Metabolic Activity in Central Neural Structures of Patients With Myocardial Injury

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Suspected or known coronary artery disease (n=302). Intervention: Myocardial injury (impaired LVEF =55%) and normal myocardial perfusion. Primary outcome: Resting 18F-FDG metabolic uptake (SUV) in the brainstem among men (myocardial ischemia vs normal perfusion) (B coefficient -0.667 (SE 0.238) in multivariate regression, p=0.016).

Q: What does this research mean for the field?

Myocardial ischemia and impaired left ventricular ejection fraction are associated with reduced resting metabolic activity in the corpus callosum, caudate nucleus, and brainstem in men, but not in women. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Michael Fiechter; Andrea Roggo; Ahmed Haider; Susan Bengs; Irene A. Burger; Monika Marędziak; Angela Portmann; Valérie Treyer; Anton S. Becker; Michael Messerli; Urs Jakob Mühlematter; Ken Kudura; Elia von Felten; Dominik C. Benz; Tobias A. Fuchs; Christoph Gräni; Aju P. Pazhenkottil; Ronny R. Buechel; Philipp A. Kaufmann; Cathérine Gebhard

doi:10.1161/jaha.119.013070

Key result

Myocardial ischemia and low LVEF are linked to lower subcortical brain metabolism in men only.

B coefficient -0.667 (SE 0.238) in multivariate regression
P=0.016
n=302

Figures

Why the study?

A better understanding of heart-brain interactions and their implications for cardiovascular treatment strategies is needed given the growing burden of ischemic cardiovascular disease.

Is myocardial injury (impaired LVEF or myocardial ischemia) associated with alterations in resting metabolic activity of central neural structures in patients with suspected or known coronary artery disease, and does this association differ by sex?

Key Points

Investigate the relationship between myocardial injury or dysfunction and resting metabolic alterations in central neural structures among patients with suspected or known coronary artery disease.
Analyzed resting neural metabolic activity and cardiac function in 302 patients (mean age 66.8±10.2 years; 70.9% men) using fluor-18-deoxyglucose PET and 99m Tc-tetrofosmin SPECT myocardial perfusion imaging.
Assessed fluor-18-deoxyglucose uptake in relation to left ventricular ejection fraction (<55% versus ≥55%) and the presence of myocardial ischemia versus normal perfusion.
Conducted sex-stratified comparisons and multivariate linear regression adjusting for active cancer, age, cardiovascular risk factors, and medications.
In men, impaired left ventricular ejection fraction (<55% versus ≥55%) was associated with reduced fluor-18-deoxyglucose uptake in the corpus callosum (SUV 58.3±37.4 versus 68.4±33.2, P=0.047), caudate nucleus (14.9±4.4 versus 16.2±3.6, P=0.022), and brainstem (4.5±1.4 versus 4.9±1.1, P=0.013), with no differences observed in women.
Men with myocardial ischemia exhibited lower neural uptake than those with normal perfusion in the corpus callosum (SUV 50.8±33.4 versus 67.9±34.4, P=0.010), caudate nucleus (14.2±4.6 versus 16.0±3.7, P=0.013), and brainstem (4.3±1.5 versus 4.9±1.2, P=0.016).
Significant sex-by-cardiac-status interaction terms predicted metabolic activity for left ventricular ejection fraction in the brainstem (P=0.015) and for myocardial ischemia across the corpus callosum (P=0.004), caudate nucleus (P=0.018), and brainstem (P=0.003).

Study Design

Type

Cohort (n=302)

Multicenter

No

Structured PICO

Is myocardial injury (impaired LVEF or myocardial ischemia) associated with alterations in resting metabolic activity of central neural structures in patients with suspected or known coronary artery disease, and does this association differ by sex?

P

Population

302 older adults (mean age 66.8 years, 29.1% female) in Switzerland with suspected or known coronary artery disease who underwent both 18F-FDG PET/CT and 99mTc-tetrofosmin MPI-SPECT within a mean interval of ~46-47 days.

E

Exposure

Myocardial injury/dysfunction (impaired LVEF <55% and/or myocardial ischemia/reversible perfusion defect assessed by 99mTc-tetrofosmin MPI-SPECT) evaluated alongside resting brain 18F-FDG PET/CT uptake (330.4 MBq weight-adapted IV).

C

Comparator

Normal left ventricular ejection fraction (LVEF ≥55%) and normal myocardial perfusion on 99mTc-tetrofosmin MPI-SPECT, stratified by sex.

O

Outcome

Resting metabolic activity (quantified as mean standardized uptake value [SUV] normalized to cerebellar mean SUV) in distinct central neural structures (corpus callosum, caudate nucleus, brainstem, amygdala, hippocampus, thalamus, and insula) on 18F-FDG PET/CT.surrogate

Main Result

Effect estimate: B coefficient -0.667 (SE 0.238) in multivariate regression

Absolute Event Rate: 4.3% vs 4.9%

p-value: p=0.016

This study demonstrates a sex-specific neurocardiac link wherein myocardial ischemia and impaired LVEF are associated with blunted resting metabolic activity in the corpus callosum, caudate nucleus, and brainstem in men but not in women.

Limitations

Single-center, retrospective study design with a limited number of patients
More male than female participants (70.9% men), which may lead to referral bias and limit generalizability
Mean time interval of ~47 days between MPI-SPECT and PET/CT examinations during which changes in coronary circulation cannot be excluded
Heterogeneous patient population with a high prevalence of active malignancies (63.9%), with potential residual confounding from ongoing chemotherapy or age-associated neurodegeneration
Volumetric region of interest analysis was based on PET images only without simultaneous MRI-based neuroimaging or standard partial volume correction
Single-center, retrospective study with a limited number of patients
Imbalance in sex distribution (more male than female participants), potentially leading to referral bias and limited generalizability
Mean time interval of ~47 days between the two imaging examinations during which changes in coronary circulation cannot be excluded
Heterogeneous patient population with 63.9% having active malignancies and potential residual confounding from systemic chemotherapy, time lag since prior MI, or age-associated neurodegeneration
Volumetric region of interest analysis was based on PET images only without simultaneous MRI neuroimaging or standard partial volume correction

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Sex-specific cardiac-brain metabolic associations should not change practice; hypothesis-generating for neurocardiac pathways in men with CAD.

Abstract

Background Increasing evidence suggests a psychosomatic link between neural systems and the heart. In light of the growing burden of ischemic cardiovascular disease across the globe, a better understanding of heart‐brain interactions and their implications for cardiovascular treatment strategies is needed. Thus, we sought to investigate the interaction between myocardial injury and metabolic alterations in central neural areas in patients with suspected or known coronary artery disease. Methods and Results The association between resting metabolic activity in distinct neural structures and cardiac function was analyzed in 302 patients (aged 66.8±10.2 years; 70.9% men) undergoing fluor‐18‐deoxyglucose positron emission tomography and 99m Tc‐tetrofosmin single‐photon emission computed tomography myocardial perfusion imaging. There was evidence for reduction of callosal, caudate, and brainstem fluor‐18‐deoxyglucose uptake in patients with impaired left ventricular ejection fraction (<55% versus ≥55%: P =0.047, P =0.022, and P =0.013, respectively) and/or in the presence of myocardial ischemia (versus normal perfusion: P =0.010, P =0.013, and P =0.016, respectively). In a sex‐stratified analysis, these differences were observed in men, but not in women. A first‐order interaction term consisting of sex and impaired left ventricular ejection fraction or myocardial ischemia was identified as predictor of metabolic activity in these neural regions (left ventricular ejection fraction: P =0.015 for brainstem; myocardial ischemia: P =0.004, P =0.018, and P =0.003 for callosal, caudate, or brainstem metabolism, respectively). Conclusions Myocardial dysfunction and injury are associated with reduced resting metabolic activity of central neural structures, including the corpus callosum, the caudate nucleus, and the brainstem. These associations differ in women and men, suggesting sex differences in the pathophysiological interplay of the nervous and cardiovascular systems.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Fiechter et al. (2019) conducted a cohort in Suspected or known coronary artery disease (n=302). Myocardial injury (impaired LVEF <55% and/or myocardial ischemia on 99mTc-tetrofosmin MPI-SPECT) vs. Normal cardiac function (LVEF >=55%) and normal myocardial perfusion was evaluated on Resting 18F-FDG metabolic uptake (SUV) in the brainstem among men (myocardial ischemia vs normal perfusion) (B coefficient -0.667 (SE 0.238) in multivariate regression, p=0.016). Myocardial ischemia and impaired LVEF (<55%) were associated with reduced resting 18F-FDG metabolic activity in the corpus callosum, caudate nucleus, and brainstem in men (p<=0.047), but not in women.

synapsesocial.com/papers/6a7dce3daf21e1248e3c9d1f https://doi.org/10.1161/jaha.119.013070

View Full Paper

Ask AI

Bookmark

Share

Metabolic Activity in Central Neural Structures of Patients With Myocardial Injury

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Metabolic Activity in Central Neural Structures of Patients With Myocardial Injury

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading