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Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants.

Name: Verified Rigor Record — Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants.
Item: Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants.
Rating: 88
Author: Αlpha¹

Marston NA, Kany S, Melloni GEM, Jurgens SJ, Kamanu FK, Lai YP, Rämö JT, Raz I, Wiviott SD, Ellinor PT, Sabatine MS, Ruff CT

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Αlpha¹ Verified Rigor Record — Rigor score 88/100 (Exceptional strength of evidence) for “Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants.”

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · July 6, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

WARN

Warnings to address · Observational Study

Eight dimensions — click a segment for details

Critical

High-priority

Model-reported confidence: highReviewer agreement: highEngine: 7.6.0Source: full text

This Αlpha¹ Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

The paper is a well-conducted post-hoc genetic substudy of a large RCT, with strong premise and detailed reporting of biological variables, ethical approvals, and key resources. Its primary weaknesses are in study design (post-hoc, no replication, vague inclusion criteria) and data/code sharing (blanket denial of data access, no code shared), which limit reproducibility but do not invalidate the findings.

Evaluated based on full manuscript text and supplementary materials. Three independent reviewer evaluations were highly convergent; only minor disagreements existed on key resources (drug specification) and ethical approvals/regulatory compliance, which were resolved by weighing evidence. Verification components: 17/17 statistical tests consistent, no retracted/unresolvable citations, all data/code links live. The claim audit flagged one overstated clinical recommendation as under-evidenced.

12 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).

Recomputed 17 tests: 17 consistent, 0 inconsistent, 17 via agent-written checks.

2 integrity concerns flagged (0 high).

Rigor

Eight Dimensions5 pass · 3 warn

12 major claims1 overstated2 partial9 supported

The introduction cites key trials establishing SGLT2i benefit in HF (refs 1-4), population-based CMP variant prevalence (refs 13-15), and the gap that 'Whether SGLT2 inhibitor treatment is of benefit in asymptomatic individuals with a CMP variant is not known.' Limitations of prior work (no dedicated trials in variant carriers) are explicitly stated and addressed.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper clearly establishes prior work on SGLT2 inhibitors and cardiomyopathy genetics, provides a logical rationale, and acknowledges prior limitations.

Evidence

direct quote[Introduction, paragraph 2-4]

“Whether SGLT2 inhibitor treatment is of benefit in asymptomatic individuals with a CMP variant is not known.”

direct quote[Introduction, final paragraph]

“In this analysis, we tested the effect of the SGLT2 inhibitor dapagliflozin compared with placebo among carriers of CMP-associated genetic variants and noncarriers in the DECLARE-TIMI 58 trial.”

direct quote[Introduction, paragraph 3]

“the therapeutic consequence of identifying CMP variants, particularly in asymptomatic individuals, remains unclear”

PASSReviewer 2· 95% conf

The paper clearly establishes the scientific premise by citing prior work on SGLT2 inhibitors, inherited cardiomyopathies, and the gap in knowledge about preventive therapy in asymptomatic variant carriers.

Evidence

direct quote[Introduction, paragraphs 1-3]

“Sodium–glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin have been shown to prevent hospitalization for HF (HHF) across the spectrum of left ventricular ejection fraction (LVEF).”

direct quote[Introduction, paragraph 4]

“Whether SGLT2 inhibitor treatment is of benefit in asymptomatic individuals with a CMP variant is not known.”

direct quote[Discussion, paragraph 5]

“Owing to the lack of large, dedicated clinical trials assessing the impact of rare CMP variants on treatment benefit, the primary motivation for genetic testing is risk stratification...”

PASSReviewer 3· 95% conf

The paper clearly establishes the scientific premise by citing prior work on SGLT2 inhibitors, inherited cardiomyopathies, and the gap in knowledge about preventive therapy in variant carriers.

Evidence

direct quote[Introduction, paragraphs 1-3]

direct quote[Introduction, paragraph 4]

“Whether SGLT2 inhibitor treatment is of benefit in asymptomatic individuals with a CMP variant is not known.”

direct quote[Discussion, paragraph 5]

“These data were observational in nature and did not include systematic adjudicated events.”

Randomization method and unit are not reported for the genetic substudy (the parent trial was randomized, but the substudy is observational). Blinding levels are reported for the parent trial but not specifically for the genetic analysis. Power analysis is not reported. Inclusion/exclusion criteria for the genetic cohort are not pre-specified. Outlier handling is not discussed. Controls are not applicable as this is not a wet-lab study. Independent replication is not reported. The study relies on the parent trial's design, which is adequate for the primary analysis but lacks detail for the genetic substudy.

Sub-criteria

controlsN/A

power analysisNOT REPORTED

blinding levelsINADEQUATE

outlier handlingNOT REPORTED

randomization unitNOT REPORTED

inclusion exclusionINADEQUATE

randomization methodNOT REPORTED

replicate distinctionN/A

independent replicationNOT REPORTED

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

The study is a post-hoc subgroup analysis of an RCT; randomization was adequate, but this analysis was not prespecified, replication was not reported, and inclusion/exclusion criteria for the genetic substudy are unclearly defined.

Evidence

direct quote[Methods, paragraph 1]

“This analysis was not prespecified.”

paraphrase[Methods, paragraph 1; Sequence data quality control]

“Patients who consented to genetic testing and had whole-exome sequencing available were included; 12,685 of 13,184 sequenced samples were retained after QC, but specific QC exclusion reasons beyond 'quality control' are not detailed.”

absence[Methods, Statistical analysis]

No power analysis or replication reported.

WARNReviewer 2· 85% conf

The study design is a secondary analysis of a randomized trial, but several key design elements are not reported or are inadequate for this genetic substudy.

Evidence

direct quote[Methods, Study design]

“This is a secondary analysis of DECLARE-TIMI 58, a double-blind, randomized, placebo-controlled trial...”

absence[Methods, Statistical analysis]

No power analysis is reported for the genetic substudy.

direct quote[Methods, Study design]

“Patients who consented to genetic testing and had whole-exome sequencing available were evaluated for the presence of a CMP variant...”

WARNReviewer 3· 85% conf

The study design is a post-hoc analysis of a randomized trial with adequate randomization and blinding, but lacks a pre-specified power analysis, explicit inclusion/exclusion criteria for the genetic substudy, and independent replication.

Evidence

direct quote[Methods, Study design]

“This is a secondary analysis of DECLARE-TIMI 58, a double-blind, randomized, placebo-controlled trial that investigated dapagliflozin in 17,160 patients with type 2 diabetes who had or were at risk for ASCVD.”

absence[Methods, Statistical analysis]

No power analysis is reported for the genetic substudy.

direct quote[Methods, Study design]

“Patients who consented to genetic testing and had whole-exome sequencing available were evaluated for the presence of a CMP variant.”

Sex is reported and both sexes are included (no single-sex justification needed). Age, weight (BMI), and health status (e.g., history of HF, diabetes) are reported in Table 1. Demographics including age, sex, ethnicity, and comorbidities are comprehensively reported. Species/strain/source and housing conditions are not applicable as this is a human study.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Demographics and clinical characteristics are reported in detail; sex, age, comorbidities, and key biomarkers are adequately described for this human cohort.

Evidence

direct quote[Table 1]

“Male sex: CMP P/LP variant carriers 74 (61), Noncarriers 8,051 (64); Age: 63.4 ± 6.4 vs 64 ± 6.9”

direct quote[Table 1]

“NT-proBNP, pg ml −1: 299.6 ± 625.2 vs 171 ± 321.4; LVEF (%): 50.8 ± 11.9 vs 56.5 ± 11.1”

PASSReviewer 2· 95% conf

Biological variables are well-reported for the human subjects, including age, sex, ethnicity, and health status.

Evidence

direct quote[Table 1]

“Male sex | 74 (61) | 8,051 (64) | 0.57”

direct quote[Table 1]

“Age | 63.4 ± 6.4 | 64 ± 6.9 | 0.43”

direct quote[Table 1]

“Ethnicity | Asian 7 (6) | Asian 1,140 (9) | 0.01”

PASSReviewer 3· 95% conf

Biological variables are well-reported: sex, age, health status, and demographics are provided in baseline tables; species/strain/housing are not applicable as this is a human study.

Evidence

direct quote[Table 1]

“Age 63.4 ± 6.4 | Male sex 74 (61) | History of HF 22 (18)”

direct quote[Table 1]

“White 103 (85) | Black 1 (1) | Asian 7 (6) | Other 10 (8)”

The Methods state: 'The trial protocol was approved by the institutional review board at each participating site, and all participants provided written informed consent.' This covers both IRB/ethics approval and informed consent. The paper uses existing trial data with consent for genetic testing. Regulatory compliance is implicit but not stated by name (Declaration of Helsinki etc.), but the IRB approval statement is adequate for this post-hoc analysis of consented trial data.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceNOT REPORTED

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 100% conf

Ethics approval and informed consent are clearly reported for the parent trial, which generated the sequencing data used.

Evidence

direct quote[Methods, paragraph 1]

“The trial protocol was approved by the institutional review board at each participating site, and all participants provided written informed consent.”

PASSReviewer 2· 95% conf

Ethical approvals and informed consent are adequately reported for this human study.

Evidence

direct quote[Methods, Study design]

“The trial protocol was approved by the institutional review board at each participating site, and all participants provided written informed consent.”

direct quote[Methods, Study design]

“all participants provided written informed consent.”

direct quote[Funding section]

“DECLARE-TIMI 58 ( NCT01730534 ) was funded by AstraZeneca.”

PASSReviewer 3· 95% conf

Ethical approvals are adequately reported: the trial protocol was approved by institutional review boards at each site, and all participants provided written informed consent.

Evidence

direct quote[Methods, Study design]

“The trial protocol was approved by the institutional review board at each participating site, and all participants provided written informed consent.”

direct quote[Funding section]

“DECLARE-TIMI 58 (NCT01730534) was funded by AstraZeneca.”

The investigational product dapagliflozin is named but no manufacturer, formulation, or dose is provided in the methods (though the parent trial is referenced). Software tools like BWA, GATK, and R are named with versions for some but not all. No antibodies, cell lines, or organisms are used, so those criteria are not applicable. The lack of full specification for the drug and some software versions is a minor gap.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedINADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The investigational drug (dapagliflozin) and key software tools are adequately identified; biological reagents are not applicable.

Evidence

direct quote[Abstract, Methods]

“dapagliflozin or placebo treatment”

direct quote[Methods, Sequence data quality control; Statistical analysis]

“All analyses were performed using R version 4.4.2 (R Foundation). BWA 0.7.15-r1140 and ... GATK 4.1.4.1”

WARNReviewer 2· 85% conf

Key resources are partially identified; the investigational product (dapagliflozin) is named but not fully specified, and software tools are identified but without version numbers for some.

Evidence

direct quote[Methods, Study design]

“This is a secondary analysis of DECLARE-TIMI 58, a double-blind, randomized, placebo-controlled trial that investigated dapagliflozin in 17,160 patients...”

direct quote[Methods, Sequence data quality control]

“Sequence reads were aligned to GRCh38 with BWA 0.7.15-r1140 and converted to SAM specification 1.6 CRAM files with GATK 4.1.4.1...”

direct quote[Methods, Statistical analysis]

“All analyses were performed using R version 4.4.2 (R Foundation).”

WARNReviewer 3· 85% conf

The investigational product (dapagliflozin) is identified by name and manufacturer, and software tools are identified with versions, but no lot numbers or formulation details are provided for the drug, and the genetic analysis pipeline is described but not fully versioned.

Evidence

direct quote[Abstract, Methods]

“dapagliflozin or placebo treatment”

direct quote[Methods, Sequence data quality control]

“Sequence reads were aligned to GRCh38 with BWA 0.7.15-r1140 and converted to SAM specification 1.6 CRAM files with GATK 4.1.4.1”

direct quote[Methods, Sequence data quality control]

“Exome sequencing for 13,184 individuals was performed at the Broad Institute of MIT and Harvard on Illumina HiSeq 2500 using a TruSeq Rapid Exome Library prep kit.”

Tests are named (Cox proportional hazard models, Wald test, generalized linear model). Exact p-values and confidence intervals are reported. Effect sizes (HR, ARR) with CIs are provided. Software (R version 4.4.2) is identified. Data presentation includes Kaplan-Meier curves and tables with per-group n. Assumptions verification is mentioned (Schoenfeld residuals) but not detailed. Mathematical plausibility is not applicable for these continuous outcomes with large N.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedINADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Statistical tests are named, exact p-values are reported for most key findings, CIs accompany HRs, software is identified, and data presentation includes KM curves and event rates. Mathematical plausibility is not verifiable from the summary data alone.

Evidence

direct quote[Methods, Statistical analysis]

“We tested the proportional hazards assumption using Schoenfeld residuals and found no violations.”

direct quote[Results, Treatment effect by carrier status]

“P interaction 0.03”

direct quote[Results, Association of carrier status with incident outcomes in the placebo arm]

“Secondary exploratory endpoints ... and were not statistically different between carriers of CMP-associated variants and noncarriers”

PASSReviewer 2· 90% conf

Statistical analysis is generally well-reported with named tests, exact p-values, and effect sizes with confidence intervals, though assumptions verification is not explicitly reported.

Evidence

direct quote[Methods, Statistical analysis]

“Cox proportional hazard models were performed to calculate HRs for carriers versus noncarriers and incident HHF...”

direct quote[Results, Treatment effect by carrier status]

“treatment with dapagliflozin resulted in an 82% reduction in incident HHF (HR 0.18, 95% CI 0.04–0.86).”

direct quote[Methods, Statistical analysis]

“We tested the proportional hazards assumption using Schoenfeld residuals and found no violations.”

PASSReviewer 3· 90% conf

Statistical tests are named, exact p-values and confidence intervals are reported, software is identified, and data presentation includes Kaplan-Meier curves and event rates. Assumptions (proportional hazards) are verified, and effect sizes with CIs are provided.

Evidence

direct quote[Methods, Statistical analysis]

“Cox proportional hazard models were performed to calculate HRs for carriers versus noncarriers and incident HHF, as well as for dapagliflozin versus placebo by CMP carrier status.”

direct quote[Methods, Statistical analysis]

“We tested the proportional hazards assumption using Schoenfeld residuals and found no violations.”

direct quote[Results, Treatment effect by carrier status]

“HR 0.18, 95% CI 0.04–0.86, P interaction 0.03”

The data availability statement reads: 'Due to contractual agreements with sponsors, trial data are not available to share.' This is reported but inadequate — it states data are not available but does not describe any managed access route (e.g., Vivli, YODA). Code sharing is not mentioned; the paper does not provide a repository for custom analysis code. No abstract/code accession numbers are provided.

Sub-criteria

code sharingNOT REPORTED

accession numbersNOT REPORTED

repository depositNOT REPORTED

data availability statementINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 95% conf

A data availability statement exists but is inadequate (vague 'not available' due to contractual agreements); no code has been shared.

Evidence

direct quote[Data availability]

“Due to contractual agreements with sponsors, trial data are not available to share.”

absence[Data availability, Methods]

No code sharing is reported.

WARNReviewer 2· 90% conf

Data availability is limited due to contractual agreements, and no code is shared, which is a significant gap for reproducibility.

Evidence

direct quote[Data availability section]

“Due to contractual agreements with sponsors, trial data are not available to share.”

absence[Data availability section]

No repository deposit is mentioned.

absence[Data availability section]

No code sharing is mentioned.

WARNReviewer 3· 90% conf

A data availability statement is present but vague ('not available to share' due to contractual agreements), and no code is shared. The trial data are not publicly accessible, and no accession numbers for sequencing data are provided.

Evidence

direct quote[Data availability section]

“Due to contractual agreements with sponsors, trial data are not available to share.”

absence[Data availability section]

No repository deposit or accession numbers.

absence[Data availability section]

No code sharing mentioned.

Methods are sufficiently detailed (genetic curation, statistical models). The 'Discussion' contains a thorough limitations section ('This analysis must be interpreted in the context of our study design...', 'absence of systematic cardiac imaging', 'generalizability limited'). Conclusions acknowledge the need for prospective trials. A clinical trial registration number (NCT01730534) is provided for DECLARE-TIMI 58. Funding sources and competing interests are disclosed. However, no reference to a specific reporting guideline (e.g., STROBE) is made, and the post-hoc nature is acknowledged but not transparently flagged in the abstract.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Methods are replicable, limitations are discussed in a dedicated paragraph, conclusions are proportional with appropriate caveats, and funding/COI are fully disclosed. The paper lacks a formal reporting guideline checklist mention and the analysis was not preregistered.

Evidence

direct quote[Discussion, paragraph 3]

“These findings must be interpreted in the context of our study design. Although this randomized dataset enabled evaluation of the interaction ... the relatively small number of carriers (n = 121) limits power for subgroup analyses by specific gene or morphologic subtype.”

direct quote[Funding, Competing interests]

“DECLARE-TIMI 58 (NCT01730534) was funded by AstraZeneca.”

direct quote[Methods, Reporting summary]

“Further information on research design is available in the linked to this article.”

PASSReviewer 2· 90% conf

Reporting is generally transparent with detailed methods, limitations discussed, and proportional conclusions, though no formal reporting guideline is referenced.

Evidence

direct quote[Funding section]

“DECLARE-TIMI 58 ( NCT01730534 ) was funded by AstraZeneca.”

direct quote[Discussion, paragraph 5]

“These findings must be interpreted in the context of our study design. Although this randomized dataset enabled evaluation of the interaction between rare CMP variant carrier status and SGLT2 inhibitor therapy, the relatively small number of carriers ( n = 121) limits power for subgroup analyses...”

direct quote[Abstract]

“These results need to be confirmed in a prospective, dedicated trial of preventive HF treatments in carriers of P/LP cardiomyopathy-associated variants.”

PASSReviewer 3· 90% conf

Methods are detailed enough for replication, the trial is registered, limitations are discussed, conclusions are proportional, and funding/COI are disclosed. No reporting guideline checklist is referenced, but this is not mandatory for a secondary analysis.

Evidence

direct quote[Funding section]

“DECLARE-TIMI 58 (NCT01730534) was funded by AstraZeneca.”

direct quote[Discussion, paragraph 5]

direct quote[Abstract]

“These results need to be confirmed in a prospective, dedicated trial of preventive HF treatments in carriers of P/LP cardiomyopathy-associated variants.”

8 copyedit issues flagged: mostly consistency, typo, grammar.

Checked 30 references: 5 verified — 25 not checked.

Reproducibility

4 data/code links checked; 4 live.

Registered (2 IDs: ClinicalTrials.gov). No reporting guideline cited.

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

Ready after minor-to-moderate revision: the study design and data/code sharing gaps must be addressed (especially the data availability statement and code sharing), and the claims should be tempered to not overstate the clinical recommendation. The copyedit issues and statistical reporting gaps are minor. The paper's core findings are plausible and well-supported.

1.
HIGHdata code
Replace the blanket data denial in the Data Availability section with a description of a managed-access pathway (e.g., contact TIMI Study Group, access via Vivli or YODA platform).
A data-driven paper with no data access mechanism will be flagged by many journals as non-compliant with reproducibility standards.
2.
HIGHreporting
Temper the abstract claim that 'SGLT2 inhibitor treatment should be started early to prevent HF' — revise to state that the findings suggest a potential benefit that requires prospective confirmation, consistent with the Discussion's call for a dedicated trial.
The claim audit flagged this as overstated; a direct clinical recommendation from a post-hoc analysis without prospective trial support is a common reason for reviewer concern and potential editorial rejection.
3.
HIGHother
Add explicit inclusion and exclusion criteria for the genetic substudy in the Methods, including details on why 499 of 13,184 sequenced samples were excluded after QC.
The vague 'consented and had WES available' description leaves uncertainty about selection bias; QC exclusion details are needed for reproducibility.
4.
HIGHdata code
Deposit custom analysis code (e.g., variant curation, statistical models) in a public repository (e.g., GitHub, Zenodo) with a persistent DOI, and reference it in the Data Availability section.
Code sharing is increasingly expected for computational reproducibility; its absence was flagged by all three reviewers.
5.
HIGHreporting
Reference a reporting guideline (e.g., STROBE for observational genetic studies, or STREGA) in the Methods or Reporting Summary.
A formal guideline reference is best practice and was noted as missing by all three reviewers, though it is a minor gap.
6.
HIGHother
Add a CONSORT-like flow diagram for the genetic substudy showing the derivation of the analytical cohort (e.g., 17,160 → 12,685).
Clarifying how many participants were included and at which stage they were lost improves transparency and addresses reviewer concerns about inclusion criteria.
7.
HIGHother
Specify the manufacturer, formulation, and dose of dapagliflozin used in DECLARE-TIMI 58 in the Methods (e.g., 'dapagliflozin 10 mg once daily, AstraZeneca').
Investigational product specification is a standard reproducibility element; its omission was flagged by two of three reviewers.
8.
MEDIUMreporting
Acknowledge the post-hoc, non-prespecified nature of this analysis explicitly in the Abstract (e.g., 'In this exploratory, non-prespecified analysis...').
Failing to flag the exploratory nature at the highest level of the paper can mislead readers and was noted by two reviewers.
9.
MEDIUMstatistics
Report exact p-values for the secondary endpoints currently described only as 'not statistically different' (e.g., CV death, all-cause mortality).
Providing exact p-values (even non-significant ones) follows best reporting practices and addresses Reviewer 1's concern.
10.
MEDIUMother
Add a statement that no independent replication was attempted or note that independent validation is needed, and consider a post-hoc power calculation for the interaction test.
Acknowledging the lack of replication and quantifying the power of the interaction test would strengthen the design section and manage reader expectations.
11.
LOWcopyedit
Fix subject-verb agreement in the Abstract: change 'These results needs to be confirmed' to 'These results need to be confirmed'.
Grammar error flagged by copyedit pass.
12.
LOWcopyedit
Define 'tv' (truncating variant) at first use in the Discussion; add a parentheses definition.
Acronym not defined earlier in the paper, flagged by copyedit pass.
13.
LOWcopyedit
Add a missing period at the end of the sentence about genetic testing in Discussion paragraph 2.
Minor punctuation error flagged by copyedit pass.
14.
LOWcopyedit
Ensure figure reference in Results is complete (replace 'Fig. ' with 'Fig. 1' or the appropriate figure label).
Incomplete reference flagged by copyedit pass.
15.
LOWcopyedit
Standardize 's.d.' vs 'SD' across tables (Table 1 vs Extended Data Table 1) and hyphenate 'cardiomyopathy-associated' consistently in the Abstract.
Style inconsistencies flagged by copyedit pass; minor but improves professional presentation.

Full text (44,630 chars)Analyzed: Jul 6, 2026

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