Aims Patients with ischaemic cardiomyopathy (ICM) referred for catheter ablation of ventricular tachycardia (VT) are at risk for end-stage heart failure (HF) due to adverse remodelling. Local... Show moreAims Patients with ischaemic cardiomyopathy (ICM) referred for catheter ablation of ventricular tachycardia (VT) are at risk for end-stage heart failure (HF) due to adverse remodelling. Local unipolar voltages (UV) decrease with loss of viable myocardium. A UV parameter reflecting global viable myocardium may predict prognosis. We evaluate if a newly proposed parameter, area-weighted unipolar voltage (awUV), can predict HF-related outcomes [HFO; HF death/left ventricular (LV) assist device/heart transplant] in ICM. Methods and results From endocardial voltage maps of consecutive patients with ICM referred for VT ablation, awUV was calculated by weighted interpolation of local UV. Associations between clinical and mapping parameters and HFO were evaluated and validated in a second cohort. The derivation cohort consisted of 90 patients [age 68 +/- 8 years; LV ejection fraction (LVEF) 35% interquartile range (IQR) (24-40)] and validation cohort of 60 patients [age 67 +/- 9, LVEF 39% IQR (29-45)]. In the derivation cohort, during a median follow-up of 45 months [IQR (34-83)], 36 (43%) patients died and 23 (26%) had HFO. Patients with HFO had lower awUV [4.51 IQR (3.69-5.31) vs. 7.03 IQR (6.08-9.2), P < 0.001]. A reduction in awUV [optimal awUV (5.58) cut-off determined by receiver operating characteristics analysis] was a strong predictor of HFO (3-year HFO survival 97% vs. 57%). The cut-off value was confirmed in the validation cohort (2-year HFO-free survival 96% vs. 60%). Conclusion The newly proposed parameter awUV, easily available from routine voltage mapping, may be useful at identifying ICM patients at high risk for HFO.[GRAPHICS] Show less
AimTo examine the ability of serum proteins in predicting future heart failure (HF) events, including HF with reduced or preserved ejection fraction (HFrEF or HFpEF), in relation to event time, and... Show moreAimTo examine the ability of serum proteins in predicting future heart failure (HF) events, including HF with reduced or preserved ejection fraction (HFrEF or HFpEF), in relation to event time, and with or without considering established HF-associated clinical variables.Methods and resultsIn the prospective population-based Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS), 440 individuals developed HF after their first visit with a median follow-up of 5.45 years. Among them, 167 were diagnosed with HFrEF and 188 with HFpEF. A least absolute shrinkage and selection operator regression model with non-parametric bootstrap were used to select predictors from an analysis of 4782 serum proteins, and several pre-established clinical parameters linked to HF. A subset of 8-10 distinct or overlapping serum proteins predicted different future HF outcomes, and C-statistics were used to assess discrimination, revealing proteins combined with a C-index of 0.80 for all incident HF, 0.78 and 0.80 for incident HFpEF or HFrEF, respectively. In the AGES-RS, protein panels alone encompassed the risk contained in the clinical information and improved the performance characteristics of prediction models based on N-terminal pro-B-type natriuretic peptide and clinical risk factors. Finally, the protein predictors performed particularly well close to the time of an HF event, an outcome that was replicated in the Cardiovascular Health Study.ConclusionA small number of circulating proteins accurately predicted future HF in the AGES-RS cohort of older adults, and they alone encompass the risk information found in a collection of clinical data. Incident HF events were predicted up to 8 years, with predictor performance significantly improving for events occurring less than 1 year ahead, a finding replicated in an external cohort study.The ability of the deep circulating proteome to predict future heart failure (HF) events, including its primary subtypes, in relation to event time and known HF-associated clinical factors was studied in two prospective population-based cohorts. AGES-RS, Age, Gene/Environment Susceptibility Reykjavik Study; CHS, Cardiovascular Health Study; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LASSO, least absolute shrinkage and selection operator; ROC, receiver operating characteristic.dagger image Show less
AimsWe sought to evaluate the mechanism of angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan-only control group in patients with heart... Show moreAimsWe sought to evaluate the mechanism of angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan-only control group in patients with heart failure with reduced ejection fraction (HFrEF).Methods and resultsThe study was a phase IV, prospective, randomized, double-blind, parallel-group study in patients with New York Heart Association class II–III heart failure and left ventricular ejection fraction (LVEF) ≤35%. During a 6-week run-in period, all patients received valsartan therapy, which was up-titrated to the highest tolerated dose level (80 mg bid or 160 mg bid) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic haemodynamics were quantified using echocardiography and 11C-acetate positron emission tomography before and after 6 weeks of therapy (on stable dose) in 55 patients (ARNI group: n = 27, mean age 63 ± 10 years, LVEF 29.2 ± 10.4%; and valsartan-only control group: n = 28, mean age 64 ± 8 years, LVEF 29.0 ± 7.3%; all p = NS). The energetic efficiency of cardiac work remained unchanged in both treatment arms. However, both diastolic (−4.5 mmHg; p = 0.026) and systolic blood pressure (−9.8 mmHg; p = 0.0007), myocardial perfusion (−0.054 ml/g/min; p = 0.045), and left ventricular mechanical work (−296; p = 0.038) decreased significantly in the ARNI group compared to the control group. Although myocardial oxygen consumption decreased in the ARNI group (−5.4%) compared with the run-in period and remained unchanged in the control group (+0.5%), the between-treatment group difference was not significant (p = 0.088).ConclusionsWe found no differences in the energetic efficiency of cardiac work between ARNI and valsartan-only groups in HFrEF patients. However, ARNI appears to have haemodynamic and cardiac mechanical effects over valsartan in heart failure patients. Show less
The Fontan procedure is currently the palliative solution for children born with a univentricular heart. Despite an improved survival rate, many patients still suffer from complications, such as... Show moreThe Fontan procedure is currently the palliative solution for children born with a univentricular heart. Despite an improved survival rate, many patients still suffer from complications, such as heart failure. For this reason, both patients with and without heart failure are often treated with angiotensin-converting enzyme (ACE) inhibitors, although the effectiveness is unclear. In this thesis, we investigated various aspects of the Fontan circulation to assess not only the efficacy and side effects of ACE inhibition, but also the limitations of exercise capacity and the response of the circulation of these patients to acute volume loading tests. We showed that short-term ACE inhibition had no positive effects on exercise capacity, haemodynamics and cardiac function. It also appeared to have no negative effect on the Fontan circulation, apart from side effects during the titration period. Furthermore, we found that even relatively healthy young Fontan patients have reduced exercise capacity associated with diastolic dysfunction and aortic stiffness. Nevertheless, we found that paediatric Fontan patients are able to respond adequately to acute volume changes and they seem to adapt well to the Fontan circulation. Show less
Adult patients with congenital heart disease and a systemic right ventricle are prone to develop late complications such as rhythm and conduction disorders and heart failure. This thesis aims to... Show moreAdult patients with congenital heart disease and a systemic right ventricle are prone to develop late complications such as rhythm and conduction disorders and heart failure. This thesis aims to clarify the pathophysiology of this condition and to explore diagnostic and treatment options. Chapter 2 describes asymmetry and heterogeneity in cardiac autonomic innervation. Chapters 3 and 4 describe ambulatory ECG-derived measures of cardiac autonomic function in patients with a systemic right ventricle, and show that these measures are related to outcomes such as supraventricular arrhythmias. In chapter 5, echocardiographic measures of systemic right ventricular function are compared with cardiac MRI. Chapter 6 describes the clinical course of patients long after atrial switch correction. Chapter 7 describes the first results of treatment of systemic right ventricular failure with sacubitril/valsartan: a.o. a small but significant improvement in systemic right ventricular function was seen. Chapter 8 describes the experience of the application of eHealth smart technology in the titration of sacubitril/valsartan in the same cohort. Chapter 9 reports the first two cases of implantation of a ventricular assist device in patients with systemic right ventricular failure. This thesis may form the base for ongoing research to improve outcome in this vulnerable group. Show less
Heemelaar, J.C.; Heemelaar, S.; Hertel, S.N.; Jukema, J.W.; Sueters, M.; Louwerens, M.; Antoni, M.L. 2023
Background: Childhood cancer survivors (CCS) are at increased risk of cardiomyopathy during pregnancy if they have prior cardiotoxic exposure. Currently, there is no consensus on the necessity,... Show moreBackground: Childhood cancer survivors (CCS) are at increased risk of cardiomyopathy during pregnancy if they have prior cardiotoxic exposure. Currently, there is no consensus on the necessity, timing and modality of cardiac monitoring during and after pregnancy. Therefore, we examined cardiac function using contemporary echocardiographic parameters during pregnancy in CCS with cardiotoxic treatment exposure, and we observed obstetric outcomes in CCS, including in women without previous cardiotoxic treatment exposure. Method: A single-center retrospective cohort study was conducted among 39 women enrolled in our institution's cancer survivorship outpatient clinic. Information on potential cardiotoxic exposure in childhood, cancer diagnosis and outcomes of all pregnancies were collected through interviews and review of health records. Echocardiographic exams before and during pregnancy were retrospectively analyzed for left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) if available. The primary outcomes were (i) left ventricular dysfunction (LVD) during pregnancy, defined as LVEF < 50% or a decline of >= 10% in LVEF below normal (< 54%), and (ii) symptomatic heart failure (HF). Rate of obstetric and fetal complications was compared to the general population through the national perinatal registry (PERINED). Results: All pregnancies (91) of 39 women were included in this study. The most common malignancy was leukemia (N = 17, 43.6%). In 22 patients, echocardiograms were retrospectively analyzed. LVEFbaseline was 55.4 +/- 1.2% and pre-existing subnormal LVEF was common (7/22, 31.8/%). The minimum value of LVEF during pregnancy was 3.8% lower than baseline (p = 0.002). LVD occurred in 9/22 (40.9%) patients and HF was not observed. When GLS was normal at baseline (< -18.0%; N = 12), none of the women developed LVD. Nine of out ten women with abnormal GLS at baseline developed LVD later in pregnancy. In our cohort, the obstetric outcomes seemed comparable with the general population unless patients underwent abdominal irradiation (N = 5), where high rates of preterm birth (only 5/18 born at term) and miscarriage (6/18 pregnancies) were observed. Conclusion: Our study suggests that women with prior cardiotoxic treatment have a low risk of LVD during pregnancy if GLS at baseline was normal. Pregnancy outcomes are similar to the healthy population except when patients underwent abdominal irradiation. Show less
Damman, K.; Caliskan, K.; Birim, O.; Kuijpers, M.; Otterspoor, L.C.; Yazdanbakhsh, A.; ... ; Laake, L.W. van 2023
Background: Left ventricular assist device (LVAD) therapy is an established treatment for advanced heart failure with reduced ejection fraction. We evaluated the characteristics and clinical... Show moreBackground: Left ventricular assist device (LVAD) therapy is an established treatment for advanced heart failure with reduced ejection fraction. We evaluated the characteristics and clinical outcomes of patients implanted with an LVAD in the Netherlands. Methods: Patients implanted with an LVAD in the Netherlands between 2016 and 2020 were included in the analysis. Baseline characteristics entered into this registry, as well as clinical outcomes (death on device, heart transplantation) and major adverse events (device dysfunction, major bleeding, major infection and cerebrovascular event), were evaluated. Results: A total of 430 patients were implanted with an LVAD; mean age was 55 +/- 13 years and 27% were female. The initial device strategy was bridge to transplant (BTT) in 50%, destination therapy (DT) in 29% and bridge to decision (BTD) in the remaining 21%. After a follow-up of 17 months, 97 (23%) patients had died during active LVAD support. Survival was 83% at 1 year, 76% at 2 years and 54% at 5 years. Patients implanted with an LVAD as a BTT had better outcomes compared with DT at all time points (1 year 86% vs 72%, 2 years 83% vs 59% and 5 years 58% vs 33%). Major adverse events were frequently observed, most often major infection, major bleeding and cerebrovascular events (0.84, 0.33 and 0.09 per patient-year at risk, respectively) and were similar across device strategies. Patients supported with HeartMate 3 had a lower incidence of major adverse events. Conclusions: Long-term survival on durable LVAD support in the Netherlands is over 50% after 5 years. Major adverse events, especially infection and bleeding, are still frequently observed, but decreasing with the contemporary use of HeartMate 3 LVAD. Show less
Luo, J.; Noordam, R.; Jukema, J.W.; Dijk, K.W. van; Hagg, S.; Grassmann, F.; ... ; Heemst, D. van 2022
Aim: Mitochondrial DNA dysfunction has been implicated in the pathogenesis of cardiovascular diseases. We aimed to investigate the associations between leukocyte mitochondrial DNA (mtDNA) abundance... Show moreAim: Mitochondrial DNA dysfunction has been implicated in the pathogenesis of cardiovascular diseases. We aimed to investigate the associations between leukocyte mitochondrial DNA (mtDNA) abundance, as a proxy of mitochondrial function, and coronary artery disease (CAD) and heart failure (HF) in a cohort study and approximate the causal nature of these relationships using Mendelian randomization (MR) in genetic studies. Methods and results: Multivariable-adjusted Cox regression analyses were conducted in 273 619 unrelated participants of European ancestry from the UK Biobank (UKB). For genetic studies, we first performed MR analyses with individual-level data from the UKB using a weighted genetic risk score (GRS); two-sample MR analyses were subsequently performed using summary-level data from the publicly available three consortia/biobank for CAD and two for HF. MR analyses were performed per database separately and results were subsequently meta-analysed using fixed-effects models. During a median follow-up of 11.8 years, restricted cubic spline Cox regression analyses showed associations between lower mtDNA abundance and higher risk of CAD and HF. Hazard ratios for participants in the lowest quintile of mtDNA abundance compared with those in the highest quintile were 1.08 (95% confidence interval: 1.03, 1.14) and 1.15 (1.05, 1.24) for CAD and HF. Genetically, no evidence was observed for a possible non-linear causal effect using individual-level weighted genetic risk scores calculated in the UKB on the study outcomes; the pooled odds ratios (95% confidence interval) from two-sample MR of genetically predicted per one-SD decrease in mtDNA abundance were 1.09 (1.03, 1.16) for CAD and 0.99 (0.92, 1.08) for HF, respectively. Conclusion: Our findings support a possible causal role of lower leukocyte mtDNA abundance in higher CAD risk, but not in HF. Show less
Luo, J.; Noordam, R.; Jukema, J.W.; Dijk, K.W. van; Hägg, S.; Grassmann, F.; ... ; Heemst, D. van 2022
AimMitochondrial DNA dysfunction has been implicated in the pathogenesis of cardiovascular diseases. We aimed to investigate the associations between leukocyte mitochondrial DNA (mtDNA) abundance,... Show moreAimMitochondrial DNA dysfunction has been implicated in the pathogenesis of cardiovascular diseases. We aimed to investigate the associations between leukocyte mitochondrial DNA (mtDNA) abundance, as a proxy of mitochondrial function, and coronary artery disease (CAD) and heart failure (HF) in a cohort study and approximate the causal nature of these relationships using Mendelian randomization (MR) in genetic studies.Methods and resultsMultivariable-adjusted Cox regression analyses were conducted in 273 619 unrelated participants of European ancestry from the UK Biobank (UKB). For genetic studies, we first performed MR analyses with individual-level data from the UKB using a weighted genetic risk score (GRS); two-sample MR analyses were subsequently performed using summary-level data from the publicly available three consortia/biobank for CAD and two for HF. MR analyses were performed per database separately and results were subsequently meta-analysed using fixed-effects models. During a median follow-up of 11.8 years, restricted cubic spline Cox regression analyses showed associations between lower mtDNA abundance and higher risk of CAD and HF. Hazard ratios for participants in the lowest quintile of mtDNA abundance compared with those in the highest quintile were 1.08 (95% confidence interval: 1.03, 1.14) and 1.15 (1.05, 1.24) for CAD and HF. Genetically, no evidence was observed for a possible non-linear causal effect using individual-level weighted genetic risk scores calculated in the UKB on the study outcomes; the pooled odds ratios (95% confidence interval) from two-sample MR of genetically predicted per one-SD decrease in mtDNA abundance were 1.09 (1.03, 1.16) for CAD and 0.99 (0.92, 1.08) for HF, respectively.ConclusionOur findings support a possible causal role of lower leukocyte mtDNA abundance in higher CAD risk, but not in HF. Show less
This thesis is the result of several studies into the clinical and echocardiographic outcome of both open and hybrid surgical ventricular reconstruction for the treatment of ischemic cardiomyopathy... Show moreThis thesis is the result of several studies into the clinical and echocardiographic outcome of both open and hybrid surgical ventricular reconstruction for the treatment of ischemic cardiomyopathy. Additionally, predictors for a favorable outcome and important associated issues such as management and late outcome of functional mitral regurgitation and the use of LV ejection fraction as a selection criterium for indication for a implantable cardioverter defibrillator for the primary prevention ofventricular arrhythmias after surgical ventricular reconstruction were studied. In chapter 2 the early and late outcome of different types of open left ventricular reconstruction surgery by means of a meta-analysis are presented. Chapter 3 describesthe use of echocardiographic wall motion score index to predict mortality and functional results after surgical ventricular reconstruction for advanced ischemic heart failure. In chapter 4 the management of functional mitral regurgitation during left ventricular reconstruction is presented followed by a landmark analysis into the 10-year outcome of functional mitral regurgitation after left ventricular reconstruction. Chapter 5 discusses the use of the improved LV ejection fraction after SVR as an indication for a implantable cardioverter defibrillator for the primary prevention of ventricular arrhythmias after surgical ventricular reconstruction in heart failure patients. Chapter 6 discusses the early experience with a minimal-invasive hybrid transcatheter surgical ventricular reconstruction technique. First the technique of hybrid transcatheter left ventricular reconstruction is described. Followed by the preliminary results of this technique from 2 cardiac centres in the Netherland. Finally, the multicenter European results of hybrid less invasive reconstruction on clinical, functional and echocardiographic outcome are presented. Show less
This study examined associations of neighbourhood walkability with cognitive functioning (i.e., global cognition, memory, language, attention-psychomotor speed, and executive functioning) in... Show moreThis study examined associations of neighbourhood walkability with cognitive functioning (i.e., global cognition, memory, language, attention-psychomotor speed, and executive functioning) in participants without or with either heart failure, carotid occlusive disease, or vascular cognitive impairment. Neighbourhood walkability at baseline was positively associated with global cognition and attention-psychomotor speed. These associations were stronger in patients with vascular cognitive impairment. Individuals who live in residential areas with higher walkability levels were less likely to have impairments in language and executive functioning at two-year follow-up. These findings highlight the importance of the built environment for cognitive functioning in healthy and vulnerable groups. Show less
BackgroundClinical factors are used to estimate late complication risk in adults after atrial switch operation (AtrSO) for transposition of the great arteries (TGA), but heterogeneity in clinical... Show moreBackgroundClinical factors are used to estimate late complication risk in adults after atrial switch operation (AtrSO) for transposition of the great arteries (TGA), but heterogeneity in clinical course remains. We studied whether common genetic variants are associated with outcome and add value to a clinical risk score in TGA-AtrSO patients.Methods and resultsThis multicenter study followed 133 TGA-AtrSO patients (aged 28 [IQR 24–35] years) for 13 (IQR 9–16) years and examined the association of genome-wide single-nucleotide polymorphisms (SNPs) with a composite endpoint of symptomatic ventricular arrhythmia, heart failure hospitalization, ventricular assist device implantation, heart transplantation, or mortality. Thirty-two patients (24%) reached the endpoint. The genome-wide association study yielded one genome-wide significant (p < 1 × 10−8) locus and 18 suggestive loci (p < 1 × 10−5). A genetic risk score constructed on the basis of independent SNPs with p < 1 × 10−5 was associated with outcome after correction for the clinical risk score (HR = 1.26/point increase [95%CI 1.17–1.35]). Risk stratification improved with a combined risk score (clinical score + genetic score) compared to the clinical score alone (p = 2 × 10−16, C-statistic 0.95 vs 0.85). In 51 patients with a clinical intermediate (5–20%) 5-year risk of events, the combined score reclassified 32 patients to low (<5%) and 5 to high (>20%) risk. Stratified by the combined score, observed 5-year event-free survival was 100%, 79% and 31% for low, intermediate, and high-risk patients, respectively.ConclusionsCommon genetic variants may explain some variation in the clinical course in TGA-AtrSO and improve risk stratification over clinical factors alone, especially in patients at intermediate clinical risk. These findings support the hypothesis that including genetic variants in risk assessment may be beneficial. Show less
Aims In symptomatic patients with heart failure and reduced ejection fraction (HFrEF), recent international guidelines recommend initiating four major therapeutic classes rather than sequential... Show moreAims In symptomatic patients with heart failure and reduced ejection fraction (HFrEF), recent international guidelines recommend initiating four major therapeutic classes rather than sequential initiation. It remains unclear how this change in guidelines is perceived by practicing cardiologists versus heart failure (HF) specialists.Methods and results An independent academic web-based survey was designed by a group of HF specialists and posted by email and through various social networks to a broad community of cardiologists worldwide 1 year after the publication of the latest European HF guidelines. Overall, 615 cardiologists (38 [32-47] years old, 63% male) completed the survey, of which 58% were working in a university hospital and 26% were HF specialists. The threshold to define HFrEF was <= 40% for 61% of the physicians. Preferred drug prescription for the sequential approach was angiotensin-converting enzyme inhibitors or angiotensin receptor-neprilysin inhibitors first (74%), beta-blockers second (55%), mineralocorticoid receptor antagonists third (52%), and sodium-glucose cotransporter 2 inhibitors (53%) fourth. Eighty-four percent of participants felt that starting all four classes was feasible within the initial hospitalization, and 58% felt that titration is less important than introducing a new class. Age, status in training, and specialization in HF field were the principal characteristics that significantly impacted the answers.Conclusion In a broad international cardiology community, the 'historical approach' to HFrEF therapies remains the preferred sequencing approach. However, accelerated introduction and uptitration are also major treatment goals. Strategy trials in treatment guidance are needed to further change practices.[GRAPHICS]. Show less
Neo(adjuvant) systemic treatment regimens containing anthracyclines such as doxorubicin cause a significant risk of heart failure. These regimens are one of the corner stones of osteosarcoma... Show moreNeo(adjuvant) systemic treatment regimens containing anthracyclines such as doxorubicin cause a significant risk of heart failure. These regimens are one of the corner stones of osteosarcoma treatment, and therefore several guidelines are in place to steer cardiotoxicity monitoring through baseline risk stratification and cardiac surveillance during and after completion of cancer therapy. Importantly, baseline risk stratification modules are dependent on age, prior cardiovascular disease and cardiovascular risk factors. Because the majority of osteosarcoma patients are below 30 years of age these criteria rarely apply and most patients are assigned to low or medium risk categories, whereas cardiovascular complications have profound impact on morbidity and mortality in this young population. Therefore, cardiac surveillance is very important in this group for timely detection of cardiotoxicity. Moreover, when severe cardiotoxicity that requires advanced heart failure treatment occurs, a cancer diagnosis has significant implications on treatment options, i.e. mechanical circulatory support and heart transplantation. These challenges are presented in this case of a patient without clinical risk factors admitted with cardiogenic shock requiring advanced heart failure treatment within 1 month after completion of doxorubicin containing chemotherapy for the treatment of high grade osteosarcoma. Show less
Vasoplegia is a common complication after heart failure surgery, although the incidence differs for each surgical procedure type. It is associated with poor early and late survival rates. In the... Show moreVasoplegia is a common complication after heart failure surgery, although the incidence differs for each surgical procedure type. It is associated with poor early and late survival rates. In the vasoplegic survivors, renal function is compromised compared to non-vasoplegic patients even though the cardiac function is similar. Preoperative factors associated with an increased risk on vasoplegia (e.g. anemia and a higher thyroxine levels) and factors associated with an decreased risk (e.g. higher creatinine clearance, beta-blocker use, prior hypertension) could be used to assess the risk on vasoplegia preoperatively for specific heart failure procedures. Also, intraoperative factors that are associated with an increased risk of vasoplegia (intraoperative vasoresponsiveness, longer cross clamp -, cardiopulmonary bypass - and procedure times) could be used to estimate the risk on vasoplegia. Further research is necessary to verify whether these results can be extrapolated to other hospitals and to validate the proposed risk model. Show less
Introduction Vasoplegia is a common complication after cardiac surgery and is associated with poor prognosis. It is characterised by refractory hypotension despite normal or even increased cardiac... Show moreIntroduction Vasoplegia is a common complication after cardiac surgery and is associated with poor prognosis. It is characterised by refractory hypotension despite normal or even increased cardiac output. The pathophysiology is complex and includes the systemic inflammatory response caused by cardiopulmonary bypass (CPB) and surgical trauma. Patients with end-stage heart failure (HF) are at increased risk for developing vasoplegia. The CytoSorb adsorber is a relatively new haemoadsorption device which can remove circulating inflammatory mediators in a concentration based manner. The CytoSorb-HF trial aims to evaluate the efficacy of CytoSorb haemoadsorption in limiting the systemic inflammatory response and preventing postoperative vasoplegia in HF patients undergoing cardiac surgery with CPB. Methods and analysis This is an investigator-initiated, single-centre, randomised, controlled clinical trial. In total 36 HF patients undergoing elective cardiac surgery with an expected CPB duration of more than 120 min will be randomised to receive CytoSorb haemoadsorption along with standard surgical treatment or standard surgical treatment alone. The primary endpoint is the change in systemic vascular resistance index with phenylephrine challenge after CPB. Secondary endpoints include inflammatory markers, sublingual microcirculation parameters and 30-day clinical indices. In addition, we will assess the cost-effectiveness of using the CytoSorb adsorber. Vascular reactivity in response to phenylephrine challenge will be assessed after induction, after CPB and on postoperative day 1. At the same time points, and before induction and on postoperative day 4 (5 time points in total), blood samples will be collected and the sublingual microcirculation will be recorded. Study participants will be followed up until day 30.Ethics and dissemination The trial protocol was approved by the Medical Ethical Committee of Leiden The Hague Delft (METC LDD, registration number P20.039). The results of the trial will be published in peer-reviewed medical journals and through scientific conferences. Show less
Janse, R.J.; Fu, E.L.; Dahlstrom, U.; Benson, L.; Lindholm, B.; Diepen, M. van; ... ; Savarese, G. 2022
Aim Half of heart failure (HF) patients have chronic kidney disease (CKD) complicating their pharmacological management. We evaluated physicians' and patients' patterns of use of evidence-based... Show moreAim Half of heart failure (HF) patients have chronic kidney disease (CKD) complicating their pharmacological management. We evaluated physicians' and patients' patterns of use of evidence-based medical therapies in HF across CKD stages.Methods and results We studied HF patients with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction enrolled in the Swedish Heart Failure Registry in 2009-2018. We investigated the likelihood of physicians to prescribe guideline-recommended therapies to patients with CKD, and of patients to fill the prescriptions within 90 days of incident HF (initiating therapy), to adhere (proportion of days covered >= 80%) and persist (continued use) on these treatments during the first year of therapy. We identified 31 668 patients with HFrEF (median age 74 years, 46% CKD). The proportions receiving a prescription for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (ACEi/ARB/ARNi) were 96%, 92%, 86%, and 68%, for estimated glomerular filtration rate (eGFR) >= 60, 45-59, 30-44, and <30 ml/min/1.73m(2), respectively; for beta-blockers 94%, 93%, 92%, and 92%, for mineralocorticoid receptor antagonists (MRAs) 45%, 44%, 37%, 24%; and for triple therapy (combination of ACEi/ARB/ARNi+ beta-blockers+ MRA) 38%, 35%, 28%, and 15%. Patients with CKD were less likely to initiate these medications, and less likely to adhere to and persist on ACEi/ARB/ARNi, MRA, and triple therapy. Among stoppers, CKD patients were less likely to restart these medications. Results were consistent after multivariable adjustment and in patients with HFmrEF (n = 15114).Conclusions Patients with HF and CKD are less likely to be prescribed and to fill prescriptions for evidence-based therapies, showing lower adherence and persistence, even at eGFR categories where these therapies are recommended and have shown efficacy in clinical trials.[GRAPHICS]. Show less
Purpose of Review: Small non-coding RNAs regulate gene expression and are highly implicated in heart failure. Recently, an additional level of post-transcriptional regulation has been identified,... Show morePurpose of Review: Small non-coding RNAs regulate gene expression and are highly implicated in heart failure. Recently, an additional level of post-transcriptional regulation has been identified, referred to as the epitranscriptome, which encompasses the body of post-transcriptional modifications that are placed on RNA molecules. In this review, we summarize the current knowledge on the small non-coding RNA epitranscriptome in heart failure. Recent Findings: With the rise of new methods to study RNA modifications, epitranscriptome research has begun to take flight. Over the past 3 years, the number of publications on the epitranscriptome in heart failure has significantly increased, and we expect many more highly relevant publications to come out over the next few years. Currently, at least six modifications on small non-coding RNAs have been investigated in heart failure-relevant studies, namely N6-adenosine, N5-cytosine and N7-guanosine methylation, 2'-O-ribose-methylation, adenosine-to-inosine editing, and isomiRs. Their potential role in heart failure is discussed. Show less
In this PhD thesis we have studied left ventricular systolic deformation with novel cardiovascular magnetic resonance (CMR) algorithm called feature-tracking in patients with acute myocardial... Show moreIn this PhD thesis we have studied left ventricular systolic deformation with novel cardiovascular magnetic resonance (CMR) algorithm called feature-tracking in patients with acute myocardial infarction (MI). We have shown that left ventricular strain with feature-tracking CMR offers an incremental value above conventional imaging parameters in the assessment of prognosis of patients with acute MI. In addition, left ventricular strain analysis confirmed a clear clinical benefit of early intravenous betablocker treatment in patients with acute MI. Moreover, we have explored the feasibility of novel automated 3D echocardiographic algorithm in the assessment of the aortic root anatomy in patients with severe aortic stenosis prior to transcatheter aortic valve replacement (TAVR). The 3D echocardiographic algorithm performed excellent against the gold standard multidetector row computed tomography to determine the aortic annulus size and to choose the correct TAVR prosthesis size; however, the accuracy was a bit lower in patients with severely calcified aortic valves. In addition, we have explored the advantages and limitations of different cardiac imaging techniques in the assessment of patients with TAVR, the role of multimodality imaging in patients with combined valvular heart disease and heart failure, and the role of myocardial fibrosis assessment with CMR in valvular heart disease. Show less
The aim of this thesis is to provide new insights on catheter ablation of VT in patients with prior MI. Improved understanding of the VT substrate in different types of MI, and in particular, in... Show moreThe aim of this thesis is to provide new insights on catheter ablation of VT in patients with prior MI. Improved understanding of the VT substrate in different types of MI, and in particular, in contemporary non-transmural reperfused infarctions, a critical reassessment of the value of non-inducibility as ablation endpoint and the development of new physiologically meaningful endpoints for substrate modification will hopefully contribute to optimize procedural outcomes in this patient population. In addition, recognition of the limitations of the technique will aid in patient selection and will help to consider alternative treatment options in some individuals. Show less
