Abnormal P‐wave terminal force in lead V₁ is a marker for atrial electrical dysfunction but not structural remodelling

Abstract

Aims There is a lack of diagnostic and therapeutic options for patients with atrial cardiomyopathy and paroxysmal atrial fibrillation. Interestingly, an abnormal P-wave terminal force in electrocardiogram lead V 1 (PTFV 1 ) has been associated with atrial cardiomyopathy, but this association is poorly understood. We investigated PTFV 1 as a marker for functional, electrical, and structural atrial remodelling. Methods and results Fifty-six patients with acute myocardial infarction and 13 kidney donors as control cohort prospectively underwent cardiac magnetic resonance imaging to evaluate the association between PTFV 1 and functional remodelling (atrial strain). To further investigate underlying pathomechanisms, right atrial appendage biopsies were collected from 32 patients undergoing elective coronary artery bypass grafting. PTFV 1 was assessed as the product of negative P-wave amplitude and duration in lead V 1 and defined as abnormal if ≥4000 ms*μV. Activity of cardiac Ca/calmodulin-dependent protein kinase II (CaMKII) was determined by a specific HDAC4 pull-down assay as a surrogate for electrical remodelling. Atrial fibrosis was quantified using Masson's trichrome staining as a measure for structural remodelling. Multivariate regression analyses were performed to account for potential confounders. A total of 16/56 (29%) of patients with acute myocardial infarction, 3/13 (23%) of kidney donors, and 15/32 (47%) of patients undergoing coronary artery bypass grafting showed an abnormal PTFV 1 . In patients with acute myocardial infarction, left atrial (LA) strain was significantly reduced in the subgroup with an abnormal

Central Sleep Apnea Is Associated with an Abnormal P-Wave Terminal Force in Lead V1 in Patients with Acute Myocardial Infarction Independent from Ventricular Function

“…The LV EF was mildly reduced in both groups but worse in patients with abnormal PTFV 1 (43.15 ± 11.51% vs. 48.93 ± 7.45%, p = 0.035). Interestingly, volumetric parameters for LA size and function, such as LA fractional area change (FAC) or systolic LA area, were not significantly increased in patients with abnormal PTFV 1 ( Table 1 ), indicating that the magnitude of PTFV 1 more likely reflects electrical but not structural remodeling as published previously [ 19 ].…”

“…In the current study, we observed significantly higher NT-proBNP levels at discharge and lower LV EF in the group with abnormal PTFV 1 , which may contribute to impaired atrial function and abnormal PTFV 1 . In accordance, we recently demonstrated a significant negative correlation between functional LA parameters, such as LA conduit and reservoir function, as measured by feature-tracking (FT) strain analysis of cardiac magnetic resonance (CMR) images, and the extent of PTFV 1 [ 19 ]. In contrast to atrial strain, volumetric MRI parameters for LA function such as systolic LA area or LA FAC did not show a significant association with PTFV 1 in the present study, which agrees with previous studies [ 31 , 32 ].…”

“…In fact, the ongoing ARCADIA trial is investigating the optimal anticoagulant therapy (anticoagulant therapy vs. standard ASA therapy) in patients with cryptogenic stroke and atrial cardiomyopathy and specifically uses an abnormal PTFV 1 as an additional clinical marker for atrial cardiomyopathy [ 26 ]. We have recently shown that an abnormal PTFV 1 is linked to increased CaMKII-dependent atrial pro-arrhythmic activity and atrial contractile dysfunction [ 4 , 19 ]. Atrial CaMKII is a key regulator of cardiac excitation–contraction coupling and plays an important role in triggering arrhythmias and atrial electrical remodeling [ 4 ].…”

“…Interestingly, in patients with abnormal PTFV 1 , atrial fibrosis was less likely to be observed [ 19 ], indicating that the generation of abnormal PTFV 1 may require functional cardiomyocytes.…”

“…Unfortunately, CPAP therapy may be without benefit for patients with sleep apnea [ 7 , 8 , 9 , 10 ], so new treatment options are urgently needed. We have recently shown that increased CaMKII activity is significantly associated with abnormal PTFV 1 [ 19 ]. Currently, several CaMKII inhibitors are under preclinical investigation [ 37 ].…”