Subclinical Myocardial Impairment Tracking the Comorbidity Burden: A Layer-Specific Strain and Myocardial Work Analysis in Patients With Preserved Ejection Fraction.

BACKGROUND

The Charlson Comorbidity Index (CCI) is a validated mortality predictor in heart failure, but its utility in tracking subclinical left ventricular (LV) mechanics remains unclear. We evaluated the relationship between cumulative comorbidity burden, assessed by a modified CCI (mCCI), and LV mechanics using layer-specific speckle tracking echocardiography and non-invasive myocardial work (MW) analysis.

METHODS

Seventy-one stable outpatients with preserved LVEF (≥50%) and no overt heart failure or significant coronary artery disease were stratified by mCCI scores (adapted by excluding CAD and including hypertension): Group 1 (Low, 0-1), Group 2 (Intermediate, 2-3), Group 3 (High, ≥4). All underwent comprehensive echocardiography, layer-specific strain, and pressure-strain loop-derived MW analysis.

RESULTS

While LVEF and epicardial GLS (Epi-GLS) were preserved across groups, Group 3 showed significantly impaired endocardial GLS (Endo-GLS) versus Group 1 (-19.7 ± 2.9% vs. -22.4 ± 2.0%, p = 0.003), with a stepwise decrease in the transmural strain gradient (Endo/Epi ratio; p < 0.001). Global Wasted Work (GWW) (p = 0.006) and Peak Systolic Dispersion (PSD) (p = 0.002) increased progressively, while Global Work Efficiency (GWE) was reduced in the high-risk group. On multivariate regression, mCCI independently predicted Endo-GLS (β = 0.236, p = 0.021) and was the sole independent predictor of GWE (β = -0.394, p = 0.002), irrespective of age and systolic blood pressure. During a median 6-month follow-up, Group 3 had a higher composite event rate than Groups 1 and 2 (44.4% vs. 7.4% and 11.1%; log-rank p = 0.001).

CONCLUSION

An increased comorbidity burden, assessed by the mCCI, is independently associated with subclinical myocardial dysfunction-selective subendocardial impairment, increased wasted work, and mechanical inefficiency-suggesting the mCCI may flag early mechanical uncoupling in preserved LVEF. Although these abnormalities correlated with adverse outcomes, their modest discriminative value (AUC 0.60-0.62) underscores the hypothesis-generating nature of these findings, warranting validation in larger prospective cohorts.