June 7, 2023International Journal of Legal MedicineOpen Access

Proteomic profiling of sudden cardiac death with acquired cardiac hypertrophy

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Sudden cardiac death with acquired cardiac hypertrophy (n=30). Intervention: Sudden cardiac death with acquired cardiac hypertrophy (SCH) vs. Compensated cardiac hypertrophy (CCH) and normal controls. Primary outcome: MYH7 protein abundance (Fold change 31.7, p=0.00001).

Q: What does this research mean for the field?

Sudden cardiac death with acquired cardiac hypertrophy is characterized by a distinct proteomic profile with significant upregulation of sarcomere proteins, including a 31.7-fold increase in MYH7 compared to controls. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

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Key result

Sudden cardiac death with acquired hypertrophy is linked to a ~32-fold increase in MYH7 protein.

Fold change 31.7
P=0.00001
n=30

Why the study?

It is sometimes difficult to differentiate sudden cardiac death with acquired cardiac hypertrophy from compensated cardiac hypertrophy at autopsy.

Does proteomic profiling differentiate sudden cardiac death with acquired cardiac hypertrophy from compensated cardiac hypertrophy?

Study Design

Type

Observational (n=30)

Multicenter

Structured PICO

Does proteomic profiling differentiate sudden cardiac death with acquired cardiac hypertrophy from compensated cardiac hypertrophy?

Population

30 autopsy cases of individuals aged > 40 years, including 10 with sudden cardiac death with acquired cardiac hypertrophy (SCH), 10 with compensated cardiac hypertrophy (CCH) who died of non-cardiac causes, and 10 controls without cardiac hypertrophy who died of non-cardiac causes.

Intervention

Proteomic profiling and quantitative polymerase chain reaction (qPCR) of cardiac tissue.

Comparator

Compensated cardiac hypertrophy (CCH) and normal control cardiac tissue.

Outcome

Proteomic alterations and differential protein expression levels.surrogate

Main Result

Effect estimate: Fold change 31.7

p-value: p=0.00001

Stepwise upregulation of sarcomere proteins like MYH7 and MYL3 may increase the risk for sudden cardiac death in acquired cardiac hypertrophy before significant cardiac fibrosis progresses, potentially aiding in postmortem diagnosis.

Limitations

Limited sample size due to selection of relatively fresh autopsy cases
Discrepancies between quantitative results obtained using proteomics and qPCR
Lack of microscopic sampling with microdissection and analyses at the single-cell level
Small sample size
Heterogeneous distribution of target proteins in the heart

Implication

May aid postmortem differentiation of sudden cardiac death in acquired hypertrophy; leaves open prospective validation and risk prediction.

Abstract

BACKGROUND: Cardiac hypertrophy, which develops in middle-aged and older individuals as a consequence of hypertension and obesity, is an established risk factor for sudden cardiac death (SCD). However, it is sometimes difficult to differentiate SCD with acquired cardiac hypertrophy (SCH) from compensated cardiac hypertrophy (CCH), at autopsy. We aimed to elucidate the proteomic alteration in SCH, which can be a guideline for future postmortem diagnosis. METHODS: Cardiac tissues were sampled at autopsy. SCH group consisted of ischemic heart failure, hypertensive heart failure, and aortic stenosis. CCH group included cases of non-cardiac death with cardiac hypertrophy. The control group comprised cases of non-cardiac death without cardiac hypertrophy. All patients were aged > 40 years, and hypertrophic cardiomyopathy was not included in this study. We performed histological examination and shotgun proteomic analysis, followed by quantitative polymerase chain reaction analysis. RESULTS: Significant obesity and myocardial hypertrophy, and mild myocardial fibrosis were comparable in SCH and CCH cases compared to control cases. The proteomic profile of SCH cases was distinguishable from those of CCH and control cases, and many sarcomere proteins were increased in SCH cases. Especially, the protein and mRNA levels of MYH7 and MYL3 were significantly increased in SCH cases. CONCLUSION: This is the first report of cardiac proteomic analysis in SCH and CCH cases. The stepwise upregulation of sarcomere proteins may increase the risk for SCD in acquired cardiac hypertrophy before cardiac fibrosis progresses significantly. These findings can possibly aid in the postmortem diagnosis of SCH in middle-aged and older individuals.

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Published by International Journal of Legal Medicine · CC BY

Cite This Study

Kakimoto et al. (2023) conducted an observational in Sudden cardiac death with acquired cardiac hypertrophy (n=30). Sudden cardiac death with acquired cardiac hypertrophy (SCH) vs. Compensated cardiac hypertrophy (CCH) and normal controls was evaluated on MYH7 protein abundance (Fold change 31.7, p=0.00001). Sudden cardiac death with acquired cardiac hypertrophy was characterized by significant upregulation of sarcomere proteins, including a 31.7-fold increase in MYH7 compared to controls.

synapsesocial.com/papers/6a18b3088dcaf40f45cfa72e https://doi.org/10.1007/s00414-023-03038-6