Changes in the diagnostic trajectory of transthyretin cardiac amyloidosis over six years.

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.

Retinal Vascular Changes in Heart Failure with Preserved Ejection Fraction Using Optical Coherence Tomography Angiography.

Background: Systemic microvascular regression and dysfunction are considered important underlying mechanisms in heart failure with preserved ejection fraction (HFpEF), but retinal changes are unknown. Methods: This prospective study aimed to investigate whether retinal microvascular and structural parameters assessed using optical coherence tomography angiography (OCT-A) differ between patients with HFpEF and control individuals (i.e., capillary vessel density, thickness of retina layers). We also aimed to assess the associations of retinal parameters with clinical and echocardiographic parameters in HFpEF. HFpEF patients, but not controls, underwent echocardiography. Macula-centered 6 × 6 mm volume scans were computed of both eyes. Results: Twenty-two HFpEF patients and 24 controls without known HFpEF were evaluated, with an age of 74 [68-80] vs. 68 [58-77] years (p = 0.027), and 73% vs. 42% females (p = 0.034), respectively. HFpEF patients showed vascular degeneration compared to controls, depicted by lower macular vessel density (p < 0.001) and macular ganglion cell-inner plexiform layer thickness (p = 0.025), and a trend towards lower total retinal volume (p = 0.050) on OCT-A. In HFpEF, a lower total retinal volume was associated with markers of diastolic dysfunction (septal e', septal and average E/e': R2 = 0.38, 0.36, 0.25, respectively; all p < 0.05), even after adjustment for age, sex, diabetes mellitus, or atrial fibrillation. Conclusions: Patients with HFpEF showed clear levels of retinal vascular changes compared to control individuals, and retinal alterations appeared to be associated with markers of more severe diastolic dysfunction in HFpEF. OCT-A may therefore be a promising technique for monitoring systemic microvascular regression and cardiac diastolic dysfunction.

Clinical Guideline for Preimplantation Genetic Testing in Inherited Cardiac Diseases.

BACKGROUND: Preimplantation genetic testing (PGT) is a reproductive technology that selects embryos without (familial) genetic variants. PGT has been applied in inherited cardiac disease and is included in the latest American Heart Association/American College of Cardiology guidelines. However, guidelines selecting eligible couples who will have the strongest risk reduction most from PGT are lacking. We developed an objective decision model to select eligibility for PGT and compared its results with those from a multidisciplinary team. METHODS: All couples with an inherited cardiac disease referred to the national PGT center were included. A multidisciplinary team approved or rejected the indication based on clinical and genetic information. We developed a decision model based on published risk prediction models and literature, to evaluate the severity of the cardiac phenotype and the penetrance of the familial variant in referred patients. The outcomes of the model and the multidisciplinary team were compared in a blinded fashion. RESULTS: Eighty-three couples were referred for PGT (1997-2022), comprising 19 different genes for 8 different inherited cardiac diseases (cardiomyopathies and arrhythmias). Using our model and proposed cutoff values, a definitive decision was reached for 76 (92%) couples, aligning with 95% of the multidisciplinary team decisions. In a prospective cohort of 11 couples, we showed the clinical applicability of the model to select couples most eligible for PGT. CONCLUSIONS: The number of PGT requests for inherited cardiac diseases increases rapidly, without the availability of specific guidelines. We propose a 2-step decision model that helps select couples with the highest risk reduction for cardiac disease in their offspring after PGT.

Epidemiology, pathophysiology, diagnosis and management of chronic right-sided heart failure and tricuspid regurgitation. A clinical consensus statement of the Heart Failure Association (HFA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Right-sided heart failure and tricuspid regurgitation are common and strongly associated with poor quality of life and an increased risk of heart failure hospitalizations and death. While medical therapy for right-sided heart failure is limited, treatment options for tricuspid regurgitation include surgery and, based on recent developments, several transcatheter interventions. However, the patients who might benefit from tricuspid valve interventions are yet unknown, as is the ideal time for these treatments given the paucity of clinical evidence. In this context, it is crucial to elucidate aetiology and pathophysiological mechanisms leading to right-sided heart failure and tricuspid regurgitation in order to recognize when tricuspid regurgitation is a mere bystander and when it can cause or contribute to heart failure progression. Notably, early identification of right heart failure and tricuspid regurgitation may be crucial and optimal management requires knowledge about the different mechanisms and causes, clinical course and presentation, as well as possible treatment options. The aim of this clinical consensus statement is to summarize current knowledge about epidemiology, pathophysiology and treatment of tricuspid regurgitation in right-sided heart failure providing practical suggestions for patient identification and management.

Biomarkers of Collagen Metabolism Are Associated with Left Ventricular Function and Prognosis in Dilated Cardiomyopathy: A Multi-Modal Study.

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.

Webtool to enhance the accuracy of diagnostic algorithms for HFpEF: a prospective cross-over study.

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 H2 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]; H2 FPEF: 50% [38-50]). Correct scoring improved to 100% using the HFpEF calculator (HFA-PEFF: 100% [88-100], P < 0.001; H2 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.

Prevalence and Incidence of Atrial Fibrillation in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: (Additive) Value of Implantable Loop Recorders.

BACKGROUND: Atrial fibrillation (AF) is common in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and has a negative impact on outcome. Reliable data on prevalence, incidence, and detection of AF from contemporary, prospective HFmrEF/HFpEF studies are scarce. METHODS: This was a prespecified sub-analysis from a prospective, multicenter study. Patients with HFmrEF/HFpEF underwent 12-lead electrocardiography (ECG), 24 h Holter monitoring, and received an implantable loop recorder (ILR) at the study start. During the 2 year follow-up, rhythm monitoring was performed via ILR, yearly ECG, and two yearly 24 h Holter monitors. RESULTS: A total of 113 patients were included (mean age 73 ± 8 years, 75% HFpEF). At baseline, 70 patients (62%) had a diagnosis of AF: 21 paroxysmal, 18 persistent, and 31 permanent AF. At study start, 45 patients were in AF. Of the 43 patients without a history of AF, 19 developed incident AF during a median follow-up of 23 [15-25] months (44%; incidence rate 27.1 (95% confidence interval 16.3-42.4) per 100 person-years). Thus, after the 2-year follow-up, 89 patients (79%) had a diagnosis of AF. In 11/19 incident AF cases (i.e., 58%), AF was solely detected on the ILR. Yearly 12-lead ECG detected six incident AF cases and four of these cases were also detected on two yearly 24 h Holter monitors. Two incident AF cases were detected on an unplanned ECG/Holter. CONCLUSIONS: Atrial fibrillation is extremely common in heart failure with HFmrEF/HFpEF and may inform on symptom evaluation and treatment options. AF screening with an ILR had a much higher diagnostic yield than conventional modalities.

Association of left ventricular strain-volume loop characteristics with adverse events in patients with heart failure with preserved ejection fraction.

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.

Left ventricular strain-volume loops and diastolic dysfunction in suspected heart failure with preserved ejection fraction.

BACKGROUND: Presence of left ventricular diastolic dysfunction (DD) is key in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, non-invasive assessment of diastolic function is complex, cumbersome, and largely based on consensus recommendations. Novel imaging techniques may help detecting DD. Therefore, we compared left ventricular strain-volume loop (SVL) characteristics and diastolic (dys-)function in suspected HFpEF patients. METHOD AND RESULTS: 257 suspected HFpEF patients with sinus rhythm during echocardiography were prospectively included. 211 patients with quality-controlled images and strain and volume analysis were classified according to the 2016 ASE/EACVI recommendations. Patients with indeterminate diastolic function were excluded, resulting in two groups: normal diastolic function (control; n = 65) and DD (n = 91). Patients with DD were older (74.8 ± 6.9 vs. 68.5 ± 9.4 years, p < 0.001), more often female (88% vs 72%, p = 0.021), and more often had a history of atrial fibrillation (42% vs. 23%, p = 0.024) and hypertension (91% vs. 71%, p = 0.001) compared to normal diastolic function. SVL analysis showed a larger uncoupling i.e., a different longitudinal strain contribution to volume change, in DD compared to controls (0.556 ± 1.10% vs. -0.051 ± 1.14%, respectively, P < 0.001). This observation suggests different deformational properties during the cardiac cycle. After adjustment for age, sex, history of atrial fibrillation and hypertension, we found an adjusted odds ratio of 1.68 (95% confidence interval 1.19-2.47) for DD per unit increase in uncoupling (range: -2.95-3.20). CONCLUSION: Uncoupling of the SVL is independently associated with DD. This might provide novel insights in cardiac mechanics and new opportunities to assess diastolic function non-invasively.

Dyspnea in patients with atrial fibrillation: Mechanisms, assessment and an interdisciplinary and integrated care approach.

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder and is often associated with symptoms that can significantly impact quality of life and daily functioning. Palpitations are the cardinal symptom of AF and many AF therapies are targeted towards relieving this symptom. However, up to two-third of patients also complain of dyspnea as a predominant self-reported symptom. In clinical practice it is often challenging to ascertain whether dyspnea represents an AF-related symptom or a symptom of concomitant cardiovascular and non-cardiovascular comorbidities, since common AF comorbidities such as heart failure and chronic obstructive pulmonary disease share similar symptoms. In addition, therapeutic approaches specifically targeting dyspnea have not been well validated. Thus, assessing and treating dyspnea can be difficult. This review describes the latest knowledge on the burden and pathophysiology of dyspnea in AF patients. We discuss the role of heart rhythm control interventions as well as the management of AF risk factors and comorbidities with the goal to achieve maximal relief of dyspnea. Given the different and often complex mechanistic pathways leading to dyspnea, dyspneic AF patients will likely profit from an integrated multidisciplinary approach to tackle all factors and mechanisms involved. Therefore, we propose an interdisciplinary and integrated care pathway for the work-up of dyspnea in AF patients.

Interatrial Block Predicts Life-Threatening Arrhythmias in Dilated Cardiomyopathy.

Background Interatrial block (IAB) has been associated with supraventricular arrhythmias and stroke, and even with sudden cardiac death in the general population. Whether IAB is associated with life-threatening arrhythmias (LTA) and sudden cardiac death in dilated cardiomyopathy (DCM) remains unknown. This study aimed to determine the association between IAB and LTA in ambulant patients with DCM. Methods and Results A derivation cohort (Maastricht Dilated Cardiomyopathy Registry; N=469) and an external validation cohort (Utrecht Cardiomyopathy Cohort; N=321) were used for this study. The presence of IAB (P-wave duration>120 milliseconds) or atrial fibrillation (AF) was determined using digital calipers by physicians blinded to the study data. In the derivation cohort, IAB and AF were present in 291 (62%) and 70 (15%) patients with DCM, respectively. LTA (defined as sudden cardiac death, justified shock from implantable cardioverter-defibrillator or anti-tachypacing, or hemodynamic unstable ventricular fibrillation/tachycardia) occurred in 49 patients (3 with no IAB, 35 with IAB, and 11 patients with AF, respectively; median follow-up, 4.4 years [2.1; 7.4]). The LTA-free survival distribution significantly differed between IAB or AF versus no IAB (both P<0.01), but not between IAB versus AF (P=0.999). This association remained statistically significant in the multivariable model (IAB: HR, 4.8 (1.4-16.1), P=0.013; AF: HR, 6.4 (1.7-24.0), P=0.007). In the external validation cohort, the survival distribution was also significantly worse for IAB or AF versus no IAB (P=0.037; P=0.005), but not for IAB versus AF (P=0.836). Conclusions IAB is an easy to assess, widely applicable marker associated with LTA in DCM. IAB and AF seem to confer similar risk of LTA. Further research on IAB in DCM, and on the management of IAB in DCM is warranted.

Rationale and Design of the ISOLATION Study: A Multicenter Prospective Cohort Study Identifying Predictors for Successful Atrial Fibrillation Ablation in an Integrated Clinical Care and Research Pathway.

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.

The HFA-PEFF score identifies 'early-HFpEF' phenogroups associated with distinct biomarker profiles.

AIMS: The HFA-PEFF score was developed to optimize diagnosis and to aid in early recognition of heart failure (HF) with preserved ejection fraction (HFpEF) in patients who present with HF-like symptoms. Recognizing early-HFpEF phenogroups is essential to better understand progression towards overt HFpEF and pave the way for early intervention and treatment. Whether the HFA-PEFF domain scores can identify 'early-HFpEF' phenogroups remains unknown. The aims of this pilot study are to (i) identify distinct phenogroups by cluster analysis of HFA-PEFF domain scores in subjects that present with HF-like symptoms and (ii) study whether these phenogroups may be associated with distinct blood proteome profiles. METHODS AND RESULTS: Subjects referred to the Cardiology Centers of the Netherlands, location Utrecht, with non-acute possibly cardiac-related symptoms (such as dyspnoea or fatigue) were prospectively enrolled in the HELPFul cohort (N = 507) and were included in the current analysis. Inclusion criteria for this study were (i) age ≥ 45 years and (ii) a left ventricular ejection fraction (LVEF) ≥ 50%, in the absence of a history of HF, coronary artery disease, congenital heart disease, or any previous cardiac interventions. Multinominal-based clustering with latent class model using the HFA-PEFF domain scores (functional, structural, and biomarker scores) as input was used to detect distinct phenotypic clusters. For each bootstrapping run, the 92 Olink proteins were analysed for their association with the identified phenogroups. Four distinct phenogroups were identified in the current analysis (validated by bootstrapping 1000×): (i) no left ventricular diastolic dysfunction (no LVDD, N = 102); (ii) LVDD with functional left ventricular (LV) abnormalities (N = 204); (iii) LVDD with functional and structural LV abnormalities (N = 204); and (iv) LVDD with functional and structural LV abnormalities and elevated BNP (N = 107). The HFA-PEFF total score risk categories significantly differed between the phenogroups (P < 0.001), with an increase of the HFA-PEFF score from Phenogroup 1 to 4 (low/intermediate/high HFA-PEFF risk score: Phenogroup 1: 88%/12%/0%; Phenogroup 2: 9%/91%/0%; Phenogroup 3: 0%/92%/8%; Phenogroup 4: 5%/83%/12%). Thirty-two out of the 92 Olink protein biomarkers significantly differed among the phenogroups. The top eight biomarkers-N-terminal prohormone brain natriuretic peptide, growth differentiation factor-15, matrix metalloproteinase-2, osteoprotegerin, tissue inhibitor of metalloproteinase-4, chitinase-3-like protein 1, insulin-like growth factor-binding protein 2, and insulin-like growth factor-binding protein 7-are mainly involved in inflammation and extracellular matrix remodelling, which are currently proposed key processes in HFpEF pathophysiology. CONCLUSIONS: This study identified distinct phenogroups by using the HFA-PEFF domain scores in ambulant subjects referred for HF-like symptoms. The newly identified phenogroups accompanied by their circulating biomarkers profile might aid in a better understanding of the pathophysiological processes involved during the early stages of the HFpEF syndrome.

The value of echocardiographic measurement of epicardial adipose tissue in heart failure patients.

AIMS: Epicardial adipose tissue (EAT) is increasingly recognized as an important factor in the pathophysiology of heart failure (HF). Cardiac magnetic resonance (CMR) imaging is the gold-standard imaging modality to evaluate EAT size, but in contrast to echocardiography, CMR is costly and not widely available. We investigated EAT thickness on echocardiography in relation to EAT volume on CMR, and we assessed the agreement between observers for measuring echocardiographic EAT. METHODS AND RESULTS: Patients with HF and left ventricular ejection fraction >40% were enrolled. All patients underwent CMR imaging and transthoracic-echocardiography. EAT volume was quantified on CMR short-axis cine-stacks. Echocardiographic EAT thickness was measured on parasternal long-axis and short-axis views. Linear regression analyses were used to assess the association between EAT volume on CMR and EAT thickness on echocardiography. Intraclass correlation coefficient (ICC) was used to assess the interobserver agreement as well as the intraobserver agreement. EAT on CMR and echocardiography was evaluated in 117 patients (mean age 71 ± 10 years, 49% women and mean left ventricular ejection fraction 54 ± 7%). Mean EAT volume on CMR was 202 ± 64 mL and ranged from 80 to 373 mL. Mean EAT thickness on echocardiography was 3.8 ± 1.5 mm and ranged from 1.7 to 10.2 mm. EAT volume on CMR and EAT thickness on echocardiography were significantly correlated (junior-observer: r = 0.62, P < 0.001, senior-observer: r = 0.33, P < 0.001), and up to one-third of the variance in EAT volume was explained by EAT thickness (R2  = 0.38, P < 0.001). The interobserver agreement between junior and senior observers for measuring echocardiographic EAT was modest [ICC, 0.65 (95% confidence interval (CI) 0.47-0.77], whereas the intraobserver agreement was good (ICC 0.98, 95% CI 0.84-0.99). CONCLUSIONS: There was a modest correlation between EAT volume on CMR and EAT thickness on echocardiography. Limited agreement between junior and senior observers for measuring echocardiographic EAT was observed. EAT thickness on echocardiography is limited in estimating EAT volume.

Improving diagnosis and risk stratification across the ejection fraction spectrum: the Maastricht Cardiomyopathy registry.

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.

The Role of Systemic Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction.

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.

The clinical and prognostic value of late Gadolinium enhancement imaging in heart failure with mid-range and preserved ejection fraction.

Heart failure (HF) with mid-range or preserved ejection fraction (HFmrEF; HFpEF) is a heterogeneous disorder that could benefit from strategies to identify subpopulations at increased risk. We tested the hypothesis that HFmrEF and HFpEF patients with myocardial scars detected with late gadolinium enhancement (LGE) are at increased risk for all-cause mortality. Symptomatic HF patients with left ventricular ejection fraction (LVEF) > 40%, who underwent cardiac magnetic resonance (CMR) imaging were included. The presence of myocardial LGE lesions was visually assessed. T1 mapping was performed to calculate extracellular volume (ECV). Multivariable logistic regression analyses were used to determine associations between clinical characteristics and LGE. Cox regression analyses were used to assess the association between LGE and all-cause mortality. A total of 110 consecutive patients were included (mean age 71 ± 10 years, 49% women, median N-terminal brain natriuretic peptide (NT-proBNP) 1259 pg/ml). LGE lesions were detected in 37 (34%) patients. Previous myocardial infarction and increased LV mass index were strong and independent predictors for the presence of LGE (odds ratio 6.32, 95% confidence interval (CI) 2.07-19.31, p = 0.001 and 1.68 (1.03-2.73), p = 0.04, respectively). ECV was increased in patients with LGE lesions compared to those without (28.6 vs. 26.6%, p = 0.04). The presence of LGE lesions was associated with a fivefold increase in the incidence of all-cause mortality (hazards ratio 5.3, CI 1.5-18.1, p = 0.009), independent of age, sex, New York Heart Association (NYHA) functional class, NT-proBNP, LGE mass and LVEF. Myocardial scarring on CMR is associated with increased mortality in HF patients with LVEF > 40% and may aid in selecting a subpopulation at increased risk.