The global prevalence of both obesity and heart failure continues to rise, and accumulating evidence suggests that their association is likely causal, giving rise to a distinct heart failure phenotype with unique pathophysiologic features compared to non-obese individuals. This review highlights the evolving role of cardiac magnetic resonance imaging (CMR) in the assessment and management of obesity-related heart failure, emphasizing it’s ability to characterize the structural, functional, and tissue-level cardiovascular abnormalities that define this increasingly prevalent condition. Obesity plays a central role in the development of heart failure with preserved ejection fraction (HFpEF), contributing to a unique pathophysiologic cardiovascular phenotype through mechanisms such as myocardial inflammation, diffuse fibrosis, abnormal ventricular loading, and pathologic expansion of adjacent epicardial adipose tissue. These structural and physiologic changes in turn lead to disproportionate atrial and ventricular remodeling, pronounced diastolic dysfunction, cardiac microvascular dysfunction, impaired interventricular mechanics, and elevated cardiac filling pressures. Together, these alterations contribute to the heightened symptom burden, exercise intolerance, and adverse outcomes observed in obese patients with HFpEF. Cardiac magnetic resonance imaging (CMR) provides a non-invasive, comprehensive platform to assess these hemodynamic, structural, and tissue-level abnormalities through an ever-expanding suite of quantitative imaging tools. CMR, with its high spatial resolution, advanced tissue characterization, and comprehensive evaluation of cardiac structure and function, has emerged as a pivotal modality for the diagnosis, phenotyping, and risk stratification of obesity related HFpEF, while also enabling differentiation from important phenocopies and alternative causes of heart failure.

Overactivation of the mineralocorticoid receptor (MR) promotes tissue remodeling in patients with heart failure (HF) and/or chronic kidney disease (CKD). These patients may benefit from MR antagonists (MRAs); however, MRAs are underutilized, partly due to the risk of hyperkalemia. Balcinrenone is a novel, selective MR modulator that demonstrated renoprotection without an acute effect on urinary electrolyte excretion in preclinical studies, suggesting reduced hyperkalemia risk. Here, we present in vivo and in vitro studies comparing balcinrenone with eplerenone, an approved MRA. Myocardial perfusion reserve (MPR), an indicator of coronary microvascular remodeling, was evaluated in mice with diet-induced HF with preserved ejection fraction (HFpEF). MR target gene expression and markers of cardiac remodeling were evaluated using a clonal cell line of rat cardiomyocytes stably expressing MR (H9C2/MR+), and inflammatory and fibrotic processes were evaluated in primary human cardiac fibroblasts. Potassium (K+) homeostasis was evaluated in mice with nephrectomy-induced CKD. In mice with diet-induced HFpEF, 30 mg/kg/day balcinrenone or 100 mg/kg/day eplerenone restored MPR to levels seen in mice without HFpEF. Balcinrenone and eplerenone inhibited aldosterone-induced expression of MR target genes and markers of cardiac remodeling in H9C2/MR+ cells, and excretion of collagen 1 and interleukin-6 in primary human cardiac fibroblasts, in a concentration-dependent manner. An overnight K+ challenge in eplerenone-treated mice with nephrectomy-induced CKD yielded a higher plasma K+ elevation than that observed in vehicle-treated CKD mice. By contrast, the plasma K+ response in balcinrenone-treated mice with CKD was similar to what was observed in vehicle-treated CKD mice. Urinary K+ excretion was not affected by balcinrenone or eplerenone treatment, but fecal K+ excretion was elevated in CKD mice that were administered balcinrenone versus eplerenone. These results suggest that balcinrenone may be suitable for patients requiring additional cardiorenal protection through MR modulation but are at high risk of hyperkalemia.

Myocardial strain analysis of cardiac magnetic resonance (CMR) images provides an important tool for evaluating cardiac function. However, current techniques require either human-adjusted post-processing with suboptimal regional accuracy, or specialized and costly imaging acquisitions. In this paper, we propose to leverage the power of generative models to synthesize high-quality motion-derived strain values from routinely acquired CMR sequences. Specifically, we develop a novel Brownian bridge diffusion model in motion space to learn the probabilistic mapping between standard CMR motion estimated from widely adopted registration methods and highly accurate motion provided by advanced strain imaging techniques. To promote the fidelity of anatomical structure in the generation process, our model is conditioned on the corresponding CMR images. We validate our method on large-scale multi-center CMR datasets including subjects of paired standard cine CMR and advanced strain imaging acquisitions. Experimental results demonstrate that our framework significantly improves the accuracy of motion prediction and strain analysis from standard CMRs compared to existing learning-based approaches. Our research represents a new paradigm for potentially developing cost-effective, clinically deployable AI tools for cardiac function assessment with enhanced strain accuracy in busy clinical workflows. Our code is publicly available at anonymous.4open.science/r/Brownian-Bridge-strain-analysis-1140.

Semaglutide (SEMA) improves cardiometabolic outcomes in obesity, but its mechanisms remain incompletely understood. We examined the effects of SEMA in mice fed a high-fat, high-sucrose diet. Obese mice were treated with SEMA and compared with pair-fed controls to account for reduced dietary intake with SEMA. Multiparametric cardiovascular magnetic resonance was used to assess epicardial adipose tissue volume and composition, myocardial fat fraction, adenosine myocardial perfusion reserve, systolic strain, and diastolic function, with histological evaluation of myocardial fibrosis. SEMA treatment reduced proinflammatory epicardial adipose tissue, reduced ectopic lipid accumulation, improved myocardial perfusion reserve, and reversed impairments in systolic and diastolic strain, whereas pair-feeding did not. Myocardial fibrosis was also reduced with SEMA treatment. These results indicate that SEMA reverses key CMR and histological features of obesity-induced cardiometabolic heart disease in mice, independent of changes in dietary intake.

This paper presents a novel motion feature guided diffusion model for unpaired video-to-video translation (MFD-V2V), designed to synthesize dynamic, high-contrast cine cardiac magnetic resonance (CMR) from lower-contrast, artifact-prone displacement encoding with stimulated echoes (DENSE) CMR sequences. To achieve this, we first introduce a Latent Temporal Multi-Attention (LTMA) registration network that effectively learns more accurate and consistent cardiac motions from cine CMR image videos. A multi-level motion feature guided diffusion model, equipped with a specialized Spatio-Temporal Motion Encoder (STME) to extract hierarchical coarse-to-fine motion conditioning, is then developed to improve synthesis quality and fidelity. We evaluate our method, MFD-V2V, on a comprehensive cardiac dataset, demonstrating superior performance over the state-of-the-art in both quantitative metrics and qualitative assessments. Furthermore, we show the benefits of our synthesized cine CMRs improving downstream clinical and analytical tasks, underscoring the broader impact of our approach. Our code is publicly available at https://github.com/SwaksharDeb/MFD-V2V.

BACKGROUND:Rapidly accelerated fibrosarcoma B-type (BRAF) and MEK inhibitors have revolutionized outcomes for patients with BRAF-mutated melanoma. However, they are associated with cardiovascular adverse effects. The real-world incidence and risk factors for these effects are poorly described. OBJECTIVES:The aim of this study was to characterize the incidence and risk factors for BRAF inhibitor- and MEK inhibitor-associated hypertension and cancer therapy-related cardiac dysfunction (CTRCD) in a real-world setting. METHODS:A prospective, longitudinal, cohort study was undertaken among patients with melanoma treated with BRAF and MEK inhibitors in a regional cancer network (March 2021 to March 2023). Baseline cardiotoxicity risk stratification was assessed using the European Society of Cardiology cardio-oncology guideline-recommended tool. Comprehensive cardiovascular assessment was performed at baseline and at 4, 12, and 24 weeks, including home and clinic blood pressure, echocardiography, stress perfusion cardiovascular magnetic resonance imaging and blood biomarkers. CTRCD was defined using International Cardio-Oncology Society definitions. RESULTS:A total of 61 participants were enrolled. Twenty-eight participants (45.9%) developed hypertension and 45.9% developed CTRCD: 24 (85.7%) mild, 3 (10.7%) moderate, and 1 (3.6%) severe. All moderate or severe CTRCD was evident by 4 weeks and at least partially reversible. No patient at low baseline risk developed moderate or severe CTRCD. Patients with CTRCD had higher median baseline N-terminal pro-B-type natriuretic peptide compared with those without (109 pg/mL [Q1-Q3: 51-380 pg/mL] vs 54 pg/mL [Q1-Q3: 29-149 pg/mL]; P = 0.047). There were no robust associations between hypertension nor cardiovascular magnetic resonance imaging-derived myocardial or perfusion characteristics and incident CTRCD. CONCLUSIONS:BRAF inhibitor- and MEK inhibitor-associated hypertension and CTRCD are common. The present results reinforce the utility of baseline cardiotoxicity risk stratification, including assessment of N-terminal pro-B-type natriuretic peptide. Future guidelines should consider recommending early surveillance echocardiography for higher risk patients.

Accurate identification of late mechanical activation (LMA) regions is crucial for optimal cardiac resynchronization therapy (CRT) lead implantation. However, existing approaches using cardiac magnetic resonance (CMR) imaging often over-look myocardial scar information, which may be mistakenly identified as delayed activation regions. To address this issue, we propose a scar-aware LMA detection network that simultaneously detects myocardial scar and prevents LMA localization in these scarred regions. More specifically, our model integrates a pre-trained scar segmentation network using late gadolinium enhancement (LGE) CMRs into a LMA detection network based on highly accurate strain derived from displacement encoding with stimulated echoes (DENSE) CMRs. We introduce a novel scar-aware loss function that utilizes the segmented scar information to discourage false-positive detections of late activated areas. Our model can be trained with or without paired LGE data. During inference, our model does not require the input of LGE images, leveraging learned patterns from strain data alone to mitigate false-positive LMA detection in potential scar regions. We evaluate our model on subjects with and without myocardial scar, demonstrating significantly improved LMA detection accuracy in both scenarios. Our work paves the way for improved CRT planning, potentially leading to better patient outcomes.

BACKGROUND:Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve metabolic and cardiovascular outcomes, but the mechanisms remain incompletely understood. We utilized cardiovascular magnetic resonance (CMR) and complementary methods to investigate whether preventive SGLT2 inhibitor administration attenuates the development of metabolic heart disease in a high-fat, high-sucrose diet (HFHSD) mouse model. METHODS:Male wild-type (WT) C57BL/6 J mice were fed an HFHSD for 18 weeks to induce obesity, coronary microvascular disease, and diastolic dysfunction. WT mice treated preventively with an SGLT2 inhibitor, empagliflozin (EMPA), were compared to untreated WT mice, and mice fed either an HFHSD or standard chow diet with myeloid cell-specific knockout of the Nos2 gene (Nos2LysMCre) were compared to floxed controls (Nos2fl/fl). CMR assessed epicardial adipose tissue (EAT) volume, fatty acid composition (FAC), proton density fat fraction (PDFF), and T1, and myocardial perfusion, and strain. EAT FAC, PDFF, and T1 were quantified using an inversion-recovery multi-echo gradient-echo sequence and a multi-resonance triglyceride model. EAT volume was quantified using cine images. Myocardial perfusion reserve (MPR) and strain were measured using arterial spin labeling, and displacement encoding with stimulated echoes (DENSE), respectively. Histology and flow cytometry assessed EAT remodeling and macrophage polarization. RESULTS:EMPA treatment reduced EAT volume (0.36±0.18 µL/g vs 0.61±0.25 µL/g, p<0.01) and saturated fatty acid fraction (38.81 [32.83-47.71]% vs 48.06 [43.82-52.65]%, p<0.05), increased EAT T1 (0.799 [0.764-0.859] s vs 0.755 [0.678-0.772] s, p<0.05), and decreased EAT NOS2+ macrophages (34.74 [21.38-42.098]% vs 46.36 [38.08-61.30]%, p<0.05) compared to controls. EMPA improved diastolic strain rate (2.96 [2.61-3.99] s-1 vs 1.68 [1.21-2.80] s-1, p<0.01) and adenosine MPR (2.00±0.54 vs 1.37±0.40, p<0.01) compared to controls. Myeloid cell NOS2 knockout mice fed an HFHSD exhibited improved adenosine MPR (1.90±0.47 vs 1.39±0.38, p<0.01) compared to floxed controls. CONCLUSIONS:In this obesity-related metabolic heart disease model, EMPA treatment prevents cardiometabolic dysfunction by improving EAT quantity and quality, coronary microvascular function, and diastolic function. These benefits are mediated in part through macrophage NOS2.

BACKGROUND:Epicardial adipose tissue (EAT) plays a central role in metabolic heart disease through local inflammatory signaling. In obesity, EAT undergoes pathological remodeling marked by increased adipocyte size, saturated fatty acids (SFAs), macrophage infiltration, and inflammatory cytokine secretion. Proton density fat fraction (PDFF), relaxation times, and the fatty acid composition (FAC) (the amount of SFAs, monounsaturated fatty acids [MUFAs], and polyunsaturated fatty acids [PUFAs]) are promising metrics of EAT quality, yet their role as biomarkers of proinflammatory EAT has not been established. This study presents an accelerated cardiovascular magnetic resonance (CMR) method for simultaneous EAT FAC and relaxation time mapping and evaluates their relationships with histological and cytokine markers of inflammation. METHODS:An electrocardiogram (ECG)-gated inversion recovery multi-echo gradient-echo sequence with radial golden-angle sampling was developed for simultaneous FAC and relaxation time mapping. A high-dimensionality patch-based low-rank reconstruction was applied to undersampled images. Phantom validation was performed using oil mixture and gadolinium phantoms, followed by in vivo imaging of mice (n=16-20/group) fed a high-fat high-sucrose diet (HFHSD), HFHSD plus the sodium-glucose cotransporter-2 inhibitor (SGLT2i) empagliflozin (HFHSD+EMPA), or a high-fat diet (HFD). PDFF, SFA fraction, MUFA fraction, PUFA fraction, R2*, and T1 measurements were made in EAT and subcutaneous adipose tissue (SAT). EAT FAC values were indexed to those of SAT. Ex vivo histology and cytokine assays were used to assess EAT and myocardial inflammation. RESULTS:Phantom validation demonstrated strong agreement between CMR-derived and reference FAC and T1 values (r>0.94, p<0.05). Diet-induced changes in adipose tissue FAC were detected by CMR. HFHSD+EMPA mice had lower EAT SFA index than both HFHSD (p<0.01) and HFD (p<0.05) mice, and higher MUFA index (p<0.01), PUFA index (p<0.05), and T1 (p<0.05) compared HFHSD mice. EAT SFA index positively correlated with macrophage infiltration and proinflammatory cytokines, while MUFA and PUFA indexes were inversely correlated with proinflammatory cytokines. EAT T1 negatively correlated with adipocyte hypertrophy. CONCLUSION:This study developed an accelerated EAT FAC and relaxation time mapping method and provides evidence that MRI-derived EAT FAC indexes and relaxation times may serve as biomarkers of proinflammatory EAT by demonstrating correlations with histological and cytokine markers.