Single center outcomes after temporary mechanical circulatory assist device prior to Heartmate 3 implantation - a retrospective cohort study.

Objectives. Temporary mechanical circulatory support (TMCS) has become a component in the therapeutic strategy for treatment of cardiogenic shock as a bridge-to-decision. TMCS can facilitate recovery of cardiopulmonary function, end-organ function, and potentially reduce the surgical risk of left ventricular assist device (LVAD) implantation. Despite the improvements of hemodynamics and end-organ function, post-LVAD operative morbidity might be increased in these high-risk patients. The aim of the study was to compare outcomes after Heartmate 3 (HM3) implantation in patients with and without TMCS prior to HM3 implant. Methods. In this retrospective cohort study of all HM3 patients in the period between November 2015 and October 2021, patients with and without prior TMCS were compared. Patients' demographics, baseline clinical characteristics, laboratory tests, intraoperative variables, postoperative outcomes, and adverse events were collected from patient records. Results. The TMCS group showed an improvement in hemodynamics prior to LVAD implantation. Median TMCS duration was 19.5 (14-26) days. However, the TMCS group were more coagulopathic, had more wound infections, neurological complications, and more patients were on dialysis compared with patient without TMCS prior to HM3 implantation. Survival four years after HM3 implantation was 80 and 82% in the TMCS (N = 22) and non-TMCS group (N = 41), respectively. Conclusion. Patients on TMCS had an acceptable short and long-term survival and comparable to patients receiving HM3 without prior TMCS. However, they had a more complicated postoperative course.

Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by high propensity to life-threatening arrhythmias and progressive loss of heart muscle. More than 40% of reported genetic variants linked to ARVC reside in the PKP2 gene, which encodes the PKP2 protein (plakophilin-2). METHODS: We describe a comprehensive characterization of the ARVC molecular landscape as determined by high-resolution mass spectrometry, RNA sequencing, and transmission electron microscopy of right ventricular biopsy samples obtained from patients with ARVC with PKP2 mutations and left ventricular ejection fraction >45%. Samples from healthy relatives served as controls. The observations led to experimental work using multiple imaging and biochemical techniques in mice with a cardiac-specific deletion of Pkp2 studied at a time of preserved left ventricular ejection fraction and in human induced pluripotent stem cell-derived PKP2-deficient myocytes. RESULTS: Samples from patients with ARVC present a loss of nuclear envelope integrity, molecular signatures indicative of increased DNA damage, and a deficit in transcripts coding for proteins in the electron transport chain. Mice with a cardiac-specific deletion of Pkp2 also present a loss of nuclear envelope integrity, which leads to DNA damage and subsequent excess oxidant production (O2.- and H2O2), the latter increased further under mechanical stress (isoproterenol or exercise). Increased oxidant production and DNA damage is recapitulated in human induced pluripotent stem cell-derived PKP2-deficient myocytes. Furthermore, PKP2-deficient cells release H2O2 into the extracellular environment, causing DNA damage and increased oxidant production in neighboring myocytes in a paracrine manner. Treatment with honokiol increases SIRT3 (mitochondrial nicotinamide adenine dinucleotide-dependent protein deacetylase sirtuin-3) activity, reduces oxidant levels and DNA damage in vitro and in vivo, reduces collagen abundance in the right ventricular free wall, and has a protective effect on right ventricular function. CONCLUSIONS: Loss of nuclear envelope integrity and subsequent DNA damage is a key substrate in the molecular pathology of ARVC. We show transcriptional downregulation of proteins of the electron transcript chain as an early event in the molecular pathophysiology of the disease (before loss of left ventricular ejection fraction <45%), which associates with increased oxidant production (O2.- and H2O2). We propose therapies that limit oxidant formation as a possible intervention to restrict DNA damage in ARVC.

Hyponatremia in Stable Patients with Advanced Heart Failure: Association to Hemodynamics and Outcome.

INTRODUCTION: Hyponatremia is associated with worse outcomes in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF). However, it is unclear whether the worse prognosis is driven by hemodynamic derangement and how this potentially could be associated with hyponatremia. METHODS: The study included 502 patients with HFrEF evaluated for advanced HF therapies, who underwent a right heart catheterization (RHC). Hyponatremia was defined as p-Na ≤136 mmol/L. The risk of all-cause mortality and a composite endpoint including mortality, left ventricular assist device (LVAD) implantation, implantation of total artificial heart (TAH), or heart transplantation (HTx) was evaluated using Cox regression analyses and Kaplan-Meier models. RESULTS: Included patients were predominantly men 79% and had a median age of 54 years (IQR: 43-62). A third (165) of the patients had hyponatremia. In both univariate and multivariate regression analyses, p-Na was associated with increased central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and mean pulmonary artery pressure (mPAP) but not with cardiac index. Hyponatremia was significantly associated with the combined endpoint (HR: 1.36 [95% CI, 1.07-1.74]; p = 0.01), but not all-cause mortality in adjusted Cox models. CONCLUSION: In stable HFrEF patients evaluated for advanced HF therapies, lower p-Na was associated with more deranged invasive hemodynamic measurements. Hyponatremia remained significantly associated with the combined endpoint but not all-cause mortality in adjusted Cox models. The study suggests that the increased mortality associated with hyponatremia in HFrEF patients could partly be driven by hemodynamic derangement.

Short-term outcomes after heart transplantation using donor hearts preserved with ex vivo perfusion.

The standard Conventional Cold Storage (CCS) during heart transplantation procurement is associated with time-dependent ischemic injury to the graft, which is a significant independent risk factor for post-transplant early morbidity and mortality - especially when cold ischemic time exceeds four hours. Since 2018, Rigshospitalet (Copenhagen, Denmark) has been utilising ex vivo perfusion (Organ Care System, OCS) in selected cases. The objective of this study was to compare the short-term clinical outcomes of patients transplanted with OCS compared to CCS. Methods: This retrospective single-centre study was based on consecutive patients undergoing a heart transplant between January 2018 and April 2021. Patients were selected for the OCS group when the cold ischemic time was expected to exceed four hours. The primary outcome measure was six-month event-free survival. Results: In total, 48 patients were included in the study; nine were transplanted with an OCS heart. The two groups had no significant differences in baseline characteristics. Six-month event-free survival was 77.8% [95% CI: 54.9-100%] in the OCS group and 79.5% [95% CI: 67.8-93.2%] in the CCS group (p = 0.91). While the OCS group had a median out-of-body time that was 183 min longer (p < 0.0001), the cold ischemic time was reduced by 51 min (p = 0.007). Conclusion: In a Scandinavian setting, our data confirms that utilising OCS in heart procurement allows for a longer out-of-body time and a reduced cold ischemic time without negatively affecting safety or early post-transplant outcomes.

Prognostic value of myocardial flow reserve obtained by 82-rubidium positron emission tomography in long-term follow-up after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplantation (HTx) and non-invasive prognostic methods in long-term CAV surveillance are needed. We evaluated the prognostic value of myocardial flow reserve (MFR) obtained by 82-rubidium (82Rb) positron emission tomography (PET). METHODS: Recipients undergoing dynamic rest-stress 82Rb PET between April 2013 and June 2017 were retrospectively evaluated in a single-center study. Evaluation by PET included quantitative myocardial blood flow and semiquantitative myocardial perfusion imaging. Patients were grouped by MFR (MFR ≤ 2.0 vs MFR > 2.0) and the primary outcome was all-cause mortality. RESULTS: A total of 50 patients (68% men, median age 57 [IQR: 43 to 68]) were included. Median time from HTx to PET was 10.0 (6.7 to 16.0) years. In 58% of patients CAV was documented prior to PET. During a median follow-up of 3.6 (2.3 to 4.3) years 12 events occurred. Survival probability by Kaplan-Meier method was significantly higher in the high-MFR group (log-rank P = .02). Revascularization (n = 1), new CAV diagnosis (n = 1), and graft failure (n = 4) were more frequent in low-MFR patients. No retransplantation occurred. CONCLUSIONS: Myocardial flow reserve appears to offer prognostic value in selected long-term HTx recipients and holds promise as a non-invasive method for CAV surveillance possibly guiding management strategy.

Three decades of heart transplantation: experience and long-term outcome.

Objectives. Heart transplantation (HTx) has become an established treatment option in patients with end-stage heart failure. The aim of this study was to report on long-term outcome over the past three decades. Design. Consecutive adult patients receiving first-time and isolated HTx from October 3, 1990, to November 2, 2020, at Rigshospitalet, Copenhagen, Denmark, were retrospectively evaluated. Data were obtained from the Scandinavian Transplant Registry and patient medical records. Recipients were grouped by time of transplantation (early era: 1990-1999; mid era: 2000-2009; recent era: 2010-2020). Results. A total of 384 recipients (77% men, median age 50 [IQR: 40-57]) were included. Median number of HTx procedures per year was 12 (10-14). Overall, 22% of patients were bridged to HTx with a mechanical circulatory support device. Median survival for the whole cohort was 13.8 years and improved numerically from the early era (12.6 years) to the mid era (14.9 years). Median survival conditional on survival to 1-year follow-up after HTx was 16.1 years. Survival probability by Kaplan-Meier method improved significantly from the mid to the recent era (log-rank p = .02). Conclusions. Heart transplantation remains an excellent treatment for selected patients with end-stage heart failure and long-term outcome has improved significantly over the past decades.

Long-term prognosis following hospitalization for acute myocarditis - a matched nationwide cohort study.

OBJECTIVE: The aim of this study was to examine the long-term risk of heart failure (HF) and all-cause mortality, in patients discharged alive following hospitalization for myocarditis. Background. Prognosis in patients with apparently uncomplicated myocarditis is in general perceived as good, but data on long-term outcomes are sparse. Methods. From nationwide Danish registries we included patients without prior cardiac disease, discharged alive with a first-time diagnosis of myocarditis 1996-2016. Patients were matched 1:10 by age- and sex, with controls from the general population. Risk of HF hospitalization and death in cases and controls was compared by use of adjusted Cox regression analyses. Results. We identified 1557 patients with a first-time diagnosis of myocarditis, 72% men, median age 39 years. Patients with myocarditis had more hypertension, diabetes, and cancer, and received more pharmacotherapy prior to hospitalization compared to matched controls. During a mean follow-up of 8.5 years, the event rate of HF hospitalization was 8.7 vs. 2.2 per 1000 patient-years (py) in cases and controls; HR 4.59 (95% CI; 3.58-5.88) and for all-cause mortality, event rate 21.9 vs 11.2 per 1000 py; HR 2.10 (95% CI; 1.82-2.43). Among 784 patients with no events or HF medication one year after diagnosis, risk of HF hospitalization (HR 2.15; 95% CI; 1.18-3.92), and all-cause mortality (HR 1.62; 95% CI; 1.21-2.16) remained elevated compared to matched controls. Conclusion. Myocarditis in younger patients without prior cardiac disease was associated with a long-term excess risk of HF hospitalization, and death, even in patients free of events and HF medication 1 year after discharge.HighlightsMyocarditis ranges from chest discomfort to severe heart failure.In most patients, left ventricular ejection fraction recovers but the long-term adverse cardiac risk is unknown.Patients with myocarditis and no prior cardiac disease were at higher risk of death and heart failureRoutine follow-up may be warranted following an episode of acute myocarditis.

Intravascular ultrasound-guided selection for early noninvasive cardiac allograft vasculopathy screening in heart transplant recipients.

BACKGROUND: Noninvasive screening for cardiac allograft vasculopathy (CAV) instead of invasive coronary angiography (ICA) within the first 3 to 5 years after heart transplantation (HTx) is controversial. We evaluated a strategy of intravascular ultrasound (IVUS)-guided conversion to early noninvasive screening post-HTx. METHODS: A single-center study of 103 consecutive HTx recipients from 2008 to 2018 undergoing ICA at 1 year post-HTx. Of 88 patients with normal 1-year ICA, sixty-six patients underwent IVUS examination for risk stratification by maximal intimal thickness (MIT) into (i) low-risk group (MIT < 0.5 mm) (n = 41, 62%) followed noninvasively versus (ii) high-risk group (MIT ≥ 0.5 mm) (n = 25, 38%) followed with yearly ICA. Both groups underwent ICA at year 5 post-HTx. We evaluated a combined endpoint of angiographic CAV and death at 5-year follow-up post-HTx. RESULTS: Median (IQR) age was 51 (33-60) years, and 62% were male. Follow-up was 1443 (1125-1456) days. Survival free from angiographic CAV (Kaplan-Meier) differed significantly between groups (log-rank p < .0001). A subgroup of 27 patients completed ICA at year 5, and the proportion of angiographic CAV was significantly lower in low-risk patients (p < .0001). CONCLUSION: IVUS-guided selection for early noninvasive CAV screening appears to be safe and holds promise as a novel strategy for early risk stratification and CAV surveillance post-HTx.

Plasma Somatostatin in Advanced Heart Failure: Association with Cardiac Filling Pressures and Outcome.

BACKGROUND: Somatostatin inhibits intestinal motility and hormonal secretion and is a potent arterial vasoconstrictor of the splanchnic blood flow. It is unknown if somatostatin concentrations are associated with central hemodynamic measurements in patients with advanced heart failure (HF). METHODS: A prospective study of HF patients with a left ventricular ejection fraction (LVEF) <45% referred to right heart catheterization (RHC) for evaluation for heart transplantation (HTX) or left ventricular assist device (LVAD). RESULTS: Fifty-three patients were included with mean LVEF 18 ± 8% and majority in NYHA-class III-IV (79%). Median plasma somatostatin concentration was 18 pmol/L. In univariable regression analysis, log(somatostatin) was associated with increased central venous pressure (CVP; r2 = 0.14, p = 0.003) and a reduced cardiac index (CI; r2 = 0.15, p = 0.004). When adjusted for selected clinical variables (age, gender, LVEF, eGFR and BMI), log(somatostatin) remained a significant predictor of CVP (p = 0.044). Increased somatostatin concentrations predicted mortality in multivariable models (hazard ratio: 5.2 [1.2-22.2], p = 0.026) but not the combined endpoint of death, LVAD implantation or HTX. CONCLUSIONS: Somatostatin concentrations were associated with CVP and CI in patients with HF. The pathophysiological mechanism may be related to congestion and/or hypoperfusion of the intestine. Somatostatin was an independent predictor of mortality in advanced HF.

Clinical presentation and outcomes in women and men with advanced heart failure.

OBJECTIVE: To examine clinical characteristics and outcomes in women and men referred for advanced heart failure (HF) therapies such as left ventricular assist device (LVAD) or heart transplantation (HTx). Design: A retrospective study of 429 (23% women) consecutive adult HF patients not on inotropic or mechanical circulatory support with left ventricular ejection fraction ≤45% referred for assessment of advanced HF therapies at a single tertiary institution between 2002 and 2016. Clinical characteristics and outcomes were compared in women and men, and all patients underwent right heart catheterization (RHC). Results: At evaluation, women were younger than men (48 ± 13 vs. 51 ± 12 years, p = .02), and less likely to have ischemic cardiomyopathy. There were no significant differences in NYHA class, contemporary HF therapy use, or physical examination findings, except for lower jugular vein distension and body surface area in women. On RHC, women had lower cardiac filling pressures, but similar pulmonary vascular resistance and cardiac index. Peak oxygen uptake from cardiopulmonary exercise testing was similar in both sexes. At total follow-up time, there were 164 deaths (21% vs. 44%, p < .0001), 46 LVADs (3% vs. 13%, p = .005), 110 HTxs (32% vs. 25%, p = .15), and 82 HTxs without requiring LVAD (29% vs. 16%, p = .03) in women and men. The time from RHC to HTx (±LVAD) was significantly shorter in women compared to men. Female sex was significantly associated with higher survival independent of time-trend, age, and comorbidities. Conclusion: At evaluation, hemodynamics were less deranged in women. A higher proportion of women received HTx, their waitlist time was shorter, and survival greater.

Pulmonary artery pressure as a method for assessing hydration status in an anuric hemodialysis patient - a case report.

BACKGROUND: Setting the dry weight and maintaining fluid balance is still a difficult challenge in dialysis patients. Overhydration is common and associated with increased cardiac morbidity and mortality. Pulmonary hypertension is associated with volume overload in end-stage renal dysfunction patients. Thus, monitoring pulmonary pressure by a CardioMEMS device could potentially be of guidance to physicians in the difficult task of assessing fluid overload in hemodialysis patients. CASE PRESENTATION: 61-year old male with known congestive heart failure deteriorated over 3 months' time from a state with congestive heart failure and diuresis to a state of chronic kidney disease and anuria. He began a thrice/week in-hospital hemodialysis regime. As he already had implanted a CardioMEMS device due to his heart condition, we were able to monitor invasive pulmonary artery pressure during the course of dialysis sessions. To compare, we estimated overhydration by both bioimpedance and clinical assessment. Pulmonary artery pressure correlated closely with fluid drainage during dialysis and inter-dialytic weight gain. The patient reached prescribed dry weight but remained pulmonary hypertensive by definition. During two episodes of intradialytic systemic hypotension, the patient still had pulmonary hypertension by current definition. CONCLUSION: This case report observes a close correlation between pulmonary artery pressure and fluid overload in a limited amount of observations. In this case we found pulmonary artery pressure to be more sensitive towards fluid overload than bioimpedance. The patient remained pulmonary hypertensive both as he reached prescribed dry weight and experienced intradialytic hypotensive symptoms. Monitoring pulmonary artery pressure via CardioMEMS could hold great potential as a real-time guidance for fluid balance during hemodialysis, though adjusted cut-off values for pulmonary pressure for anuric patients may be needed. Further studies are needed to confirm the findings of this case report and the applicability of pulmonary pressure in assessing optimal fluid balance.

Relationship between invasive hemodynamics and liver function in advanced heart failure.

Objective. To examine how liver function (LF) relates to invasive hemodynamics cross-sectionally and longitudinally, in advanced heart failure (AHF) patients treated with maximally tolerated medical HF therapy. Design. A retrospective study of 309 consecutive AHF patients with a left ventricular ejection fraction < 45% treated with maximally tolerated medical HF therapy who were referred for AHF therapies. All patients underwent right heart catheterization (RHC) using Swan-Ganz catheters. Cardiac output was measured using thermodilution. Measurements of pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac index (CI) and mean arterial pressure (MAP) were obtained. RHC and evaluation of LF were repeated (median (IQR) = 186.5 (150-208) days) in 33 patients. Results. Mean (SD) age was 50 (±13) years, and 239 (77%) were men. Only 22 (7%) were treated with inotropes, and none were receiving mechanical circulatory support. Median (IQR) plasma alanine transaminase (ALT) was 32 (22-53) U/l, alkaline phosphatase (ALP) 82 (63-122) U/l, bilirubin 14 (9-22) µmol/l, albumin 39 (35-43) g/l, lactate dehydrogenase 212 (175-275) U/l, and the prothrombin time/International Normalized Ratio (PT/INR) 1.1 (1.0-1.3). In multivariate analyses significant associations between LF tests and hemodynamics were seen for CVP: ALP (ß = 0.031, p = .0002), bilirubin (ß = 0.027, p = .004), and INR (ß = 0.013, p = .002). PCWP (ß = 0.020, p = .002) and CI (ß = -0.17, p = .005) were also associated with bilirubin. Over time, changes in bilirubin correlated positively with changes in CVP (ß = 1.496, p = .005). Conclusion. In optimally treated AHF patients, CVP was associated with both markers of biliary excretion and liver synthesis function, whereas changes in CVP were associated with changes in markers of biliary excretion. Decongestion may improve measures of LF in AHF.

Relation between invasive hemodynamics and measured glomerular filtration rate by 51Cr-EDTA clearance in advanced heart failure.

The interaction between hemodynamics and kidney function in heart failure (HF) is incompletely understood. We investigated the association between invasive hemodynamic parameters and measured glomerular filtration rate (mGFR) by plasma clearance of 51-chromium-labeled ethylenediamine tetra-acetic acid (51Cr-EDTA) in patients with advanced HF and tested the hypothesis that patients with reduced mGFR have lower cardiac index (CI) and mean arterial pressure (MAP) as well as higher central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP). We retrospectively studied 242 patients (mean age 50 ± 13 years) referred for evaluation for heart transplantation or implantation of a left ventricular assist device with a left ventricular ejection fraction < 45% on optimal medical therapy, who underwent right heart catheterization (RHC) and measurement of 51Cr-EDTA clearance. Mean mGFR was 63 ± 21 mL/min/1.73 m2, CI was 2.3 ± 0.7 L/min/m2, PCWP was 21 ± 9 mmHg, and CVP was 10.3 ± 5.2 mmHg. Univariate analysis demonstrated a significant correlation between mGFR and CI (r2 = 0.030, p = .007) and CVP (r2 = 0.017, p = .049) but not between mGFR and MAP or PCWP. In multivariate analyses, none of the hemodynamic variables remained significantly associated with mGFR. While CVP and CI were correlated with mGFR in univariate analysis the results of analyses adjusted for multiple covariates suggest that hemodynamics are only correlated to renal function in advanced HF to a modest degree challenging the hypothesis that renal dysfunction in HF mainly is a consequence of renal congestion.

Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus.

BACKGROUND: Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response to ARBs in patients with diabetes mellitus and micro- or macroalbuminuria. METHODS: Liquid chromatography-tandem mass spectrometry metabolomics was performed on serum samples. Data from patients with type 2 diabetes and microalbuminuria (n = 49) treated with irbesartan 300 mg/day were used for discovery. LASSO and ridge regression were performed to develop the classifier. Improvement in albuminuria response prediction was assessed by calculating differences in R(2) between a reference model of clinical parameters and a model with clinical parameters and the classifier. The classifier was externally validated in patients with type 1 diabetes and macroalbuminuria (n = 50) treated with losartan 100 mg/day. Molecular process analysis was performed to link metabolites to molecular mechanisms contributing to ARB response. RESULTS: In discovery, median change in urinary albumin excretion (UAE) was -42 % [Q1-Q3: -69 to -8]. The classifier, consisting of 21 metabolites, was significantly associated with UAE response to irbesartan (p < 0.001) and improved prediction of UAE response on top of the clinical reference model (R(2) increase from 0.10 to 0.70; p < 0.001). In external validation, median change in UAE was -43 % [Q1-Q35: -63 to -23]. The classifier improved prediction of UAE response to losartan (R(2) increase from 0.20 to 0.59; p < 0.001). Specifically ADMA impacting eNOS activity appears to be a relevant factor in ARB response. CONCLUSIONS: A serum metabolite classifier was discovered and externally validated to significantly improve prediction of albuminuria response to ARBs in diabetes mellitus.

Outcomes and hospital admissions during long-term support with a HeartMate II.

OBJECTIVES: Continuous-flow left ventricular assist devices like the HeartMate II (HMII) improves survival in severe heart failure but little is known about the incidence and causes of hospitalizations during long-term support which was evaluated in this study. DESIGN: Observational follow-up study comprising all patients who received a HMII at our institution either as bridge-to-transplantation (BTT) or destination therapy (DT). All patients were followed from HMII implantation to transplantation, device explantation, death, or May 2015. RESULTS: The HMII was implanted in 66(44 BTT, 22 DT) patients with a median (range) duration of support since implantation of 329(2-2707) days with 260(2-1080) days in the BTT group and 608(6-2707) days in the DT group. Thirty-day mortality was 12% and one-year survival 76%, comparable for DT and BTT. Among 56 (19 DT and 37 BTT) patients discharged alive with a HMII there were 161 hospital readmissions during a follow-up of 336(37-2682) days corresponding to a hospitalization rate of 1.3(0-19) per patient year and with a length of stay of 5(2-72) days per admission. Most frequent cause of readmission was infections (29%). A history of atrial fibrillation was the only independent factor associated with increased readmission rates. CONCLUSIONS: Our single-center study demonstrated encouraging survival following HMII implantation. Hospital readmissions were frequent, mostly of short duration, mainly due to infections and increased in patients with atrial fibrillation.

The impact of age and body composition on the agreement between estimated and measured GFR in heart transplant recipients.

Background Estimated GFR (eGFR) has shown poor agreement with measured GFR (mGFR) in several populations. We investigated the impact of age and body composition on the accuracy and precision of eGFR in heart transplant (HTx) recipients. Methods In a longitudinal, observational, retrospective study-design, patients receiving first-time HTx with at least one registered mGFR value within 15 months after HTx and a corresponding plasma creatinine were included. GFR was measured by 51Cr-EDTA and eGFR calculated by creatinine-based CKD-EPI formula. Results 150 patients with a total of 723 mGFR measurements were included. During the first year after HTx, mean weight increased by 4.2 kg (CI:3.2-5.1) followed by an annual decrease of 0.35 kg/year (Cl:-0.05-0.74). mGFR increased by 7.5 ml/min (Cl:3.2-11.8) the first year but was stable hereafter (0.0 ml/min/year CI:-1.0-1.0). The initial weigh gain and increase in mGFR were most pronounced in patients <45 years. Neither eGFR adjusted nor unadjusted for BSA detected the initial increase in mGFR. At one year after HTx, limits of agreement on the Bland-Altman plot were -37.2-33.1 ml/min with a bias of -2.1 ml/min (Cl:-5.0-0.9). In patients <45 years, eGFR significantly overestimated mGFR by 7.1 ml/min (Cl:1.0-13.2) and showed a significant lower precision than patients >45 years. There was no effect of BMI class, weight, BSA or change in BMI class on the difference between eGFR and mGFR. Conclusion eGFR is, on average, accurate but imprecise in HTx patients. The agreement is affected by age, but not body composition.

Pleural Effusion and Invasive Hemodynamic Measurements in Advanced Heart Failure.

BACKGROUND: Pleural effusion is present in 50% to 80% of patients with acute heart failure, depending on image modality. We aim to describe the association between the presence and size of pleural effusion and central hemodynamics, including pulmonary capillary wedge pressure (PCWP) in an advanced heart failure population. METHODS: An observational, cross-sectional study in a cohort of patients with advanced heart failure (left ventricular ejection fraction ≤45%) who underwent right heart catheterization at The Department of Cardiology at Copenhagen University Hospital, Rigshospitalet, Denmark, between January 1, 2002 and October 31, 2020. The presence and size of pleural effusion were determined by a semiquantitative score of chest x-rays or computed tomography scans performed within 2 days of right heart catheterization. RESULTS: In 346 patients (50±13 years; 78% males) with median left ventricular ejection fraction of 20% (15-25), we identified 162 (47%) with pleural effusion. The pleural effusion size was medium in 38 (24%) and large in 30 (19%). Patients with pleural effusion had a 4.3 mm Hg (2.5-6.1) higher PCWP and 2.4 mm Hg (1.2-3.6) higher central venous pressure (P<0.001 for both). Patients with a medium/large pleural effusion had statistically significantly higher filling pressures than patients with a small effusion. Higher PCWP (odds ratio [OR], 1.06 [1.03-1.10]) and central venous pressure (OR, 1.09 [1.05-1.15]) were associated with pleural effusion in multivariable logistic regression adjusted for age, sex, and heart failure medications (P<0.001 for both). In a subgroup of 204 (63%) patients with serum albumin data, PCWP (OR, 1.06 [1.01-1.11]; P=0.032), central venous pressure (OR, 1.14 [1.06-1.23]; P<0.001) and serum albumin level (OR, 0.89 [0.83-0.95]; P<0.001) were independently associated with the presence of a medium/large-sized pleural effusion. CONCLUSIONS: In patients with left ventricular ejection fraction ≤45% undergoing right heart catheterization as part of advanced heart failure work-up, pleural effusion was associated with higher PCWP and central venous pressure and lower serum albumin.

Influence of socioeconomic status on rates of advanced heart failure therapies.

BACKGROUND: Socioeconomic deprivation is associated with a lower likelihood of referral for advanced heart failure (HF) evaluation, but it is not known whether it influences rates of advanced HF therapies independently of key hemodynamic measures and comorbidity following advanced HF evaluation in a universal healthcare system. METHODS: We linked data from a single-center Danish clinical registry of consecutive patients evaluated for advanced HF with patient-level information on socioeconomic status. Patients were divided into groups based on the level of education (low, medium, and high), combined degree of socioeconomic deprivation (low, medium, and high), and household income quartiles. Rates of the combined outcome of left ventricular assist device implantation or heart transplantation (advanced HF therapy) with death as a competing risk were estimated with cumulative incidence functions, and Cox proportional hazards models adjusted for age, sex, central venous pressure, cardiac index, and comorbidities. RESULTS: We included 629 patients, median age 53 years, of whom 77% were men. During a median follow-up of 5 years, 179 (28%) underwent advanced HF therapy. The highest level of education was associated with higher rates (high vs low, adjusted HR 1.81 95% CI 1.14-2.89, p = 0.01), whereas household income quartile groups (Q4 vs Q1, adjusted HR 1.37 95% CI 0.76-2.47, p = 0.30) or groups of combined socioeconomic deprivation (high vs low degree of deprivation, adjusted HR 0.86 95% CI 0.50-1.46, p = 0.56) were not significantly associated with rates of advanced HF therapy. CONCLUSIONS: Patients with a lower level of education might be disfavored for advanced HF therapies and could require specific attention in the advanced HF care center.

Long-Term Risk of VTE in Sarcoidosis: A Nationwide Cohort Study.

BACKGROUND: Chronic inflammation is increasingly recognized as a risk factor for VTE, but unlike other inflammatory diseases including systemic lupus erythematosus and rheumatoid arthritis, data on the risk of VTE in patients with sarcoidosis are sparse. RESEARCH QUESTION: Do patients with sarcoidosis have a higher long-term risk of VTE (pulmonary embolism or DVT, and each of these individually) compared with the background population? STUDY DESIGN AND METHODS: Using Danish nationwide registries, patients aged ≥ 18 years with newly diagnosed sarcoidosis (two or more inpatient/outpatient visits, 1996-2020) without prior VTE were matched 1:4 by age, sex, and comorbidities with individuals from the background population. The primary outcome was VTE. RESULTS: We included 14,742 patients with sarcoidosis and 58,968 matched individuals (median age, 44.7 years; 57.2% male). The median follow-up was 8.8 years. Absolute 10-year risks of outcomes for patients with sarcoidosis vs the background population were the following: VTE, 2.9% vs 1.6% (P < .0001), pulmonary embolism, 1.5% vs 0.7% (P < .0001), and DVT, 1.6% vs 1.0% (P < .0001), respectively. In multivariable Cox regression, sarcoidosis was associated with an increased rate of all outcomes in the first year after diagnosis (VTE: hazard ratio [HR], 4.94; 95% CI, 3.61-6.75) and after the first year (VTE: HR, 1.65; 95% CI, 1.45-1.87) compared with the background population. These associations persisted when excluding patients with a history of cancer and censoring patients with incident cancer during follow-up. Three-month mortality was not significantly different between patients with VTE with and without sarcoidosis (adjusted HR, 0.84; 95% CI, 0.61-1.15). INTERPRETATION: In this nationwide cohort study, sarcoidosis was associated with a higher long-term risk of VTE compared with a matched background population.

Thoracentesis to alleviate pleural effusion in acute heart failure: study protocol for the multicentre, open-label, randomised controlled TAP-IT trial.

INTRODUCTION: Pleural effusion is present in half of the patients hospitalised with acute heart failure. The condition is treated with diuretics and/or therapeutic thoracentesis for larger effusions. No evidence from randomised trials or guidelines supports thoracentesis to alleviate pleural effusion due to acute heart failure. The Thoracentesis to Alleviate cardiac Pleural effusion Interventional Trial (TAP-IT) will investigate if a strategy of referring patients with acute heart failure and pleural effusion to up-front thoracentesis by pleural pigtail catheter insertion in addition to pharmacological therapy compared with pharmacological therapy alone can increase the number of days the participants are alive and not hospitalised during the 90 days following randomisation. METHODS AND ANALYSIS: TAP-IT is a pragmatic, multicentre, open-label, randomised controlled trial aiming to include 126 adult patients with left ventricular ejection fraction ≤45% and a non-negligible pleural effusion due to heart failure. Participants will be randomised 1:1, stratified according to site and anticoagulant treatment, and assigned to referral to up-front ultrasound-guided pleural pigtail catheter thoracentesis in addition to standard pharmacological therapy or to standard pharmacological therapy only. Thoracentesis is performed according to local guidelines and can be performed in participants in the pharmacological treatment arm if their condition deteriorates or if no significant improvement is observed within 5 days. The primary endpoint is how many days participants are alive and not hospitalised within 90 days from randomisation and will be analysed in the intention-to-treat population. Key secondary outcomes include 90-day mortality, complications, readmissions, and quality of life. ETHICS AND DISSEMINATION: The study has been approved by the Capital Region of Denmark Scientific Ethical Committee (H-20060817) and Knowledge Center for Data Reviews (P-2021-149). All participants will sign an informed consent form. Enrolment began in August 2021. Regardless of the nature, results will be published in a peer-reviewed medical journal. TRIAL REGISTRATION NUMBER: NCT05017753.