Diffusion Tensor Phenomapping of the Healthy and Pressure-Overloaded Human Heart.

Current techniques to image the microstructure of the heart with diffusion tensor MRI (DTI) are highly under-resolved. We present a technique to improve the spatial resolution of cardiac DTI by almost 10-fold and leverage this to measure local gradients in cardiomyocyte alignment or helix angle (HA). We further introduce a phenomapping approach based on voxel-wise hierarchical clustering of these gradients to identify distinct microstructural microenvironments in the heart. Initial development was performed in healthy volunteers (n=8). Thereader, subjects with severe but well-compensated aortic stenosis (AS, n=10) were compared to age-matched controls (CTL, n=10). Radial HA gradient was significantly reduced in AS (8.0±0.8°/mm vs. 10.2±1.8°/mm, p=0.001) but the other HA gradients did not change significantly. Four distinct microstructural clusters could be idenJfied in both the CTL and AS subjects and did not differ significantly in their properties or distribution. Despite marked hypertrophy, our data suggest that the myocardium in well-compensated AS can maintain its microstructural coherence. The described phenomapping approach can be used to characterize microstructural plasticity and perturbation in any organ system and disease.

Cardiac MRI-Enriched Phenomapping Classification and Differential Treatment Outcomes in Patients With Ischemic Cardiomyopathy.

BACKGROUND: Significant controversy continues to confound patient selection and referral for revascularization and mitral valve intervention in patients with ischemic cardiomyopathy (ICM). Cardiac magnetic resonance (CMR) enables comprehensive phenotyping with gold-standard tissue characterization and volumetric/functional measures. Therefore, we sought to determine the impact of CMR-enriched phenomapping patients with ICM to identify differential outcomes following surgical revascularization and surgical mitral valve intervention (sMVi). METHODS: Consecutive patients with ICM referred for CMR between 2002 and 2017 were evaluated. Latent class analysis was performed to identify phenotypes enriched by comprehensive CMR assessment. The primary end point was death, heart transplant, or left ventricular assist device implantation. A multivariable Cox survival model was developed to determine the association of phenogroups with overall survival. Subgroup analysis was performed to assess the presence of differential response to post-magnetic resonance imaging procedural interventions. RESULTS: A total of 787 patients were evaluated (63.0±11.2 years, 24.8% women), with 464 primary events. Subsequent surgical revascularization and sMVi occurred in 380 (48.3%) and 157 (19.9%) patients, respectively. Latent class analysis identified 3 distinct clusters of patients, which demonstrated significant differences in overall outcome (P<0.001). Latent class analysis identified differential survival benefit of revascularization in patients as well as patients who underwent revascularization with sMVi, based on phenogroup classification, with phenogroup 3 deriving the most survival benefit from revascularization and revascularization with sMVi (hazard ratio, 0.61 [0.43-0.88]; P=0.0081). CONCLUSIONS: CMR-enriched unsupervised phenomapping identified distinct phenogroups, which were associated with significant differential survival benefit following surgical revascularization and sMVi in patients with ICM. Phenomapping provides a novel approach for patient selection, which may enable personalized therapeutic decision-making for patients with ICM.

Biorobotic hybrid heart as a benchtop cardiac mitral valve simulator.

In this work, we developed a high-fidelity beating heart simulator that provides accurate mitral valve pathophysiology. The benchtop platform is based on a biorobotic hybrid heart that combines preserved intracardiac tissue with soft robotic cardiac muscle providing dynamic left ventricular motion and precise anatomical features designed for testing intracardiac devices, particularly for mitral valve repair. The heart model is integrated into a mock circulatory loop, and the active myocardium drives fluid circulation producing physiological hemodynamics without an external pulsatile pump. Using biomimetic soft robotic technology, the heart can replicate both ventricular and septal wall motion, as well as intraventricular pressure-volume relationships. This enables the system to recreate the natural motion and function of the mitral valve, which allows us to demonstrate various surgical and interventional techniques. The biorobotic cardiovascular simulator allows for real-time hemodynamic data collection, direct visualization of the intracardiac procedure, and compatibility with clinical imaging modalities.

Facilitating diffusion tensor imaging of the brain during continuous gross head motion with first and second order motion compensating diffusion gradients.

PURPOSE: To demonstrate the feasibility of motion compensating diffusion gradient schemes in the acquisition of quality diffusion tensor images (DTI) of the brain during continuous gross head motion. METHODS: Five healthy subjects were scanned using a clinical 3 T MRI with and without continuous head motion. For one volunteer, DTI data was acquired using standard (M0) diffusion-weighted (DW) gradients, and first (M1) and second (M2) order gradient schemes that were previously developed for use in cardiac DTI. In four additional volunteers, DTI data was acquired with M0 and M2 gradients. DTI parameters were calculated and compared with established retrospective motion corrections. RESULTS: In the absence of motion, DTI parameters calculated from M0, M1, and M2 data were consistent. In the presence of motion, up to 44% of DW images acquired with M0 gradients were corrupted by signal dropout, compared to 0% of the M2 images. In voxelwise comparisons, DTI parameters calculated using motion-M0 data were elevated compared to reference data. Retrospective corrections for extreme motion applied to motion-M0 data did not improve consistency with reference data in cases where motion corrupted >15% of DW images. In contrast, DTI parameters calculated with motion-M2 data were consistent with reference data. CONCLUSION: This proof-of-principle study demonstrates that motion compensating diffusion gradients can mitigate artifacts because of continuous motion in DTI of the brain and offers promise for improved DTI accessibility. Further study will be necessary to determine the robustness of the approach in patient populations with high susceptibility to head motion.

Soft robotic platform for controlled, progressive and reversible aortic constriction in a small animal model.

Our understanding of cardiac remodeling processes due to left ventricular pressure overload derives largely from animal models of aortic banding. However, these studies fail to simultaneously enable control over disease progression and reversal, hindering their clinical relevance. Here, we describe a method for controlled, progressive, and reversible aortic banding based on an implantable expandable actuator that can be finely controlled to modulate aortic banding and debanding in a rat model. Through catheterization, imaging, and histologic studies, we demonstrate that our model can recapitulate the hemodynamic and structural changes associated with pressure overload in a controllable manner. We leverage the ability of our model to enable non-invasive aortic debanding to show that these changes can be partly reversed due to cessation of the biomechanical stimulus. By recapitulating longitudinal disease progression and reversibility, this model could elucidate fundamental mechanisms of cardiac remodeling and optimize timing of intervention for pressure overload.

Prediction of experimental cardiac magnetostimulation thresholds using pig-specific body models.

PURPOSE: Modern high-amplitude gradient systems can be limited by the International Electrotechnical Commission 60601-2-33 cardiac stimulation (CS) limit, which was set in a conservative manner based on electrode experiments and E-field simulations in uniform ellipsoidal body models. Here, we show that coupled electromagnetic-electrophysiological modeling in detailed body and heart models can predict CS thresholds, suggesting that such modeling might lead to more detailed threshold estimates in humans. Specifically, we compare measured and predicted CS thresholds in eight pigs. METHODS: We created individualized porcine body models using MRI (Dixon for the whole body, CINE for the heart) that replicate the anatomy and posture of the animals used in our previous experimental CS study. We model the electric fields induced along cardiac Purkinje and ventricular muscle fibers and predict the electrophysiological response of these fibers, yielding CS threshold predictions in absolute units for each animal. Additionally, we assess the total modeling uncertainty through a variability analysis of the 25 main model parameters. RESULTS: Predicted and experimental CS thresholds agree within 19% on average (normalized RMS error), which is smaller than the 27% modeling uncertainty. No significant difference was found between the modeling predictions and experiments (p < 0.05, paired t-test). CONCLUSION: Predicted thresholds matched the experimental data within the modeling uncertainty, supporting the model validity. We believe that our modeling approach can be applied to study CS thresholds in humans for various gradient coils, body shapes/postures, and waveforms, which is difficult to do experimentally.

Ketone ester supplementation suppresses cardiac inflammation and improves cardiac energetics in a swine model of acute myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a major risk factor for the development of heart failure with reduce ejection fraction (HFrEF). While previous studies have focused on HFrEF, the cardiovascular effects of ketone bodies in acute MI are unclear. We examined the effects of oral ketone supplementation as a potential treatment strategy in a swine acute MI model. METHODS: Farm pigs underwent percutaneous balloon occlusion of the LAD for 80 min followed by 72 h reperfusion period. Oral ketone ester or vehicle was administered during reperfusion and continued during the follow-up period. RESULTS: Oral KE supplementation induced ketonemia 2-3 mmol/l within 30 min after ingestion. KE increased ketone (ßHB) extraction in healthy hearts without affecting glucose and fatty acid (FA) consumption. During reperfusion, the MI hearts consumed less FA with no change in glucose consumption, whereas hearts from MI-KE-fed animals consumed more ßHB and FA, as well as improved myocardial ATP production. A significant elevation of infarct T2 values indicative of inflammation was found only in untreated MI group compared to sham. Concordantly, cardiac expression of inflammatory markers, oxidative stress, and apoptosis were reduced by KE. RNA-seq analysis identified differentially expressed genes related to mitochondrial energy metabolism and inflammation. CONCLUSIONS: Oral KE supplementation induced ketosis and enhanced myocardial ßHB extraction in both healthy and infarcted hearts. Acute oral supplementation with KE favorably altered cardiac substrate uptake and utilization, improved cardiac ATP levels, and reduced cardiac inflammation following MI.

Mapping the Unseen: In Vivo CEST-MRI of Creatine Reveals Improved Cardiac Energetics in Subjects with Obesity Following Bariatric Surgery.

BACKGROUND: Obesity is associated with derangement of cardiac metabolism and the development of subclinical cardiovascular disease. This prospective study examined the impact of bariatric surgery on cardiac function and metabolism. METHODS: Subjects with obesity underwent cardiac magnetic resonance imaging (CMR) at Massachusetts General Hospital before and after bariatric surgery between 2019 and 2021. The imaging protocol included Cine for global cardiac function assessment and creatine chemical exchange saturation transfer (CEST) CMR for myocardial creatine mapping. RESULTS: Thirteen subjects were enrolled, and 6 subjects [mean BMI 40.5 ± 2.6] had completed the second CMR (i.e. post-surgery), with a median follow-up of 10 months. The median age was 46.5 years, 67% were female, and 16.67% had diabetes. Bariatric surgery led to significant weight loss, with achieved mean BMI of 31.0 ± 2.0. Additionally, bariatric surgery resulted in significant reduction in left ventricular (LV) mass, LV mass index, and epicardial adipose tissue (EAT) volume. This was accompanied by slight improvement in LV ejection fraction compared to baseline. Following bariatric surgery, there was a significant increase in creatine CEST contrast. Subjects with obesity had significantly lower CEST contrast compared to subjects with normal BMI (n = 10), but this contrast was normalized after the surgery, and statistically similar to non-obese cohort, indicating an improvement in myocardial energetics. CONCLUSIONS: CEST-CMR has the ability to identify and characterize myocardial metabolism in vivo non-invasively. These results demonstrate that in addition to reducing BMI, bariatric surgery may favorably affect cardiac function and metabolism.

Soft robotic patient-specific hydrodynamic model of aortic stenosis and ventricular remodeling.

Aortic stenosis (AS) affects about 1.5 million people in the United States and is associated with a 5-year survival rate of 20% if untreated. In these patients, aortic valve replacement is performed to restore adequate hemodynamics and alleviate symptoms. The development of next-generation prosthetic aortic valves seeks to provide enhanced hemodynamic performance, durability, and long-term safety, emphasizing the need for high-fidelity testing platforms for these devices. We propose a soft robotic model that recapitulates patient-specific hemodynamics of AS and secondary ventricular remodeling which we validated against clinical data. The model leverages 3D-printed replicas of each patient's cardiac anatomy and patient-specific soft robotic sleeves to recreate the patients' hemodynamics. An aortic sleeve allows mimicry of AS lesions due to degenerative or congenital disease, whereas a left ventricular sleeve recapitulates loss of ventricular compliance and diastolic dysfunction (DD) associated with AS. Through a combination of echocardiographic and catheterization techniques, this system is shown to recreate clinical metrics of AS with greater controllability compared with methods based on image-guided aortic root reconstruction and parameters of cardiac function that rigid systems fail to mimic physiologically. Last, we leverage this model to evaluate the hemodynamic benefit of transcatheter aortic valves in a subset of patients with diverse anatomies, etiologies, and disease states. Through the development of a high-fidelity model of AS and DD, this work demonstrates the use of soft robotics to recreate cardiovascular disease, with potential applications in device development, procedural planning, and outcome prediction in industrial and clinical settings.

Cilia function as calcium-mediated mechanosensors that instruct left-right asymmetry.

The breaking of bilateral symmetry in most vertebrates is critically dependent upon the motile cilia of the embryonic left-right organizer (LRO), which generate a directional fluid flow; however, it remains unclear how this flow is sensed. Here, we demonstrated that immotile LRO cilia are mechanosensors for shear force using a methodological pipeline that combines optical tweezers, light sheet microscopy, and deep learning to permit in vivo analyses in zebrafish. Mechanical manipulation of immotile LRO cilia activated intraciliary calcium transients that required the cation channel Polycystin-2. Furthermore, mechanical force applied to LRO cilia was sufficient to rescue and reverse cardiac situs in zebrafish that lack motile cilia. Thus, LRO cilia are mechanosensitive cellular levers that convert biomechanical forces into calcium signals to instruct left-right asymmetry.

Asynchronous magnetic resonance elastography: Shear wave speed reconstruction using noise correlation of incoherent waves.

PURPOSE: The noninvasive measurement of biological tissue elasticity is an evolving technology that enables the robust characterization of soft tissue mechanics for a wide array of biomedical engineering and clinical applications. We propose, design, and implement here a new MRI technique termed asynchronous magnetic resonance elastography (aMRE) that pushes the measurement technology toward a driverless implementation. This technique can be added to clinical MRI scanners without any additional specialized hardware. THEORY: Asynchronous MRE is founded on the theory of diffuse wavefields and noise correlation previously developed in ultrasound to reconstruct shear wave speeds using seemingly incoherent wavefields. Unlike conventional elastography methods that solve an inverse problem, aMRE directly reconstructs a pixel-wise mapping of wave speed using the spatial-temporal statistics of the measured wavefield. METHODS: Incoherent finger tapping served as the wave-generating source for all aMRE measurements. Asynchronous MRE was performed on a phantom using a Siemens Prismafit as an experimental validation of the theory. It was further performed on thigh muscles as a proof-of-concept implementation of in vivo imaging using a Siemens Skyra scanner. RESULTS: Numerical and phantom experiments show an accurate reconstruction of wave speeds from seemingly noisy wavefields. The proof-of-concept thigh experiments also show that the aMRE protocol can reconstruct a pixel-wise mapping of wave speeds. CONCLUSION: Asynchronous MRE is shown to accurately reconstruct shear wave speeds in phantom experiments and remains at the proof-of-concept stage for in vivo imaging. After further validation and improvements, it has the potential to lower both the technical and monetary barriers of entry to measuring tissue elasticity.

Interpretation of pre-morbid cardiac 3T MRI findings in overweight and hypertensive young adults.

In young adults, overweight and hypertension possibly already trigger cardiac remodeling as seen in mature adults, potentially overlapping non-ischemic cardiomyopathy findings. To this end, in young overweight and hypertensive adults, we aimed to investigate changes in left ventricular mass (LVM) and cardiac volumes, and the impact of different body scales for indexation. We also aimed to explore the presence of myocardial fibrosis, fat and edema, and changes in cellular mass with extracellular volume (ECV), T1 and T2 tissue characteristics. We prospectively recruited 126 asymptomatic subjects (51% male) aged 27-41 years for 3T cardiac magnetic resonance imaging: 40 controls, 40 overweight, 17 hypertensive and 29 hypertensive overweight. Myocyte mass was calculated as (100%-ECV) * height2.7-indexed LVM. Absolute LVM was significantly increased in overweight, hypertensive and hypertensive overweight groups (104 ± 23, 109 ± 27, 112 ± 26 g) versus controls (87 ± 21 g), with similar volumes. Body surface area (BSA) indexation resulted in LVM normalization in overweights (48 ± 8 g/m2) versus controls (47 ± 9 g/m2), but not in hypertensives (55 ± 9 g/m2) and hypertensive overweights (52 ± 9 g/m2). BSA-indexation overly decreased volumes in overweight versus normal-weight (LV end-diastolic volume; 80 ± 14 versus 92 ± 13 ml/m2), where height2.7-indexation did not. All risk groups had lower ECV (23 ± 2%, 23 ± 2%, 23 ± 3%) than controls (25 ± 2%) (P = 0.006, P = 0.113, P = 0.039), indicating increased myocyte mass (16.9 ± 2.7, 16.5 ± 2.3, 18.1 ± 3.5 versus 14.0 ± 2.9 g/m2.7). Native T1 values were similar. Lower T2 values in the hypertensive overweight group related to heart rate. In conclusion, BSA-indexation masks hypertrophy and causes volume overcorrection in overweight subjects compared to controls, height2.7-indexation therefore seems advisable.

A soft robotic sleeve mimicking the haemodynamics and biomechanics of left ventricular pressure overload and aortic stenosis.

Preclinical models of aortic stenosis can induce left ventricular pressure overload and coarsely control the severity of aortic constriction. However, they do not recapitulate the haemodynamics and flow patterns associated with the disease. Here we report the development of a customizable soft robotic aortic sleeve that can mimic the haemodynamics and biomechanics of aortic stenosis. By allowing for the adjustment of actuation patterns and blood-flow dynamics, the robotic sleeve recapitulates clinically relevant haemodynamics in a porcine model of aortic stenosis, as we show via in vivo echocardiography and catheterization studies, and a combination of in vitro and computational analyses. Using in vivo and in vitro magnetic resonance imaging, we also quantified the four-dimensional blood-flow velocity profiles associated with the disease and with bicommissural and unicommissural defects re-created by the robotic sleeve. The design of the sleeve, which can be adjusted on the basis of computed tomography data, allows for the design of patient-specific devices that may guide clinical decisions and improve the management and treatment of patients with aortic stenosis.

Measurement of magnetostimulation thresholds in the porcine heart.

PURPOSE: Powerful MRI gradient systems can surpass the International Electrotechnical Commission (IEC) 60601-2-33 limit for cardiac stimulation (CS), which was determined by simple electromagnetic simulations and electrode stimulation experiments. Only a few canine studies measured magnetically induced CS thresholds in vivo and extrapolating them to human safety limits can be challenging. METHODS: We measured cardiac magnetostimulation thresholds in 10 healthy, anesthetized pigs using capacitors discharged into a flat spiral coil to produce damped sinusoidal waveforms with effective stimulus duration ts,eff  = 0.45 ms. Electrocardiography (ECG), blood pressure, and peripheral oximetry signals were recorded to determine threshold coil currents yielding cardiac capture. Dixon and CINE MR volumes from each animal were segmented to generate porcine-specific electromagnetic models to calculate dB/dt and E-field values in the porcine heart at threshold. For comparison, we also simulated maximum dB/dt and E-field values created by three MRI gradient systems in the heart of a human body model. RESULTS: The average dB/dt threshold estimated in the porcine heart was 1.66 ± 0.23 kT/s, which is 11-fold greater than the IEC dB/dt limit at ts,eff  = 0.45 ms, and 31-fold greater than the maximum value created by the investigated MRI gradients in the human heart. The average E-field threshold estimated in the porcine heart was 92.9 ± 13.5 V/m, which is 6-fold greater than the IEC E-field limit at ts,eff  = 0.45 ms and 37-fold greater than the maximum gradient-induced E-field in the human heart. CONCLUSION: This first measurement of cardiac magnetostimulation thresholds in pigs indicates that the IEC cardiac safety limit is conservative for the investigated stimulus duration (ts,eff  = 0.45 ms).

Exercise-induced CITED4 expression is necessary for regional remodeling of cardiac microstructural tissue helicity.

Both exercise-induced molecular mechanisms and physiological cardiac remodeling have been previously studied on a whole heart level. However, the regional microstructural tissue effects of these molecular mechanisms in the heart have yet to be spatially linked and further elucidated. We show in exercised mice that the expression of CITED4, a transcriptional co-regulator necessary for cardioprotection, is regionally heterogenous in the heart with preferential significant increases in the lateral wall compared with sedentary mice. Concordantly in this same region, the heart's local microstructural tissue helicity is also selectively increased in exercised mice. Quantification of CITED4 expression and microstructural tissue helicity reveals a significant correlation across both sedentary and exercise mouse cohorts. Furthermore, genetic deletion of CITED4 in the heart prohibits regional exercise-induced microstructural helicity remodeling. Taken together, CITED4 expression is necessary for exercise-induced regional remodeling of the heart's microstructural helicity revealing how a key molecular regulator of cardiac remodeling manifests into downstream local tissue-level changes.

Magnetic resonance imaging of cardiac metabolism in heart failure: how far have we come?

As one of the highest energy consumer organs in the body, the heart requires tremendous amount of adenosine triphosphate (ATP) to maintain its continuous mechanical work. Fatty acids, glucose, and ketone bodies are the primary fuel source of the heart to generate ATP with perturbations in ATP generation possibly leading to contractile dysfunction. Cardiac metabolic imaging with magnetic resonance imaging (MRI) plays a crucial role in understanding the dynamic metabolic changes occurring in the failing heart, where the cardiac metabolism is deranged. Also, targeting and quantifying metabolic changes in vivo noninvasively is a promising approach to facilitate diagnosis, determine prognosis, and evaluate therapeutic response. Here, we summarize novel MRI techniques used for detailed investigation of cardiac metabolism in heart failure including magnetic resonance spectroscopy (MRS), hyperpolarized MRS, and chemical exchange saturation transfer based on evidence from preclinical and clinical studies and to discuss the potential clinical application in heart failure.

Targeting Myocardial Substrate Metabolism in the Failing Heart: Ready for Prime Time?

PURPOSE OF REVIEW: We review the clinical benefits of altering myocardial substrate metabolism in heart failure. RECENT FINDINGS: Modulation of cardiac substrates (fatty acid, glucose, or ketone metabolism) offers a wide range of therapeutic possibilities which may be applicable to heart failure. Augmenting ketone oxidation seems to offer great promise as a new therapeutic modality in heart failure. The heart has long been recognized as metabolic omnivore, meaning it can utilize a variety of energy substrates to maintain adequate ATP production. The adult heart uses fatty acid as a major fuel source, but it can also derive energy from other substrates including glucose and ketone, and to some extent pyruvate, lactate, and amino acids. However, cardiomyocytes of the failing heart endure remarkable metabolic remodeling including a shift in substrate utilization and reduced ATP production, which account for cardiac remodeling and dysfunction. Research to understand the implication of myocardial metabolic perturbation in heart failure has grown in recent years, and this has raised interest in targeting myocardial substrate metabolism for heart failure therapy. Due to the interdependency between different pathways, the main therapeutic metabolic approaches include inhibiting fatty acid uptake/fatty acid oxidation, reducing circulating fatty acid levels, increasing glucose oxidation, and augmenting ketone oxidation.

Cardiac Alterations on 3T MRI in Young Adults With Sedentary Lifestyle-Related Risk Factors.

Background: Young adult populations with the sedentary lifestyle-related risk factors overweight, hypertension, and type 2 diabetes (T2D) are growing, and associated cardiac alterations could overlap early findings in non-ischemic cardiomyopathy on cardiovascular MRI. We aimed to investigate cardiac morphology, function, and tissue characteristics for these cardiovascular risk factors. Methods: Non-athletic non-smoking asymptomatic adults aged 18-45 years were prospectively recruited and underwent 3Tesla cardiac MRI. Multivariate linear regression was performed to investigate independent associations of risk factor-related parameters with cardiac MRI values. Results: We included 311 adults (age, 32 ± 7 years; men, 49%). Of them, 220 subjects had one or multiple risk factors, while 91 subjects were free of risk factors. For overweight, increased body mass index (per SD = 5.3 kg/m2) was associated with increased left ventricular (LV) mass (+7.3 g), biventricular higher end-diastolic (LV, +8.6 ml), and stroke volumes (SV; +5.0 ml), higher native T1 (+7.3 ms), and lower extracellular volume (ECV, -0.38%), whereas the higher waist-hip ratio was associated with lower biventricular volumes. Regarding hypertension, increased systolic blood pressure (per SD = 14 mmHg) was associated with increased LV mass (+6.9 g), higher LV ejection fraction (EF; +1.0%), and lower ECV (-0.48%), whereas increased diastolic blood pressure was associated with lower LV EF. In T2D, increased HbA1c (per SD = 9.0 mmol/mol) was associated with increased LV mass (+2.2 g), higher right ventricular end-diastolic volume (+3.2 ml), and higher ECV (+0.27%). Increased heart rate was linked with decreased LV mass, lower biventricular volumes, and lower T2 values. Conclusions: Young asymptomatic adults with overweight, hypertension, and T2D show subclinical alterations in cardiac morphology, function, and tissue characteristics. These alterations should be considered in cardiac MRI-based clinical decision making.