Left Atrial Function in Patients with Titin Cardiomyopathy.

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.

Liver stiffness as a cornerstone in heart disease risk assessment.

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.

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.

Loop diuretics in chronic heart failure: how to manage congestion?

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.

Titin cardiomyopathy leads to altered mitochondrial energetics, increased fibrosis and long-term life-threatening arrhythmias.

Aims: Truncating titin variants (TTNtv) are the most prevalent genetic cause of dilated cardiomyopathy (DCM). We aim to study clinical parameters and long-term outcomes related to the TTNtv genotype and determine the related molecular changes at tissue level in TTNtv DCM patients. Methods and results: A total of 303 consecutive and extensively phenotyped DCM patients (including cardiac imaging, Holter monitoring, and endomyocardial biopsy) underwent DNA sequencing of 47 cardiomyopathy-associated genes including TTN, yielding 38 TTNtv positive (13%) patients. At long-term follow-up (median of 45 months, up to 12 years), TTNtv DCM patients had increased ventricular arrhythmias compared to other DCM, but a similar survival. Arrhythmias are especially prominent in TTNtv patients with an additional environmental trigger (i.e. virus infection, cardiac inflammation, systemic disease, toxic exposure). Importantly, cardiac mass is reduced in TTNtv patients, despite similar cardiac function and dimensions at cardiac magnetic resonance. These enhanced life-threatening arrhythmias and decreased cardiac mass in TTNtv DCM patients go along with significant cardiac energetic and matrix alterations. All components of the mitochondrial electron transport chain are significantly upregulated in TTNtv hearts at RNA-sequencing. Also, interstitial fibrosis was augmented in TTNtv patients at histological and transcript level. Conclusion: Truncating titin variants lead to pronounced cardiac alterations in mitochondrial function, with increased interstitial fibrosis and reduced hypertrophy. Those structural and metabolic alterations in TTNtv hearts go along with increased ventricular arrhythmias at long-term follow-up, with a similar survival and overall cardiac function.

Internet-based training of coronary artery patients: the Heart Cycle Trial.

Low adherence to cardiac rehabilitation (CR) might be improved by remote monitoring systems that can be used to motivate and supervise patients and tailor CR safely and effectively to their needs. The main objective of this study was to evaluate the feasibility of a smartphone-guided training system (GEX) and whether it could improve exercise capacity compared to CR delivered by conventional methods for patients with coronary artery disease (CAD). A prospective, randomized, international, multi-center study comparing CR delivered by conventional means (CG) or by remote monitoring (IG) using a new training steering/feedback tool (GEx System). This consisted of a sensor monitoring breathing rate and the electrocardiogram that transmitted information on training intensity, arrhythmias and adherence to training prescriptions, wirelessly via the internet, to a medical team that provided feedback and adjusted training prescriptions. Exercise capacity was evaluated prior to and 6 months after intervention. 118 patients (58 ± 10 years, 105 men) with CAD referred for CR were randomized (IG: n = 55, CG: n = 63). However, 15 patients (27 %) in the IG and 18 (29 %) in the CG withdrew participation and technical problems prevented a further 21 patients (38 %) in the IG from participating. No training-related complications occurred. For those who completed the study, peak VO2 improved more (p = 0.005) in the IG (1.76 ± 4.1 ml/min/kg) compared to CG (-0.4 ± 2.7 ml/min/kg). A newly designed system for home-based CR appears feasible, safe and improves exercise capacity compared to national CR. Technical problems reflected the complexity of applying remote monitoring solutions at an international level.

Electromagnetic interference with implantable cardioverter-defibrillators at power frequency: an in vivo study.

BACKGROUND: The number of implantable cardioverter-defibrillators (ICDs) for the prevention of sudden cardiac death is continuing to increase. Given the technological complexity of ICDs, it is of critical importance to identify and control possible harmful electromagnetic interferences between various sources of electromagnetic fields and ICDs in daily life and occupational environments. METHODS AND RESULTS: Interference thresholds of 110 ICD patients (1-, 2-, and 3-chamber ICDs) were evaluated in a specifically developed test site. Patients were exposed to single and combined electric and magnetic 50-Hz fields with strengths of up to 30 kV·m⁻¹ and 2.55 mT. Tests were conducted considering worst-case conditions, including maximum sensitivity of the device or full inspiration. With devices being programmed to nominal sensitivity, ICDs remained unaffected in 91 patients (83%). Five of 110 devices (5%) showed transient loss of accurate right ventricular sensing, whereas 14 of 31 (45%) of the 2- and 3-chamber devices displayed impaired right atrial sensing. No interference was detected in 71 patients (65%) within the tested limits with programming to maximum sensitivity, whereas 20 of 110 subjects (18%) exhibited right ventricular disturbances and 19 of 31 (61%) subjects exhibited right atrial disturbances. CONCLUSIONS: Extremely low-frequency daily-life electromagnetic fields do not disturb sensing capabilities of ICDs. However, strong 50-Hz electromagnetic fields, present in certain occupational environments, may cause inappropriate sensing, potentially leading to false detection of atrial/ventricular arrhythmic events. When the right atrial/right ventricular interferences are compared, the atrial lead is more susceptible to electromagnetic fields. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/ct2/show/NCT01626261. Unique identifier: NCT01626261.

Long-term follow-up of former world-class swimmers: evaluation of cardiovascular function.

There is some evidence that long-term high-intensity endurance training might be associated with deterioration in cardiac function and might impose a potential risk for cardiovascular events. Thus, the intention was to retrospectively evaluate the cardiac status in former endurance athletes, particularly right ventricular (RV) dimension and function, to reveal potential cardiac damage. A group of 12 former world-class swimmers (45 ± 1.5 years) was examined 24.9 ± 4.3 years after cessation of high-intensity endurance training. They underwent history taking, physical examination, ECG, exercise testing and echocardiography. Furthermore, functional and echocardiography data that were also available from former evaluations were included in the analysis. There was a significant decline in exercise capacity. LV function was normal with a decrease in septal thickness to 9.1 ± 1.3 (p < 0.05) and LV diastolic diameter to 48.9 ± 5.6 (p < 0.05). Still, there was a remaining septal hypertrophy. RV function was 55.3 ± 4.2% and there were normal RV dimensions adjusted for body surface area. 25 years after the cessation of endurance training there was a normal RV and LV function with a normalization of almost all diameters, still there was a mild LV hypertrophy in some athletes. Consequently, no relevant long-term cardiac remodeling after intensive endurance training was depicted in this group of athletes.

Depression, psychological distress, and quality of life in patients with cardioverter defibrillator with or without cardiac resynchronization therapy.

Congestive heart failure is frequent and leads to reduced exercise capacity, reduced quality of life (QoL), and depression in many patients. Cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators (ICD) offer therapeutic options and may have an impact on QoL and depression. This study was performed to evaluate physical and mental health in patients undergoing ICD or combined CRT/ICD-implantation (CRT-D). Echocardiography, spiroergometry, and psychometric questionnaires [Beck Depression Inventory, General World Health Organization Five Well-being Index (WHO-5), Brief Symptom Inventory and 36-item Short Form (SF-36)] were obtained in 39 patients (ICD: 17, CRT-D: 22) at baseline and 6-month follow-up (FU) after device implantation. CRT-D patients had a higher NYHA class and broader left bundle branch block than ICD patients at baseline. At FU, ejection fraction (EF), peak oxygen uptake, and NYHA class improved significantly in CRT-D patients but remained unchanged in ICD patients. Patients with CRT-D implantation showed higher levels of depressive symptoms, psychological distress, and impairment in QoL at baseline and FU compared to ICD patients. These impairments remained mostly unchanged in all patients after 6 months. Overall, these findings imply that there is a need for careful assessment and treatment of psychological distress and depression in ICD and CRT-D patients in the course of device implantation as psychological burden seems to persist irrespective of physical improvement.

Detection of cardiac amyloidosis on routine bone scintigraphy: an important gatekeeper role for the nuclear medicine physician.

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.

Evaluation of the 2021 ESC recommendations for family screening in hereditary transthyretin cardiac amyloidosis.

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.

Functional and topographic concordance of right atrial neural structures inducing sinus tachycardia.

Cardiorespiratory autonomic control is in tight interaction with an intracardiac neural network modulating sinus node function. To gain novel mechanistical insights and to investigate possible novel targets concerning the treatment of inadequate sinus tachycardia, we aimed to characterize functionally and topographically the right atrial neural network modulating sinus node function. In 16 sheep 3-dimensional electro-anatomical mapping of the right atrium was performed. In five animals additionally magnetically steered remote navigation was used. Selective stimulation of nerve fibers was conducted by applying high frequency (200 Hz) electrical impulses within the atrial refractory period. Histological analysis of whole heart preparations by acetylcholinesterase staining was performed and compared to the acquired neuroanatomical mapping.We found that neural stimulation in the cranial part of the right atrium, within a perimeter around the sinus node area, elicited predominantly shortening of the sinus cycle length of -20.3 ± 10.1 % (n = 80, P < 0.05). Along the course of the crista terminalis atrial premature beats (n = 117) and atrial fibrillation (n = 123) could be induced. Catheter stability was excellent during remote catheter navigation. Histological work-up (n = 4) was in accord with the distribution of neurostimulation sites. Ganglions were mainly innervated by the dorsal right-atrial subplexus, with substantial additional input from the ventral right atrial subplexus. In conclusion, our findings suggest a functional and topographic concordance of right atrial neural structures inducing sinus tachycardia. This might open up new avenues in the treatment of heart rate related disorders.

Left Atrial Reverse Remodeling in Dilated Cardiomyopathy.

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/m2, 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/m2). 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/m2; 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.

A graphical analysis of aspects contributing to the spreading of measurements of left ventricular function.

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).

Evaluating subclinical left ventricular and left atrial dysfunction in idiopathic atrial fibrillation: A speckle-tracking based strain-analysis.

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.

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.

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.

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.