Although genetic variant effects often interact nonadditively, strategies to uncover epistasis remain in their infancy. Here we develop low-signal signed iterative random forests to elucidate the complex genetic architecture of cardiac hypertrophy, using deep learning-derived left ventricular mass estimates from 29,661 UK Biobank cardiac magnetic resonance images. We report epistatic variants near CCDC141, IGF1R, TTN and TNKS, identifying loci deemed insignificant in genome-wide association studies. Functional genomic and integrative enrichment analyses reveal that genes mapped from these loci share biological process gene ontologies and myogenic regulatory factors. Transcriptomic network analyses using 313 human hearts demonstrate strong co-expression correlations among these genes in healthy hearts, with significantly reduced connectivity in failing hearts. To assess causality, RNA silencing in human induced pluripotent stem cell-derived cardiomyocytes, combined with novel microfluidic single-cell morphology analysis, confirms that cardiomyocyte hypertrophy is nonadditively modifiable by interactions between CCDC141, TTN and IGF1R. Our results expand the scope of cardiac genetic regulation to epistasis.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy, caused by either sarcomere protein or other gene mutations. It is a complex and highly heterogeneous disorder, with phenotypes ranging from asymptomatic to severe disease, characterized by asymmetric left ventricular (LV) hypertrophy unexplained by loading conditions, which is also associated with myocardial fiber disarray, and preserved or increased ejection fraction without LV dilation. Comprehensive personal and family history, physical examination, and ECG testing raise suspicion of HCM, and echocardiogram represents the first-line imaging modality for confirming a diagnosis. Moreover, contrast-enhanced cardiac magnetic resonance (CMR) imaging has increasingly emerged as a fundamental diagnostic and prognostic tool in HCM management. This article reviews the role of CMR in HCM identification and differentiation from phenotypic mimics, characterization of HCM phenotypes, monitoring of disease progression, evaluation of pre- and post-septal reduction treatments, and selection of candidates for implantable cardioverter-defibrillator. By providing information on cardiac morphology and function and tissue characterization, CMR is particularly helpful in the quantification of myocardial wall thickness, the detection of hypertrophy in areas blind to echocardiogram, subtle morphologic features in the absence of LV hypertrophy, myocardial fibrosis, and apical aneurysm, the evaluation of LV outflow tract obstruction, and the assessment of LV function in end-stage dilated HCM.

Comparing transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) is crucial for cardiac assessment. This study aims to clarify their comparability in a large population sample.

CMR and two- (2D) and three-dimensional (3D) TTE were used to quantify left and right heart dimensions in participants of the Hamburg City Health Study. Intertechnique agreement was evaluated using Bland-Altman analyses, Pearson correlation coefficients, and Cohen's Kappa.

Data from 2126 participants (median age 67 [IQR: 59-72] years, 897 (42.2%) female) were analyzed. Left ventricular (LV) diastolic volumes were similar (CMR: 117.0 [96.2, 138.0] ml, 2D-TTE: 111.8 [93.6, 134.3] ml, r = 0.7, p < 0.001), while systolic volumes were lower with CMR (CMR: 36.0 [26.9, 46.0] ml, 2D-TTE: 46.7 [37.9, 57.5] ml, r = 0.67, p < 0.001). CMR LV ejection fraction (LVEF) was 10% higher than 2D-TTE (CMR = 69.0 [64.0, 74.0]%, 2D-TTE = 58.3 [55.5, 61.7]%, p < 0.001; r = 0.40, p < 0.001). Left atrial volumes correlated moderately with low bias (CMR: 53.0 [40.0, 68.0] ml, 2D-TTE: 51.6 [41.5, 64.0] ml, r = 0.63, p < 0.001). LV mass showed good correlation but was higher using 2D-TTE (r = 0.74, p < 0.001). Right ventricular (RV) volumes showed the largest differences, with CMR demonstrating lower interobserver variability (ICC = 0.97 vs. 0.61 for 2D-TTE) and markedly larger volumes (RVEDV mean bias = 74.8 ml, r = 0.50, p < 0.001).

In a large general population, CMR quantifies cardiac function and dimensions more reliably than TTE. Both modalities provide significantly different absolute values, limiting intertechnique transferability.

Retrospectively registered at ClinicalTrial.gov, registration number: NCT03934957, registration date: 04/01/2019, https://clinicaltrials.gov/study/NCT03934957 .

Cardiovascular diseases are the number one cause of death globally, making cardiac magnetic resonance image segmentation a popular research topic. Existing schemas relying on manual user interaction or semi-automatic segmentation are infeasible when dealing thousands of cardiac MRI studies. Thus, we proposed a full automatic and robust algorithm for large-scale cardiac MRI segmentation by combining the advantages of deep learning localization and 3D-ASM restriction.

The proposed method comprises several key techniques: 1) a hybrid network integrating CNNs and Transformer as a encoder with the EFG (Edge feature guidance) module (named as CTr-HNs) to localize the target regions of the cardiac on MRI images, 2) initial shape acquisition by alignment of coarse segmentation contours to the initial surface model of 3D-ASM, 3) refinement of the initial shape to cover all slices of MRI in the short axis by complex transformation. The datasets used are from the UK BioBank and the CAP (Cardiac Atlas Project). In cardiac coarse segmentation experiments on MR images, Dice coefficients (Dice), mean contour distances (MCD), and mean Hausdorff distances (HD95) are used to evaluate segmentation performance. In SPASM experiments, Point-to-surface (P2S) distances, Dice score are compared between automatic results and ground truth.

The CTr-HNs from our proposed method achieves Dice coefficients (Dice), mean contour distances (MCD), and mean Hausdorff distances (HD95) of 0.95, 0.10 and 1.54 for the LV segmentation respectively, 0.88, 0.13 and 1.94 for the LV myocardium segmentation, and 0.91, 0.24 and 3.25 for the RV segmentation. The overall P2S errors from our proposed schema is 1.45 mm. For endocardium and epicardium, the Dice scores are 0.87 and 0.91 respectively.

Our experimental results show that the proposed schema can automatically analyze large-scale quantification from population cardiac images with robustness and accuracy.

Remote Dielectric Sensing (ReDS) is a fast and non-invasive method that estimates lung fluid. We previously described moderate accuracies for ReDS to detect acute heart failure in consecutive patients. We hypothesise that unprecise ReDS values may stem from concomitant pulmonary diseases.

To examine the ReDS reproducibility and the effect of pulmonary comorbidities on ReDS values in acute dyspnoeic patients.

This prospective observational study included 97 consecutive patients ≥50 years with acute dyspnoea. Upon admission, patients underwent low-dose chest computed tomography (CT), echocardiography and ReDS examination. ReDS is by default performed on the right hemithorax in sitting position. For reproducibility comparisons, we conducted additional ReDS measurements two centimetres above and below the default placement, and in sitting and supine position. Two blinded radiologists evaluated the CT scans for pulmonary congestion and pulmonary diseases.

Comparing three ReDS measurements on the right hemithorax revealed coefficients of variations of 9.6 %, 8.2 %, and 8.3 %. For sitting versus supine comparison, the coefficient of variation was 9.5 % for the default ReDS placement. Patients with CT-verified pulmonary congestion had a coefficient of variation of 5.9 % in sitting versus supine comparison, while those without had 10.3 %. In multivariable regression, lower ReDS values were observed in patients with pneumonia (-1.81, p = 0.215, N = 51), emphysema (-5.44, p = 0.001, N = 26), and higher in fibrosis (5.58, p = 0.032, N = 8) and congestion (5.79, p = 0.002, N = 17), compared to those without.

ReDS values of lung fluid content and reproducibility were affected by pulmonary diseases. ReDS showed consistent reproducibility for patients with CT-verified pulmonary congestion.

Prospective electrocardiogram (ECG)-triggered cardiovascular computed tomography (CCT) is primarily utilized for anatomical information in congenital heart disease (CHD) and has not been utilized for calculation of the end-diastolic volume (EDV); however, the mid-diastolic volume (MDV) may be measured. The objective of this study was to evaluate the feasibility and agreement between ventricular EDV and MDV. 31 retrospectively ECG-gated CCT were analyzed for the study of the 450 consecutive CCT. CCT images were processed using syngo.via with automatic contouring followed by manual adjustment of the endocardial borders of the left ventricles (LV) and right ventricles (RV) at end-diastolic and mid-diastolic phase (measured at 70% of cardiac cycle). The correlation and agreements between EDV and MDV were demonstrated using Spearman rank coefficient and intraclass correlation coefficient (ICC), respectively. Mean age ± SD was 28.8 ± 12.5 years, 19 were male (61.3%) and tetralogy of Fallot (TOF) was the most common diagnosis (58.1%), 35% (11/31) patients with a pacemaker, ICD or other such contraindication for a CMRI, 23% (7/31) with claustrophobia, and 6.5% (2/31) with developmental delay with refusal for sedation did not have a previous CMRI. The mean ± SD indexed LV EDV and LV MDV were 91.1 ± 24.5 and 84.8 ± 22.3 ml/m2, respectively. The mean ± SD indexed RV EDV and RV MDV were 136.8 ± 41 and 130.2 ± 41.5 ml/m2, respectively. EDV and MDV had a strong positive correlation and good agreement (ICC 0.92 for LV and 0.95 for RV). This agreement was preserved in a subset of patients (21) with dilated RV (indexed RV EDV z-score > 2). Intra-observer reliability (0.97 and 0.98 for LV and RV MDV, respectively) and inter-observer reliability (0.96 and 0.90 for LV and RV MDV, respectively) were excellent. In a select group of patients with CHD, measuring MDV by CCT is feasible and these values have good agreements with EDV. This may be used to derive functional data from prospectively ECG-triggered CCT studies. Further large-scale analysis is needed to determine accuracy and clinical correlation.

Primary mitral regurgitation (MR) is a prevalent valvular heart disease. Therapy stratification for MR depends on accurate assessment of MR severity and left ventricular (LV) dimensions. While trans-thoracic echocardiography (TTE) has been the standard/preferred assessment method, cardiovascular magnetic resonance imaging (CMR) has gained recognition for its superior assessment of LV dimensions and MR severity. Both imaging modalities have their own advantages and limitation for therapy guidance. However, the differences between the two modalities for assessing/grade severity and clinical impact of MR remains unclear. This systematic review aims to evaluate the differences between TTE and CMR in quantifying MR severity and LV dimensions, providing insights for optimal clinical management. A literature search was performed from inception up to March 21st 2023. This resulted in 2,728 articles. After screening, 22 articles were deemed eligible for inclusion in the meta-analysis. The included study variables were, mitral valve regurgitation volume (MRVOL), regurgitation fraction (MRFRAC), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), and LV ejection fraction (LVEF). TTE showed a significant higher MRVOL (10.4 ml, I2 = 88%, p = 0.002) and MRFRAC (6.3%, I2 = 51%, p = 0.05) compared to CMR, while CMR demonstrated a higher LVEDV (21.9 ml, I2 = 66%, p =  < 0.001) and LVESV (16.8 ml, I2 = 0%, p =  < 0.001) compared to TTE. Our findings demonstrate substantial disparities in TTE and CMR derived measurements for parameters that play a pivotal role in the clinical stratification guidelines. This discrepancy prompts a critical question regarding the prognostic value of both imaging modalities, which warrants future research.

Immune checkpoint inhibitors (ICIs) revolutionized cancer therapy, yet require management of immune-related adverse events (irAEs). Fulminant myocarditis is a rare irAE, but lower-severity cardiac events are being reported more frequently, leading to an unmet need for irAE prevention, early diagnosis, and treatment, especially for long-life-expectancy patients. We recruited 57 patients, stratified according to therapy regime (monotherapy (30%) or combination (33%) cohort) or history of cardiac disease or presence of at least two cardiovascular risk factors other than prior or active smoking (cardiovascular cohort (37%)). We performed a complete cardiological assessment with clinical visit, 12-lead ECG, multiparametric cardiac MRI as well as peripheral blood mononuclear cell immunophenotyping, prior to ICI initiation and around 2 months later. ICI treatment was associated with a significant left ventricular ejection function (LVEF) reduction pre-ICI versus post-ICI treatment (60.1±8% to 58.1±8%, p=0.002, paired t-test) and more than 3% LVEF loss in a substantial proportion of patients (18; 32%). These patients also showed significantly higher T2 values (p=0.037, unpaired t-test), putative sign of cardiac edema. The loss of cardiac function did not differ among patients with different tumor types, therapy regimes or history of cardiac disease. Immunophenotyping analyses showed a reduction of programmed cell death protein 1 staining on both CD4+ and CD8+ T cells, and an upregulation of HLA-DR on CD8+ T cells. Using a very sensitive and comprehensive approach in patients unselected for cardiac history, we found a subclinical but significant LVEF decrease. These findings may inform ongoing discussions on optimal management of cardiac irAEs in patients undergoing ICI treatment and warrant further evaluation.

High-altitude pulmonary hypertension (HAPH) is characterized by an increase in pulmonary artery pressure due to prolonged exposure to hypoxic environment at high altitudes. The development of HAPH involves various factors such as pressure changes, inflammation, oxidative stress, gene regulation, and signal transduction. The pathophysiological mechanisms of this condition operate at molecular, cellular, and genetic levels. Diagnosis of HAPH often relies on echocardiography, cardiac catheterization, and other methods to assess pulmonary artery pressure and its impact on cardiac function. Treatment options for HAPH encompass both nondrug and drug therapies. While advancements have been made in understanding the pathological mechanisms through research on animal models and clinical trials, there are still limitations to be addressed. Future research should focus on exploring molecular targets, personalized medicine, long-term management strategies, and interdisciplinary approaches. By leveraging advanced technologies like systems biology, omics technology, big data, and artificial intelligence, a comprehensive analysis of HAPH pathogenesis can lead to the identification of new treatment targets and strategies, ultimately enhancing patient quality of life and prognosis. Furthermore, research on health monitoring and preventive measures for populations living at high altitudes should be intensified to reduce the incidence and mortality of HAPH.

Tricuspid annular plane systolic excursion (TAPSE), Doppler tissue imaging-derived tricuspid lateral annular systolic wave velocity (S'), and right ventricular fractional area change (RV-FAC) are the most widely used echocardiographic measures of right ventricular systolic function. This study aimed to compare the prognostic value of TAPSE, S', and RV-FAC in a large cohort of patients with chronic heart failure.

Consecutive outpatients with heart failure and left ventricular ejection fraction <50% on guideline-recommended therapies undergoing echocardiography were followed up for the end point of cardiac and all-cause death.

Among 1590 patients (71±12 years, 77% men, left ventricular ejection fraction 34%±9%), 202 (13%) died from cardiac causes during a median follow-up of 28 (interquartile range, 14-40) months. According to the recommended cut points for TAPSE (<17 mm), S' (<9.5 cm/s), or RV-FAC (<35%), right ventricular systolic dysfunction was found in 37%, 40%, and 35% of patients, respectively, with 21%, 31%, and 33% of discordant cases comparing TAPSE versus S', TAPSE versus RV-FAC, and S' versus RV-FAC. Both TAPSE <17 mm and RV-FAC <35% were more accurate than S' <9.5 cm/s in predicting the risk of cardiac death (P<0.001), and their combination showed incremental prognostic power (P<0.001). Adding S' to the combination of TAPSE and RV-FAC did not provide further incremental value (P=0.145). Similar findings were obtained when all-cause death was considered as the end point.

In patients with chronic heart failure and left ventricular ejection fraction <50%, TAPSE, and RV-FAC are more accurate than S' in predicting the risk of cardiac and all-cause death. Considering both RV-FAC and TAPSE provides incremental prognostic value.

Cardiorespiratory fitness (CRF) exists on a spectrum and is driven by a constellation of factors, including genetic and environmental differences. This results in wide interindividual variation in baseline CRF and the ability to improve CRF with regular endurance exercise training. As opposed to monogenic conditions, CRF is described as a complex genetic trait as it is believed to be influenced by multiple common genetic variants in addition to exogenous factors. Importantly, CRF is an independent predictor of morbidity and mortality, and so understanding the impact of genetic variation on CRF may provide insights into both human athletic performance and personalized risk assessment and prevention. Despite rapidly advancing technology, progress in this field has been restricted by small sample sizes and the limited number of genetic studies using the "gold standard" objective measure of peak oxygen consumption (VO2peak) for CRF assessment. In recent years, there has been increasing interest in the heritability of numerous parameters of cardiac structure and function and how this may relate to both normal cardiac physiology and disease pathology. Regular endurance training can result in exercise-induced cardiac remodelling, which manifests as balanced dilation of cardiac chambers and is associated with superior CRF. This results in a complex relationship between CRF, cardiac size, and exercise, and whether shared genetic pathways may influence this remains unknown. In this review we highlight recent and relevant studies into the genomic predictors of CRF with a unique emphasis on how this may relate to cardiac remodelling and human adaptation to endurance exercise.

Obesity is a known risk factor for heart failure with preserved ejection fraction (HFpEF) and is considered a distinct phenotype with more concentric remodeling. Epicardial adipose tissue (EAT) is also increased in obesity-related HFpEF and is associated with adverse events.

The cardiac magnetic resonance (CMR) substudy of the SUMMIT trial aimed to examine the effects of tirzepatide on cardiac structure and function with the underlying hypothesis that it would reduce left ventricular (LV) mass and EAT in obesity-related HFpEF.

A total of 175 patients with obesity-related HFpEF from the parent study of tirzepatide (2.5 mg subcutaneously weekly, increasing to a maximum of 15 mg weekly) or matching placebo underwent CMR at baseline, which consisted of multiplanar cine imaging. A total of 106 patients completed the CMR and had adequate image quality for analysis of LV and left atrial structure and function and paracardiac (epicardial plus pericardial) adipose tissue at both baseline and 52 weeks. The prespecified primary endpoint of this substudy was between-group changes in LV mass.

LV mass decreased by 11 g (95% CI: -19 to -4 g) in the treated group (n = 50) when corrected for placebo (n = 56) (P = 0.004). Paracardiac adipose tissue decreased in the treated group by 45 mL (95% CI: -69 to -22 mL) when corrected for placebo (P < 0.001). The change in LV mass in the treated group correlated with changes in body weight (P < 0.02) and tended to correlate with changes in waist circumference and blood pressure (P = 0.06 for both). The LV mass change also correlated with changes in LV end-diastolic volume and left atrial end-diastolic and end-systolic volumes (P < 0.03 for all).

The CMR substudy of the SUMMIT trial demonstrated that tirzepatide therapy in obesity-related HFpEF led to reduced LV mass and paracardiac adipose tissue as compared with placebo, and the change in LV mass paralleled weight loss. These physiologic changes may contribute to the reduction in heart failure events seen in the main SUMMIT trial. (A Study of Tirzepatide [LY3298176] in Participants With Heart Failure With Preserved Ejection Fraction [HFpEF] and Obesity: The SUMMIT Trial; NCT04847557).

Cardiac resynchronization therapy (CRT) produces long-term reverse remodelling which requires greater adenosine triphosphate delivery to the contractile machinery. Whilst the heart retains some metabolic flexibility in non-ischaemic cardiomyopathy, whether this correlates with reverse remodelling is unknown. This study investigated whether CRT acutely changes cardiac substrate uptake, and whether this translates to favourable reverse remodelling.

The effect of CRT on cardiac substrate uptake was assessed via direct coronary flow and arteriovenous measurements, with metabolomic/lipidomic analysis on infusions of insulin/glucose and intralipid. Cardiac function was assessed with left ventricular pressure-volume loops during implantation, and cardiac magnetic resonance before and 6 months following CRT, with and without biventricular pacing.

Regardless of substrate infusion, CRT acutely improved stroke work without increasing O2 uptake on both insulin/glucose (by 34%, P = .05) and intralipid (by 36%, P = .03). This was followed by increased fatty acid (FA) uptake on insulin/glucose (R = 0.89, P = .03) and increased β-hydroxybutyrate uptake (R = 0.81, P = .05) during intralipid infusion. After 6 months, there was a 48% (P < .001) reduction in left ventricular end diastolic volume, beyond that achievable by acutely shortening or lengthening QRS duration. Reverse remodelling significantly correlated with increased FA uptake with CRT on insulin/glucose (R = 0.71, P = .05) driven by long and medium chain uptake, and increased ketone uptake with CRT on intralipid (R = 0.79, P = .05).

CRT acutely alters the metabolic phenotype of non-ischaemic cardiomyopathy towards a more physiological picture of FA uptake which correlates with reverse remodelling. Retained metabolic flexibility may therefore be critical for subsequent reverse remodelling.

Two-dimensional (2D) cine imaging is essential in routine clinical cardiac MR (CMR) exams for assessing cardiac structure and function. Traditional cine imaging requires patients to hold their breath for extended periods and maintain consistent heartbeats for optimal image quality, which can be challenging for those with impaired breath-holding capacity or irregular heart rhythms. This study aims to systematically assess the performance of a deep learning-based reconstruction (Sonic DL Cine, GE HealthCare, Waukesha, WI, USA) for accelerated cardiac cine acquisition. Multiple retrospective experiments were designed and conducted to comprehensively evaluate the technique using data from an MR-dedicated extended cardiac torso anatomical phantom (digital phantom) and healthy volunteers on different cardiac planes. Image quality, spatiotemporal sharpness, and biventricular cardiac function were qualitatively and quantitatively compared between Sonic DL Cine-reconstructed images with various accelerations (4-fold to 12-fold) and fully sampled reference images. Both digital phantom and in vivo experiments demonstrate that Sonic DL Cine can accelerate cine acquisitions by up to 12-fold while preserving comparable SNR, contrast, and spatiotemporal sharpness to fully sampled reference images. Measurements of cardiac function metrics indicate that function measurements from Sonic DL Cine-reconstructed images align well with those from fully sampled reference images. In conclusion, this study demonstrates that Sonic DL Cine is able to reconstruct highly under-sampled (up to 12-fold acceleration) cine datasets while preserving SNR, contrast, spatiotemporal sharpness, and quantification accuracy for cardiac function measurements. It also provides a feasible approach for thoroughly evaluating the deep learning-based method.

This study investigates the long-term cardiac effects of trastuzumab-based chemotherapy in early breast cancer (EBC) survivors. We extend the original MANTICORE trial which showed that angiotensin-converting enzyme inhibitors (ACEI) and beta-blockers (BB) could mitigate the decline in left ventricular (LV) ejection fraction (EF) during the first year of trastuzumab treatment.

We hypothesized that, over time, cardiac function would decline further and adverse changes in cardiac geometry would occur due to the aging of the population and prior treatment.

The study enrolled 52 participants from the original MANTICORE trial cohort, with cardiac magnetic resonance (CMR) imaging conducted at a median of 6.5 years post randomization to treatment.

We found that, contrary to the hypothesis, participants maintained LV EF over the follow-up period. Specifically, the placebo group exhibited a recovery in LV EF to levels comparable with the treatment groups, suggesting no long-term differential impact on cardiac function. However, a significant reduction in LV mass was observed across all groups, the clinical implications of which remain unclear.

The findings suggest that in a selected population receiving trastuzumab-based chemotherapy, extended cardiac imaging surveillance beyond one-year post-treatment may be unnecessary. We posit that the presence of HER2 overexpressing breast cancer influenced hypertrophic changes to cardiac geometry observed at baseline and one year, which resolved after completing HER2-blocking treatment. The study also highlights the need for further research to understand the significance of changes in cardiac geometry during and after breast cancer treatment​.

Treatment of heart failure and reduced ejection fraction (HFrEF) using angiotensin receptor-neprilysin inhibitor demonstrates beneficial effects on cardiac remodeling (CR). We assessed the impact of sacubitril/valsartan on the concentrations of HF biomarkers in relation to parameters of CR using imaging techniques in patients with HFrEF. In a prospective single-center open-label study, 68 patients with symptomatic HFrEF were treated with sacubitril/valsartan and followed-up every three months for 12 months. Soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin I (hs-cTnI) were measured in blood samples. Additionally, echocardiography and cardiac magnetic resonance imaging (cMRI) were performed to assess heart structural and functional changes. Following treatment initiation, follow-up visits revealed an improved NYHA functional class in these patients, alongside significant decreases in all circulating biomarkers, increases in left ventricular ejection fraction (LVEF), and reductions in volume- and diameter-related LV parameters. Sustained gradual decreases in sST2 concentrations over time correlated with NT-proBNP concentrations (rho=+0.26, P < 0.001). Both biomarkers were inversely correlated with LVEF, and positively correlated with volume- and diameter-related LV parameters from echocardiography and cMRI. However, NT-proBNP concentrations exhibited stronger correlations with these LV parameters and were associated with the number of LV segments showing fibrosis, unlike sST2. Sacubitril/valsartan treatment in HFrEF leads to reduced sST2 and NT-proBNP concentrations with distinct decreasing curves, which are linked to reverse CR through LV-related parameters. In contrast to sST2, NT-proBNP is also associated with fibrosis, suggesting that both biomarkers unveil distinct mechanisms during CR in patients treated with sacubitril/valsartan.

Previous studies suggest that prevalent heart failure (HF) differs based on left ventricular ejection fraction (LVEF) and left ventricular (LV) chamber size. Furthermore, the prevalence of HF with preserved ejection fraction (HFpEF) is often considered approaching, or exceeding that of HF with reduced ejection fraction in the community.

The aim of this study was to evaluate prevalent and incident HF based on LVEF and CMR-determined LV size within a large community-dwelling cohort.

Individuals from the United Kingdom Biobank (UKB) who underwent CMR and had available health record linkage to allow ascertainment of HF diagnosis were included. The cohort was analysed according to LVEF, LV end-diastolic volume (LVEDV) quartiles and LVEDV indexed to body surface area (LVEDVi).

38,129 individuals were included, comprising those with reduced LVEF (LVEF<50 %, n = 5096) and preserved LVEF (LVEF 50-60 %, n = 22,907, LVEF≥60 %, n = 10,126). Prevalent HF was highest in males with LVEF<50 %, and participants with reduced LVEF had higher rates of incident HF (p < 0.001) during the follow-up period (median = 2.46 years from CMR). Mean LVEDV and LVEDVi were largest in individuals with EF < 50 % (146.9 ± 36.2 ml and 76.8 ± 16.4 ml/m2 respectively). Compared to the smallest quartiles, the largest quartiles for LVEDV were associated with increased odds of HF (odds ratio 2.14 [95 % confidence interval 1.47-3.12], p < 0.001).

Over 50 % of HF cases occur in individuals with LVEF ≥50 %, however HF prevalence is highest in those with reduced LVEF, particularly in males. Larger LV size is associated with increased HF across the LVEF spectrum.

Heart failure (HF) is an imminent global health problem. Yet established screening algorithms for asymptomatic pre-HF, allowing for early and effective preventive interventions, are largely lacking. The HERZCHECK trial, conducted in structurally underserved rural regions of North-Eastern Germany, aims to close this gap by evaluating the feasibility, diagnostic efficacy, and cost-effectiveness of a fully mobile, telemedically-supervised screening approach, combining cardiovascular magnetic resonance (CMR) imaging and laboratory testing as central elements.

The HERZCHECK trial is a prospective, randomized controlled trial employing a prospective randomized open blinded endpoint design. The study targets asymptomatic adults aged 40-69 years without a history of HF, but with at least one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, obesity, smoking/tobacco consumption, chronic diabetes mellitus, or chronic kidney disease. Participants undergo a comprehensive screening examination including a questionnaire-based medical history, laboratory testing, and CMR at baseline. Based on CMR-derived global longitudinal strain (GLS), participants are classified as stratum A (GLS < -15%), B (GLS ≥ -15% to < -11%), or C (GLS ≥ -11%), with strata B and C being defined as asymptomatic pre-HF. Ten percent of participants in stratum A and all of stratum B and C are subsequently randomized into two groups, receiving either conventional or innovative medical reports, the latter including information on GLS, guideline-based recommendations, and access to a lifestyle intervention app for cardiovascular prevention. Additionally, treating physicians of participants in the innovative group are granted access to an expert center for telemedical inquiries. Follow-up assessments are performed over 12 months to evaluate changes in GLS, as well as adverse cardiac events and quality of life.

HERZCHECK aims to provide a blueprint for a comprehensive, contemporary screening approach tailored to the needs of the targeted structurally underserved population. By implementing this approach in a representative at-risk cohort, HERZCHECK will provide important new information about (a) the prevalence of asymptomatic pre-HF in at-risk patients and (b) the feasibility, added diagnostic value and health economic aspects of CMR exams as part of future screening mechanisms for HF in clinical routine care (NCT05122793).

Highly-undersampled, dynamic MRI reconstruction, particularly in multi-coil scenarios, is a challenging inverse problem. Unrolled networks achieve state-of-the-art performance in MRI reconstruction but suffer from long training times and extensive GPU memory cost.

In this work, we propose a novel training strategy for IMplicit UNrolled NEtworks (IMUNNE) for highly-undersampled, multi-coil dynamic MRI reconstruction. It formulates the MRI reconstruction problem as an implicit fixed-point equation and leverages gradient approximation for backpropagation, enabling training of deep architectures with fixed memory cost. This study represents the first application of implicit network theory in the context of real-time cine MRI. The proposed method is evaluated using a prospectively undersampled, real-time cine dataset using radial k-space sampling, comprising balanced steady-state free precession (b-SSFP) readouts. Experiments include a hyperparameter search, head-to-head comparisons with a complex U-Net (CU-Net) and an alternating unrolled network (Alt-UN), and an analysis of robustness under noise perturbations; peak signal-to-noise ratio, structural similarity index, normalized root mean-square error, spatio-temporal entropic difference, and a blur metric were used.

IMUNNE produced significantly and slightly better image quality compared to CU-Net and Alt-UN, respectively. Compared with Alt-UN, IMUNNE significantly reduced training and inference times, making it a promising approach for highly-accelerated, multi-coil real-time cine MRI reconstruction.

IMUNNE strategy successfully applies unrolled networks to image reconstruction of highly-accelerated, real-time radial cine MRI.

Implicit training enables rapid, high-quality, and cost-effective CMR exams by reducing training and inference times and lowering memory cost associated with advanced reconstruction methods.

The development of cell therapy as a widely available clinical option for ischaemic cardiomyopathy is hindered by the invasive nature of current cell delivery methods. Furthermore, the rapid disappearance of cells after transplantation provides a cogent rationale for using repeated cell doses, which, however, has not been done thus far in clinical trials because it is not feasible with invasive approaches. The goal of this translational study was to test the therapeutic utility of the intravenous route for cell delivery.

Pigs with chronic ischaemic cardiomyopathy induced by myocardial infarction received one or three intravenous doses of allogeneic bone marrow mesenchymal stromal cells (MSCs) or placebo 35 days apart. Rigour guidelines, including blinding and randomization, were strictly followed. A comprehensive assessment of left ventricular (LV) function was conducted with three independent methods (echocardiography, magnetic resonance imaging, and haemodynamic studies). The results demonstrate that three doses of MSCs improved both load-dependent and independent indices of LV function and reduced myocardial hypertrophy and fibrosis; in contrast, one dose failed to produce most of these benefits.

To our knowledge, this is the first study to show that intravenous infusion of a cell product improves LV function and structure in a large animal model of chronic ischaemic cardiomyopathy and that repeated infusions are necessary to produce robust effects. This study, conducted in a clinically relevant model, supports a new therapeutic strategy based on repeated intravenous infusions of allogeneic MSCs and provides a foundation for a first-in-human trial testing this strategy in patients with chronic ischaemic cardiomyopathy.

Heart failure with reduced ejection fraction (HFrEF) guidelines recommend 'four pillars' of medical therapy and device therapy if left ventricular ejection fraction (LVEF) remains ≤35% after 3 months optimum medical therapy.We conducted the first study to examine the effects of optimisation to contemporary medical therapy on cardiac reverse remodelling, as demonstrated by cardiac magnetic resonance imaging (CMR).We hypothesised a proportion of patients would undergo beneficial remodelling and LVEF improvement above the threshold for complex device prescription after 6 months.

HFrEF patients with symptomatic LVEF≤35% despite ACE inhibitor/beta blocker/mineralocorticoid receptor antagonist therapy, and qualified for sacubitril/valsartan switchover were recruited to this single centre prospective study.CMR was performed at baseline and at follow-up. Clinical, volumetric and outcome data were collected and compared.

Between June 2021 and August 2022, 49 patients were recruited. The majority (80%) were male, mean age 63±14 years. 35 (71%) had non-ischaemic cardiomyopathy. 2 (4%) patients died and 47 were followed up for a median of 7.4 months. There were no heart failure hospitalisations.Significant reductions were seen in median indexed left atrial volume: 54 mL/m2 (41-72) to 39 mL/m2 (30-60) (p<0.001); indexed left ventricular end-diastolic volume: 109 mL/m2 (74-125) to 76 mL/m2 (58-102) (p<0.001); indexed left ventricular end-systolic volume: 74mL/m2 (50-92) to 43 mL/m2 (27-58) (p<0.001) and mean indexed left ventricular mass: 72±13 g/m2 to 62±13 g/m2 (p<0.001).Median LVEF increased by 12 points from 31% to 43% (p<0.001). 29 (59%) patients improved to LVEF>35%. 13 (27%) patients improved to LVEF≥50%.Median N-terminal pro B type natriuretic peptide (NTproBNP) reduced from 883 ng/L (293-2043) to 429 ng/L (171-1421) (p<0.001).

Optimisation to contemporary HFrEF medical therapy results in beneficial cardiac reverse remodelling and significant improvements in LVEF and NTproBNP at 6 months as demonstrated by CMR. 59% of our cohort no longer met complex device indications. Guidelines suggest re-assessment of LVEF at 3 months, but our data suggests a longer period is required.

NCT05348226.

Cardiovascular magnetic resonance imaging (CMR) has received extensive validation for the assessment of valvular heart disease (VHD) and offers an accurate and direct method for the quantification of aortic regurgitation (AR). According to the current guidelines, CMR represents a useful second-line investigation in patients with poor acoustic windows or when echocardiography is inconclusive, for example, in cases of multiple or eccentric aortic jets. Without ionizing radiation exposure, CMR provides in-depth information not only on the severity degree of AR, providing a precise quantification of regurgitant volume and fraction, but also on cardiac structure and function, being recognized as the gold standard for the assessment of heart chamber size and systolic function. CMR allows a free choice of cardiac imaging planes and provides further information on the myocardium, thanks to the tissue characterization ability offered by several sequences, such as the late gadolinium enhancement technique. The possibilities offered by CMR become even more interesting in the context of mixed and multiple VHD, where the echocardiographic assessments often encounter difficulties in the quantification of each single valve lesion. The current scientific data support a greater expansion of CMR in this field, thanks to its additional advantages for the diagnosis, risk stratification, and to guide treatment. This review investigates the current CMR techniques and protocols in AR, with special insights into the evaluation of mixed aortic valve disease and multiple VHD including AR.

Accurate measurements of flow and ventricular volume and function are critical for clinical decision-making in cardiovascular medicine. Cardiac magnetic resonance (CMR) is the current gold standard for ventricular functional evaluation but is relatively expensive and time-consuming, thus limiting the scale of clinical applications. New volumetric acquisition techniques, such as four-dimensional flow (4D-flow) and three-dimensional volumetric cine (3D-cine) MRI, could potentially reduce acquisition time without loss in accuracy; however, this has not been formally tested on a large scale.

4DCarE (4D-flow MRI for cardiovascular evaluation) is a prospective, multi-centre study designed to test the non-inferiority of a compressed 20 min exam based on volumetric CMR compared with a conventional CMR exam (45-60 min). The compressed exam utilises 4D-flow together with a single breath-hold 3D-cine to provide a rapid, accurate quantitative assessment of the whole heart function. Outcome measures are (i) flow and chamber volume measurements and (ii) overall functional evaluation. Secondary analyses will explore clinical applications of 4D-flow-derived parameters, including wall shear stress, flow kinetic energy quantification, and vortex analysis in large-scale cohorts. A target of 1200 participants will enter the study across three sites. The analysis will be performed at a single core laboratory site. Pilot Results: We present a pilot analysis of 196 participants comparing flow measurements obtained by 4D-flow and conventional 2D phase contrast, which demonstrated moderate-good consistency in ascending aorta and main pulmonary artery flow measurements between the two techniques. Four-dimensional flow underestimated the flow compared with 2D-PC, by approximately 3 mL/beat in both vessels.

We present the study protocol of a prospective non-inferiority study of a rapid cardiac MRI exam compared with conventional CMR. The pilot analysis supports the continuation of the study.

This study is registered with the Australia and New Zealand Clinical Trials Registry (Registry number ACTRN12622000047796, Universal Trial Number: U1111-1270-6509, registered 17 January 2022-Retrospectively registered).

The detection of cancer therapy-related cardiac dysfunction (CTRCD) by reduction of left ventricular ejection fraction (LVEF) during chemotherapy usually triggers the initiation of cardioprotective therapy. This study addressed whether the same approach should be applied to patients with worsening of global longitudinal strain (GLS) without attaining thresholds of LVEF.

Strain surveillance during chemotherapy for improving cardiovascular outcomes (SUCCOUR-MRI) was a prospective multicentre randomized controlled trial involving 14 sites. Of 355 patients receiving anthracyclines with normal baseline LVEF, 333 patients (age 59 ± 13 years, 79% women) with at least one other CTRCD risk factor, able to undergo magnetic resonance imaging (MRI), GLS, and three-dimensional echocardiography were tracked over 12 months. A total of 105 patients (age 59 ± 13 years, 75% women, 69% breast cancer) developing GLS-CTRCD (>12% relative reduction of GLS without a change in LVEF) were randomized to cardioprotection with neurohormonal antagonists vs. usual care. The primary endpoint was 12-month change in MRI-LVEF; the secondary endpoint was MRI-LVEF-defined CTRCD.

During follow-up, two patients died, and two developed heart failure. Most patients were randomized at 3 months (62%). Median doses of angiotensin inhibition/blockade and beta-blockade were 75% and 50% of respective targets; 21 (43%) had side-effects attributed to cardioprotection. Due to a smaller LVEF change from baseline with cardioprotection than usual care (-2.5 ± 5.4% vs. -5.6 ± 5.9%, P = .009), follow-up LVEF was higher after cardioprotection (59 ± 5% vs. 55 ± 6%, P < .0001). After adjustment for baseline LVEF, the mean (95% confidence interval) difference in the change in LVEF between the two groups was -3.6% (-1.8% to -5.5%, P < .001). After cardioprotection, 1/49 patients developed 12-month LVEF-CTRCD, compared to 6/56 in usual care (P = .075). Global longitudinal strain improved at 3 months post-randomization in the cardioprotection group, with little change with usual care.

In patients with isolated GLS reduction after anthracyclines, cardioprotection is associated with better preservation of 12-month MRI-LVEF compared with usual care.

Background Left ventricular mass (LVM) is an established marker of cardiovascular risk; however, long-term follow-up studies in individuals with low to intermediate risk are lacking. Purpose To assess the sex-specific association of LVM measured with cardiac MRI with cardiovascular outcomes in those with a less than 20% 10-year risk of cardiovascular disease (CVD). Materials and Methods A total of 1528 volunteers older than 40 years of age with no history of CVD, a 10-year risk of CVD of less than 20%, and a B-type natriuretic peptide level greater than their sex-specific median underwent cardiac MRI between June 2008 and February 2013 as part of the Tayside Screening for Cardiac Events, or TASCFORCE, prospective study. LVM was indexed to body surface area, and the LVM-to-volume ratio was calculated. Follow-up for cardiovascular events was performed using national electronic health records. Cox proportional hazard models and Kaplan-Meier curves were applied to assess the impact of LVM. Results A total of 1495 participants (mean age, 54.5 years ± 8.3 [SD]; 925 female, 570 male) completed cardiac MRI, with a median follow-up of 10 years (IQR, 3 years). In female participants, LVM was associated with age, blood pressure, smoking status, and cholesterol level, while in male participants, LVM was associated with age and blood pressure. In female participants, the LVM-to-volume ratio was associated with cardiovascular events (hazard ratio [HR], 2.3 [95% CI: 1.1, 4.9] for the highest quartile vs the lowest quartile), while the LVM was not. In male participants, the LVM was associated with cardiovascular events (HR, 3.2 [95% CI: 1.5,7.0] for the highest quartile vs the lowest quartile), while the LVM-to-volume ratio was not. Conclusion In those with low to intermediate risk without established CVD, different remodeling patterns predict cardiovascular events, with increased LVM predictive in male participants, while LVM-to-volume ratio is predictive in female participants. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Garot and Duhamel in this issue.

Left atrial volume index (LAVI) serves as a crucial marker for assessing left atrial (LA) remodeling, particularly in patients with mitral valve regurgitation (MR). Recent guidelines recommend a LAVI exceeding 60 mL/m2 as Class IIa recommendation for mitral valve repair surgery in asymptomatic MR patients with preserved left ventricular function. Traditionally, echocardiography is the standard for assessing LAVI in MR patients. However, cardiac magnetic resonance imaging (CMR) is increasingly recognized for its more precise measurements of cardiac dimensions and volumes. But still, literature remains scarce on comparing the efficacy of both modalities in assessing LAVI measurements.

This retrospective study included 168 MR patients undergoing both echocardiography and CMR assessments within a six-month period. LAVI measurements were compared using Pearson correlation and Bland-Altman plots. Patients were stratified based on MR grades, and clinical implications were assessed.

Mean LAVI differed significantly between echocardiography and CMR (47.1 ± 20.8 mL/m2 versus 70 ± 20.3 mL/m2, p < 0.001, respectively). CMR consistently yielded higher LAVI measurements compared to echocardiography, with a mean difference of approximately 20 mL/m2. CMR measurements resulted in an increased incidence of patients meeting the class IIa LAVI criterion (LAVI >60 mL/m2) by 37%. Variations in LAVI did not differ across MR grades.

Echocardiography systematically underestimates LAVI compared to CMR in MR patients. While current guidelines rely on echocardiography, CMR's precision suggests the need for CMR-specific LAVI cutoff values to guide clinical management effectively. Establishing such values could refine patient stratification and timing of surgery, potentially improving clinical outcomes for MR patients.

Adverse left ventricular remodeling (ALVR) and subsequent heart failure after myocardial infarction (MI) remain a major cause of patient morbidity and mortality worldwide. Overt inflammation has been identified as the common pathway underlying myocardial fibrosis and development of ALVR post-MI. With its ability to simultaneously provide information about cardiac structure, function, perfusion, and tissue characteristics, cardiac magnetic resonance (CMR) is well poised to inform prognosis and guide early surveillance and therapeutics in high-risk cohorts. Further, established and evolving CMR-derived biomarkers may serve as clinical endpoints in prospective trials evaluating the efficacy of novel anti-inflammatory and antifibrotic therapies. This review provides an overview of post-MI ALVR and illustrates how CMR may help clinical adoption of novel therapies via mechanistic or prognostic imaging markers.

In nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the strongest predictor of adverse outcomes. We sought to investigate the relationship between liver fibrosis and cardiac remodeling in participants from the general population using magnetic resonance imaging (MRI), as well as explore potential mechanistic pathways by analyzing circulating cardiovascular biomarkers.

In this cross-sectional study, we prospectively included participants with type 2 diabetes and individually matched controls from the SCAPIS (Swedish CArdioPulmonary bioImage Study) cohort in Linköping, Sweden. Between November 2017 and July 2018, participants underwent MRI at 1.5 Tesla for quantification of liver proton density fat fraction (spectroscopy), liver fibrosis (stiffness from elastography), left ventricular (LV) structure and function, as well as myocardial native T1 mapping. We analyzed 278 circulating cardiovascular biomarkers using a Bayesian statistical approach.

In total, 92 participants were enrolled (mean age 59.5 ± 4.6 years, 32 women). The mean liver stiffness was 2.1 ± 0.4 kPa. 53 participants displayed hepatic steatosis. LV concentricity increased across quartiles of liver stiffness. Neither liver fat nor liver stiffness displayed any relationships to myocardial tissue characteristics (native T1). In a regression analysis, liver stiffness was related to increased LV concentricity. This association was independent of diabetes and liver fat (Beta = 0.26, p = 0.0053), but was attenuated (Beta = 0.17, p = 0.077) when also adjusting for circulating levels of interleukin-1 receptor type 2.

MRI reveals that liver fibrosis is associated to structural LV remodeling, in terms of increased concentricity, in participants from the general population. This relationship could involve the interleukin-1 signaling.

Liver fibrosis may be considered a cardiovascular risk factor in patients without cirrhosis. Further research on the mechanisms that link liver fibrosis to left ventricular concentricity may reveal potential therapeutic targets in patients with non-alcoholic fatty liver disease (NAFLD).

Previously, studies on liver fibrosis and cardiac remodeling have focused on advanced stages of liver fibrosis. Liver fibrosis is associated with left ventricular (LV) concentricity and may relate to interleukin-1 receptor type 2. Interleukin-1 signaling is a potential mechanistic interlink between early liver fibrosis and LV remodeling.

Despite remarkable progress in therapeutic drugs, morbidity, and mortality for heart failure (HF) remains high in developed countries. HF with preserved ejection fraction (HFpEF) now accounts for around half of all HF cases. It is a heterogeneous disease, with multiple aetiologies, and as such poses a significant diagnostic challenge. Cardiac magnetic resonance (CMR) has become a valuable non-invasive modality to assess cardiac morphology and function, but beyond that, the multi-parametric nature of CMR allows novel approaches to characterize haemodynamics and with magnetic resonance spectroscopy (MRS), the study of metabolism. Furthermore, exercise CMR, when combined with lung water imaging provides an in-depth understanding of the underlying pathophysiological and mechanistic processes in HFpEF. Thus, CMR provides a comprehensive phenotyping tool for HFpEF, which points towards a targeted and personalized therapy with improved diagnostics and prevention.

Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute coronavirus disease 2019 (COVID-19) illness and without overt structural heart disease. Cardiovascular magnetic resonance (CMR) imaging can identify the underlying subclinical disease process, which is associated with chronic cardiac symptoms. Specific therapy directed at reducing postacute cardiac inflammatory involvement before development of myocardial injury and impairment is missing.

Prospective multicenter randomized placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodeling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no pre-existing significant comorbidities or structural heart disease, undergo standardized assessments with questionnaires, CMR imaging, and cardiopulmonary exercise testing (CPET). Eligible participants fulfilling the criteria of subclinical post-COVID inflammatory heart involvement on baseline CMR examination are randomized to treatment with either verum or placebo for a total of 16 weeks (W16). Participants and investigators remain blinded to the group allocation throughout the study duration. The primary efficacy endpoint is the absolute change of left ventricular ejection fraction to baseline at W16, measured by CMR, between the verum treatment and placebo group by absolute difference, using unpaired t-test confirmatively at a significance level of 0.05 significance level. Secondary endpoints include assessment of changes of symptoms, CMR parameters, and CPET after W16, and frequency of major adverse cardiac events after 1 year. Safety data will be analyzed for frequency, severity, and types of adverse events (AEs) for all treatment groups. The proportion of AEs related to the contrast agent gadobutrol will also be analyzed. A calculated sample size is a total of 280 participants (accounting for 22 subjects (8%) drop out), randomized in 1:1 fashion to 140 in the verum and 140 placebo groups.

Myoflame-19 study will examine the efficacy of a myocardial protection therapy in symptomatic participants with post-COVID inflammatory cardiac involvement determined by CMR. The aim of the intervention is to reduce the symptoms and inflammatory myocardial injury, improve exercise tolerance, and preclude the development of cardiac impairment.

The therapeutic effects of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular outcome are not fully understood. This study aimed to evaluate the efficacy and safety of ertugliflozin on cardiac function in people with type 2 diabetes and pre-heart failure.

We conducted a 24-week randomized, double-blind, placebo-controlled trial involving individuals with type 2 diabetes inadequately controlled with antidiabetic medications. Participants with left ventricular hypertrophy, E/e' >15, or impaired left ventricular global longitudinal strain (LVGLS) were randomized 1:1 to receive either ertugliflozin (5 mg once daily) or a placebo. The primary outcome was the change in LVGLS. Secondary outcomes included changes in left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Prespecified exploratory outcomes, including angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) levels, were also assessed.

A total of 102 individuals (mean age, 63.9 ± 9.2 years; 38% women) were included. The ertugliflozin group showed a significant improvement in LVGLS (- 15.5 ± 3.1% to - 16.6 ± 2.8%, P = 0.004) compared to the placebo group (- 16.7 ± 2.7% to - 16.4 ± 2.6%, P = 0.509), with a significant between-group difference (P = 0.013). Improvements in LVMI and LVEF were also observed. Additionally, significant reductions in HbA1c, systolic blood pressure, whole-body and visceral fat, uric acid, proteinuria, N-terminal pro-B-type natriuretic peptide, and lipoprotein(a) were noted. ACE2 and angiotensin (1-7) levels significantly increased in the ertugliflozin group compared to the placebo group and correlated with changes in LVGLS [r = 0.456, P < 0.001 for ACE2; r = 0.541, P < 0.001 for angiotensin (1-7)]. Adverse events were similar between the two groups.

This study demonstrated that ertugliflozin has beneficial effects on left ventricular function in individuals with type 2 diabetes and pre-heart failure, and it provided insights into potential underlying mechanisms.

ClinicalTrials.gov Identifier: NCT03717194.