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Aims: Inter-atrial block (IAB), a marker of electrical atrial dysfunction, is associated with an increased risk of atrial fibrillation (AF) and adverse events in various populations. The prognostic impact of IAB in heart failure (HF) with preserved ejection fraction (HFpEF) remains unknown. The aim of this study is to determine the prevalence of IAB and the association of IAB and AF with adverse events in HFpEF across different healthcare settings., Methods and Results: To identify electrical atrial dysfunction, baseline ECG's and medical history were analysed in HFpEF patients in an ambulatory setting and after recent HF hospitalisation. Patients were categorised into (i) HFpEF No IAB , (ii) HFpEF IAB , or (iii) HFpEF AF . Adverse events included HF hospitalisation, cardiac/sudden death and a composite of both. The ambulatory cohort included 372 patients [mean age 75 ± 7 years, 252 (68%) females]. The recently hospitalised cohort included 132 patients [mean age 81 ± 10 years, 80 (61%) females]. Ambulatory patients included 17 (4%) HFpEF noIAB , 114 (31%) HFpEF IAB and 241 (65%) HFpEF AF , while recently hospitalised patients included 31 (23%), 73 (55%) and 28 (21%), respectively. After 33 months of follow-up of ambulatory patients, composite endpoints occurred in 0 (0%) HFpEF noIAB , 12 (11%) HFpEF IAB [HR 4.1 (95% CI 0.5-522.6)] and 59 (24%) HFpEF AF patients [HR 10.1 (95% CI 1.5-1270.4), P < 0.001]. Recently hospitalised patients showed a similar trend, with composite endpoints in 10 (32%) HFpEF noIAB , 31 (42%) HFpEF IAB (HR 1.5 [95% CI 0.7-3.1]) and 22 (79%) HFpEF AF (HR 3.8 [95% CI 1.8-8.1], P < 0.001)., Conclusions: Progressive stages of electrical atrial dysfunction appeared to be prognostic markers of adverse outcomes in ambulatory and recently hospitalised patients with HFpEF. Ambulatory patients with HFpEF and no early stages of electrical atrial dysfunction showed to be at very low risk for adverse outcomes. Whether such patients benefit less strict management remains to be investigated., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Current guidelines recommend suspecting transthyretin amyloid cardiomyopathy (ATTR-CM) in patients over 65 years of age with unexplained left ventricular (LV) hypertrophy in a non-dilated LV, heart failure (HF) and preserved ejection fraction (HFpEF), hypertrophic cardiomyopathy or severe aortic stenosis. However, there is evidence indicating a high prevalence of ATTR-CM in other HF phenotypes. As such, this study aimed to characterize the diversity of HF phenotypes of ATTR-CM by examining the LV ejection fraction and LV dilatation using echocardiography., Methods: This multicentre, retrospective observational study included patients diagnosed with ATTR-CM between 2015-2023. The diagnosis was based on a positive cardiac biopsy or positive bone scintigraphy without monoclonal gammopathy. Echocardiographic measurements were categorized according to LV ejection fraction (LVEF) into HFpEF (LVEF ≥50%), HF with mildly reduced EF (HFmrEF, LVEF 40-49%), and HF with reduced EF (HFrEF, LVEF <40%). LV cavity size was categorized by LV end-diastolic diameter (LVEDD) and volume index (LVEDVi) as normal, moderately increased and severe dilatation., Results: The study included 135 patients with ATTR-CM (mean age, 78 years; 89% male; 89% wild-type ATTR-CM). Most patients were screened for ATTR-CM because of unexplained HF and increased LV wall thickness (57%). Echocardiography showed LVEF <50% in 60% of the patients, with a significant portion presenting with HFrEF. Patients with LVEF <50% had higher NYHA class and elevated N-terminal pro-B-type natriuretic peptide levels than HFpEF patients. LV dilatation was observed in 43% of the patients, with 10% presenting with both LVEF <50% and severe LV dilatation., Conclusion: This study revealed significant variability in HF phenotypes among patients with ATTR-CM, from HFpEF without LV dilatation to HFrEF with severe LV dilatation. Relying solely on HFpEF for screening may lead to under-diagnosis. These findings suggest the need for more comprehensive diagnostic criteria beyond echocardiographic measures to improve ATTR-CM detection and management.

Aims: Nocturnal hypoxaemic burden, quantified as time spent with oxygen saturation below 90% (T90), is an established independent predictor of mortality in heart failure (HF) with reduced ejection fraction. The prognostic value of T90 in HF with preserved ejection fraction (HFpEF) is unknown. This study aims to determine the association of T90 with adverse outcomes in HFpEF., Methods and Results: One hundred twenty-six patients prospectively included from our specialised HFpEF outpatient clinic underwent ambulatory home sleep monitoring to obtain oximetry data, including T90. We investigated the association between T90 and a composite endpoint of HF hospitalisations or all-cause mortality. Nocturnal hypoxaemic burden in this HFpEF population was high, with a median T90 of 13.7 min. In only 10 patients (7.9%), oxygen saturation was at no time point below 90%. After median 34 months [IQR 18.4-52.0] of follow-up, 32 patients (25%) reached the composite endpoint. T90 was significantly associated with the composite endpoint, also after adjusting for potential confounders (HR 1.004 (95% CI 1.001-1.007, P = 0.019) per 1 min T90 increase or HR 1.265 (95% CI 1.061-1.488) per 1 h T90 increase). Patients with HFpEF in the highest T90 tertile (T90 ≥ 31.4 min) had a significantly higher event rate compared to patients in the lowest two T90 tertiles, with 19 (45%) versus 13 (15%) events, respectively (P < 0.001)., Conclusions: Nocturnal hypoxaemic burden is an independent prognostic marker for the composite of HF hospitalisations or all-cause mortality in HFpEF. Whether reduction of T90 improves the prognosis of patients with HFpEF warrants further research., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Awareness of transthyretin amyloid cardiomyopathy (ATTR-CM) has increased over the years due to diagnostic and therapeutic developments. Timely initiation of novel disease-modifying treatments improves both morbidity and mortality, which underlines the necessity for a prompt diagnosis. Nevertheless, early diagnosis of ATTR-CM remains challenging. This is a retrospective observational cohort study of patients diagnosed with ATTR-CM. Between 2016 and 2023, 87 patients were diagnosed with cardiac amyloidosis of which 65 (75%) patients with ATTR-CM and 22 (25%) patients with light chain amyloidosis. This study included 65 ATTR-CM patients (mean age 77 ± 7 years; 86% male) of whom 59 (91%) with wild-type ATTR-CM (ATTRwt) and six (9%) with variant ATTR-CM. We observed a surge in ATTR-CM diagnoses from 3 patients/year (2016-2020) to 16 patients/year (2021-2023), driven by ATTRwt. Nevertheless, the interval between the onset of heart failure symptoms and ATTR-CM diagnosis has not changed significantly (2016-2020 27.3 months [18.6-62.4]; 2021-2023 30.0 months [8.6-57.2]; p = 0.546), driven by time to referral. Red flags for ATTR-CM preceded diagnosis by several years: left ventricular hypertrophy (79%, 5.8 years [3.3-7.0]) and carpal tunnel syndrome (49%, 6.8 years [2.3-12.1]). Despite the presence of typical red flags, symptom-to-diagnosis duration has remained similar driven by time to referral. Improved recognition of red flags for ATTR-CM could reduce the time to diagnosis and improve overall recognition., (© 2024. The Author(s).)

Aims: The 2021 European Society of Cardiology (ESC) screening recommendations for individuals carrying a pathogenic transthyretin amyloidosis variant (ATTRv) are based on expert opinion. We aimed to (i) determine the penetrance of ATTRv cardiomyopathy (ATTRv-CM) at baseline; (ii) examine the value of serial evaluation; and (iii) establish the yield of first-line diagnostic tests (i.e. electrocardiogram, echocardiogram, and laboratory tests) as per 2021 ESC position statement., Methods and Results: We included 159 relatives (median age 55.6 [43.2-65.9] years, 52% male) at risk for ATTRv-CM from 10 centres. The primary endpoint, ATTRv-CM diagnosis, was defined as the presence of (i) cardiac tracer uptake in bone scintigraphy; or (ii) transthyretin-positive cardiac biopsy. The secondary endpoint was a composite of heart failure (New York Heart Association class ≥II) and pacemaker-requiring conduction disorders. At baseline, 40/159 (25%) relatives were diagnosed with ATTRv-CM. Of those, 20 (50%) met the secondary endpoint. Indication to screen (≤10 years prior to predicted disease onset and absence of extracardiac amyloidosis) had an excellent negative predictive value (97%). Other pre-screening predictors for ATTRv-CM were infrequently identified variants and male sex. Importantly, 13% of relatives with ATTRv-CM did not show any signs of cardiac involvement on first-line diagnostic tests. The yield of serial evaluation (n = 41 relatives; follow-up 3.1 [2.2-5.2] years) at 3-year interval was 9.4%., Conclusions: Screening according to the 2021 ESC position statement performs well in daily clinical practice. Clinicians should adhere to repeating bone scintigraphy after 3 years, as progressing to ATTRv-CM without signs of ATTRv-CM on first-line diagnostic tests or symptoms is common., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Cardiac amyloidosis (CA)-mostly transthyretin-related (ATTR-CA)-has recently gained interest in cardiology. Bone scintigraphy (BS) is one of the main screening tools for ATTR-CA but also used for various other reasons. The objective was to evaluate whether all CA cases are detected and what happens during follow-up. All routine BS performed at the Maastricht University Medical Center (May 2012-August 2020) were screened for the presence of CA. Scans performed for suspected CA were excluded. A Perugini stage ≥1 was classified as positive necessitating further examination. The electronic medical record system was evaluated for any contact with cardiology or other specialists until 2021. Of the 2738 BS evaluated, 40 scans (1.46%; median age 73.5 [IQR: 65.8-79.5], 82.5% male) were positive (Perugini grade 1: 31/77.5%, grade 2: 6/15%, grade 3: 3/7.5%); the potential diagnosis ATTR-CA was not seen in 38 patients (95%) by the nuclear medicine specialist. During follow-up, 19 out of those 40 patients (47.5%) underwent cardiac evaluation without diagnosing CA. Available echocardiograms of patients with a positive BS showed left ventricular hypertrophy, a preserved ejection fraction, and diastolic dysfunction ≥2 in 9/47%, 10/53%, and 4/21% of patients, respectively. Additionally, 20 (50%) patients presented to at least one specialty with symptoms indicative of cardiac amyloidosis. The prevalence of a positive BS indicating potential CA in an unselected population is low but substantial. The majority was not detected which asks for better awareness for CA of all involved specialists to ensure appropriate treatment and follow-up., (© 2024. The Author(s).)

Metabolic dysfunction-associated steatotic liver disease (MASLD) typically presents with hepatic fibrosis in advanced disease, resulting in increased liver stiffness. A subset of patients further develops liver cirrhosis and hepatocellular carcinoma. Cardiovascular disease is a common comorbidity in patients with MASLD and its prevalence is increasing in parallel. Recent evidence suggests that especially liver stiffness, whether or not existing against a background of MASLD, is associated with heart diseases. We conducted a narrative review on the role of liver stiffness in the prediction of highly prevalent heart diseases including heart failure, cardiac arrhythmias (in particular atrial fibrillation), coronary heart disease, and aortic valve sclerosis. Research papers were retrieved from major scientific databases (PubMed, Web of Science) until September 2023 using 'liver stiffness' and 'liver fibrosis' as keywords along with the latter cardiac conditions. Increased liver stiffness, determined by vibration-controlled transient elastography or hepatic fibrosis as predicted by biomarker panels, are associated with a variety of cardiovascular diseases, including heart failure, atrial fibrillation, and coronary heart disease. Elevated liver stiffness in patients with metabolic liver disease should lead to considerations of cardiac workup including N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptide determination, electrocardiography, and coronary computed tomography angiography. In addition, patients with MASLD would benefit from heart disease case-finding strategies in which liver stiffness measurements can play a key role. In conclusion, increased liver stiffness should be a trigger to consider a cardiac workup in metabolically compromised patients., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Truncating variants in titin (TTNtv) are the most prevalent genetic etiology of dilated cardiomyopathy (DCM). Although TTNtv has been associated with atrial fibrillation, it remains unknown whether and how left atrial (LA) function differs between patients with DCM with and without TTNtv. We aimed to determine and compare LA function in patients with DCM with and without TTNtv and to evaluate whether and how left ventricular (LV) function affects the LA using computational modeling., Methods and Results: Patients with DCM from the Maastricht DCM registry that underwent genetic testing and cardiovascular magnetic resonance (CMR) were included in the current study. Subsequent computational modeling (CircAdapt model) was performed to identify potential LV and LA myocardial hemodynamic substrates. In total, 377 patients with DCM (n = 42 with TTNtv, n = 335 without a genetic variant) were included (median age 55 years, interquartile range [IQR] 46-62 years, 62% men). Patients with TTNtv had a larger LA volume and decreased LA strain compared with patients without a genetic variant (LA volume index 60 mLm -2 [IQR 49-83] vs 51 mLm -2 [IQR 42-64]; LA reservoir strain 24% [IQR 10-29] vs 28% [IQR 20-34]; LA booster strain 9% [IQR 4-14] vs 14% [IQR 10-17], respectively; all P < .01). Computational modeling suggests that while the observed LV dysfunction partially explains the observed LA dysfunction in the patients with TTNtv, both intrinsic LV and LA dysfunction are present in patients with and without a TTNtv., Conclusions: Patients with DCM with TTNtv have more severe LA dysfunction compared with patients without a genetic variant. Insights from computational modeling suggest that both intrinsic LV and LA dysfunction are present in patients with DCM with and without TTNtv., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Heart failure is a serious burden on health care systems due to frequent hospital admissions. Early recognition of outpatients at risk for clinical deterioration could prevent hospitalization. Still, the role of signs and symptoms in monitoring heart failure patients is not clear. The heart failure coach is a web-based telemonitoring application consisting of a 9-item questionnaire assessment of heart failure signs and symptoms and developed to identify outpatients at risk for clinical deterioration. If deterioration was suspected, patients were contacted by a heart failure nurse for further evaluation., Methods: Heart failure coach questionnaires completed between 2015 and 2018 were collected from 287 patients, completing 18,176 questionnaires. Adverse events were defined as all-cause mortality, heart failure- or cardiac-related hospital admission or emergency cardiac care visits within 30 days after completion of each questionnaire. Multilevel logistic regression analyses were performed to assess the association between the heart failure coach questionnaire items and the odds of an adverse event., Results: No association between dyspnea and adverse events was observed (odds ratio 1.02, 95% confidence interval 0.79-1.30). Peripheral edema (odds ratio 2.21, 95% confidence interval 1.58-3.11), persistent chest pain (odds 2.06, 95% confidence interval 1.19-3.58), anxiety about heart failure (odds ratio 2.12, 95% confidence interval 1.44-3.13), and extensive struggle to perform daily activities (odds ratio 2.23, 95% confidence interval 1.38-3.62) were significantly associated with adverse outcome., Discussion: Regular assessment of more than the classical signs and symptoms may be helpful to identify heart failure patients at risk for clinical deterioration and should be an integrated part of heart failure telemonitoring programs., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: Diagnosis of heart failure with preserved ejection fraction (HFpEF) can be challenging. This study aimed to evaluate the potential of a webtool to enhance the scoring accuracy when applying the complex HFA-PEFF and H 2 FPEF algorithms, which are commonly used for diagnosing HFpEF., Methods and Results: We developed an online tool, the HFpEF calculator, that enables the automatic calculation of current HFpEF algorithms. We assessed the accuracy of manual vs. automatic scoring, defined as the percentage of correct scores, in a cohort of cardiologists with varying clinical experience. Cardiologists scored eight online clinical cases using a triple cross-over design (i.e. two manual-two automatic-two manual-two automatic). Data were analysed in study completers (n = 55, 29% heart failure specialists, 42% general cardiologists, and 29% cardiology residents). Manually calculated scores were correct in 50% (HFA-PEFF: 50% [50-75]; H 2 FPEF: 50% [38-50]). Correct scoring improved to 100% using the HFpEF calculator (HFA-PEFF: 100% [88-100], P < 0.001; H 2 FPEF: 100% [75-100], P < 0.001). Time spent on clinical cases was similar between scoring methods (±4 min). When corrections for faulty algorithm scores were displayed, cardiologists changed their diagnostic decision in up to 67% of cases. At least 67% of cardiologists preferred using the online tool for future cases in clinical practice., Conclusions: Manual calculation of HFpEF diagnostic algorithms is often inaccurate. Using an automated webtool to calculate HFpEF algorithms significantly improved correct scoring. This new approach may impact the eventual diagnostic decision in up to two-thirds of cases, supporting its routine use in clinical practice., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Competing Interests: Conflicts of Interest C.K. has received travel grants and software/hardware support for this and other studies from TOMTEC Imaging Systems. G.S. and M.S. are employees of TOMTEC Imaging Systems. TOMTEC Imaging Systems/Unterschleissheim provided software and sponsoring for this project. The remaining authors have nothing to disclose.

Background: Collagen cross-linking is a fundamental process in dilated cardiomyopathy (DCM) and occurs when collagen deposition exceeds degradation, leading to impaired prognosis. This study investigated the associations of collagen-metabolism biomarkers with left ventricular function and prognosis in DCM., Methods: DCM patients who underwent endomyocardial biopsy, blood sampling, and cardiac MRI were included. The primary endpoint included death, heart failure hospitalization, or life-threatening arrhythmias, with a follow-up of 6 years (5-8)., Results: In total, 209 DCM patients were included (aged 54 ± 13 years, 65% male). No associations were observed between collagen volume fraction, circulating carboxy-terminal propeptide of procollagen type-I (PICP), or collagen type I carboxy-terminal telopeptide [CITP] and matrix metalloproteinase [MMP]-1 ratio and cardiac function parameters. However, CITP:MMP-1 was significantly correlated with global longitudinal strain (GLS) in the total study sample (R = -0.40, p < 0.0001; lower CITP:MMP-1 ratio was associated with impaired GLS), with even stronger correlations in patients with LVEF > 40% (R = -0.70, p < 0.0001). Forty-seven (22%) patients reached the primary endpoint. Higher MMP-1 levels were associated with a worse outcome, even after adjustment for clinical and imaging predictors (1.026, 95% CI 1.002-1.051, p = 0.037), but CITP and CITP:MMP-1 were not. Combining MMP-1 and PICP improved the goodness-of-fit (LHR36.67, p = 0.004)., Conclusion: The degree of myocardial cross-linking (CITP:MMP-1) is associated with myocardial longitudinal contraction, and MMP-1 is an independent predictor of outcome in DCM patients.

Aims: Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by impaired diastolic function. Left ventricular (LV) strain-volume loops (SVL) represent the relation between strain and volume during the cardiac cycle and provide insight into systolic and diastolic function characteristics. In this study, we examined the association of SVL parameters and adverse events in HFpEF., Methods and Results: In 235 patients diagnosed with HFpEF, LV-SVL were constructed based on echocardiography images. The endpoint was a composite of all-cause mortality and Heart Failure (HF)-related hospitalization, which was extracted from electronic medical records. Cox-regression analysis was used to assess the association of SVL parameters and the composite endpoint, while adjusting for age, sex, and NYHA class. HFpEF patients (72.3% female) were 75.8 ± 6.9 years old, had a BMI of 29.9 ± 5.4 kg/m2, and a left ventricular ejection fraction of 60.3 ± 7.0%. Across 2.9 years (1.8-4.1) of follow-up, 73 Patients (31%) experienced an event. Early diastolic slope was significantly associated with adverse events [second quartile vs. first quartile: adjusted hazards ratio (HR) 0.42 (95%CI 0.20-0.88)] after adjusting for age, sex, and NYHA class. The association between LV peak strain and adverse events disappeared upon correction for potential confounders [adjusted HR 1.02 (95% CI 0.96-1.08)]., Conclusion: Early diastolic slope, representing the relationship between changes in LV volume and strain during early diastole, but not other SVL-parameters, was associated with adverse events in patients with HFpEF during 2.9 years of follow-up., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: A subset of patients with atrial fibrillation (AF) presents without established AF risk factors and normal left ventricular (LV) systolic function, called idiopathic AF (IAF). Traditionally, echocardiography derived LV dimensions and ejection fraction (EF) are used to exclude LV dysfunction in IAF, but their sensitivity is limited. Our objective is to evaluate the presence of subtle alterations in LV function despite normal LVEF in patients with IAF compared to healthy controls, using speckle-tracking echocardiography (STE) based global longitudinal strain (GLS)., Methods: Standard transthoracic echocardiography was performed in 80 patients with IAF and 129 healthy controls. Patients with overt cardiac disease as well as known established AF risk factors were excluded. STE analysis was performed to assess GLS of the LV, and left atrial strain (LAS)., Results: LVEF was normal and comparable between patients with IAF and healthy controls (63 ± 4% for both groups; p = 0.801). Mean GLS was within normal limits for both groups but statistically significantly more negative in patients with IAF (-20.6 ± 2.5% vs. -19.7 ± 2.5%; p = 0.016), however not when indexed for ventricular cycle length (p = 0.784). No differences in LA volume or non-indexed LAS were seen in patients with IAF compared to healthy controls., Conclusions: In this selected group of IAF patients, STE did not detect any overt LV or LA dysfunction compared to healthy controls. Thus, IAF occurred in these patients not only in the absence of established AF risk factors but also without evidence of ventricular or atrial dysfunction., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The Simpson's method is the standard technique to determine left ventricular (LV) ejection fraction (EF) on echocardiography. The large inter-observer variability of measuring LVEF is well documented but not fully understood. A graphical analysis was used to elaborate what contributes to the inter-observer difference. Forty-two cardiologists (32 male, 39 ± 7 years) evaluated the LVEF using the Simpson's method on 15 different echocardiograms (2 and 4 chamber view (2CH/4CH)); the program did not show the result of EF to prevent a bias. End-diastolic (ED) and end-systolic (ES) frames were predefined ensuring measurement at the same time point of the cardiac cycles. After standardization of the LV contour, the differences of the individual contours compared to a reference contour were measured. Also, the spreading of lateral/medial mitral annulus contours and the apex were depicted. A significant spreading of LV-contours was seen with larger contours leading to higher EFs (p < 0.001). Experience did not influence the determination of LVEF. ED-volumes showed more spreading than ES-volumes ((3.6 mm (IQR: 2.6-4.0) vs. 3.4 mm (IQR: 2.8-3.8), p < 0.001). Also, the differences were larger for the 2CH compared to the 4CH (p < 0.001). Variability was significantly larger for lateral than septal wall (p < 0.001) as well as the anterior compared to the inferior wall (p < 0.001). There was a relevant scattering of the apex and medial/ lateral mitral annulus ring. There was a large variability of LV-volumes and LVEF as well as position of mitral valve ring and apex. There were global differences (apical 2CH or 4CH), regional aspects (LV walls) and temporal factors (ED vs. ES). Thus, multiple factors contributed to the large variability.Trial registration: The study was registered at "Netherlands Trial Register" ( www.trialregister.nl ; study number: NL5131)., (© 2023. The Author(s).)

Background: Left atrial (LA) dilation is associated with a worse prognosis in several cardiovascular settings, but therapies can promote LA reverse remodeling. The aim of this study was to characterize and define the prognostic implications of LA volume index (LAVI) reduction in patients with dilated cardiomyopathy (DCM)., Methods: Consecutive patients with DCM from two tertiary care centers, with available echocardiograms at baseline and at 1-year follow-up, were retrospectively analyzed. LA dilation was defined as LAVI > 34 mL/m 2 , and change in LAVI (ΔLAVI) was defined as the 1-year relative LAVI reduction. The outcome was a composite of death, heart transplantation (HTx), or heart failure hospitalization (HFH)., Results: Five hundred sixty patients were included (mean age, 54 ± 13 years; mean left ventricular ejection fraction, 31 ± 10%; mean LAVI, 45 ± 18 mL/m 2 ). Baseline LAVI had a non-linear association with the risk for death, HTx, or HFH, independent of age, left ventricular ejection fraction, mitral regurgitation, and medical therapy (P < .01). At 1-year follow-up, LAVI decreased in 374 patients (67%; median ΔLAVI, -24%; interquartile range, -37% to -11%). Factors independently associated with ΔLAVI were higher baseline LAVI and lower baseline left ventricular ejection fraction. After multivariable adjustment, ΔLAVI showed a linear association with the risk for death, HTx, or HFH (hazard ratio, 0.96 per 5% decrease; 95% CI, 0.93-0.99; P = .042). At 1-year follow-up, patients with reductions in LAVI of >10% and LAVI normalization (i.e., follow-up LAVI ≤ 34 mL/m 2 ; 31% of the overall cohort) were at lower risk for death, HTx, or HFH (hazard ratio, 0.37; 95% CI, 0.35-0.97; P = .028)., Conclusions: In a large cohort of patients with DCM, 1-year reduction in LAVI was observed in a number of patients. The association between reduction in LAVI and death, HTx, or HFH suggests that LA structural reverse remodeling might be considered an additional parameter useful in the individualized risk stratification of patients with DCM., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiac resynchronization therapy (CRT) requires intensive, complex, and multidisciplinary care for heart failure (HF) patients. Due to limitations in time, resources, and coordination of care, in current practice, this is often incomplete. We evaluated the effect of the introduction of a CRT-care pathway (CRT-CPW) on clinical outcome and costs., Methods and Results: The CRT-CPW focused on structuring CRT patient selection, implantation, and follow-up management. To facilitate and guarantee quality, checklists were introduced. The CRT-CPW was implemented in the Maastricht University Medical Centre in 2014. Physician-led usual care was restructured to a nurse-led care pathway. A retrospective comparison of data from CRT patients receiving usual care (2012-2014, 222 patients) and patients receiving care according to CRT-CPW (2015-2018, 241 patients) was performed. The primary outcome was the composite of all-cause mortality and HF hospitalization. Hospital-related costs of cardiovascular care after CRT implantation were analysed to address cost-effectiveness of the CRT-CPW. Demographics were comparable in the usual care and CRT-CPW groups. Kaplan-Meier estimates of the occurrence of the primary endpoint showed a significant improvement in the CRT-CPW group (25.7% vs. 34.7%, hazard ratio 0.56; confidence interval 0.40-0.78; P < 0.005), at 36 months of follow-up. The total costs for cardiology-related hospitalizations were significantly reduced in the CRT-CPW group [€17 698 (14 192-21 195) vs. 19 933 (16 980-22 991), P < 0.001]. Bootstrap cost-effectiveness analyses showed that implementation of CRT-CPW would be an economically dominant strategy in 90.7% of bootstrap samples., Conclusions: The introduction of a novel multidisciplinary, nurse-led care pathway for CRT patients resulted in significant reduction of the combination of all-cause mortality and HF hospitalizations, at reduced cardiovascular-related hospital costs., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: In coronavirus disease 2019 (COVID-19), cardiovascular risk factors and myocardial injury relate to increased mortality. We evaluated the extent of cardiac sequelae 6 months after hospital discharge in patients surviving ICU hospitalization for COVID-19., Methods: All survivors of Maastricht-ICU were invited for comprehensive cardiovascular evaluation 6 months after discharge from ICU. Cardiac screening included an electrocardiogram, cardiac biomarkers, echocardiography, cardiac magnetic resonance (CMR) and, wherever indicated, cardiac computed tomography or coronary angiogram., Results: Out of 52 survivors, 81% ( n  = 42) participated to the cardiovascular follow-up [median follow-up of 6 months, interquartile range (IQR) 6.1-6.7]. Eight patients (19%) had newly diagnosed coronary artery disease (CAD), of which two required a percutaneous intervention. Echocardiographic global longitudinal strain (GLS) was abnormal in 24% and CMR-derived GLS was abnormal in 12%, despite normal left ventricular ejection fraction in all. None of the patients showed elevated T 1 relaxation times and five patients (14%) had an elevated T 2 relaxation time. Late gadolinium enhancement (LGE) reflecting regional myocardial fibrosis was increased in eight patients (21%), of which three had myocarditis and three had pericarditis., Conclusion: Cardiovascular follow-up at 6 months after ICU-admission for severe COVID-19 revealed that one out of five invasively mechanically ventilated survivors had CAD, a quarter had subclinical left ventricular dysfunction defined as reduced echocardiographic GLS, and 42% of the patients had CMR abnormalities (reduced LVEF, reduced GLS, LGE presence, and elevated T 2 ). On the basis of these findings, long-term cardiovascular follow-up is strongly recommended in all post-IC COVID-19 patients., Clinical Trial Registration: Trial Register number [NL8613]) https://www.trialregister.nl/trial/8613Video abstract:http://links.lww.com/HJH/B899 ., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Continuous progress in atrial fibrillation (AF) ablation techniques has led to an increasing number of procedures with improved outcome. However, about 30-50% of patients still experience recurrences within 1 year after their ablation. Comprehensive translational research approaches integrated in clinical care pathways may improve our understanding of the complex pathophysiology of AF and improve patient selection for AF ablation., Objectives: Within the "IntenSive mOlecular and eLectropathological chAracterization of patienTs undergoIng atrial fibrillatiOn ablatioN" (ISOLATION) study, we aim to identify predictors of successful AF ablation in the following domains: (1) clinical factors, (2) AF patterns, (3) anatomical characteristics, (4) electrophysiological characteristics, (5) circulating biomarkers, and (6) genetic background. Herein, the design of the ISOLATION study and the integration of all study procedures into a standardized pathway for patients undergoing AF ablation are described., Methods: ISOLATION (NCT04342312) is a two-center prospective cohort study including 650 patients undergoing AF ablation. Clinical characteristics and routine clinical test results will be collected, as well as results from the following additional diagnostics: determination of body composition, pre-procedural rhythm monitoring, extended surface electrocardiogram, biomarker testing, genetic analysis, and questionnaires. A multimodality model including a combination of established predictors and novel techniques will be developed to predict ablation success., Discussion: In this study, several domains will be examined to identify predictors of successful AF ablation. The results may be used to improve patient selection for invasive AF management and to tailor treatment decisions to individual patients., Competing Interests: CM received consultancy fees for Bayer Healthcare. SS received grants from Boehringer Ingelheim, AstraZeneca and GlaxoSmithKline, honorary fees for presentations from AstraZeneca and Chiesi, consultancy fees from GlaxoSmithKline, payment for advisory boards from Chiesi and GlaxoSmithKline, all outside the submitted work, and payed to his institution. KV was consultant for Medtronic, Abbott, Philips, Biosense Webster. US received consultancy fees or honoraria from Università della Svizzera Italiana (USI, Switzerland), Roche Diagnostics (Switzerland), EP Solutions Inc. (Switzerland), Johnson & Johnson Medical Limited (United Kingdom), Bayer Healthcare (Germany). US was co-founder and shareholder of YourRhythmics BV, a spin-off company of the University Maastricht. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Verhaert, Linz, Chaldoupi, Westra, den Uijl, Philippens, Kerperien, Habibi, Vorstermans, ter Bekke, Beukema, Evertz, Hemels, Luermans, Manusama, Lankveld, van der Heijden, Bidar, Hermans, Zeemering, Bijvoet, Habets, Holtackers, Mihl, Nijveldt, van Empel, Knackstedt, Simons, Buhre, Tijssen, Isaacs, Crijns, Maesen, Vernooy and Schotten.)

Background: The left atrium is an early sensor of left ventricular (LV) dysfunction. Still, the prognostic value of left atrial (LA) function (strain) on cardiac magnetic resonance (CMR) in dilated cardiomyopathy (DCM) remains unknown., Objectives: The goal of this study was to evaluate the prognostic value of CMR-derived LA strain in DCM., Methods: Patients with DCM from the Maastricht Cardiomyopathy Registry with available CMR imaging were included. The primary endpoint was the combination of sudden or cardiac death, heart failure (HF) hospitalization, or life-threatening arrhythmias. Given the nonlinearity of continuous variables, cubic spline analysis was performed to dichotomize., Results: A total of 488 patients with DCM were included (median age: 54 [IQR: 46-62] years; 61% male). Seventy patients (14%) reached the primary endpoint (median follow-up: 6 [IQR: 4-9] years). Age, New York Heart Association (NYHA) functional class >II, presence of late gadolinium enhancement (LGE), LV ejection fraction (LVEF), LA volume index (LAVI), LV global longitudinal strain (GLS), and LA reservoir and conduit strain were univariably associated with the outcome (all P < 0.02). LA conduit strain was a stronger predictor of outcome compared with reservoir strain. LA conduit strain, NYHA functional class >II, and LGE remained associated in the multivariable model (LA conduit strain HR: 3.65 [95% CI: 2.01-6.64; P < 0.001]; NYHA functional class >II HR: 1.81 [95% CI: 1.05-3.12; P = 0.033]; and LGE HR: 2.33 [95% CI: 1.42-3.85; P < 0.001]), whereas age, N-terminal pro-B-type natriuretic peptide, LVEF, left atrial ejection fraction, LAVI, and LV GLS were not. Adding LA conduit strain to other independent predictors (NYHA functional class and LGE) significantly improved the calibration, accuracy, and reclassification of the prediction model (P < 0.05)., Conclusions: LA conduit strain on CMR is a strong independent prognostic predictor in DCM, superior to LV GLS, LVEF, and LAVI and incremental to LGE. Including LA conduit strain in DCM patient management should be considered to improve risk stratification., Competing Interests: Funding Support and Author Disclosures This study was supported by the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON She-PREDICTS, grant 2017-21, CVON-DCVA Double Dosis 2021. Dr Heymans has provided current and previous scientific advice to AstraZeneca, CellProthera, Novo Nordisk, Bayer, Pfizer, CSL Behring, and Merck on heart failure and cardiomyopathies. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Heart failure (HF) represents a clinical syndrome resulting from different aetiologies and degrees of heart diseases. Among these, a key role is played by primary heart muscle disease (cardiomyopathies), which are the combination of multifactorial environmental insults in the presence or absence of a known genetic predisposition. The aim of the Maastricht Cardiomyopathy registry (mCMP-registry; NCT04976348) is to improve (early) diagnosis, risk stratification, and management of cardiomyopathy phenotypes beyond the limits of left ventricular ejection fraction (LVEF)., Methods and Results: The mCMP-registry is an investigator-initiated prospective registry including patient characteristics, diagnostic measurements performed as part of routine clinical care, treatment information, sequential biobanking, quality of life and economic impact assessment, and regular follow-up. All subjects aged ≥16 years referred to the cardiology department of the Maastricht University Medical Center (MUMC+) for HF-like symptoms or cardiac screening for cardiomyopathies are eligible for inclusion, irrespective of phenotype or underlying causes. Informed consented subjects will be followed up for 15 years. Two central approaches will be used to answer the research questions related to the aims of this registry: (i) a data-driven approach to predict clinical outcome and response to therapy and to identify clusters of patients who share underlying pathophysiological processes; and (ii) a hypothesis-driven approach in which clinical parameters are tested for their (incremental) diagnostic, prognostic, or therapeutic value. The study allows other centres to easily join this initiative, which will further boost research within this field., Conclusions: The broad inclusion criteria, systematic routine clinical care data-collection, extensive study-related data-collection, sequential biobanking, and multi-disciplinary approach gives the mCMP-registry a unique opportunity to improve diagnosis, risk stratification, and management of HF and (early) cardiomyopathy phenotypes beyond the LVEF limits., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background Speckle tracking echocardiographic global longitudinal strain (GLS) predicts outcome in patients with new onset heart failure. Still, its incremental value on top of left ventricular ejection fraction (LVEF) in patients with nonischemic, nonvalvular dilated cardiomyopathy (DCM) after optimal heart failure treatment remains unknown. Methods and Results Patients with DCM were included at the outpatient clinics of 2 centers in the Netherlands and Italy. The prognostic value of 2-dimensional speckle tracking echocardiographic global longitudinal strain was evaluated when being on optimal heart failure medication for at least 6 months. Outcome was defined as the combination of sudden or cardiac death, life-threatening arrhythmias, and heart failure hospitalization. A total of 323 patients with DCM (66% men, age 55±14 years) were included. The mean LVEF was 42%±11% and mean GLS after optimal heart failure treatment was -15%±4%. Twenty percent (64/323) of all patients reached the primary outcome after optimal heart failure treatment (median follow-up of 6[4-9] years). New York Heart Association class ≥3, LVEF, and GLS remained associated with the outcome in the multivariable-adjusted model (New York Heart Association class: hazard ratio [HR], 3.43; 95% CI, 1.49-7.90, P =0.004; LVEF: HR, 2.13; 95% CI, 1.11-4.10, P =0.024; GLS: HR, 2.24; 95% CI, 1.18-4.29, P =0.015), whereas left ventricular end-diastolic diameter index, left atrial volume index, and delta GLS were not. The addition of GLS to New York Heart Association class and LVEF improved the goodness of fit (log likelihood ratio test P <0.001) and discrimination (Harrell's C 0.703). Conclusions Within this bicenter study, GLS emerged as an independent and incremental predictor of adverse outcome, which exceeded LVEF in patients with optimally treated DCM. This presses the need to routinely include GLS in the echocardiographic follow-up of DCM.

Heart failure with preserved ejection fraction (HFpEF) is a condition with increasing incidence, leading to a health care problem of epidemic proportions for which no curative treatments exist. Consequently, an urge exists to better understand the pathophysiology of HFpEF. Accumulating evidence suggests a key pathophysiological role for coronary microvascular dysfunction (MVD), with an underlying mechanism of low-grade pro-inflammatory state caused by systemic comorbidities. The systemic entity of comorbidities and inflammation in HFpEF imply that patients develop HFpEF due to systemic mechanisms causing coronary MVD, or systemic MVD. The absence or presence of peripheral MVD in HFpEF would reflect HFpEF being predominantly a cardiac or a systemic disease. Here, we will review the current state of the art of cardiac and systemic microvascular dysfunction in HFpEF (Graphical Abstract), resulting in future perspectives on new diagnostic modalities and therapeutic strategies.

Aims: This study assessed the prognostic implications of mechanical atrial dysfunction in heart failure with preserved ejection fraction (HFpEF) patients with different stages of atrial fibrillation (AF) in detail., Methods and Results: HFpEF patients (n = 258) systemically underwent an extensive clinical characterization, including 24-h Holter monitoring and speckle-tracking echocardiography. Patients were categorized according to rhythm and stages of AF: 112 with no history of AF (no AF), 56 with paroxysmal AF (PAF), and 90 with sustained (persistent/permanent) AF (SAF). A progressive decrease in mechanical atrial function was seen: left atrial reservoir strain (LASr) 30.5 ± 10.5% (no AF), 22.3 ± 10.5% (PAF), and 13.9 ± 7.8% (SAF), P < 0.001. Independent predictors for lower LASr values were AF, absence of chronic obstructive pulmonary disease, higher N-terminal-pro hormone B-type natriuretic peptide, left atrial volume index, and relative wall thickness, lower left ventricular global longitudinal strain, and echocardiographic signs of elevated left ventricular filling pressure. LASr was an independent predictor of adverse outcome (hazard ratio per 1% decrease =1.049, 95% confidence interval 1.014-1.085, P = 0.006), whereas AF was not when the multivariable model included LASr. Moreover, LASr mediated the adverse outcome associated with AF in HFpEF (P = 0.008)., Conclusion: Mechanical atrial dysfunction has a possible greater prognostic role in HFpEF compared to AF status alone. Mechanical atrial dysfunction is a predictor of adverse outcome independently of AF presence or stage, and may be an underlying mechanism (mediator) for the worse outcome associated with AF in HFpEF. This may suggest mechanical atrial dysfunction plays a crucial role in disease progression in HFpEF patients with AF, and possibly also in HFpEF patients without AF., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Global longitudinal strain (GLS) has become an alternative to left ventricular ejection fraction (LVEF) to determine systolic function of the heart. The absence of cut-off values is one of the limitations preventing full clinical implementation. The aim of this study is to determine a cut-off value of GLS for an increased risk of adverse events in individuals with a normal LVEF., Methods and Results: Echocardiographic images of 502 subjects (52% female, mean age 48 ± 15) with an LVEF ≥ 55% were analysed using speckle tracking-based GLS. The primary endpoint was cardiovascular death or cardiac hospitalization. The analysis of Cox models with splines was performed to visualize the effect of GLS on outcome. A cut-off value was suggested by determining the optimal specificity and sensitivity. The median GLS was -22.2% (inter-quartile range -20.0 to -24.9%). In total, 35 subjects (7%) had a cardiac hospitalization and/or died because of cardiovascular disease during a follow-up of 40 (5-80) months. There was a linear correlation between the risk for adverse events and GLS value. Subjects with a normal LVEF and a GLS between -22.9% and -20.9% had a mildly increased risk (hazard ratio 1.01-2.0) for cardiac hospitalization or cardiovascular mortality, and the risk was doubled for subjects with a GLS of -20.9% and higher. The optimal specificity and sensitivity were determined at a GLS value of -20.0% (hazard ratio 2.49; 95% confidence interval: 1.71-3.61)., Conclusions: There is a strong correlation between cardiac adverse events and GLS values in subjects with a normal LVEF. In our single-centre study, -20.0% was determined as a cut-off value to identify subjects at risk. A next step should be to integrate GLS values in a multi-parametric model., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Circulating biomarkers and imaging techniques provide independent and complementary information to guide management of heart failure (HF). This consensus document by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) presents current evidence-based indications relevant to integration of imaging techniques and biomarkers in HF. The document first focuses on application of circulating biomarkers together with imaging findings, in the broad domains of screening, diagnosis, risk stratification, guidance of treatment and monitoring, and then discusses specific challenging settings. In each section we crystallize clinically relevant recommendations and identify directions for future research. The target readership of this document includes cardiologists, internal medicine specialists and other clinicians dealing with HF patients., (© 2021 European Society of Cardiology.)

Aims: To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients., Methods and Results: We quantified fibrosis in 209 DCM patients at three levels: (i) non-invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life-threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90-6.60; P < 0.001 and PICP 1.02, 95% CI 1.01-1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles., Conclusion: The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Whether and how iron deficiency (ID) impacts patients with heart failure (HF) with preserved ejection fraction (HFpEF) remain unclear. The aim of our study was to investigate the impact of ID on functional status, exercise capacity, and prognosis in HFpEF., Methods and Results: The study population consisted of 300 HFpEF patients. ID was defined as serum ferritin <100 μg/L or 100-300 μg/L and transferrin-saturation <20%. Baseline functional status, quality of life (HADS score and EQ 5D index), 6 min walking test, echocardiography, and outcome (all-cause mortality and combined all cause-mortality and HF hospitalization) were evaluated. ID was found in 159 (53%) patients. Patients with ID had a worse prognosis with a higher combined endpoint of all-cause mortality and HF hospitalization after 4 years of follow-up (log rank = 0.008). Pulmonary hypertension, depression, and thyroid disease were more prevalent in the ID group. Multivariable analysis showed that ID was independently associated with body mass index (P = 0.003), pulmonary hypertension (P = 0.008), and thyroid disease (P = 0.01). Although patients with ID had a lower exercise capacity compared with patients without ID (393 m [294-455] vs. 344 m [260-441], P = 0.008), there was no significant correlation after multivariable correction for age, BMI, NT-proBNP, DM, and depression., Conclusions: Heart failure with preserved ejection fraction patients with ID have a worse prognosis and impaired exercise capacity compared with those without ID. However, although a trend was observed, after multivariable correction ID was no longer significantly associated with a reduced exercise capacity. This reflects that impaired exercise capacity in HFpEF is complex and seems multifactorial. Interestingly, pulmonary hypertension was an independent predictor of both ID and exercise capacity., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Cardiac resynchronisation therapy (CRT) requires intensive, complex and multidisciplinary care to maximize the clinical benefit. In current practice this is typically a task for highly specialised physicians. We report on a novel multidisciplinary, standardised CRT care pathway (CRT-CPW). Experienced clinicians developed a CPW with simple and broadly applicable aids based on clinical evidence and identified shortcomings in the current CRT care. The resulting CPW was implemented at the Maastricht University Medical Center, aiming at a transfer from heterogeneous physician-led care to standardized nurse-led care., Methods: Two CRT patient cohorts were compared in this analysis. The benchmarked usual care cohort (2012-2014, 122 patients) was compared with the CRT-CPW cohort (2015-2017, 115 patients). The primary outcomes were process-related: number of physician consultations, nurse consultations, length of stay (LOS) at implantation and total hospitalisation days during 1-year follow-up, and referral-to-treatment time. Clinical outcomes were assessed to adress non-inferiority of quality of care., Results: Patients in the CRT-CPW cohort consulted nurses and technicians significantly more often than patients in the usual care cohort (2.4±1.5 vs 1.7±2.0, p<0.0001 and 4.3±2.5 vs 3.7±1.5, p=0.063, respectively). Patients with CRT-CPW consulted physicians significantly less often (1.7±1.4 vs 2.6±2.1, p<0.001). Referral to treatment time was significantly reduced in the CRT-CPW group (23.6±18.4 vs 37.0±26.3 days, p=0.002). LOS at implantation and total hospitalisation days were significantly reduced in the CRT-CPW group (1.1±1.2 vs 1.5±0.7 days, p<0.0001 and 2.4±4.8 vs 4.8±9.3, p<0.0001, respectively). Clinical outcome analyses showed no significant difference in 12-month all-cause mortality and heart failure hospitalisations., Conclusion: The introduction of a novel CRT-CPW resulted in a successful transition of physician-led to nurse-led care, with a significantly reduced resource use and equal clinical outcomes. Future evaluations will focus on impact on outcomes versus costs, to evaluate cost-effectiveness of the CRT-CPW., Competing Interests: Competing interests: AVS, WD, CK and KV have nothing to disclose; SS is employee of Medtronic and HP B-lR reports grants from Vifor, Novartis and Roche Diagnostics, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Previous uncontrolled studies suggested a possible benefit of intravenous immunoglobulin (IVIg) in parvovirus B19 (B19V)-related dilated cardiomyopathy (DCM). This randomized, double-blind, placebo-controlled, single-centre trial investigated the benefits of IVIg beyond conventional therapy in idiopathic chronic DCM patients with B19V persistence., Methods and Results: Fifty patients (39 men; mean age 54 ± 11 years) with idiopathic chronic (>6 months) DCM on optimal medical therapy, left ventricular ejection fraction (LVEF) <45%, and endomyocardial biopsy (EMB) B19V load of >200 copies/µg DNA were blindly randomized to either IVIg (n = 26, 2 g/kg over 4 days) or placebo (n = 24). The primary outcome was change in LVEF at 6 months after randomization. Secondary outcomes were change in functional capacity assessed by 6-min walk test (6MWT), quality of life [Minnesota Living with Heart Failure Questionnaire (MLHFQ)], left ventricular end-diastolic volume (LVEDV), and EMB B19V load at 6 months after randomization. LVEF significantly improved in both IVIg and placebo groups (absolute mean increase 5 ± 9%, P = 0.011 and 6 ± 10%, P = 0.008, respectively), without a significant difference between groups (P = 0.609). Additionally, change in 6MWT [median (interquartile range) IVIg 36 (13;82) vs. placebo 32 (5;80) m; P = 0.573], MLHFQ [IVIg 0 (-7;5) vs. placebo -2 (-6;6), P = 0.904] and LVEDV (IVIg -16 ± 49 mL/m 2 vs. placebo -29 ± 40 mL/m 2 ; P = 0.334) did not significantly differ between groups. Moreover, despite increased circulating B19V antibodies upon IVIg administration, reduction in cardiac B19V did not significantly differ between groups., Conclusion: Intravenous immunoglobulin therapy does not significantly improve cardiac systolic function or functional capacity beyond standard medical therapy in patients with idiopathic chronic DCM and cardiac B19V persistence., Clinical Trial Registration: ClinicalTrials.gov ID NCT00892112., (© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: The relative impact of left ventricular (LV) diastolic dysfunction (LVDD) and impaired left atrial (LA) function on cardiovascular haemodynamics in heart failure with preserved ejection fraction (HFpEF) is largely unknown. We performed virtual patient simulations to elucidate the relative effects of these factors on haemodynamics at rest and during exercise., Methods and Results: The CircAdapt cardiovascular system model was used to simulate cardiac haemodynamics in wide ranges of impaired LV relaxation function, increased LV passive stiffness, and impaired LA function. Simulations showed that LV ejection fraction (LVEF) was preserved (>50%), despite these changes in LV and LA function. Impairment of LV relaxation function decreased E / A ratio and mildly increased LV filling pressure at rest. Increased LV passive stiffness resulted in increased E / A ratio, LA dilation and markedly elevated LV filling pressure. Impairment of LA function increased E / A ratio and LV filling pressure, explaining inconsistent grading of LVDD using echocardiographic indices. Exercise simulations showed that increased LV passive stiffness exerts a stronger exercise-limiting effect than impaired LV relaxation function does, especially with impaired LA function., Conclusion: The CircAdapt model enabled realistic simulation of virtual HFpEF patients, covering a wide spectrum of LVDD and related limitations of cardiac exercise performance, all with preserved resting LVEF. Simulations suggest that increased LV passive stiffness, more than impaired relaxation function, reduces exercise tolerance, especially when LA function is impaired. In future studies, the CircAdapt model can serve as a valuable platform for patient-specific simulations to identify the disease substrate(s) underlying the individual HFpEF patient's cardiovascular phenotype., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cardiac resynchronization therapy (CRT) is an established therapy in patients with dilated cardiomyopathy (DCM) and conduction disorders. Still, one-third of the patients with DCM do not respond to CRT. This study aims to depict the underlying cardiac pathophysiological processes of nonresponse to CRT in patients with DCM using endomyocardial biopsies., Methods: Within the Maastricht and Innsbruck registries of patients with DCM, 99 patients underwent endomyocardial biopsies before CRT implantation, with histological quantification of fibrosis and inflammation, where inflammation was defined as >14 infiltrating cells/mm 2 . Echocardiographic left ventricular end-systolic volume reduction ≥15% after 6 months was defined as response to CRT. RNA was isolated from cardiac biopsies of a representative subset of responders and nonresponders., Results: Sixty-seven patients responded (68%), whereas 32 (32%) did not respond to CRT. Cardiac inflammation before implantation was negatively associated with response to CRT (25% of responders, 47% of nonresponders; odds ratio 0.3 [0.12-0.76]; P =0.01). Endomyocardial biopsies fibrosis did not relate to CRT response. Cardiac inflammation improved the robustness of prediction beyond well-known clinical predictors of CRT response (likelihood ratio test P <0.001). Cardiac transcriptomic profiling of endomyocardial biopsies reveals a strong proinflammatory and profibrotic signature in the hearts of nonresponders compared with responders. In particular, COL1A1, COL1A2, COL3A1, COL5A1, POSTN, CTGF, LOX, TGFβ1, PDGFRA, TNC, BGN , and TSP2 were significantly higher expressed in the hearts of nonresponders., Conclusions: Cardiac inflammation along with a transcriptomic profile of high expression of combined proinflammatory and profibrotic genes are associated with a poor response to CRT in patients with DCM.

Objectives: This study sought to investigate the prevalence of systolic dysfunction using global longitudinal strain (GLS) and its prognostic value in relatives of dilated cardiomyopathy (DCM) patients that had normal left ventricular ejection fraction (LVEF)., Background: DCM relatives are advised to undergo cardiac assessment including echocardiography, irrespective of the genetic status of the index patient. Even though LVEF is normal, the question remains whether this indicates absence of disease or simply normal cardiac volumes. GLS may provide additional information regarding (sub)clinical cardiac abnormalities and thus allow earlier disease detection., Methods: A total of 251 DCM relatives and 251 control subjects with a normal LVEF (≥55%) were screened. Automated software measured the GLS on echocardiographic 2-, 3-, and 4-chamber views. The cutoff value for abnormal strain was >-21.5. Median follow-up was 40 months (interquartile range: 5 to 80 months). Primary outcome was the combination of death and cardiac hospitalization., Results: A total of 120 relatives and 83 control subjects showed abnormal GLS (48% vs. 33%, respectively; p < 0.001). Abnormal GLS was independently associated with DCM relatives and cardiovascular risk factors, rather than genetic mutations. Subjects with abnormal GLS had more frequent cardiac hospitalizations and a higher mortality as compared with subjects with normal GLS (hazard ratio: 3.29; 95% confidence interval: 1.58 to 6.87; p = 0.001). Additionally, follow-up LVEF was measured in a subset of relatives, and it decreased significantly in those with abnormal as compared with normal GLS (p = 0.006)., Conclusions: Relatives of DCM patients had a significantly higher prevalence of systolic dysfunction detected by GLS despite normal LVEF compared with control subjects, independent of age, sex, comorbidities, and genotype. Abnormal GLS was associated with LVEF deterioration, cardiac hospitalization, and death., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between longitudinal clinical congestion pattern and heart failure outcome is uncertain. This study was designed to assess the prevalence of congestion over time and to investigate its impact on outcome in chronic heart failure., Methods: A total of 588 patients with chronic heart failure older than 60 years of age with New York Heart Association (NYHA) functional class ≥II from the TIME-CHF study were included. The endpoints for this study were survival and hospitalization-free heart failure survival. Orthopnea, NYHA ≥III, paroxysmal nocturnal dyspnea, hepatomegaly, peripheral pitting edema, jugular venous distension, and rales were repeatedly investigated and related to outcomes. These congestion-related signs and symptoms were used to design a 7-item Clinical Congestion Index., Results: Sixty-one percent of patients had a Clinical Congestion Index ≥3 at baseline, which decreased to 18% at month 18. During the median [interquartile range] follow-up of 27.2 [14.3-39.8] months, 17%, 27%, and 47% of patients with baseline Clinical Congestion Index of 0, 1-2, and ≥3 at inclusion, respectively, died (P <.001). Clinical Congestion Index was identified as an independent predictor of mortality at all visits (P <.05) except month 6 and reduced hospitalization-free heart failure survival (P <.05). Successful decongestion was related to better outcome as compared to persistent congestion or partial decongestion (log-rank P <0.001)., Conclusions: The extent of congestion as assessed by means of clinical signs and symptoms decreased over time with intensified treatment, but it remained present or relapsed in a substantial number of patients with heart failure and was associated with poor outcome. This highlights the importance of appropriate decongestion in chronic heart failure., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Evidence suggests that telemonitoring decreases mortality and heart failure (HF)-related hospital admission in patients with HF. However, most studies follow their patients for only several months. Little is known about the long-term effects of telemonitoring after a period of application., Methods: In 2007, the TEHAF study was initiated to compare tailored telemonitoring with usual care with respect to time until first HF-related hospital admission. In total, 301 patients completed the study after a follow-up period of one year. No differences could be found in time to first HF-related admission between intervention and control groups. Here, we performed a retrospective analysis in order to investigate potential long-term effects of telemonitoring. The primary endpoint was time to first HF-related hospital admission. Secondary endpoints were, amongst others, all-cause mortality, hospital admission due to HF and days alive and out of hospital (DAOOH). Electronic files of all included patients were reviewed between October 2007 and September 2015., Result: Mean follow-up duration was 1652 days (standard deviation: 1055 days). No significant difference in time to first HF-related hospital admission (log-rank test, p = 0.15), all-cause mortality (log-rank test, p = 0.43), or DAOOH (two-sample t-test, p = 0.87) could be found. However, patients that underwent telemonitoring had significantly fewer HF-related hospital admissions (incident rate ratio 0.54, 95% confidence interval 0.31-0.88)., Discussion: Telemonitoring did not significantly influence the long-term outcome in our study. Therefore, extending the follow-up period of telemonitoring studies in HF patients is probably not beneficial.

Objective: This study aims to compare the informative value of a capacitively coupled electrocardiogram (cECG) to a conventional galvanic reference ECG (rECG) in patients after a major cardiac event under simulated driving conditions. Addressed research questions are the comparison and coherence of cECG and rECG by means of the signal quality, the artifact rate, the rate of assessable data for differential diagnosis, the visibility of characteristic ECG structures in cECG, the precision of ECG time intervals, and heart rate (in particular, despite possible waveform deformations due to the cardiac preconditions)., Methods: In a clinical trial, cECG and rECG data were recorded from ten patients after a major cardiac event. The cECG and rECG data were blindly evaluated by two cardiologists with regard to signal quality, artifacts, assessable data for differential diagnosis, visibility of ECG structures, and ECG time intervals. The results were statistically compared., Results: The cECG presented with more artifacts, an inferior signal quality, and less assessable data. However, when the data were assessable, determination of the ECG interval lengths was coherent to the one obtained from the rECG., Conclusion: When the signal quality is sufficient, the cECG yields the same informative value as the rECG., Significance: For certain scenarios, cECG might replace rECG systems. Hence, it is an important research question whether a similar amount of information can be obtained using a cECG system.

Background: The aim of this study was to investigate whether speckle-tracking echocardiography (STE) improves the detection of myocardial infarction (MI) over visual assessment of systolic wall motion abnormalities (SWMAs) using delayed enhancement cardiac magnetic resonance imaging as a reference., Methods: Transthoracic echocardiography was performed in 95 patients with first ST segment elevation MI 110 days (interquartile range, 97-171 days) after MI and in 48 healthy control subjects. Two experienced observers independently assessed SWMAs. Separately, longitudinal peak negative, peak systolic, end-systolic, global strain, and strain rate were measured and averaged for the American Heart Association-recommended coronary artery perfusion territories. Receiver operating characteristic analysis was used to determine a single optimal cutoff value for each strain parameter. The diagnostic accuracy of an algorithm combining visual assessment and STE was evaluated., Results: Median infarct size and transmurality were 15% (interquartile range, 7%-24%) and 64% (interquartile range, 46%-78%), respectively. Sensitivity, specificity, and accuracy of visual assessment to detect MI were 74% (95% CI, 63%-82%), 85% (95% CI, 72%-93%), and 78% (95% CI, 70%-84%), respectively. Among the strain parameters, SR had the highest diagnostic accuracy (area under the curve, 0.88; 95% CI, 0.83-0.94; cutoff value, -0.97 sec -1 ). The combination with STE improved sensitivity compared with visual assessment alone (94%; 95% CI, 86%-97%; P < .001), minimally affecting specificity (79%; 95% CI, 65%-89%; P = .607). Overall accuracy improved to 89% (95% CI, 82%-93%; P = .011). Multivariate analysis accounting for age and sex demonstrated that SR was independently associated with MI (odds ratio, 2.0; 95% CI, 1.6-2.7)., Conclusions: The sensitivity and diagnostic accuracy of visually detecting chronic MI by assessing SWMAs are moderate but substantially improve when adding STE., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Loop diuretics remain the cornerstone of congestion management in contemporary chronic heart failure care. However, their use is not supported by high quality data, and there is doubt about the safety in the outpatient heart failure setting. Still, congestion is related to a worse outcome, and there is general consensus among experts that congestion should not be tolerated in heart failure patients. Recommendations in international guidelines, regarding decongestion strategies in chronic heart failure, are limited. Thus, there is an emerging need for clinical decision-making support about the best strategy for using loop diuretics and decongestion in the chronic setting. The present review provides a comprehensive overview over the evidence of chronic loop diuretic use. Strategies for the assessment of congestion in the outpatient setting and decongestion algorithm are provided to assist health care specialists in delivering high-quality heart failure care.

Introduction Home-based programmes for cardiac rehabilitation play a key role in the recovery of patients with coronary artery disease. However, their necessary educational and motivational components have been rarely implemented with the help of modern mobile technologies. We developed a mobile health system designed for motivating patients to adhere to their rehabilitation programme by providing exercise monitoring, guidance, motivational feedback, and educational content. Methods Our multi-disciplinary approach is based on mapping "desired behaviours" into specific system's specifications, borrowing concepts from Fogg's Persuasive Systems Design principles. A randomised controlled trial was conducted to compare mobile-based rehabilitation (55 patients) versus standard care (63 patients). Results Some technical issues related to connectivity, usability and exercise sessions interrupted by safety algorithms affected the trial. For those who completed the rehabilitation (19 of 55), results show high levels of both user acceptance and perceived usefulness. Adherence in terms of started exercise sessions was high, but not in terms of total time of performed exercise or drop-outs. Educational level about heart-related health improved more in the intervention group than the control. Exercise habits at 6 months follow-up also improved, although without statistical significance. Discussion Results indicate that the adopted design methodology is promising for creating applications that help improve education and foster better exercise habits, but further studies would be needed to confirm these indications.

Background: Inflammatory cardiomyopathy (infl-CMP) is characterized by increased cardiac inflammation in the absence of viruses, ischemia, valvular disease, or other apparent causes. Studies addressing the efficacy of immunosuppressive therapy in patients with infl-CMP are sparse. This study retrospectively investigates whether immunosuppressive agents on top of heart failure therapy according to current guidelines improves cardiac function and long-term outcome in patients with infl-CMP., Methods and Results: Within the Innsbruck and Maastricht Cardiomyopathy Registry, a total of 209 patients fulfilled the criteria for infl-CMP using endomyocardial biopsy (≥14 infiltrating inflammatory cells/mm 2 ). A total of 110 (53%) patients received immunosuppressive therapy and 99 (47%) did not. To correct for potential selection bias, 1:1 propensity score matching was used on all significant baseline parameters, resulting in a total of 90 patients per group. Baseline characteristics did not significantly differ between both patient groups, reflecting optimal propensity score matching. After a median follow-up of 31 (15-47) months, immunosuppressive therapy resulted in an improved long-term outcome (eg, heart transplantation-free survival) as compared with standard heart failure therapy alone (Log-rank P =0.043; hazard ratio, 0.34 [95% CI, 0.17-0.92]) and in a significant larger increase of left ventricular ejection fraction after a mean of 12 months follow-up, as compared with patients receiving standard heart failure treatment only (12.2% versus 7.3%, respectively; P =0.036)., Conclusions: To conclude, this study suggests that immunosuppressive therapy in infl-CMP patients results in an improved heart transplantation-free survival as compared with standard heart failure therapy alone, underscoring the urgent need for a large prospective multicenter trial., (© 2018 American Heart Association, Inc.)

Heart failure is a complex disease with poor outcome. This complexity may prevent care providers from covering all aspects of care. This could not only be relevant for individual patient care, but also for care organisation. Disease management programmes applying a multidisciplinary approach are recommended to improve heart failure care. However, there is a scarcity of research considering how disease management programme perform, in what form they should be offered, and what care and support patients and care providers would benefit most. Therefore, the Improving kNowledge Transfer to Efficaciously Raise the level of Contemporary Treatment in Heart Failure (INTERACT-in-HF) study aims to explore the current processes of heart failure care and to identify factors that may facilitate and factors that may hamper heart failure care and guideline adherence. Within a cross-sectional mixed method design in three regions of the North-West part of Europe, patients (n = 88) and their care providers (n = 59) were interviewed. Prior to the in-depth interviews, patients were asked to complete three questionnaires: The Dutch Heart Failure Knowledge scale, The European Heart Failure Self-care Behaviour Scale and The global health status and social economic status. In parallel, retrospective data based on records from these (n = 88) and additional patients (n = 82) are reviewed. All interviews were audiotaped and transcribed verbatim for analysis.