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OBJECTIVE: Osteoporosis is frequently observed in patients after heart transplantation (HT), although the prevalence long-term post-HT is unknown. Most studies investigating bone mineral density (BD) after HT were performed using dual-energy X-ray absorptiometry. In this study BD, including the prevalence of osteopenia and osteoporosis, was investigated using coronary computed tomography (CCT) long-term post-HT. Moreover, risk factors for abnormal BD were investigated. METHODS: All first CCT scans between February 2018 and June 2020 used for the annual screening for cardiac allograft vasculopathy were included. Retransplantations and scans with not fully imaged vertebrae were excluded. BD was measured as a mean of the BD of three consecutive thoracic vertebrae and categorized into normal BD, osteopenia or osteoporosis. Binary logistic regression was used to find determinants for an abnormal BD. Linear regression was used to explore determinants for the mean Hounsfield unit (HU) value of the BD. RESULTS: In total, 140 patients were included (median age 55.2 [42.9-64.9] years, 51 (36%) female). Time between HT and CT scan was 11.0 [7.3-16.1] years. In total, 80 (57%), 43 (31%), and 17 (12%) patients had a normal BD, osteopenia, or osteoporosis, respectively. Osteoporotic fracture or vertebrae fractures was seen in 11 (8%) patients. Determinants for an abnormal BD were recipient age (OR 1.10 (1.06-1.14), p<0.001) and prednisolone use (OR 3.75 (1.27-11.01), p=0.016). In linear regression, left ventricular assist device use pre-HT (p=0.024) and time since HT (p=0.046) were additional BD determinants. DISCUSSION: Osteopenia and osteoporosis are frequently seen on CCT post-HT. More investigation on appropriate measures to maintain a normal BD in these patients are needed.
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Doenças Ósseas Metabólicas , Transplante de Coração , Osteoporose , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Prevalência , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/epidemiologia , Densidade Óssea , Absorciometria de Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Transplante de Coração/efeitos adversos , Vértebras Lombares , Estudos RetrospectivosRESUMO
AIM: Cardiac diseases remain a leading cause of cardiovascular disease (CVD) related hospitalisation and mortality. That is why research to improve our understanding of pathophysiological processes underlying cardiac diseases is of great importance. There is a strong need for healthy and diseased human cardiac tissue and related clinical data to accomplish this, since currently used animal and in vitro disease models do not fully grasp the pathophysiological processes observed in humans. This design paper describes the initiative of the Netherlands Heart Tissue Bank (NHTB) that aims to boost CVD-related research by providing an open-access biobank. METHODS: The NHTB, founded in June 2020, is a non-profit biobank that collects and stores biomaterial (including but not limited to myocardial tissue and blood samples) and clinical data of individuals with and without previously known cardiac diseases. All individuals aged ≥â¯18 years living in the Netherlands are eligible for inclusion as a potential future donor. The stored samples and clinical data will be available upon request for cardiovascular researchers. CONCLUSION: To improve the availability of cardiac tissue for cardiovascular research, the NHTB will include extensive (cardiac) biosamples, medical images, and clinical data of donors with and without a previously known cardiac disease. As such, the NHTB will function as a translational bridge to boost a wide range of cardiac disease-related fundamental and translational studies.
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Background: In heart transplant recipients, donor-derived cell-free DNA (ddcfDNA) is a potential biomarker for acute rejection (AR), in that increased values may indicate rejection. For the assessment of ddcfDNA as new biomarker for rejection, blood plasma sampling around the endomyocardial biopsy (EMB) seems a practical approach. To evaluate the effect of the EMB procedure on ddcfDNA values, ddcfDNA values before the EMB were pairwise compared to ddcfDNA values after the EMB. We aimed at evaluating whether it matters whether the ddcfDNA sampling is done before or after the EMB-procedure. Methods: Plasma samples from heart transplant recipients were obtained pre-EMB and post-EMB. A droplet digital PCR method was used for measuring ddcfDNA, making use of single-nucleotide polymorphisms that allowed both relative quantification, as well as absolute quantification of ddcfDNA. Results: Pairwise comparison of ddcfDNA values pre-EMB with post-EMB samples (n = 113) showed significantly increased ddcfDNA concentrations and ddcfDNA% in post-EMB samples: an average 1.28-fold increase in ddcfDNA concentrations and a 1.31-fold increase in ddcfDNA% was observed (p = 0.007 and p = 0.03, respectively). Conclusion: The EMB procedure causes iatrogenic injury to the allograft that results in an increase in ddcfDNA% and ddcfDNA concentrations. For the assessment of ddcfDNA as marker for AR, collection of plasma samples before the EMB procedure is therefore essential.
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Ácidos Nucleicos Livres , Transplante de Coração , Aloenxertos , Biomarcadores , Biópsia , Rejeição de Enxerto/diagnóstico , Humanos , Biópsia LíquidaRESUMO
BACKGROUND: Immunocompromised patients are at high risk of complicated severe acute respiratory coronavirus 2 infection. The aim of this retrospective study was to describe the characteristics and outcomes of heart transplantation (HTx) recipients with coronavirus disease 2019 (COVID-19) in the Netherlands. METHODS: HTx patients from one of the three HTx centres in the Netherlands with COVID-19 (proven by positive reverse-transcription polymerase chain reaction or serology test result) between February 2020 and June 2021 were included. The primary endpoint was all-cause mortality and the secondary endpoint was disease severity. RESULTS: COVID-19 was diagnosed in 54/665 HTx patients (8%), with a mean (±â¯standard deviation (SD)) time after HTx of 11⯱ 8 years. Mean (±â¯SD) age was 53⯱ 14 years and 39% were female. Immunosuppressive therapy dosage was reduced in 37% patients (20/54). Hospitalisation was required in 39% patients (21/54), and 13% patients (7/54) had severe COVID-19 (leading to intensive care unit (ICU) admission or death). In-hospital mortality was 14% (3/21), and all-cause mortality was 6%. Compared with patients with moderate COVID-19 (hospitalised without ICU indication), severe COVID-19 patients tended to be transplanted earlier and had a significantly higher mean (±â¯SD) body mass index (26⯱ 3 vs 30⯱ 3â¯kg/m2, pâ¯= 0.01). Myocardial infarction, cellular rejection and pulmonary embolism were observed once in three different HTx patients. CONCLUSION: HTx patients were at increased risk of complicated COVID-19 with frequent hospitalisation, but the all-cause mortality was substantially lower than previously described (7-33%).
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There is a need for timely, accurate diagnosis, and personalised management in lung diseases. Exhaled breath reflects inflammatory and metabolic processes in the human body, especially in the lungs. The analysis of exhaled breath using electronic nose (eNose) technology has gained increasing attention in the past years. This technique has great potential to be used in clinical practice as a real-time non-invasive diagnostic tool, and for monitoring disease course and therapeutic effects. To date, multiple eNoses have been developed and evaluated in clinical studies across a wide spectrum of lung diseases, mainly for diagnostic purposes. Heterogeneity in study design, analysis techniques, and differences between eNose devices currently hamper generalization and comparison of study results. Moreover, many pilot studies have been performed, while validation and implementation studies are scarce. These studies are needed before implementation in clinical practice can be realised. This review summarises the technical aspects of available eNose devices and the available evidence for clinical application of eNose technology in different lung diseases. Furthermore, recommendations for future research to pave the way for clinical implementation of eNose technology are provided.
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Nariz Eletrônico/tendências , Expiração/fisiologia , Pneumopatias/diagnóstico , Aprendizado de Máquina/tendências , Olfato/fisiologia , Humanos , Pneumopatias/metabolismo , Pneumopatias/fisiopatologia , Medicina de Precisão/métodos , Medicina de Precisão/tendênciasRESUMO
BACKGROUND: With more patients qualifying for heart transplantation (HT) and fewer hearts being transplanted, it is vital to look for other options. To date, only organs from brain-dead donors have been used for HT in the Netherlands. We investigated waiting list mortality in all Dutch HT centres and the potential of donation after circulatory death (DCD) HT in the Netherlands. METHODS: Two different cohorts were evaluated. One cohort was defined as patients who were newly listed or were already on the waiting list for HT between January 2013 and December 2017. Follow-up continued until September 2018 and waiting list mortality was calculated. A second cohort of all DCD donors in the Netherlands (lung, liver, kidney and pancreas) between January 2013 and December 2017 was used to calculate the potential of DCD HT. RESULTS: Out of 395 patients on the waiting list for HT, 196 (50%) received transplants after a median waiting time of 2.6 years. In total, 15% died while on the waiting list before a suitable donor heart became available. We identified 1006 DCD donors. After applying exclusion criteria and an age limit of 50 years, 122 potential heart donors remained. This number increased to 220 when the age limit was extended to 57 years. CONCLUSION: Waiting list mortality in the Netherlands is high. HT using organs from DCD donors has great potential in the Netherlands and could lead to a reduction in waiting list mortality. Cardiac screening will eventually determine the true potential.
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BACKGROUND: The relative new subspecialty 'cardio-oncology' was established to meet the growing demand for an interdisciplinary approach to the management of cancer therapy-related cardiovascular adverse events. In recent years, specialised cardio-oncology services have been implemented worldwide, which all strive to improve the cardiovascular health of cancer patients. However, limited data are currently available on the outcomes and experiences of these specialised services, and optimal strategies for cardio-oncological care have not been established. AIM: The ONCOR registry has been created for prospective data collection and evaluation of cardio-oncological care in daily practice. METHODS: Dutch hospitals using a standardised cardio-oncology care pathway are included in this national, multicentre, observational cohort study. All patients visiting these cardio-oncology services are eligible for study inclusion. Data collection at baseline consists of the (planned) cancer treatment and the cardiovascular risk profile, which are used to estimate the cardiotoxic risk. Information regarding invasive and noninvasive tests is collected during the time patients receive cardio-oncological care. Outcome data consist of the incidence of cardiovascular complications and major adverse cardiac events, and the impact of these events on the oncological treatment. DISCUSSION: Outcomes of the ONCOR registry may aid in gaining more insight into the incidence of cancer therapy-related cardiovascular complications. The registry facilitates research on mechanisms of cardiovascular complications and on diagnostic, prognostic and therapeutic strategies. In addition, it provides a platform for future (interventional) studies. Centres with cardio-oncology services that are interested in contributing to the ONCOR registry are hereby invited to participate.
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The Impella percutaneous mechanical circulatory support device is designed to augment cardiac output and reduce left ventricular wall stress and aims to improve survival in cases of cardiogenic shock. In this meta-analysis we investigated the haemodynamic effects of the Impella device in a clinical setting. We systematically searched all articles in PubMed/Medline and Embase up to July 2019. The primary outcomes were cardiac power (CP) and cardiac power index (CPI). Survival rates and other haemodynamic data were included as secondary outcomes. For the critical appraisal, we used a modified version of the U.S. Department of Health and Human Services quality assessment form. The systematic review included 12 studies with a total of 596 patients. In 258 patients the CP and/or CPI could be extracted. Our meta-analysis showed an increase of 0.39â¯W [95% confidence interval (CI): 0.24, 0.54], (pâ¯= 0.01) and 0.22â¯W/m2 (95% CI: 0.18, 0.26), (pâ¯< 0.01) for the CP and CPI, respectively. The overall survival rate was 56% (95% CI: 0.50, 0.62), (pâ¯= 0.09). The quality of the studies was moderate, mostly due to the presence of confounders. Our study suggests that in patients with cardiogenic shock, Impella support seems effective in augmenting CP(I). This study merely investigates the haemodynamic effectiveness of the Impella device and does not reflect the complete clinical impact for the patient.
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BACKGROUND: Assessing haemodynamic congestion based on filling pressures instead of clinical congestion can be a way to further improve quality of life (QoL) and clinical outcome by intervening before symptoms or weight gain occur in heart failure (HF) patients. The clinical efficacy of remote monitoring of pulmonary artery (PA) pressures (CardioMEMS; Abbott Inc., Atlanta, GA, USA) has been demonstrated in the USA. Currently, the PA sensor is not reimbursed in the European Union as its benefit when applied in addition to standard HF care is unknown in Western European countries, including the Netherlands. AIMS: To demonstrate the efficacy and cost-effectiveness of haemodynamic PA monitoring in addition to contemporary standard HF care in a high-quality Western European health care system. METHODS: The current study is a prospective, multi-centre, randomised clinical trial in 340 patients with chronic HF (New York Heart Association functional class III) randomised to HF care including remote monitoring with the CardioMEMS PA sensor or standard HF care alone. Eligible patients have at least one hospitalisation for HF in 12 months before enrolment and will be randomised in a 1:1 ratio. Minimum follow-up will be 1 year. The primary endpoint is the change in QoL as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Secondary endpoints are the number of HF hospital admissions and changes in health status assessed by EQ-5D-5L questionnaire including health care utilisation and formal cost-effectiveness analysis. CONCLUSION: The MONITOR HF trial will evaluate the efficacy and cost-effectiveness of haemodynamic monitoring by CardioMEMS in addition to standard HF care in patients with chronic HF. Clinical Trial Registration number NTR7672.
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BACKGROUND: The purpose of this study is to investigate the prevalence of a history of malignancy in patients with chest pain who were referred for computed tomography angiography as well as the long-term survival and cardiovascular outcomes, including coronary artery disease (CAD) and coronary artery calcium (CAC) percentiles of cancer survivors. These data are relevant since it is unknown how cancer survivors, who underwent cardio-toxic therapies, should be monitored. METHODS: We analysed all patients with chest pain, who came to the outpatient clinic and underwent computed tomography angiography. The primary study endpoint was long-term survival. The secondary endpoints included CAD on computed tomography angiogram (CTA), CAC percentiles, suspected and confirmed malignancy on CTA, and other accidental findings on CTA. RESULTS: Of all 1,892 patients included in the analyses, 133 (7%) had a history of malignancy and 1,759 (93%) did not. Mortality rates were higher for the cancer survivors (6.5% vs 20.9% after ten years, pâ¯< 0.001). The multivariable Cox regression model also showed higher mortality for cancer survivors after ten years (adjusted hazard ratio 2.48 [95% confidence interval: 1.58-3.90]). CAD did not differ between both groups. CAC percentiles were higher in cancer survivors (pâ¯= 0.037). Cancer survivors had more suspected malignancies (3.8% vs 0.5%; pâ¯= 0.001) and also more confirmed malignancies on CTA (3.0% vs 0.1%; pâ¯< 0.001). CONCLUSIONS: Cancer survivors have higher mortality rates, no difference in CAD on CTA, higher CAC percentiles and more often malignancy on CTA compared with patients without a cancer history.
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We report the first patient experiences with the CardioMEMS device in the Erasmus MC Thorax Center in the Netherlands. In line with clinical trial evidence, the device is applicable in patients with chronic heart failure in functional New York Heart Association class III with at least 1 admission for heart failure in the past 12 months. CardioMEMS has been shown to be safe and reliable, and effective in reducing the number of hospitalisations for heart failure by guided therapy based on pulmonary artery pressures.
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INTRODUCTION: Blood biomarkers have the potential to monitor the severity of chronic heart failure (CHF). Studies correlating repeated measurements of blood biomarkers with repeatedly assessed New York Heart Association (NYHA) class over a prolonged follow-up period, and concomitantly investigating their associations with clinical endpoints, have not yet been performed. METHODS: Between 2011-2013, 263 CHF patients were included. At inclusion and subsequently every 3 months, we measured Nterminal pro-B-type natriuretic (NT-proBNP), high-sensitivity troponin T (Hs-TnT) and Creactive protein (CRP), and assessed NYHA class. The primary endpoint comprised heart failure hospitalisation, cardiovascular mortality, cardiac transplantation or left ventricular assist device implantation. Time-dependent Cox models were used. RESULTS: Mean age was 67 ± 13 years, 72% were men and 27% were in NYHA class III-IV. We obtained 886 repeated measures (median 3 [IQR 2-5] per patient). The primary endpoint was reached in 41 patients during a median follow-up of 1.0 [0.6-1.4] year. Repeatedly measured NT-proBNP and Hs-TnT were significantly associated with repeatedly assessed NYHA class, whereas CRP was not (NT-proBNP: ß [95% CI]: 1.56 [1.17-2.06]ln(ng/l) increase per point increase in NYHA class, p = 0.002; HsTNT: ß [95% CI]: 1.58 [1.21-2.07]). Serially measured NT-proBNP (HR [95% CI]:2.86 [1.73-4.73]), CRP (1.69 [1.21-2.34]) and NYHA class (2.33 [1.51-3.62]) were positively and independently associated with the primary endpoint, whereas Hs-TnT lost statistical significance after multivariable adjustment. A model containing serially measured NYHA class and NT-proBNP displayed a C-index of 0.84, while serially measured NYHA class and CRP showed a C-index of 0.82. CONCLUSION: Temporal NT-proBNP, CRP and NYHA class patterns are independently associated with adverse clinical outcome. Serially measured NT-proBNP and NYHA class are best suited for monitoring CHF outpatients.
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BACKGROUND: Cardiac allograft vasculopathy (CAV) is a multifactorial disease and a major cause of graft failure after heart transplantation. However, the impact of CAV may vary according to the definition and the regional differences in transplantation settings. OBJECTIVES: We sought to assess CAV prevalence, predictors and prognosis in Dutch heart transplant recipients based on coronary angiography, following the 2010 standard nomenclature of the International Society for Heart and Lung Transplantation. METHODS: Patients ≥18 years who underwent heart transplantation at our centre with at least one coronary angiography during follow-up were included in the analysis. Clinical variables were collected prospectively. RESULTS: Among 495 analysed recipients, there were 238 (48 %) with CAV. The prevalence of CAV was 18, 47 and 70 % at 4, 12 and 20 years, respectively. In the multivariable proportional hazards regression analysis, only male donor gender and increasing donor age were significantly associated with the risk of CAV. The long-term prognosis of the patients with CAV at fourth-year angiography was significantly worse as compared with that of CAV-free patients, independently of the severity of CAV (p < 0.001). CONCLUSION: The prevalence of CAV increased gradually over time, with a similar trend as in other registries. Post-transplant survival is decreased in patients with any degree of early CAV, indicating that management strategies should start with donor selection and preventive measures immediately after transplantation.
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All transplant recipients receive tacrolimus, mycophenolate and glucocorticoids and these drugs have many side-effects and drug-drug interactions. Common complications include surgical complications, infections, rejection and acute kidney injury. Infections as CMV and PJP can be prevented with prophylactic treatment. Given the complexity of organ transplant recipients a multi-disciplinary team of intensivists, surgeons, pharmacists and transplant specialists is essential. After heart transplantation a temporary pacemaker is required until the conduction system recovers. Stiffening of the heart and increased cardiac markers indicate rejection. An endomyocardial biopsy is performed via the right jugular vein, necessitating its preservation. For lung transplant patients, early intervention for aspiration is warranted to prevent chronic rejection. Risk of any infection is high, requiring active surveillance and intensive treatment, mainly of fungal infections. The liver is immunotolerant requiring lower immunosuppression. Transplantation surgery is often accompanied by massive blood loss and coagulopathy. Other complications include portal vein or hepatic artery thrombosis and biliary leakage or stenosis. Kidney transplant recipients have a high risk of cardiovascular disease and posttransplant anemia should be treated liberally. After postmortal transplantation, delayed graft function is common and dialysis is continued. Ureteral anastomosis complications can be diagnosed with ultrasound.
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Transplante de Órgãos , Transplantados , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores , Unidades de Terapia Intensiva , Transplante de Órgãos/efeitos adversos , Diálise RenalRESUMO
Secretion of ectopic adrenocorticotropic hormone (ACTH) with consequently Cushing's syndrome is a rare paraneoplastic phenomenon. It has been described in a variety of malignancies, like bronchial carcinoids, small-cell lung carcinoma, thymoma, pancreatic carcinoma and other. In many cases of suspected ectopic ACTH secretion, it is difficult to histologically or cytochemically confirm the diagnosis. We present a 63-year-old woman with a recurrent poorly differentiated squamous cell lung carcinoma with clinical and biochemical features consistent with ectopic Cushing's syndrome. Immunocytochemical staining confirmed the secretion of ACTH by tumour cells.
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Síndrome de ACTH Ectópico/etiologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Síndrome de Cushing/etiologia , Neoplasias Pulmonares/complicações , Hormônio Adrenocorticotrópico/metabolismo , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Ischaemic postconditioning (IPOC) is an intervention in which brief, intermittent periods of reocclusion at the onset of reperfusion (i.e. stuttering reperfusion) protect myocardium from lethal reperfusion injury. The mechanism underlying the cardioprotective effects of IPOC is incompletely understood. However, it is perceived that IPOC begins with specific cell-surface receptors responsible for activating a number of signalling pathways, many of which appear to converge at the mitochondrial level. IPOC has been demonstrated both in animal models and in patients with acute myocardial infarction (AMI) in small proof-of-concept trials. This intervention offers the possibility of further limiting infarct size in patients undergoing primary percutaneous coronary intervention (PCI). Here, we provide a brief overview of the concept of IPOC and the mechanisms underlying this phenomenon. (Neth Heart J 2010;18:389-93.).