Novel method in mice to evaluate left atrial (LA) systolic contribution to left ventricular volume (LV) using pressure-volume (PV) loops

Abstract Background LA myopathy is a critically important non-LV contributor to the progression of HFpEF (heart failure with preserved ejection fraction) in patients and is associated with a severe phenotype, leading to impaired cardiac output reserve and reduced exercise capacity. In normal humans LA systole contributes ~20% of total LV filling, but with HFpEF, this contribution decreases to <16% with a greater reliance on this contribution to LV filling. Purpose We sought to investigate LA function as a critical component of cardiac function analysis by utilizing the LV pressure signal to identify and quantify the contribution of volume during LA systole to the total LV volume in mice with HFpEF. Methods Hypertension (HTN)-associated HFpEF C57BL/6J mice were subjected to chronic aldosterone infusion and 1% NaCl for 4 weeks (SAUNA model). Obesity after a high fat diet (HFD: 60% fat diet) for 16 weeks followed by the SAUNA protocol, induced HTN and obesity associated HFpEF. Blood pressure was monitored weekly. Mice were anesthetized with isoflurane, intubated, chest opened to expose the heart and allow placement of a PV catheter (Transonic) which was introduced into the LV via apical stab with a 27G needle. Calibration of the PV catheter was performed according to the manufacturer’s instructions. Atrial systole was identified using 2nd order derivative of the LV pressure signal. Contribution of LA systole was calculated using volume at the beginning of LA systole identified by the 2nd order derivative of the LV pressure signal and subtracting from the LV end diastolic volume. The % of LA systole contribution was calculated as a % of the total LV stroke volume. Data was analyzed with LabChart pro software (AD Instruments). Results SAUNA mice had normal LVEF, moderate HTN and lung congestion. PV relationships demonstrated Tau was impaired in HFpEF vs. control mice (14±1 vs. 10±0.5 ms) with a shift of the PV loop to the left (Fig. A.) In control mice, the atrial systole contributed 39± 4% to LV volume and was impaired in HFpEF mice 20± 3% a 1.95-fold reduction (P<0.01). Importantly atrial systole contribution was increased in obese mice 53±5 %. However, the combination of obesity and HTN, both common comorbidities in HFpEF, resulted in a reduced LA systole contribution by 1.43-fold to 37± 9%, (P<0.005; Fig B). Conclusion A novel method of % atrial systole from LV PV loop using 2nd order derivative to quantify the volume contribution of atrial systole to total LV stroke volume was identified in mice. LA dysfunction was present in murine HTN-associated HFpEF with/without obesity.