Poor R-wave progression and long-term outcomes in the multi-ethnic study of atherosclerosis (MESA)

Poor R-wave progression (PRWP) has been interpreted as a marker of anterior myocardial injury since the 1970s, but its temporal stability, substrate, and independent prognostic value in a CAD-free cohort remain uncertain.

We studied 6323 MESA participants free of clinical cardiovascular disease with standardized 12‑lead ECGs at baseline (Exam 1, 2000-02) and after a median of 10 years (Exam 5, 2010-12). PRWP was defined as R-wave amplitude ≤3 mm in V3 with RV3 > RV2. We assessed 10-year test-retest stability (Cohen's κ), pulmonary/thoracic correlates, mechanistic substrate via cardiac magnetic resonance, high-sensitivity troponin T, NT-proBNP, and polysomnography, and long-term outcomes (all-cause death, cardiovascular death, MACE) over median 14 years using Cox and Fine-Gray models.

PRWP prevalence was 3.2% at Exam 1 and 6.2% at Exam 5. Binary test-retest agreement was limited (κ = 0.344; 95% CI 0.283-0.406) despite good continuous R-V3 reliability (ICC = 0.73); only 52% of baseline PRWP persisted at 10 years. Self-reported emphysema (OR 4.48; 2.30-8.22) and current smoking (OR 1.77; 1.14-2.73) were the strongest PRWP predictors. PRWP was not associated with RV volumes, RV ejection fraction, NT-proBNP, or sleep apnea. After adjustment for smoking and emphysema, PRWP was not independently associated with all-cause mortality (HR 1.19; 0.90-1.58), cardiovascular death (HR 1.02; 0.67-1.57), or MACE (HR 0.89; 0.54-1.47). Time-updated and Fine-Gray models confirmed null associations.

In a CAD-free multi-ethnic cohort, isolated PRWP is an ECG pattern with limited binary reproducibility, linked to pulmonary exposure and thoracic habitus rather than myocardial substrate, and carries no independent cardiovascular prognostic value.