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
Aims The effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) in routine clinical practice is not extensively studied. This study aimed to... Show moreAims The effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) in routine clinical practice is not extensively studied. This study aimed to evaluate the comparative effectiveness of SGLT2i vs. sitagliptin in older adults with HF and type 2 diabetes and to investigate whether there were any differences between agents within the SGLT2i class or for reduced and preserved ejection fraction. Methods and results Using Medicare claims data (April 2013 to December 2019), 16 253 SGLT2i initiators vs. 43 352 initiators of sitagliptin aged >= 65 years with type 2 diabetes and HF were included. The primary outcome was a composite of all-cause mortality, hospitalization for HF or urgent visit requiring intravenous diuretics; secondary outcomes included its individual components. Propensity score fine stratification weighted Cox regression was used to adjust for 100 pre-exposure characteristics. Mean age was 74 years; 49.8% were women. Initiation of SGLT2i vs. sitagliptin was associated with a lower risk of the primary composite outcome [adjusted hazard ratio (HR) 0.72; 95% confidence interval 0.67-0.77]. The adjusted HRs were 0.70 (0.63-0.78) for all-cause mortality, 0.64 (0.58-0.70) for hospitalization for HF, and 0.77 (0.69-0.86) for urgent visit requiring intravenous diuretics. Similar associations with the primary composite outcome were observed for all three agents within the SGLT2i class, for reduced and preserved ejection fraction, and subgroups based on demographics, comorbidities, and other HF treatments. Bias-calibrated HRs for the primary endpoint using negative and positive control outcomes ranged between 0.81 and 0.89, suggesting that the observed benefit could not be fully explained by residual confounding. Conclusion In routine US clinical practice, SGLT2i demonstrated robust clinical effectiveness in older adults with HF and type 2 diabetes compared with sitagliptin, with no evidence of heterogeneity across the SGLT2i class or across ejection fraction. 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
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
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
BACKGROUND Left ventricular (LV) dilatation may limit LV reverse remodeling after cardiac resynchronization therapy (CRT). OBJECTIVE The purpose of this study was to evaluate the impact of baseline... Show moreBACKGROUND Left ventricular (LV) dilatation may limit LV reverse remodeling after cardiac resynchronization therapy (CRT). OBJECTIVE The purpose of this study was to evaluate the impact of baseline LV volumes on LV reverse remodeling after CRT and whether this is associated with improved survival. METHODS Patients were stratified into quintiles according to baseline LV end-diastolic volume indexed for body surface area (LVEDVi). LV reverse remodeling was defined as >= 15% reduction in LV end-systolic volume at 6-month follow-up after CRT. Independent associates of LV remodeling were assessed and long-term mortality rates were compared between patients with and without LV reverse remodeling (across LVEDVi quintiles). RESULTS A total of 864 patients were included (mean age 66 +/- 10 years; 657 patients (76%) were male), of whom 101 (12%) were in quintile 1 (<65 mL/m(2)), 272 (32%) in quintile 2 (65-95 mL/m(2)), 247 (29%) in quintile 3 (95-125 mL/m(2)), 151 (18%) in quintile 4 (125-155 mL/m(2)), and 93 (11%) in quintile 5 (.155 mL/m(2)). Patients with larger baseline LVEDVi had worse survival after CRT (log-rank, P = .019). The cumulative 10-year survival was significantly better in patients with vs without LV reverse remodeling (48.7% vs 33.9%; P < .001). Significant LV reverse remodeling was observed in all LVEDVi quintiles. In addition, patients with LV reverse remodeling had superior survival than did patients without LV reverse remodeling, regardless of baseline LVEDVi quintile (log-rank, P < .05 for all). CONCLUSION Many patients with larger baseline LV volumes still show significant LV reverse remodeling after CRT and had superior survival (regardless of baseline LV volumes) than did patients without LV reverse remodeling. Therefore, CRT should not be denied on the basis of severe LV dilatation. Show less
Aims: Myocardial infarction (MI) is among the commonest attributable risk factors for heart failure (HF). We compared clinical characteristics associated with the progression to HF in patients with... Show moreAims: Myocardial infarction (MI) is among the commonest attributable risk factors for heart failure (HF). We compared clinical characteristics associated with the progression to HF in patients with or without a history of MI in the HOMAGE cohort and validated our results in UK Biobank. Methods and results: During a follow-up of 5.2 (3.5-5.9) years, 177 (2.4%) patients with prior MI and 370 (1.92%) patients without prior MI experienced HF onset in the HOMAGE cohort (n = 26 478, history of MI: n = 7241). Older age, male sex and higher heart rate were significant risk factors of HF onset in patients with and without prior MI. Lower renal function was more strongly associated with HF onset in patients with prior MI. Higher body mass index (BMI), systolic blood pressure and blood glucose were significantly associated with HF onset only in patients without prior MI (all p for interactions <0.05). In the UK Biobank (n = 500 001, history of MI: n = 4555), higher BMI, glycated haemoglobin, diabetes and hypertension had a stronger association with HF onset in participants without prior MI compared to participants with MI (all p for interactions <0.05). Conclusion: The importance of clinical risk factors associated with HF onset is dependent on whether the patient has had a prior MI. Diabetes and hypertension are associated with new-onset HF only in the absence of MI history. Patients may benefit from targeted risk management based on MI history. Show less
Egorova, A.D.; Nederend, M.; Tops, L.F.; Vliegen, H.W.; Jongbloed, M.R.M.; Kies, P. 2022
In congenitally corrected transposition of the great arteries, the morphological right ventricle supports the systemic circulation. This chronic exposure to pressure overload ultimately leads to... Show moreIn congenitally corrected transposition of the great arteries, the morphological right ventricle supports the systemic circulation. This chronic exposure to pressure overload ultimately leads to systemic right ventricular (sRV) dysfunction and heart failure. Pharmacological options for the treatment of sRV failure are poorly defined and no solid recommendations are made in the most recent guidelines. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a new class of antihyperglycaemic drugs that have been demonstrated to significantly reduce the risk of worsening heart failure and death from cardiovascular causes in patients with chronic heart failure with reduced left ventricular ejection fraction, yet no data are available in sRV patients. We report on the treatment and clinical follow-up of a patient with advanced heart failure and poor sRV function in the context of congenitally corrected transposition of the great arteries, who did not tolerate sacubitril/valsartan and had a high burden of heart-failure-related hospitalizations. Treatment with dapagliflozin was well tolerated and resulted in (small) subjective and objective functional and echocardiographic improvement and a reduction in heart-failure-related hospitalizations. Show less
Stassen, J.; Galloo, X.; Hirasawa, K.; Marsan, N.A.; Bijl, P. van der; Delgado, V.; Bax, J.J. 2022
Aims Tricuspid regurgitation (TR) is common in patients with heart failure (HF) and is associated with worse outcome. This study investigated the effect of cardiac resynchronization therapy (CRT)... Show moreAims Tricuspid regurgitation (TR) is common in patients with heart failure (HF) and is associated with worse outcome. This study investigated the effect of cardiac resynchronization therapy (CRT) on TR severity and long-term outcome. Methods and results Tricuspid regurgitation severity was assessed at baseline and 6 months after CRT implantation, using a multiparametric approach. Patients were divided into four groups: (i) no or mild TR without progression; (ii) no or mild TR with progression to significant (moderate-severe) TR; (iii) significant TR with improvement to no or mild TR; and (iv) significant TR without improvement. The primary endpoint was all-cause mortality. A total of 852 patients (mean age 65 +/- 11 years, 77% male) were included. At baseline, 184 (22%) patients had significant TR, with 75 (41%) showing significant improvement at 6-month follow-up. After a median follow-up of 92 (50-137) months, 494 (58%) patients died. Patients with significant TR showing improvement at follow-up had better outcomes than those showing no improvement (P = 0.016). On multivariable analysis, no or mild TR progressing to significant TR [hazard ratio (HR) 1.745; 95% confidence interval (CI): 1.287-2.366; P < 0.001] and significant TR without improvement (HR 1.572; 95% CI: 1.198-2.063; P = 0.001) were independently associated with all-cause mortality, whereas significant TR with improvement at follow-up was not (HR: 1.153; 95% CI: 0.814-1.633; P = 0.424). Conclusion Improvement of significant TR after CRT is observed in a substantial proportion of patients, highlighting the potential benefit of CRT for patients with HF having significant TR. Significant TR at 6 months after CRT is independently associated with increased long-term mortality. Show less
Introduction: Hospital admissions for heart failure (HF) are frequent and pose a heavy burden on health care resources. Currently, the decision to hospitalise is based on clinical judgement rather... Show moreIntroduction: Hospital admissions for heart failure (HF) are frequent and pose a heavy burden on health care resources. Currently, the decision to hospitalise is based on clinical judgement rather than on prognostic risk stratification. The Emergency Heart failure Mortality Risk Grade (EHMRG) was recently developed to identify high-risk HF patients in the emergency department (ED). Objective: To assess the ability of the EHMRG to predict 30-day mortality in Dutch HF patients visiting the ED and to evaluate whether the EHMRG could help to reduce the number of hospital admissions for decompensated HF. Methods: Patients visiting the ED for decompensated HF were included. The decision to hospitalise or discharge was based on clinical judgement. The EHMRG was calculated retrospectively. Based on their EHMRG, patients were stratified as very low risk, low risk, intermediate risk, high risk and very high risk. Results: In 227 patients (age 73 +/- 12 years, 69% male) 30-day mortality was 11%. Mortality differed significantly among the EHMRG risk groups at 7-day (p = 0.012) and 30-day follow-up (p < 0.01). Based on clinical judgement, 76% of patients were hospitalised. If decision-making had been based on EHMRG, the hospitalisation rate could have been reduced to 66% (p < 0.01), particularly by reducing hospitalisations in patients at low risk of death. Mortality in discharged patients, whether the decision was based on EHMRG or clinical judgement, was 0%. Conclusion: The EHMRG accurately differentiates between high- and low-risk decompensated HF patients visiting the ED, making it a promising tool to safely reduce the number of HF admissions. Show less
Aims Chronic pressure overload and right ventricular (RV) dysfunction can lead to RV-pulmonary artery (PA) uncoupling in patients with heart failure. The evolution and prognostic values of RV-PA... Show moreAims Chronic pressure overload and right ventricular (RV) dysfunction can lead to RV-pulmonary artery (PA) uncoupling in patients with heart failure. The evolution and prognostic values of RV-PA coupling assessed by echocardiography in patients undergoing cardiac resynchronization therapy (CRT) have not been thoroughly investigated. The aim of this study was to evaluate the evolution and prognostic value of tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio in CRT recipients.Methods and results The RV-PA coupling was measured non-invasively with echocardiography using the TAPSE/PASP ratio at baseline and 6 month follow-up in CRT recipients. The cut-off value for TAPSE/PASP uncoupling was derived from spline curve analysis (i.e. <0.45 mm/mmHg). The primary endpoint was all-cause mortality. A total of 807 patients (age 66 +/- 11 years, 76% men) were analysed. During a median follow-up of 97 (54-143) months, 483 (60%) patients died. Survival rates at 3 and 5 year follow-up were significantly lower for patients with a TAPSE/PASP ratio <0.45 mm/mmHg (76% and 58%, respectively), compared with those with a TAPSE/PASP ratio >= 0.45 mm/mmHg (91% and 82%, respectively) (P < 0.001). On multivariable analysis, TAPSE/PASP ratio <0.45 mm/mmHg (hazard ratio 1.437; 95% confidence interval: 1.145-1.805; P = 0.002) was independently associated with all-cause mortality, whereas TAPSE <17 mm (hazard ratio 1.237; 95% confidence interval: 0.990-1.546; P = 0.061) was not. In addition, no improvement of the TAPSE/PASP ratio after CRT implantation was independently associated with worse survival.Conclusions The TAPSE/PASP ratio at baseline is independently associated with long-term outcomes in CRT recipients. The baseline TAPSE/PASP ratio has incremental value over TAPSE, which does not take account of RV afterload. A lack of improvement in the TAPSE/PASP ratio after CRT implantation is associated with worse survival. Show less
Nederend, M.; Zeppenfeld, K.; Jongbloed, M.R.M.; Egorova, A.D. 2022
Background Patients with a systemic right ventricle (sRV) in the context of transposition of the great arteries (TGA) late after atrial switch are prone to heart failure. Complications like... Show moreBackground Patients with a systemic right ventricle (sRV) in the context of transposition of the great arteries (TGA) late after atrial switch are prone to heart failure. Complications like tricuspid valve regurgitation (TR) can further aggravate sRV dysfunction. Tricuspid valve regurgitation is usually secondary to annular dilatation and restriction. Criteria for cardiac resynchronization therapy (CRT) in this patient group are not well defined and should be considered on a case-by-case basis. Case summary We present a case of a 42-year-old male with sRV failure and TR in the context of TGA after atrial switch. Patient had progressive reduction in exercise capacity. Electrocardiogram showed a wide QRS complex (right bundle branch block configuration). Echocardiography showed significant TR and signs of electromechanical dyssynchrony of the failing sRV with severely reduced systolic function. He underwent heart catheterization and invasive haemodynamic evaluation to assess the potential benefit of CRT. During sequential atrial-sRV pacing, 20% increase in Dp/Dt was measured, suggesting that he would be a CRT responder. Concomitant angiography showed no baffle leakage nor obstructive coronary artery disease. Hybrid CRT-defibrillator implantation resulted in successful resynchronization and improved sRV function, reduced TR and better exercise capacity. Discussion Invasive haemodynamic contractility evaluation can help assess the potential benefit of CRT in patients with systemic right ventricular failure in the context of transposition of TGA after atrial switch. Successful CRT can result in improved sRV function, reduced TR and improved exercise capacity. Show less
