Background The temporal relationship between left atrial (LA) functional recovery and structural remodeling after radiofrequency catheter ablation for paroxysmal atrial fibrillation remains incompletely characterized. Objective To characterize the temporal evolution of LA volume and function after ablation using serial cardiac magnetic resonance imaging (CMR). Methods Patients with paroxysmal atrial fibrillation underwent CMR before ablation (T0), immediately after (T1), and at three months (T3). Each patient also underwent one intermediate follow-up scan at either 24 hours (T2a), one week (T2b), or one month (T2c) after ablation. LA volume, total, active, and passive emptying fractions, and reservoir, conduit, and booster pump strain were quantified using CMR feature tracking on steady state-free precession cine 2-chamber and 4-chamber acquisitions. Results 26 patients (19% female, age 62.5 ± 6.6) were enrolled. LA function decreased significantly immediately after ablation, consistent with acute atrial stunning. This decrease was most pronounced in LA active emptying fraction (from 35.9 ± 16.7 at T0 to 11.6 ± 13.7 at T1, p < 0.001) and LA booster pump strain (from 13.3 ± 8.0 at T0 to 3.9 ± 2.0 at T1, p < 0.001). Functional parameters recovered between one week and one month after ablation. LA maximum volume demonstrated a delayed but progressive reduction (from 88.3 ± 26.5 ml at T0 to 79.5 ± 22.8 ml at T3, p = 0.026), consistent with reverse atrial remodeling. Conclusion Following radiofrequency catheter ablation for paroxysmal atrial fibrillation, LA stunning and functional recovery precede structural volumetric remodeling, suggesting distinct temporal mechanisms.

Management of asymptomatic severe mitral regurgitation (MR) is challenging. Both early mitral valve repair surgery and active surveillance with facilitated surgery are possible strategies. The DutchAMR registry compares clinical outcomes between these two strategies. Patients were included between 2013–2019. Primary endpoints were cerebrovascular accidents (CVA), reoperations, and mortality. Facilitated surgery was defined as mitral valve repair surgery performed after developing a surgical indication during active surveillance. Ninety-nine patients were enrolled; 71 in active surveillance and 28 in early surgery. Over a median follow-up time of 5.1 years, 51

Atrial fibrillation (AF) recurrence after catheter ablation (CA), often due to incomplete lesions, remains a challenge. In this study, we evaluate the role of cardiac magnetic resonance (CMR) in characterizing lesion formation and guiding re-ablation strategies in patients with paroxysmal AF undergoing radiofrequency catheter ablation (RFCA). This prospective, single-center study enrolled patients undergoing first-time RFCA for paroxysmal AF. Pre-ablation CMR was performed for functional, anatomical, and fibrosis assessment. Repeat CMR 3 months post-ablation was performed to quantify fibrosis using Image Intensity Ratio (IIR) and detect lesion gaps, defined as ≥ 3 mm discontinuities in late gadolinium enhancement (LGE). AF recurrence was monitored for 18 months. 25 patients (20

BACKGROUND:Current guidelines recommend regular screening for first-degree relatives of gene-elusive arrhythmogenic right ventricular cardiomyopathy (ARVC) patients using a similar regimen as for genotype-positive/phenotype-negative relatives. However, the multifactorial nature of gene-elusive ARVC may necessitate a different approach. This study aimed to determine the yield of cardiac screening in first-degree relatives of ARVC probands without a validated genetic cause. METHODS:We included all first-degree relatives of probands who (1) met the 2010 Task Force Criteria, (2) underwent next-generation sequencing that included all genes with at least moderate evidence for ARVC causation per Clinical Genome Resource appraisal (validated ARVC genes), and (3) had no pathogenic/likely pathogenic (P/LP) variants identified in these genes. The primary and secondary end points were definite ARVC by the 2010 Task Force Criteria and ventricular arrhythmia, respectively. RESULTS:We included 44 relatives (39.0 [22.3-45.8] years; 36% male) from 24 families. In 4 (17%) families, a P/LP variant was identified in a different cardiomyopathy/arrhythmia gene (SCN5A, LMNA, CDH2, FLNC). Overall, 10 (23%) relatives had definite ARVC at baseline evaluation. Of the 20 relatives without definite ARVC who had follow-up available, 8/20 (40%) relatives progressed to definite ARVC during 9.0 (5.8-14.4) years of follow-up. No statistical difference in the yield of baseline screening or serial evaluation between relatives from families with a P/LP variant and relatives from families without a P/LP variant was observed. Of the 27 relatives who had follow-up available, ventricular arrhythmia was observed in 2/27 (7%) relatives and occurred 6.3 and 13.8 years after definite ARVC diagnosis. Both of those relatives were from families without a P/LP variant. CONCLUSIONS:These findings highlight the importance of managing first-degree relatives of ARVC probands without a validated genetic cause similarly to genotype-positive ARVC relatives. Furthermore, using a broad cardiomyopathy and arrhythmia gene panel in ARVC probands, rather than limiting testing to validated ARVC genes alone, is warranted.

AIMS:Conflicting results have been reported on the prognostic value of coronary stenosis grade and plaque burden. We aimed to investigate the time-varying risk for cardiovascular events associated with diameter stenosis (DS%) and plaque burden. METHODS AND RESULTS:Patients without a documented cardiac history who underwent coronary computed tomography angiography for suspected coronary artery disease were included. The most severe DS% and plaque burden, defined as percentage atheroma volume (PAV), were used for analysis. The primary endpoint was a composite of all-cause mortality and non-fatal myocardial infarction. For analysis, the maximal follow-up time was 8 years. Among 2819 patients [mean age 62 ± 10; 1245 (45%) male], 235 events occurred during a median follow-up of 6.9 years. Cox models including cardiovascular risk factors, DS%, and PAV demonstrated that DS% but not PAV was predictive for short-term events at 1-year follow-up [adjusted hazard ratio (aHR) 1.028, 95% confidence interval (CI) 1.013-1.044 vs. 1.015, 95% CI 0.978-1.053]. In contrast, PAV but not DS% was predictive for long-term events at 8-year follow-up (aHR 1.035, 95% CI 1.021-1.050 vs. 1.005, 95% CI 0.999-1.012). The predictive value of DS% was stronger before than after 1 year of follow-up (aHR <1 year 1.027, 95% CI 1.012-1.042 vs. aHR 1-8 years 1.001, 95% CI 0.994-1.008; P < 0.01 for difference), while the predictive value of PAV did not significantly change (P = 0.12). CONCLUSION:Coronary diameter stenosis holds the highest prognostic significance for short-term cardiovascular events, while plaque burden predicts events in the long term.

BACKGROUND:Thoracic aortic aneurysms and dissections (TAAD) are life-threatening vascular disorders affecting the medial layer of the aortic wall, associated with high mortality when a rupture or dissection occurs. Though numerous genes are associated with familial TAAD (FTAAD), pathogenic variants in MYH11, encoding smooth muscle cell specific myosin heavy chain (SM-MHC), represent a rare but interesting subgroup as many gaps remain in the knowledge of disease mechanisms, phenotype presentation and gene-environmental interactions. No reliable therapy exists in halting aneurysm growth in affected individuals. SCOPE OF REVIEW:This review aims to summarize current evidence on disease pathophysiological mechanisms. Furthermore, phenotypic variability, extrathoracic vascular involvement and the possibility of future curative gene therapy options are evaluated. FINDINGS:Most reported pathogenic MYH11 variants are missense or splice-site variants that disrupt the C-terminal coiled-coil dimerization and therefore thick filament assembly. Evidence from mouse models, patient-derived cells and limited human ex vivo tissue studies shows that these variants are associated with impaired thick filament organization, reduced force generation and disruption of the elastin-contractile unit, with subsequent alterations in ECM remodelling. However, the precise causal sequence in human disease has not yet been established. Clinically, MYH11-associated disease is associated with FTAAD and patent ductus arteriosus (PDA). Reduced penetrance, variable expression of disease and unknown potential gene-environment interactions complicate risk prediction and clinical counselling of affected individuals. Emerging RNA-therapy strategies aimed at allele-specific correction of genetic disease offer interesting future therapeutic targets, although vascular delivery and long-term safety remain challenges. CONCLUSION:MYH11 should be viewed as a clinically meaningful gene that is associated with TAAD and PDA. Current limited evidence shows that the phenotype is characterized by contractile dysfunction, increased aortic stiffness and potential susceptibility to hemodynamic stress. Future work should investigate translatable mechanistic studies, larger registries for genotype-phenotype correlations and evaluation of targeted gene therapy approaches.

BACKGROUND:Cardiac resynchronization therapy (CRT) improves survival and symptoms in patients with heart failure with reduced ejection fraction and electromechanical dyssynchrony, yet up to 30-40% do not respond despite guideline-based selection. Hemodynamic forces (HDF) quantify intraventricular pressure gradients and can be derived from routine echocardiographic images. The aim of this study was to assess the predictive and prognostic value of HDF parameters in patients undergoing CRT and to investigate changes in HDF after CRT implantation. METHODS:The following HDF parameters were assessed in 198 patients from the multicenter, prospective MARC study: (i) apical-basal force, (ii) latero-septal force (iii) their ratio (iv) force vector angle, (v) systolic apical-basal force, (vi) systolic angle. CRT response was defined as ≥15% reduction in left ventricular end-systolic volume (LVESV) at 6 months. The composite outcome of all-cause mortality or cardiovascular hospitalization was analyzed using Cox regression models with long-term follow-up. RESULTS:120 patients (60.6%) demonstrated echocardiographic response to CRT at 6 months. The addition of baseline systolic angle to clinical, electrocardiographic, and conventional echocardiographic markers of dyssynchrony significantly improved model fit for CRT response, although discrimination was not significantly improved. Responders showed significant improvement in HDF parameters after CRT, whereas no significant changes were observed in non-responders. During a median follow-up of 9.3 years, baseline systolic angle was independently associated with the composite endpoint of all-cause mortality or cardiovascular hospitalization and significantly improved risk stratification when added to established prognostic markers. CONCLUSION:HDF parameters provide complementary descriptive insight into ventricular mechanics in patients undergoing CRT. Baseline systolic angle was independently associated with both reverse remodeling and long-term outcome, although discrimination was not significantly improved. While these findings suggest potential value for HDF assessment, further research is warranted to determine the clinical relevance in CRT patients.

The left atrioventricular coupling index (LACI), defined as the ratio of left atrial (LA) to left ventricular (LV) end-diastolic volumes, serves as a surrogate for atrioventricular coupling. Cardiac resynchronization therapy (CRT) promotes reverse remodeling of both chambers and may enhance atrioventricular coupling, yet the clinical utility of LACI in CRT patients remains unclear. This study evaluated the effect of CRT on LACI and assessed its prognostic value for CRT response. In 123 patients enrolled in the ADVISE-CRT III trial (mean age 66 ± 10 years; 63

The integration of telehealth, particularly remote monitoring (RM), has profoundly improved the care of patients with cardiac implantable electronic devices (CIEDs). The recent COVID-19 pandemic has further accelerated the adoption of RM systems. The implementation of RM to standard clinical care has been accompanied by a surge of device transmissions. Especially unscheduled transmissions have resulted in an overwhelming workload for clinicians. As the number of device transmissions is expected to increase further while clinical resources remain limited, workflow optimization is crucial. Artificial intelligence (AI) presents a promising solution. This review outlines recent advances in RM and AI applications for CIEDs. It explores the potential of AI to streamline RM workflows, reduce clinician workload, and enhance heart failure care by enabling early detection of clinical deterioration and timely intervention. In addition, key barriers to implementation are addressed, including data standardization and regulatory considerations. Beyond improving monitoring efficiency and patient outcomes, AI-supported RM may also help expand access to care through more effective resource allocation and contribute to a more sustainable, future-proof healthcare system.

Introduction This study investigates the interplay between the circulating plasma proteome and echocardiographic parameters in patients across the spectrum of heart failure (HF) (ranging from patients at risk of/with preserved (HFpEF) to reduced (HFrEF) ejection fraction). Methods Data from two cohort studies, HELPFul and Bio-SHiFT, were analyzed. We measured 4210 circulating plasma proteins in a total of 750 patients using SomaScan® proteomics. Echocardiographic parameters in both studies included left ventricular ejection fraction (LVEF) and the ratio of the peak early left ventricular (LV) filling velocity and early diastolic mitral annular velocity (E/e’). In further analyses, we classified patients in left ventricular diastolic dysfunction (LVDD) groups according to the prevailing guidelines. Results Out of the 4210 plasma proteins, 21 proteins were significantly associated with E/e’ in patients at risk of/with HFpEF, whereas 9 proteins were associated with LVEF. Approximately 43 % (n = 1822) of the proteins showed significant interactions between E/e’ and HF subtype. All of these proteins showed weaker associations with E/e’ in patients at risk of/with HFpEF compared to the ones with HFrEF. These proteins were related to the extracellular matrix, cellular processes, insulin-like growth factor (IGF) transport, metabolic and catabolic processes. Furthermore, comparisons between LVDD groups and those with normal diastolic function identified 40 proteins associated with grade 2 (top 5: Cystatin C, TMEDA, NT-proBNP, GDF-15 and PXDN) and 198 with grade 3 LVDD (top 5: NT-proBNP, Cystatin C, PXDN, RNasa1, and Factor D). Conclusion In patients at risk of/with HFpEF, biological processes and pathways showed weaker associations with E/e’ compared to patients with HFrEF. Varying pathways identified through proteomics were associated with deterioration of LVDD across the ejection fraction spectrum. Our results are in line with the mechanistic frameworks currently thought to underlie the various types of HF.

BACKGROUND:Penetrance and risk of ventricular arrhythmias (VAs) in arrhythmogenic right ventricular cardiomyopathy (ARVC) are increasingly recognized as being genotype specific. Therefore, genotype-informed family screening protocols may lead to safer and more personalized recommendations than the current one-size-fits-all screening recommendations. We aimed to develop a safe, evidence-based plakophilin-2 (PKP2)-specific longitudinal screening algorithm. METHODS:We included 295 relatives (41% male; age 30.9 years [18.0-47.7 years]) with a pathogenic or likely pathogenic PKP2 variant from 145 families. Phenotype was ascertained with ECG, Holter monitoring, and cardiac imaging and classified by the 2010 Task Force Criteria. VA was defined as a composite of sudden cardiac arrest or death, spontaneous sustained ventricular tachycardia, ventricular fibrillation, or appropriate implantable cardioverter defibrillator intervention. We performed Cox regression to determine predictors of ARVC development and multistate modeling to assess the probability of ARVC development and occurrence of VA. RESULTS:At baseline, 110 relatives (37%) had definite ARVC. During 8.5 years (4.2-12.9 years) of follow-up, 62 of 185 relatives (34%) without definite ARVC at baseline progressed to definite ARVC diagnosis, and 35 of 295 of all relatives (12%) had VA. VAs occurred only in relatives who previously fulfilled definite ARVC diagnosis. Relatives with borderline ARVC (fulfillment of one minor criterion plus the major family history criterion) progressed 5 times faster in the multistate model to definite ARVC diagnosis and compared with genotype-positive/phenotype-negative (G+/P-) relatives (ie, major family history criterion alone). Relatives 20 to 40 years of age had increased risk for developing definite ARVC (hazard ratio, 2.23; P=0.012) compared with those ≥40 years of age. New Task Force Criteria fulfillment most commonly occurred first on ECGs, followed by Holter monitoring and cardiac imaging. Consequently, 3 risk profiles were identified, and appropriate screening protocols were derived: relatives with borderline ARVC (annual ECG and Holter monitoring; complete evaluation [ie, ECGs, Holter monitoring, and imaging] every 2 years), younger (<40 years of age) or symptomatic G+/P- relatives (every 2 years an ECG and Holter monitoring; complete evaluation every 4 years), and older (≥40 years of age) and asymptomatic G+/P- relatives (complete evaluation every 5 years). CONCLUSIONS:An evidence-based longitudinal screening algorithm that integrates age, symptoms, and baseline clinical phenotype may improve patient care and improve efficiency of clinical resource allocation.

Background Advances in implantable cardioverter-defibrillator (ICD) programming strategies have achieved significant reductions in inappropriate shocks. However, further refinement is needed to minimize appropriate but unnecessary therapies. The ENHANCED-ICD study initially demonstrated the short-term safety and efficacy of programming a number of intervals to detect (NID) of 60/80 over a median follow-up of 1.3 years. A decade later, this study presents the long-term impacts of this programming strategy.Objective To assess the long-term impact of programming NID 60/80 for ventricular tachycardia (VT)/ventricular fibrillation (VF) detection on adverse events related to shocks and arrhythmias, as well as on ICD therapies-both delivered and avoided.Methods A retrospective analysis was conducted on 60 patients from the ENHANCED-ICD study, a prospective, single-center trial. The median age was 60 years, 78% were men, and 53% had a primary prevention ICD indication. A prolonged detection interval of NID 60/80 was programmed for VT/VF detection. The cycle lengths for VT/fast VT/VF were set at 360/330/240 ms, respectively.Results After a median follow-up of 9.4 years, Enhanced programming prevented unnecessary ICD therapies in 16.7% of patients and reduced the overall therapy rate by 25.9%. A total of 26.7% of patients received ICD therapy, with appropriate therapy delivered in 23.3% and inappropriate therapy occurring in 3.3% of patients. No arrhythmic deaths were observed, while syncope was reported in 10.0% of patients (1.63 per 100 patient-years).Conclusion Prolonging the ICD detection interval to an NID of 60/80 successfully prevented appropriate but unnecessary therapy, while maintaining safety during long-term follow-up.

Abstract Background Hyponatremia is one of the complicating findings in acute decompensated heart failure. Decrease in cardiac output and systemic blood pressure triggers activation of renin–angiotensin–aldosterone system, antidiuretic hormone, and norepinephrine due to the perceived hypovolemia. Fluid-overloaded heart failure patients are commonly treated with loop diuretics, acutely decompensated heart failure patients tend to be less responsive to conventional oral doses of a loop diuretic, while other different diuretics could work in different part of nephron circulation system. In this study, we aim to further examine the role of tolvaptan, a vasopressin receptor antagonist, in the treatment of hyponatremia secondary to acutely decompensated heart failure. Results A total of 71 patients with hyponatremia secondary to ADHF were included, and all patients were given tolvaptan. 37 patients were administered tolvaptan early (up until 5 th day of admission). 34 patients received tolvaptan after 5 th day of admission mean administration as 6.86 th day, and median administration was 5 th day. Analysis showed lower length of stay in patients receiving early administration of tolvaptan compared to late administration (8.86 ± 5.06 vs 18.5 ± 9.05 p0.001, respectively). Patients with early initiation of tolvaptan also achieved a larger net increase in sodium levels at discharge compared to admission (6.46 ± 6.69 vs 3.68 ± 4.70 p0.048, respectively). Conclusions Early administration of tolvaptan in treating hyponatremia in acutely decompensated heart failure patients is associated with a lower length of hospitalization and a higher increase in serum sodium of patients in hyponatremic ADHF patients.

BACKGROUND:Routine echocardiographic monitoring is recommended in muscular dystrophy patients to detect left ventricular systolic dysfunction (LVSD) but is often challenging due to physical limitations. This study evaluates whether artificial intelligence-based electrocardiogram interpretation (AI-ECG) can detect and predict LVSD in muscular dystrophy patients. METHODS:Patients aged >16 years who underwent an ECG and echocardiogram within 90 days at the University Medical Center Utrecht were included. Patients with Duchenne (DMD), Becker (BMD), limb-girdle muscular dystrophy (LGMD). myotonic dystrophy (MD), and female DMD/BMD carriers, were identified. A convolutional neural network (CNN) was trained on a derivation cohort of patients without muscular dystrophy to detect LVSD and tested on muscular dystrophy patients. A Cox proportional hazards model assessed AI-ECG's predictive value for new-onset LVSD. RESULTS:The derivation cohort included 53,874 ECG-echocardiogram pairs from 30,978 patients, while the muscular dystrophy test set comprised 390 ECG-echo pairs from 390 patients. LVSD prevalence varied from 81.3 % in DMD to 13.4 % in MD. The model achieved an AUROC of 0.83 (0.79-0.87) in the muscular dystrophy test set, with sensitivity 0.87 (0.81-0.93), specificity 0.58 (0.52-0.63), NPV 0.91 (0.86-0.95), and PPV 0.49 (0.43-0.56). AI-ECG predicted new-onset LVSD with an AUROC of 0.72 (0.66-0.78), with AI-ECG probability being a significant predictor. CONCLUSIONS:AI-ECG can detect LVSD in muscular dystrophy patients, offering a non-invasive, accessible tool for risk stratification and an alternative to routine echocardiography. It may also predict new-onset LVSD, enabling earlier intervention. Further research should explore external validation, pediatric application, and integration within the clinical care plan.

The left atrioventricular coupling index (LACI) is a novel imaging metric, providing insight into the relationship between the left atrium (LA) and left ventricle (LV). LACI has been shown to be an independent predictor of atrial fibrillation, heart failure, cardiovascular-related hospitalization, and mortality in different patient populations. It is also strongly correlated with diastolic function. Cardiac resynchronization therapy (CRT) promotes remodeling of both the LA and LV, along with the restoration of atrioventricular coupling, thereby improving diastolic function. However, no research has yet been conducted on comparing LACI in CRT responders and non-responders. To assess LACI in CRT patients, with stratification for responders and non-responders. A total of 127 heart failure patients scheduled for CRT implantation were included. LA and LV volumes were assessed by transthoracic echocardiography at baseline and six months post-implantation. LACI was calculated as the ratio of LA to LV end-diastolic volumes. Changes in LACI after six months of follow-up, in addition to between-group differences in responders and non-responders were tested for significance. CRT response was defined as ≥ 15% reduction in LV end-systolic volume six months post-implantation. LACI at baseline was 16.96% [12.94 to 23.52] for responders and 21.87% [17.86 to 42.93] for non-responders, with a significant difference between the groups (p=0.009). After six months, LACI remained consistent in non-responders (21.85% [10.83 to 29.57]), whereas it showed an increase in responders, resulting in comparable values between both groups (21.28% [16.12 to 28.19]; p=0.70). This increase in LACI was driven by a substantial decrease in LV end-diastolic volume (99.78 [80.65 to 125.98] to 65.15 [50.49 to 77.18] mL/m2; p<0.001) in responders, outweighing the reduction in LA end-diastolic volume (18.62 [11.11 to 25.04] to 14.45 [9.92 to 19.52] mL/ m2; p<0.001). In contrast, no significant differences in end-diastolic LA or LV volume were observed in non-responders after six months (p>0.05). Responders also demonstrated a more pronounced percentage change in end-diastolic LV volume compared with non-responders (-36.27% [-46.29 to -25.50] vs +2.90% [-2.66 to 11.33]; p<0.001), while the percentage change in LA end-diastolic volume did not differ between the groups (p>0.05). CRT responders show a worsening in LACI six months after CRT implantation, whereas non-responders remain stable. The increase in LACI among responders is driven by a substantial decrease in LV end-diastolic volume, outweighing the reduction in LA end-diastolic volume. This increase contradicts the expected improvement in atrioventricular coupling as a result of CRT response. Therefore, LACI may not be a reliable parameter for assessing atrioventricular coupling in CRT responders.Responders Non-responders

Background To improve cardiac resynchronization therapy (CRT) an on-screen image-guidance platform, CARTBox-Suite (CART-Tech B.V.), was developed to identify left ventricular pacing electrode (LVPE) implantation sites and facilitate precise LVPE placement. This multicenter randomized trial evaluated the efficacy of image guidance on LVPE implantation accuracy and its impact on left ventricular end-systolic volume (LVESV) reduction 6 months after CRT. Objectives The aim of this trial is to improve the accuracy and efficacy of LVPE placement in CRT. Methods A total of 131 heart failure patients (80% with Class I CRT indication) were enrolled across 7 hospitals in the Netherlands. CARTBox-Suite, which utilizes a cloud-based AI algorithm, was used to identify a target area with late mechanical activation based on cardiac magnetic resonance imaging. Scarred areas marked by late gadolinium enhancement were excluded. Patients were randomized to image-guided implantation, with on-screen guidance during the procedure or conventional implantation. Results The primary endpoint, LVPE implantation in the target area, was achieved significantly more often in the image-guided group (66.7% vs 29.2%; P < 0.001). The secondary endpoint was fewer LVPE placed in scarred areas in the image-guided group (7.1% vs 36.4%; P = 0.006). Mean LVESV reduction was greater in the image-guided group (43.2% vs. 37.6%), although not significantly (P = 0.166). Patients with myocardial scar showed greater LVESV reduction with image guidance (40.7% vs 27.7%; P = 0.028). Conclusions Image-guided implantation resulted in significantly more LVPE placed in the target area and greater LVESV reduction in patients with myocardial scar.

Left ventricular (LV) lead position is an important determinant for response to cardiac resynchronisation therapy (CRT). However, optimising LV lead position remains challenging due to variations in myocardial activation patterns and scar tissue between patients. Therefore, an image guidance platform was developed that can detect scar tissue and determine mechanical activation of the LV based on MRI images for the individual patient. This led to the formulation of a novel index, the CART score, which quantifies mechanical activation by combining time-to-peak strain and peak strain amplitude in individual myocardial segments. This study tested the hypothesis that higher CART scores, indicating later mechanical activation, are associated with greater reductions in left ventricular end-systolic volume (LVESV) following CRT. This sub-analysis utilised data from the ADVISE-CRT III randomised trial, where patients received CRT implantation using either on-screen image guidance to mechanically late-activated segments or conventional implantation. On a specially developed cloud-based platform, MRI feature tracking was used to determine mechanical activation in a 36-segment model of the LV. Septal segments were excluded from the analysis. The CART score (0–100) for the LV lead-implanted segment was calculated by summing the relative time to peak strain (0–50) and peak strain amplitude (0–50) for each individual patient. Scar burden, the percentage of the area of the lead-implanted segment affected by scar tissue, and scar transmurality, the depth of the scar tissue across the LV wall of the lead-implanted segment, were also measured. LVESV was measured at baseline and after six months using echocardiography. A significant positive correlation was observed between the CART score of the LV lead-implanted segment and LVESV reduction after six months of CRT (B=0.310, 95% confidence interval=0.088–0.533, p = 0.007), indicating that each unit increase in CART score was associated with a 0.31% mean reduction in LVESV. Scarred segments exhibited significantly lower peak strain amplitude compared to non-scarred segments (20.5±18.4% vs. 33.05±24.1%, p<0.001). Additionally, both scar burden (B=-0.114, p<0.001) and scar transmurality (B=-0.202, p<0.001) were associated with reduced strain amplitude, reflecting impaired contractile function in scarred tissue. Selecting myocardial segments with higher CART scores for LV lead implantation may enhance LVESV reduction. The lower strain amplitude observed in scarred segments underscores the importance of avoiding scar tissue.

Genetic cardiomyopathies (CMPs) are a known cause of morbidity and mortality, with up to 50% of patients diagnosed below the age of 40 years for certain CMPs. With the improved availability of advanced imaging tools, significant progress has been made in early diagnosis and subsequent management. Due to the growing scientific interest in the genetic variants underlying these CMPs, data supporting a possible direct effect of the disease-defining genetic variant on cardiac metabolism have accumulated. Moreover, metabolic impairment seems to be correlated with phenotype, performance status and eventually prognosis at any stage of the disease. In this review we aim to outline the existing evidence supporting the use of imaging techniques to visualize and quantify myocardial metabolism in different CMPs. The review focuses on positron emission tomography (PET), single photon emission computed tomography (SPECT) and magnetic resonance spectroscopy (MRS), describing the basics of their functioning, strengths and weaknesses, and their use in the context of different CMPs. Finally, the latest technologies in this field and potential future directions in disease diagnosis and management are described.

BACKGROUND:Inflammatory conditions such as obesity and diabetes are linked to intermediate/non-classical monocyte activation, contributing to left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF). OBJECTIVE:To investigate whether circulating monocyte subtypes and their activity are associated with the presence LVDD and HFpEF. METHODS:We analyzed peripheral blood mononuclear cells (PBMCs) from 73 patients with or without LVDD/HFpEF. Cytokine secretion was measured post-stimulation, and gene expression was assessed via RNA sequencing. Monocyte subtypes were characterized using flow cytometry, and macrophage polarization was evaluated. We also examined the relationship between immunological markers and echocardiographic indicators of LVDD. RESULTS:Among the participants, 24 were controls, 23 had LVDD, and 26 had HFpEF. PBMCs from LVDD patients secreted significantly less Interleukin-6 compared to controls (2053 ± 708 pg/mL vs 12,273 ± 3357 pg/mL, p = 0.008). RNA sequencing indicated increased estrogen receptor pathway activity in LVDD. HFpEF patients exhibited a 1.5-fold increase in intermediate monocytes and a significant rise in non-classical monocytes compared to controls. Stimulated macrophages from LVDD and HFpEF patients showed less CD206/CD80 expression, indicating a shift towards M2-macrophage polarization. Notably, higher non-classical monocyte counts correlated with lower E' septal velocity, suggesting an association with diastolic impairment (β = -0.15, p = 0.041). CONCLUSIONS:LVDD and HFpEF are associated with a shift towards non-classical monocyte subtypes and higher numbers of non-classical monocytes are associated with signs of diastolic impairment. These findings highlight the importance of the inflammatory component in LVDD and HFpEF.