PTFV1 is associated with functional atrial myopathy and atrial inflammation in HFpEF patients undergoing CABG

Background Patients with severe coronary artery disease are at increased risk for secondary disorders and comorbidities. P wave terminal force in ECG lead V1 (PTFV1) is a noninvasive parameter indicating increased risk of atrial fibrillation (AF) and heart failure (HF). However, there remains a paucity of data on PTFV1 and functional parameters in HF with preserved ejection fraction (HFpEF). Purpose We aimed to investigate the association of PTFV1 with HFpEF, left atrial and ventricular functional parameters, and atrial myocardial inflammation in patients undergoing coronary artery bypass grafting (CABG). Methods and results We analyzed preoperative echocardiographic data and ECGs of 105 patients undergoing elective CABG with ejection fraction ≥ 50%. Elevated PTFV1 was defined as >4000 µV*ms. HFpEF was diagnosed according to ESC guidelines. Right-atrial appendage biopsies from 53 patients were obtained intraoperatively for qPCR analysis quantifying mRNA expression of interleukin 1β (IL-1β) and the NLRP3 inflammasome components NLRP3, ASC and caspase 1 (% β-actin). Linear regression derived a positive correlation between NTproBNP as indicator of increased filling pressures and PTFV1 (r2=0.16, p<0.001, Fig. A). This correlation was driven by the subgroup of HFpEF patients (r2=0.16, p=0.019, Fig. A) and was not observed in those without. HFpEF patients exhibited higher PTFV1 (4088±1700 µV*ms vs. 2771±1463, p<0.001, Fig. B). In ROC analysis, PTFV1 showed fair diagnostic accuracy for identifying HFpEF (AUC=0.73±0.06, p<0.001, Fig. C). Further, left atrial reservoir (LASr) and conduit (LAScd) strain were impaired in patients with HFpEF, indicating functional impairment (LASr: 24.4±8.8 vs. 34.8±9.5%, p<0.001; LAScd: -11.5± 4.8 vs. -18.8±7.2%, p<0.001). In linear regression LAScd was positively correlated with PTFV1 (r2=0.14, p=0.005, Fig. D), whereas LASr showed no significant association. Additionally, linear regression demonstrated a positive correlation between global longitudinal strain and PTFV1 (r2=0.14, p=0.004, Fig. E). IL-1β and ASC mRNA expression were increased in patients with HFpEF, indicating atrial myocardial inflammation (IL-1β: 0.023±0.01 %ACTB vs. 0.01±0.003, p<0.001; ASC: 0.381±0.111 vs. 0.276±0.123, p=0.01; Fig. F+G). Expression of NLRP3 and Caspase 1 mRNA showed a non-significant trend. Interestingly, patients with elevated PTFV1 exhibited decreased mRNA expression of NLRP3 (0.077±0.068 %ACTB vs. 2.829±3.778, p=0.008, Fig. H) and Caspase 1 (1.174±0.666 %ACTB vs. 109.5±149.6, p<0.001, Fig. I) but increased IL-1β mRNA expression (0.184±0.243 %ACTB vs. 0.016±0.008, p=0.002, Fig. J). Conclusion Elevated PTFV1 was associated with HFpEF, elevated NTproBNP, and impaired GLS and LAScd. PTFV1 may serve as an easily obtainable marker indicating pathophysiological mechanisms associated with HFpEF in CABG patients, with differential regulation of atrial inflammation as a potential underlying pathophysiological mechanism.