The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index; 15 of the 22 sources its claims cite were checked for support.
Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure
Open accessAbstract
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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).
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In the CMR substudy of the SUMMIT trial, tirzepatide reduced left ventricular mass and paracardiac adipose tissue versus placebo in patients with obesity-related HFpEF over 52 weeks. The LV mass reduction paralleled weight loss, suggesting a mechanism that may contribute to the heart failure event reduction seen in the main trial.
Key findings
- Placebo-corrected LV mass decreased by −11 g (95% CI: −19 to −4 g; P = 0.004) in the tirzepatide group (n = 50) versus placebo (n = 56).
- Placebo-corrected paracardiac adipose tissue decreased by −45 mL (95% CI: −69 to −22 mL; P < 0.001), driven by pericardial fat (−43 g; 95% CI: −65 to −21 g; P < 0.001); epicardial adipose tissue decreased in both groups with no between-group difference.
- Between-group difference in stroke volume change was −8 mL (95% CI: −14 to −2 mL; P = 0.011); no between-group differences in end-systolic volume, cardiac output, ejection fraction, LV strain, or LA volumes/function/strain.
- In the treated group, LV mass change correlated with body weight change (r = 0.34; P < 0.02), LV end-diastolic volume (r = 0.33; P < 0.03), LA end-systolic volume (r = 0.42; P = 0.003), and LA end-diastolic volume (r = 0.50; P < 0.001); it tended to correlate with waist circumference and systolic blood pressure (r = 0.27; P = 0.06 for both).
- Substudy heart failure outcome events: 3 in tirzepatide (6.0%) vs 8 in placebo (14.2%).
Methods
- Substudy of the SUMMIT trial (NCT04847557); 175 of 731 parent-trial patients with obesity-related HFpEF (EF ≥50%, BMI ≥30 kg/m², NYHA II–IV) underwent baseline CMR; 106 (50 tirzepatide, 56 placebo) completed baseline and 52-week CMR with adequate image quality.
- Randomized to tirzepatide (2.5 mg SC weekly titrated to a maximum of 15 mg weekly) or matching placebo; CMR protocol used ECG-gated, breath-held steady-state free precession cine imaging at 1.5-T or 3-T, analyzed at a core laboratory blinded to treatment and timepoint.
- Prespecified primary endpoint: between-group change in LV mass; analyzed by ANCOVA with baseline measure as covariate and fixed effects for treatment, type 2 diabetes, and baseline BMI group (<35, ≥35 kg/m²); Pearson correlations for associations; no correction for multiple comparisons.
Limitations
- Stated: 58 of 175 enrollees (33%) had inadequate CMR images for primary endpoint analysis; sites could perform CMR but were not necessarily expert, and obesity complicated gating and breath holding. Excluded/non-imaged patients differed only by country of origin, ethnicity, and minor height and systolic blood pressure differences.
- Stated: LA volumes were analyzed from biplane long-axis images rather than modified Simpson's method from short-axis stacks, potentially lowering reproducibility; T1 mapping/ECV and late gadolinium enhancement were not performed, so it is unknown whether LV mass reduction reflected reduced cardiomyocyte mass, interstitial fibrosis, or both; right ventricular structure/function were not prespecified.
- Evident from the text: the substudy was not powered for clinical events (3 vs 8 events reported as a trend), and no corrections were made for multiple comparisons across the many secondary measures analyzed.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
31 Own result · 14 Own method · 8 Own interpretation · 7 Supported · 5 No full text of the sources · 4 Partly supported · 2 Not checked yet · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“LA volume was reduced by 6 mL with treatment in the STEP-HFpEF echocardiographic substudy as well”
What the sources say
- Partly supportedcites [11] Solomon, 2024, Effect of semaglutide on cardiac structure and function in patients with obesity-related heart failure, J Am Coll Cardiol sourceExperimental — accuracy not yet measured
The Results (Treatment effects of semaglutide on echocardiography parameters) report a 6.13 mL smaller increase in LA volume with semaglutide than with placebo over 52 weeks. LA volume increased in both arms, so it was not reduced by 6 mL from baseline. The Methods also specify that the echocardiography substudy pooled STEP-HFpEF and STEP-HFpEF DM participants. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In contrast with the aforementioned study of GLP-1 RA,21 we found no effect on epicardial fat volume”
What the sources say
- Supportedcites [21] Manubolu, 2024, Effect of semaglutide on epicardial adipose tissue in type 2 diabetes, J Am Coll Cardiol source
The cited study reports a significant reduction in epicardial adipose tissue volume with semaglutide, a GLP-1 receptor agonist (Abstract). That supports the contrast the citing authors draw; their finding of no effect is their own, not a finding attributed to this source. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In the echocardiographic analysis from the STEP-HFpEF study, effects of semaglutide on paracardiac fat were not reported.11”
What the sources say
- Supportedcites [11] Solomon, 2024, Effect of semaglutide on cardiac structure and function in patients with obesity-related heart failure, J Am Coll Cardiol source
The Methods section lists the echocardiographic outcomes, including chamber measurements and cardiac function, but not paracardiac fat. The Discussion mentions an expected reduction in epicardial adipose tissue as a possible mechanism, not a measured treatment effect. No page numbers are available in our copy. (LLM, conf=0.89)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the STEP-HFpEF (Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity) study in a similar patient population to the present study, LV mass reduction was not seen in the semaglutide group over 52 weeks of therapy”
What the sources say
- Partly supportedcites [11] Solomon, 2024, Effect of semaglutide on cardiac structure and function in patients with obesity-related heart failure, J Am Coll Cardiol sourceExperimental — accuracy not yet measured
The Results (page unavailable) report no significant effect of semaglutide on LV mass over 52 weeks, supporting the claim if “reduction was not seen” means no significant reduction. The Discussion (page unavailable) nevertheless notes a numerical reduction in LV mass, so the claim is too categorical. The analysis also pooled STEP-HFpEF and STEP-HFpEF DM rather than reporting this finding for STEP-HFpEF alone. (LLM, conf=0.88)
plainn = 363- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
- Also stated in: § Results · plain
“The placebo-corrected decline in LV mass was −11 g (95% CI: −19 to −4 g; P = 0.004) (Table 2).”
plaindirectn = 50 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared with healthy patients, at baseline, patients with obesity-related HFpEF exhibited an increase in LV mass and LA end-systolic and end-diastolic volumes when compared with normal values in the literature (Supplemental Table 2).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no between-group differences in LA end-systolic or end-diastolic volumes, ejection fraction, or strain.”
plainn = 106- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no between-group differences in LA end-systolic or end-diastolic volumes, ejection fraction, or strain.”
plainn = 106- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“LV end-diastolic volume and stroke volume decreased by at least 6 mL in the treated group.”
plaindirectn = 106 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no between-group differences in LA end-systolic or end-diastolic volumes, ejection fraction, or strain.”
plainn = 106- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 26
- It may state two separate claims as one. 12
Every source the paper cites for this claim was checked and supports it.
In the paper
“Investigators have demonstrated the ability to use CMR to assess fatty acid composition (saturated vs unsaturated) within EAT,23,24 and this may better differentiate HFpEF subtypes and response to therapy than volume alone.”
What the sources say
- Supportedcites [23] Shah, 2022, Accelerated fatty acid composition MRI of epicardial adipose tissue: Development and application to eplerenone treatment in a mouse model of obesity-induced coronary microvascular disease, Magn Reson Med source
The Conclusion reports that accelerated fatty acid composition MRI quantified saturated fatty acid fraction and degree of unsaturation in mouse epicardial adipose tissue. That supports the clause to which the citation is attached. The subsequent suggestion about differentiating HFpEF subtypes is not established by this mouse study. (LLM, conf=0.93)
- Supportedcites [24] Echols, 2024, Fatty acid composition MRI of epicardial adipose tissue: methods and detection of proinflammatory biomarkers in ST-segment elevation myocardial infarction patients, Magn Reson Med source
The Introduction describes an MRI method for quantifying saturated, monounsaturated, and polyunsaturated fatty acids within EAT, and the Discussion identifies this as FAC MRI of human EAT. The citation is attached to that demonstrated measurement capability; the subsequent suggestion about HFpEF subtypes and treatment response is the citing authors’ own framing. (LLM, conf=0.94)
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In the present study, EAT was lower than that measured in the study by Nakamori et al,16 whereas paracardiac adipose tissue values were similar to what was termed “EAT” in the latter study.”
What the sources say
- Supportedcites [16] Nakamori, 2023, Obesity-related differences in pathomechanism and outcomes in patients with HFpEF: a CMR study, JACC Adv source
The citation identifies Nakamori et al.’s study as the source of an EAT measurement, and the Methods (Image analysis; page unavailable) describe how that study measured EAT volume. The lower and similar values are comparisons made by the citing authors about their own study, not findings attributed to Nakamori et al. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Paracardiac adipose tissue has been hypothesized to act in a paracrine manner, with release of proinflammatory and profibrotic adipocytokines and excess free fatty acids with resultant intramyocardial lipid accumulation and myocardial inflammation and fibrosis.19”
What the sources say
- Partly supportedcites [19] Iacobellis, 2022, Epicardial adipose tissue in contemporary cardiology, Nat Rev Cardiol sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“At baseline, the mean LV mass, volumes and ejection fraction were similar to those of a prior CMR study in a HFpEF population.16”
What the sources say
- Supportedcites [16] Nakamori, 2023, Obesity-related differences in pathomechanism and outcomes in patients with HFpEF: a CMR study, JACC Adv source
The Methods (Study population) identify this as a CMR study of patients with HFpEF. Table 2 in Results (Patient population) reports mean LV mass, end-diastolic and end-systolic volumes, and ejection fraction, providing the prior-study values used for the citing authors’ comparison. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“There is also some evidence for intramyocardial steatosis contributing to interstitial fibrosis in HFpEF, especially in women.22”
What the sources say
- Supportedcites [22] Ng, 2024, Sexual dimorphism in the relationships between intramyocardial fat, myocardial fibrosis, and exercise intolerance in heart failure with preserved ejection fraction, Eur J Heart Fail source
The Results report that higher intramyocardial fat was associated with higher extracellular volume, a surrogate for interstitial fibrosis, and that this relationship was stronger in women with HFpEF. The discussion describes this as a potentially important sex difference. The paper notes that its observational data cannot establish causality, consistent with the claim’s cautious wording, 'some evidence.' (LLM, conf=0.87)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“LA diameter, but not volumes, was measured in the latter study, so no comparison can be made.”
What the sources say
- Supportedcites [16] Nakamori, 2023, Obesity-related differences in pathomechanism and outcomes in patients with HFpEF: a CMR study, JACC Adv source
Table 2 (Results, Patient population; page unavailable) reports LA diameter and other LA dimensions but no LA volume. The Methods describe ventricular volume measurements and LA strain, not LA volume measurement. The paper therefore provides no LA volume values for the comparison described. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Paracardiac adipose tissue (epicardial and pericardial adipose tissue) in patients with obesity may also impair LV relaxation20 and increase cardiac filling pressures, owing to increases in extrinsic restraint on the heart in obesity-related HFpEF.2,6,7”
What the sources say
- Partly supportedcites [20] Wu, 2020, Myocardial adipose deposition and the development of heart failure with preserved ejection fraction, Eur J Heart Fail sourceExperimental — accuracy not yet measured
The Fat distribution and HFpEF section (page not provided) reports that epicardial fat correlated with LV diastolic dysfunction parameters in men, but not women, and discusses cardiac dysfunction in obesity. It does not establish the same relationship for pericardial fat or for patients with obesity generally. The filling-pressure and extrinsic-restraint clause is attached to other citations, not this source. (LLM, conf=0.84)
- Supportedcites [2] Obokata, 2017, Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction, Circulation source
The Discussion (Clinical Implications) says epicardial fat may mechanically contribute to increased intracardiac pressures in obese HFpEF. The Results (Myocardial, Pericardial and Ventricular Interactions) also report greater pericardial restraint and higher filling pressure needed to achieve a given LV distending pressure. The separate LV-relaxation clause is attached to citation 20, not this source. (LLM, conf=0.91)
- Supportedcites [6] Obokata, 2022, Uncoupling between intravascular and distending pressures leads to underestimation of circulatory congestion in obesity, Eur J Heart Fail source
The cited paper supports the part of the sentence concerning increased filling pressures and extrinsic restraint; the separate claim about LV relaxation is attached to citation 20. In “Mechanism for underestimation of filling pressures in obesity” (page unavailable), it says obesity increases external pressure on the heart, potentially through pericardial and intrathoracic fat, while intravascular pressures are elevated. (LLM, conf=0.87)
- Supportedcites [7] Koepp, 2020, Hemodynamic and functional impact of epicardial adipose tissue in heart failure with preserved ejection fraction, JACC Heart Fail source
The Results (Resting Hemodynamics; page unavailable) report higher right and left heart filling pressures in obese patients with HFpEF and increased epicardial adipose tissue. The Discussion (Epicardial Fat and Diastolic Ventricular Interaction; page unavailable) links these findings to enhanced pericardial restraint. The separate claim about impaired LV relaxation is attached to citation 20, not this source. (LLM, conf=0.90)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pericardial adipose tissue decreased significantly in the treated group and, although not statistically significant, tended to increase in the placebo group, with the placebo-corrected difference of −43 g (95% CI: −65 to −21 g; P < 0.001).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and although not statistically significant, tended to correlate with change in systolic blood pressure (r = 0.27; P = 0.06).”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and although not statistically significant, tended to correlate with waist circumference (r = 0.27; P = 0.06).”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“EAT decreased in both groups, with no differences between them.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At baseline, there was 4-fold more pericardial adipose tissue than EAT in both groups (Table 2).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“A recent randomized study using noncontrast computed tomography in a prespecified secondary analysis of the STOP (Semaglutide Treatment effect On coronary atherosclerosis Progression) trial, the GLP-1 RA semaglutide was shown to reduce EAT by 19.3 mm3 as compared with placebo in 115 diabetic patients with known coronary artery disease.21”
What the sources say
- Not checked yetcites [21] Manubolu, 2024, Effect of semaglutide on epicardial adipose tissue in type 2 diabetes, J Am Coll Cardiol source
Checked before — its earlier verdict is held back until a new check runs.
plaindirectn = 115- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not checked yet
In the paper
“In the meta-analysis of studies of GLP-1 RA in diabetes discussed previously, LA volume decrease of 8 mL was similar to that noted in the present study, but no change was noted in LV end-diastolic volume.9”
What the sources say
- Not checked — no full text of the sourcecites [9] Zhang, 2024, The effect of glucagon-like peptide-1 receptor agonists on cardiac function and structure in patients with or without type 2 diabetes mellitus: An updated systematic review and meta-analysis, Diabetes Obes Metab source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This finding demonstrates the power of CMR to differentiate these 2 fat depots.”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All hypothesis testing was performed at the 0.05 significance level with no corrections made for multiple comparisons across the multiple different measure analyses.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No differences were noted between groups at baseline, neither for the 175 who enrolled (Supplemental Table 1) nor for the 106 who completed.”
plainn = 175- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“LA volumes were analyzed from biplane long-axis images rather than a modified Simpson’s method from stacks of short-axis images, which may lead to lower reproducibility.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, late gadolinium enhancement imaging was not performed”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The ethics committee at each investigative site approved the trial, and all patients provided written informed consent.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but tirzepatide may have an effect on EAT biology that cannot be discerned by CMR.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Echocardiographically estimated LV filling pressures have been shown to improve with GLP-1 RA in HFpEF, as shown in the STEP-HFpEF echocardiographic substudy with improved E-wave velocity, early/late mitral inflow velocity ratio, and early mitral inflow velocity/early diastolic mitral annular velocity.11”
What the sources say
- Not checked yetcites [11] Solomon, 2024, Effect of semaglutide on cardiac structure and function in patients with obesity-related heart failure, J Am Coll Cardiol source
Checked before — its earlier verdict is held back until a new check runs.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not checked yet
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The prespecified primary endpoint of this substudy was between-group changes in LV mass.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of 58 (33%) of 175 enrollees had inadequate CMR images for analysis of the primary endpoint despite a straightforward protocol.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Prior studies show that, due to improved interstudy reproducibility of CMR, sample sizes for clinical trials that seek to look for changes in LV mass can be significantly smaller as compared with echocardiography.17”
What the sources say
- Not checked — no full text of the sourcecites [17] Grothues, 2002, Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy, Am J Cardiol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Right ventricular structure and function were not prespecified analyses in the present study.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The same scanner was used at baseline and follow-up imaging.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The effect on pericardial fat reflects the effect of tirzepatide on visceral fat.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Care was taken in the present study to meticulously differentiate epicardial and pericardial adipose tissue using the visceral pericardial layer as a landmark.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“T1 mapping to measure ECV was not performed as part of the CMR protocol, largely due to its complexity in a multicenter international trial.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“An image analyst (J.M.D.) with 25 years of experience performed image analysis blinded to the treatment group and time of image acquisition.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper relies on this without support.
There is a paucity of data regarding the relationship between reduction in LV mass and improved outcomes in HFpEF.
“There is a paucity of data with regard to reduction in LV mass and improved outcomes in HFpEF.”
Citations
Cites
Schulz‐Menger, J., Bluemke, D. A., Bremerich, J., Flamm, S. D., Fogel, M. A., Friedrich, M. G., Kim, R. J., von Knobelsdorff‐Brenkenhoff, F., Kramer, C. M., Pennell, D. J., et al. (2013) · Journal of Cardiovascular Magnetic Resonance · doi:10.1186/1532-429x-15-35 · Cited by 2,157
Self-citationGrothues, F., Smith, G. C., Moon, J. C. C., Bellenger, N. G., Collins, P., Klein, H. U., & Pennell, D. J. (2002) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)02381-0 · Cited by 1,267
Obokata, M., Reddy, Y. N. V., Pislaru, S. V., Melenovsky, V., & Borlaug, B. A. (2017) · Circulation · doi:10.1161/circulationaha.116.026807 · Cited by 1,179
Self-citationEpicardial adipose tissue: Anatomic, biomolecular and clinical relationships with the heart
Iacobellis, G., Corradi, D., & Sharma, A. M. (2005) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio0319 · Cited by 1,015
Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity
Packer, M., Zile, M. R., Kramer, C. M., Baum, S. J., Litwin, S. E., Menon, V., Ge, J., Weerakkody, G. J., Ou, Y., Bunck, M. C., et al. (2025) · New England Journal of Medicine · doi:10.1056/nejmoa2410027 · Cited by 1,009
Self-citationEpicardial adipose tissue in contemporary cardiology
Iacobellis, G. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00679-9 · Cited by 797
Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes
Kosiborod, M. N., Petrie, M. C., Borlaug, B. A., Butler, J., Davies, M. J., Hovingh, G. K., Kitzman, D. W., Møller, D. V., Treppendahl, M. B., Verma, S., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2313917 · Cited by 758
Self-citationThe Association of Obesity and Cardiometabolic Traits With Incident HFpEF and HFrEF
Savji, N., Meijers, W. C., Bartz, T. M., Bhambhani, V., Cushman, M., Nayor, M., Kizer, J. R., Sarma, A., Blaha, M. J., Gansevoort, R. T., et al. (2018) · JACC: Heart Failure · doi:10.1016/j.jchf.2018.05.018 · Cited by 499
Koepp, K. E., Obokata, M., Reddy, Y. N. V., Olson, T. P., & Borlaug, B. A. (2020) · JACC Heart Failure · doi:10.1016/j.jchf.2020.04.016 · Cited by 269
Self-citationAndré, F., Steen, H., Matheis, P., Westkott, M., Breuninger, K., Sander, Y., Kammerer, R., Galuschky, C., Giannitsis, E., Korosoglou, G., et al. (2015) · Journal of Cardiovascular Magnetic Resonance · doi:10.1186/s12968-015-0123-3 · Cited by 225
Cited by
Sorted by citations
The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction
Packer, M. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.06.055 · Cited by 213
Self-citationPeikert, A., Vaduganathan, M., Claggett, B. L., Kulac, I. J., Litwin, S. E., Zile, M. R., Desai, A. S., Jhund, P. S., Butt, J. H., Lam, C. S. P., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf057 · Cited by 126
Self-citationKarakasis, P., Theofilis, P., Vlachakis, P. K., Korantzopoulos, P. G., Patoulias, D., Antoniadis, A. P., & Fragakis, N. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms26010209 · Cited by 104
2025 ACC Scientific Statement on the Management of Obesity in Adults With Heart Failure
Kittleson, M. M., Benjamin, E. J., Blumer, V., Harrington, J., Januzzi, J. L., McMurray, J. J. V., & Vest, A. R. (2025) · JACC · doi:10.1016/j.jacc.2025.05.008 · Cited by 79
Peikert, A., Fontana, M., Solomon, S. D., & Thum, T. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf524 · Cited by 61
Metadata
- Authors
- Kramer, C. M., Borlaug, B. A., Zile, M. R., Ruff, D., DiMaria, J. M., Menon, V., Ou, Y., Zarante, A. M., Hurt, K. C., Murakami, M., & Packer, M.
- Affiliations
- University of Virginia Health System (US)
- Mayo Clinic (US)
- Medical University of South Carolina (US)
- Eli Lilly (United States) (US)
- Cleveland Clinic (US)
- Baylor University Medical Center (US)
- Corresponding author
- Kramer, Christopher M.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2025-02
- Volume
- 85
- Issue
- 7
- Pages
- 699-706
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W4404470149
- Cited by
- 200
- References
- 25
- Citations by year
- 2026: 97 · 2025: 101
- FWCI
- 56.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- heart failure with preserved ejection fraction, left ventricular mass, epicardial adipose tissue, cardiac magnetic resonance, weight loss, left atrial volume, SUMMIT trial, GLP-1 receptor agonists, cardiac remodeling, blood pressure, waist circumference, left ventricular function
- MeSH terms
- Tirzepatide, Adipose Tissue, Aged, Double-Blind Method, Female, Heart Failure, Heart Ventricles, Humans, Male, Middle Aged, Obesity, Stroke Volume, Magnetic Resonance Imaging, Cine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
