.9 mmHg; р<0.001. relative to no-CPAP group – start 131.2±9.8 mmHg vs. end 131.3±7.7 mmHg; р=0.965. DBP in CPAP group at start 85.9±6.7 mmHg vs. end 77.3±5.3 mmHg; р<0.001 and no-CPAP group start 82.1±7.4 mmHg vs. end 81.7±5.7 mmHg, р=0.644. There is a significant change in LVEF between the two groups at the beginning and at the end of the follow-up (in CPAP group at start 47.5±8.7, vs. at end 50.07±7.5; р=0.005, between no-CPAP at start 52.5±6.9 vs. at end 52.2±7.1; р=0.389). The CPAP group had a median survival of 11.7 months vs. 10.1 months in no CPAP group(Log Rank (Mental-Cox) p=0.044 ). Conclusion Obstructive sleep apnea is a common comorbidity in patients with acute decompensated heart failure. The addition of CPAP therapy in these patients improved BMI, SBP, DBP and increases LVEF. All this improves the prognosis for these patients.

Management of aortic valve insufficiency in patients with continuous-flow left ventricular assist device: a republication of the review published in Japanese Journal of Artificial Organs.

Since 2011, implantable ventricular assist devices have been a standard treatment for severe heart failure alongside heart transplantation in Japan. However, the limited availability of donors has led to a prolonged wait for transplants, now averaging 1719days, intensifying the issue of aortic insufficiency in patients with continuous flow ventricular assist devices. These devices limit the opening of the aortic valve, leading to sustained closure and increased shear stress, which accelerates valve degradation. Risk factors for aortic insufficiency include having a smaller body surface area, being of advanced age, and the presence of mild aortic insufficiency prior to device implantation. In patients presenting with mild or moderate aortic regurgitation at the time of ventricular assist device implantation, interventions such as aortic valve repair or bioprosthetic valve replacement are performed with the aim of halting its progression. The choice of surgical procedure should be tailored to each patient's individual condition. The management of de novo aortic insufficiency in patients with continuous flow ventricular assist devices remains challenging, with no clear consensus on when to intervene. Interventions for significant aortic insufficiency typically consider the patient's symptoms and aortic insufficiency severity. De novo aortic insufficiency progression in continuous flow ventricular assist devices patients necessitates careful monitoring and intervention based on individual patient assessments and valve condition. This review was created based on a translation of the Japanese review written in the Japanese Journal of Artificial Organs in 2023 (Vol. 52, No. 1, pp. 77-80), with some modifications.

The impact of empagliflozin and metformin on cardiac parameters in patients with mid-range ejection fraction heart failure without diabetes.

Heart failure (HF) remains a significant problem for healthcare systems, requiring the use of intervention and multimodal management strategies. We aimed to assess the short-term effect of empagliflozin (EMPA) and metformin on cardiac function parameters, including ventricular dimension-hypertrophy, septal thickness, ejection fraction (EF), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with HF and mildly reduced EF. A case-control study included 60 newly diagnosed patients with HF. Patients were divided into two groups: Group E received standard HF treatment (carvedilol, bumetanide, sacubitril-valsartan, spironolactone) plus EMPA 10 mg daily, and Group M received standard HF treatment plus metformin 500 mg daily. After three months of treatment, Group E had a significantly higher EF than Group M compared to initial measurements (a change of 9.2% versus 6.1%, respectively). We found similar results in the left ventricular end-systolic dimension (LVESD), with mean reductions of 0.72 mm for Group E and 0.23 mm for Group M. Regarding cardiac indicators, the level of NT-proBNP was considerably decreased in both groups. However, the reduction was significantly greater in group E than in group M compared to the initial level (mean reduction: 719.9 vs. 973.6, respectively). When combined with quadruple anti-heart failure therapy, metformin enhanced several echocardiographic parameters, showing effects similar to those of EMPA when used in the same treatment regimen. However, the benefits of EMPA were more pronounced, particularly regarding improvements in EF and LVESD.

Pharmacological inhibition of the cysteine protease cathepsin C improves graft function after heart transplantation in rats

BackgroundHeart transplantation (HTX) is the standard treatment for end-stage heart failure. However, reperfusion following an ischemic period can contribute to myocardial injury. Neutrophil infiltration, along with the subsequent release of tissue-degrading neutrophil elastase (NE)-related serine proteases and oxygen-derived radicals, is associated with adverse graft outcomes. The inhibition of cathepsin C (CatC) has been shown to block NE-related protease activation. We hypothesized that the CatC inhibitor BI-9740 improves graft function after HTX.MethodsIn a rat model of HTX, the recipient Lewis rats were orally administered with either a placebo (n = 12) or BI-9740 (n = 11, 20 mg/kg) once daily for 12 days. Donor hearts from untreated Lewis rats were explanted, preserved in a cardioplegic solution, and subsequently heterotopically implanted. In vivo left-ventricular (LV) graft function was assessed after 1 h of reperfusion. The proteolytic activity of neutrophil serine proteases was determined in bone marrow lysates from BI-9740-treated and control rats. Additionally, myocardial morphological changes were examined, and heart samples underwent immunohistochemistry and western blot analysis.ResultsThe NE-related proteolytic activity in bone marrow cell lysates was markedly decreased in the BI-9740-treated rats compared to those of the placebo group. Histopathological lesions, elevated CatC and myeloperoxidase-positive cell infiltration, and nitrotyrosine immunoreactivity with an increased number of poly(ADP-ribose) polymerase (PARP)-1-positive cells were lowered in the hearts of animals treated with BI-9740 compared to placebo groups. Regarding the functional parameters of the implanted graft, improvements were observed in both systolic function (LV systolic pressure 110 ± 6 vs 74 ± 6 mmHg; dP/dtmax 2782 ± 149 vs 2076 ± 167 mmHg/s, LV developed pressure, at an intraventricular volume of 200 µl, p < 0.05) and diastolic function in the hearts of BI-9740 treated animals compared with those receiving the only placebo. Furthermore, the administration of BI-9740 resulted in a shorter graft re-beating time compared to the placebo group. However, this study did not provide evidence of DNA fragmentation, the generation of both superoxide anions and hydrogen peroxide, correlating with the absence of protein alterations related to apoptosis, as evidenced by western blot in grafts after HTX.ConclusionsWe provided experimental evidence that pharmacological inhibition of CatC improves graft function following HTX in rats.

Abstract 18037: Left Bundle Branch Area versus Biventricular Pacing in Cardiac Resynchronization Therapy: A Systematic Review and Meta-Analysis

Introduction: Cardiac resynchronization therapy (CRT) through biventricular pacing (BVP) is the standard treatment for heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB). Left bundle-branch area pacing (LBBAP) has emerged as a potentially more effective approach. However, its superiority over BVP remains unclear. Hypothesis: Is LBBAP more effective and safer than BVP for CRT in patients with HFrEF? Methods: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) or observational studies that reported adjusted effect estimates (i.e propensity score-matched populations or multivariate analysis), comparing the efficacy and safety of LBBAP versus BVP. We applied the random-effects model to calculate adjusted hazard ratio (aHR) and mean difference (aMD), with the corresponding 95% confidence interval. Heterogeneity was assessed using I 2 statistics. Statistical analysis was performed using R version 4.2.1. Results: Our analysis included 7 studies, yielding 2,743 patients, of whom 1,164 (42.4%) were assigned to LBBAP group. Compared with BVP, LBBAP was associated with a significant reduction of the composite of overall mortality and heart failure hospitalizations (aHR 0.67; 95% CI 0.56-0.80; I 2 =0%; p&lt;0.001; Figure 1A). Additionally, LBBAP demonstrated a significant increase in LVEF (aMD 5.77%; 95% CI 2.94-8.60; I 2 =68%; p&lt;0.001; Figure 1B) and shortening of QRS duration (aMD -25.71 ms; 95% CI -35.87 to -15.55; I 2 =0%; p&lt;0.001; Figure 2A) compared with BVP. Sub-analysis of patients with LBBB also demonstrated a significant reduction of the composite of overall mortality and heart failure hospitalizations (aHR 0.64; 95% CI 0.49 to 0.85; I 2 =0%; p&lt;0.001; Figure 2B) in LBBAP. Conclusions: This meta-analysis of RCTs and multivariable adjusted studies suggests that LBBAP is superior to BVP in patients with HFrEF undergoing CRT for both electrophysiological and clinical outcomes.

Heart graft preservation technics and limits: an update and perspectives.

Heart transplantation, the gold standard treatment for end-stage heart failure, is limited by heart graft shortage, justifying expansion of the donor pool. Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard practice, but it is usually limited to 240 min. Prolonged cold ischemia and ischemia-reperfusion injury (IRI) have been recognized as major causes of post-transplant graft failure. Continuous ex situ perfusion is a new approach for donor organ management to expand the donor pool and/or increase the utilization rate. Continuous ex situ machine perfusion (MP) can satisfy the metabolic needs of the myocardium, minimizing irreversible ischemic cell damage and cell death. Several hypothermic or normothermic MP methods have been developed and studied, particularly in the preclinical setting, but whether MP is superior to SCS remains controversial. Other approaches seem to be interesting for extending the pool of heart graft donors, such as blocking the paths of apoptosis and necrosis, extracellular vesicle therapy, or donor heart-specific gene therapy. In this systematic review, we summarize the mechanisms involved in IRI during heart transplantation and existing targeting therapies. We also critically evaluate all available data on continuous ex situ perfusion devices for adult donor hearts, highlighting its therapeutic potential and current limitations and shortcomings.

Genetics of Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is defined as dilation and/or reduced function of one or both ventricles and remains a common disease worldwide. An estimated 40% of cases of familial DCM have an identifiable genetic cause. Accordingly, there is a fast-growing interest in the field of molecular genetics as it pertains to DCM. Many gene mutations have been identified that contribute to phenotypically significant cardiomyopathy. DCM genes can affect a variety of cardiomyocyte functions, and particular genes whose function affects the cell-cell junction and cytoskeleton are associated with increased risk of arrhythmias and sudden cardiac death. Through advancements in next-generation sequencing and cardiac imaging, identification of genetic DCM has improved over the past couple decades, and precision medicine is now at the forefront of treatment for these patients and their families. In addition to standard treatment of heart failure and prevention of arrhythmias and sudden cardiac death, patients with genetic cardiomyopathy stand to benefit from gene mechanism-specific therapies.

Metformin effects on cardiac parameters in non-diabetic Iraqi patients with heart failure and mid-range ejection fraction - a comparative two-arm parallel clinical study.

Heart failure (HF) remains a difficult challenge to the healthcare system, necessitating promoting interventions and multidrug management. Metformin, typically used to manage diabetes, has emerged as a promising intervention in the treatment of HF. This study aimed to assess the effect of adding metformin to the standard treatment of HF on cardiac parameters. This clinical study comprised 60 newly diagnosed HF patients randomly assigned to two groups: Group C received standard HF treatment, while Group M received standard HF treatment in addition to daily metformin (500 mg). After 3 months of treatment, group M showed a significantly higher ejection fraction (EF) compared to Group C (6.1% and 3.2%, respectively; p-value=0.023) and a reduction in the left ventricular end-diastolic pressure (LVEDD) (0.28, and 0.21 mm respectively; p-value=0.029). No significant differences were observed in the interventricular septal thickness (IVST) or left ventricular end-systolic pressure (LVESD). For cardiac markers, N-Terminal pro-BNP (NT-proBNP) showed the highest reduction in Group M compared to Group C (719.9 pg/ml and 271.9 pg/ml respectively; p-value=0.009). No significant changes were reported for soluble ST2. Metformin demonstrated cardiac protective effects by increasing EF and reducing NT-proBNP. Given its affordability and accessibility, metformin offers a valuable addition to the current HF treatment options. This positive effect may be attributed to mechanisms that enhance the impact of conventional HF treatments or vice versa.

The role of innovative modeling and imaging techniques in improving outcomes in patients with LVAD.

Heart failure remains a significant cause of mortality in the United States and around the world. While organ transplantation is acknowledged as the gold standard treatment for end stage heart failure, supply is limited, and many patients are treated with left ventricular assist devices (LVADs). LVADs extend and improve patients' lives, but they are not without their own complications, particularly the hemocompatibility related adverse events (HRAE) including stroke, bleeding and pump thrombosis. Mainstream imaging techniques currently in use to assess appropriate device function and troubleshoot complications, such as echocardiography and cardiac computed tomography, provide some insight but do not provide a holistic understanding of pump induced flow alterations that leads to HRAEs. In contrast, there are technologies restricted to the benchtop-such as computational fluid dynamics and mock circulatory loops paired with methods like particle image velocimetry-that can assess flow metrics but have not been optimized for clinical care. In this review, we outline the potential role and current limitations of converging available technologies to produce novel imaging techniques, and the potential utility in evaluating hemodynamic flow to determine whether LVAD patients may be at higher risk of HRAEs. This addition to diagnostic and monitoring capabilities could improve prevention and treatment of LVAD-induced complications in heart failure patients.

Simultaneous heart and kidney transplantation: Our first experience

The gold standard treatment for end-stage heart and kidney failure is simultaneous heart and kidney transplantation. The global number of recipients on the waiting list and performed organ transplants increases annually. However, there is a lack of well-defined selection criteria for multi-organ transplants, leading to variations based on geographic region and local protocols.&#x0D; In this study, we present our initial experience with simultaneous heart and kidney transplantation in Patient P, a 51-year-old individual with severe calcification of the mitral valve and end-stage chronic kidney disease. Surgical correction was not possible, and thus the patient underwent orthotopic simultaneous heart and kidney transplantation. During the early postoperative period, the patient experienced acute renal failure in the transplanted kidney, which was managed through courses of hemodialysis.&#x0D; The findings of this clinical observation represent the first experience of multi-organ transplantation in Ukraine. Our clinical observation illustrates the successful feasibility of simultaneous orthotopic heart and kidney transplantation, showcasing promising immediate and medium-term follow-up results.

Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography.

Heart transplantation remains the gold standard treatment for advanced heart failure. However, the current critical organ shortage has resulted in the allocation of a growing number of donor hearts with extended criteria. These marginal grafts are associated with a high risk of primary graft failure and may benefit from ex situ perfusion before transplant. This technology allows for extended organ preservation using warm oxygenated blood perfusion with continuous metabolic monitoring. The only NESP device currently available for clinical practice perfuses the organ in an unloaded non-working state, which does not allow for functional assessment of the beating heart. We therefore developed an original platform of NESP in working mode conditions with adjustment of left ventricular preload and afterload. This protocol was applied in porcine hearts. Ex situ functional assessment of the heart was achieved with intracardiac conductance catheterization and surface echocardiography. Along with a description of the experimental protocol, we herein report the main results, as well as pearls and pitfalls associated with the acquisition of pressure-volume loops and myocardial power during NESP. Correlations between hemodynamic findings and ultrasound variables are of major interest, especially for further rehabilitation of donor hearts before transplantation. This protocol aims to improve the assessment of donor hearts to both increase the donor pool and reduce the incidence of primary graft failure.

Functional Assessment of the Donor Heart During &lt;em&gt;Ex Situ&lt;/em&gt; Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography

Heart transplantation remains the gold standard treatment for advanced heart failure. However, the current critical organ shortage has resulted in the allocation of a growing number of donor hearts with extended criteria. These marginal grafts are associated with a high risk of primary graft failure and may benefit from ex situ perfusion before transplant. This technology allows for extended organ preservation using warm oxygenated blood perfusion with continuous metabolic monitoring. The only NESP device currently available for clinical practice perfuses the organ in an unloaded non-working state, which does not allow for functional assessment of the beating heart. We therefore developed an original platform of NESP in working mode conditions with adjustment of left ventricular preload and afterload. This protocol was applied in porcine hearts. Ex situ functional assessment of the heart was achieved with intracardiac conductance catheterization and surface echocardiography. Along with a description of the experimental protocol, we herein report the main results, as well as pearls and pitfalls associated with the acquisition of pressure-volume loops and myocardial power during NESP. Correlations between hemodynamic findings and ultrasound variables are of major interest, especially for further rehabilitation of donor hearts before transplantation. This protocol aims to improve the assessment of donor hearts to both increase the donor pool and reduce the incidence of primary graft failure.

Cost-Effectiveness of Adding Empagliflozin to Standard Treatment for Heart Failure with Preserved Ejection Fraction Patients in China.

Heart failure is a worldwide health problem and is the leading cause of hospitalization in older patients. Heart failure with preserved ejection fraction (HFpEF) accounts for about 38% of heart failure cases. The latest EMPEROR-Preserved study shows that empagliflozin can reduce the risk of hospitalization in HFpEF, but whether empagliflozin is cost-effective in HFpEF in a Chinese setting remained uninvestigated. A simulation of lifetime horizon for a 72-year-old HFpEF patient was conducted using a Markov model. The primary outcome was incremental cost-effectiveness ratio (ICER), expressed as incremental costs per quality-adjusted life-year (QALY). Three times the per capita GDP of China was set as the willingness-to-pay (WTP) threshold. Empagliflozin was considered cost-effective if the ICER was below the WTP threshold, otherwise it would be regarded as not cost-effective. One-way sensitivity and probabilistic sensitivity analysis (PSA) were used to assess uncertainty. After a simulation of lifetime horizon, a 72-year-old HFpEF patient is expected to have an expected QALY of 4.80 in the empagliflozin group, and 4.67 QALY with standard treatment. The costs of empagliflozin and standard treatment are 34,987 (US$5423) and 27,027 (US$4189) Chinese Yuan (CNY), respectively, with an ICER of 63,746 (US$9881)/QALY, lower than the WTP threshold. One-way sensitivity and PSA show that our results are robust. In Chinese HFpEF patients, adding empagliflozin to standard treatment is cost-effective, but studies based on real-world data are needed.

247.7: Trends and Risk Factors for Mortality While Awaiting Heart Transplantation: A UNOS Registry Analysis

Background: Orthotopic heart transplantation (OHT) remains the gold standard treatment of end-stage heart failure. In order to address organ scarcity, allocation systems aim to decrease waitlist mortality while maintaining acceptable post-transplant outcomes. The purpose of this study was to examine the characteristics of patients who suffered mortality on the waitlist versus those who underwent transplantation, as well as the impact of recent changes in the United States heart allocation policies on these outcomes. Methods: The United Network for Organ Sharing database was queried, and adult, isolated OHT candidates listed for transplant within the United States from 11/5/2015 to 9/30/2021 were analyzed. Baseline characteristics among candidates that either were transplanted, or had been removed from the waitlist due to death clinical deterioration were compared. Comparisons were also made between heart allocation policy (pre or post-10/18/2018) time eras. Multivariable competing risk regression was conducted to identify risk-adjusted predictors of transplantation from the waitlist. Additionally, predictors of the outcome of death or de-listing from the waitlist due to clinical decline were also modeled. Results: During the study period, a total of 13,575 recipients were transplanted (6,926 under the old policy and 6,649 under the new). A total of 1,875 candidates died or were de-listed (1,235 listed under the old policy and 640 listed under the new). In a comparison of baseline characteristics at time of listing, candidates that were transplanted differed significantly to those who were de-listed due to death or clinical decline with respect to age, heart failure etiology, mechanical circulatory support bridging, and baseline comorbidity (Table). In a multivariable model, waitlisting under the new allocation policy was associated with reduced hazards for death or de-listing (HR 0.57, 95% CI 0.51-0.63; P<0.001), and increased hazards for undergoing transplantation (HR 1.36; 95% CI 1.31-1.41; P<0.001). The two largest predictors of transplantation were bridging with an intra-aortic balloon pump (HR 2.13, 95% CI 1.97-2.31; P<0.001) and AB blood type (HR 1.43, 95% CI 1.30-1.57; P<0.001). The strongest predictors of death or de-listing were diagnosis of hypertrophic cardiomyopathy (HR 3.77, 95% CI 2.69-5.29; P<0.001) or biventricular hemodynamic support in the form of either extracorporeal membrane oxygenation (HR 2.59, 95% CI 1.96-3.42; P<0.001), total artificial heart (HR 2.36, 95% CI 1.28-4.35; P=0.006), or combined right and left ventricular assist device support (HR 2.45, 95% CI 1.71-3.50; P<0.001). Conclusions: Since the United States 2018 heart allocation policy change, waitlisted candidates are more likely to be transplanted and less likely be de-listed due to death or clinical decline. Need for biventricular mechanical circulatory support at time of waitlisting are associated with higher risk of death or falling too ill for transplantation.

Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF).

Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear. In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L [95% CI, 8.4 to 3.6]; P=0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6-27.7]; P=0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51±19 versus 54±17 mL/min per 1.73 m²; P=0.599) or injury (total urinary protein, 492±845 versus 503±847 mg/g creatinine; P=0.975; and urinary α1-microglobulin, 55.4±38.6 versus 31.3±33.6 mg/g creatinine; P=0.066) with more pronounced decrease in NT-proBNP in the empagliflozin group compared with placebo (-1861 versus -727.2 pg/mL after 5 days; quotient in slope, 0.89 [95% CI, 0.83-0.95]; P<0.001). There were no differences in the incidence of safety events between groups. Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure. URL: https://www. gov; Unique identifier: NCT04049045.

Efficacy and Safety of Granulocyte-Colony Stimulating Factor Therapy in Chagas Cardiomyopathy: A Phase II Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

AimPrevious studies showed that granulocyte-colony stimulating factor (G-CSF) improved heart function in a mice model of Chronic Chagas Cardiomyopathy (CCC). Herein, we report the interim results of the safety and efficacy of G-CSF therapy vs. placebo in adults with Chagas cardiomyopathy.MethodsPatients with CCC, New York Heart Association (NYHA) functional class II to IV and left ventricular ejection fraction (LVEF) 50% or below were included. A randomization list using blocks of 2 and 4 and an allocation rate of 1:1 was generated by R software which was stratified by functional class. Double blinding was done to both arms and assessors were masked to allocations. All patients received standard heart failure treatment for 2 months before 1:1 randomization to either the G-CSF (10 mcg/kg/day subcutaneously) or placebo group (1 mL of 0.9% saline subcutaneously). The primary endpoint was either maintenance or improvement of NYHA class from baseline to 6–12 months after treatment, and intention-to-treat analysis was used.ResultsWe screened 535 patients with CCC in Salvador, Brazil, of whom 37 were randomized. Overall, baseline characteristics were well-balanced between groups. Most patients had NYHA class II heart failure (86.4%); low mean LVEF was 32 ± 7% in the G-CSF group and 33 ± 10% in the placebo group. Frequency of primary endpoint was 78% (95% CI 0.60–0.97) vs. 66% (95% CI 0.40–0.86), p = 0.47, at 6 months and 68% (95% CI 0.43–0.87) vs. 72% (95% CI 0.46–0.90), p = 0.80, at 12 months in placebo and G-CSF groups, respectively. G-CSF treatment was safe, without any related serious adverse events. There was no difference in mortality between both arms, with five deaths (18.5%) in treatment vs. four (12.5%) in the placebo arm. Exploratory analysis demonstrated that the maximum rate of oxygen consumption during exercise (VO2 max) showed an improving trend in the G-CSF group.ConclusionG-CSF therapy was safe and well-tolerated in 12 months of follow-up. Although prevention of symptom progression could not be demonstrated in the present study, our results support further investigation of G-CSF therapy in Chagas cardiomyopathy patients.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT02154269].

Marginal Cardiac Donors and Transplant Outcomes: An 11-Year Experience

<h3>Purpose</h3> Heart transplantation is the gold standard treatment for end-stage heart failure. However, the number of available organs is numerically inadequate to address this problem. One potential way to overcome the organ shortage is to broaden criteria for acceptable donations to include a sub-pool of marginal donors. This study aims to assess our outcomes for patients receiving marginal cardiac transplants compared to their counterparts. The analysis is particularly important as our centre has recently begun to utilise the XVIVO hypothermic perfusion machine for organ storage, challenging accepted definitions of organ marginality based on ischaemic time. <h3>Methods</h3> We conducted a single-centre retrospective cohort study to identify all heart transplant recipients from 2010-2021. Patients who received a combined heart-lung transplant were excluded, as were organs obtained through the donation after circulatory death (DCD) pathway. We identified all marginal donors meeting any of the accepted criteria; donor age >60 years, donor LVEF <55%, use of T3 in the donor, or donor ischemic time >6hrs or >4hrs if donor age >40 years. <h3>Results</h3> 371 patients met our inclusion criteria for this study. Based on accepted criteria, 120 (32%) of donors were identified as marginal. Of these 120 marginal donors, 64 (53%) met the prolonged ischaemic time criteria. Overall mean donor age was 37.2 years +/- 12.6 and mean donor ischaemic time was 225 minutes +/- 67 minutes. Utilisation of extra-corporeal membrane oxygenation (ECMO) was higher in the marginal donor group (33 patients, 28%) compared to the non-marginal group (35 patients, 14%), p=0.002. There was no difference in new renal failure, requirement for dialysis or post-operative length of stay. 14 patients (6%) in the non-marginal group died within 30-days of their transplant, compared to 5 patients (4%) in the marginal group, p=0.56). <h3>Conclusion</h3> Our centre's experience indicates that carefully selected marginal donors demonstrate similar short term post-transplant outcomes when compared to their non-marginal counterparts. Furthermore, our utilisation of the XVIVO hypothermic perfusion organ storage device is likely to further challenge the accepted definition of marginal cardiac donors by allowing for longer periods of donor ischaemic time and may improve post-operative ECMO rates in the marginal donor group.

A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft.

Cardiac transplantation is the gold standard treatment for end-stage heart failure. However, it remains limited by the number of available donor hearts and complications such as primary graft dysfunction and graft rejection. The recent clinical use of an ex vivo perfusion device in cardiac transplantation introduces a unique opportunity for treating cardiac allografts with therapeutic interventions to improve function and avoid deleterious recipient responses. Establishing a translational, large-animal model for therapeutic delivery to the entire allograft is essential for testing novel therapeutic approaches in cardiac transplantation. The porcine, heterotopic heart transplantation model in the intraabdominal position serves as an excellent model for assessing the effects of novel interventions and the immunopathology of graft rejection. This model additionally offers long-term survival for the pig, given that the graft is not required to maintain the recipient's circulation. The aim of this protocol is to provide a reproducible and robust approach for achieving ex vivo delivery of a therapeutic to the entire cardiac allograft prior to transplantation and provide technical details to perform a survival heterotopic transplant of the ex vivo perfused heart.

Machine Preservation and Ex Situ Assessment of the Donor Heart: A New Paradigm in Heart Transplantation

Heart transplantation is the gold standard treatment for advanced heart failure in selected patients. Organ shortage is however a major concern, leading transplant teams to expand the criteria for donor selection. Organ retrieval is routinely performed nowadays in donors older than 55 years, with impaired left ventricular function and/or hypertrophy, or after prolonged cardiac arrest such as after circulatory-determined death. All these conditions are associated with an increased high of primary graft failure, the main cause of early death after heart transplantation. Machine preservation technology has been recently applied to allow for extended preservation of the donor heart. Compared to conventional static cold storage, this approach can also provide viability assessment of the donor heart before transplant, especially in case of ex situ normothermic blood perfusion. After a brief review of currently available preservation machines, we sought to describe different approaches for assessment of the donor heart using ex situ organ perfusion, from metabolic monitoring to cardiac imaging and hemodynamic investigations.

Machine preservation and ex situ assessment of the donor heart: a new paradigm in heart transplantation

Heart transplantation is the gold standard treatment for advanced heart failure in selected patients. Organ shortage is however a major concern, leading transplant teams to expand the criteria for donor selection. Organ retrieval is routinely performed nowadays in donors older than 55 years, with impaired left ventricular function and/or hypertrophy, or after prolonged cardiac arrest such as after circulatory-determined death. All these conditions are associated with an increased high of primary graft failure, the main cause of early death after heart transplantation. Machine preservation technology has been recently applied to allow for extended preservation of the donor heart. Compared to conventional static cold storage, this approach can also provide viability assessment of the donor heart before transplant, especially in case of ex situ normothermic blood perfusion. After a brief review of currently available preservation machines, we sought to describe different approaches for assessment of the donor heart using ex situ organ perfusion, from metabolic monitoring to cardiac imaging and hemodynamic investigations.