The Effect Of Spinal Cord Stimulation On Heart Failure With Preserved Ejection Fraction

Background: Heart failure with preserved ejection fraction(HFpEF),which is a primary driver of morbidity and mortality,accounts for approximately half of all heart failure cases.Spinal cord stimulation(SCS)is a widely used clinical technique to treat ischemia in peripheral,cardiac and cerebral vascular diseases.SCS at thoracic spinal segments(between T1-T5 areas)has been reported to significantly improve cardiac contractile function.Therefore,we hypothesize that a combination of deoxycorticosterone acetate(DOCA),Western diet(WD)and angiotensin II infusion can be used to create a porcine model of HFpEF,and SCS at T1-T2 epidural space would improve the cardiac function.Methods: In the first section,we created a porcine model of severe hypertension and hyperlipidemia by using a combination of DOCA(100 mg/kg),Western diet(WD)and angiotensin II infusion(0.15mg/h).Systolic blood pressure,echocardiography and invasive pressure–volume loop were assessed.A detailed histological assessment was also performed to determine the cardiac structural remodeling.In the second section,HFpEF animals were randomized to SCS therapy group(n = 10)or HFpEF control group(n = 10).During this period,pigs in SCS group underwent SCS devices implantation under sterile conditions and X-ray guidance.Systolic blood pressure assessment,echocardiography assessment,invasive pressure–volume loop assessment and a detailed histological assessment were performed.Results: In the first section,compared with controls(n = 10),HFpEF animals(n = 10)showed markedly higher systolic blood pressure(181 vs.86 mm Hg)in the 18 th week.Concentric remodeling,characterized by a normal chamber size with a thicker wall,was observed in HFpEF animals.Left ventricle diastolic function showed a tendency toward decline,according to the echocardiographic data.Haemodynamic data showed that the end-diastolic pressure–volume relationship and end-systolic pressure–volume relationship elevated.Histological results revealed that the fibrotic area in HFpEF animals were larger(P < 0.05 vs.controls),and the fibrotic area in the posterior wall of HFp EF animals’ left atria were larger than other sites of the left atria(P < 0.05 vs.other sites).In the second section,compared with HFpEF control group,systolic blood pressure,pulmonary arterial systolic pressure,pulmonary capillary wedge pressure showed a tendency toward decline(P < 0.05).Wall thickness and left atrial diameter also showed a tendency toward decline,according to the echocardiographic data(P < 0.05).When it comes to diastolic function,no significant difference was observed.Conclusion: This model can mimic clinical HFp EF to some degree.We found that the posterior wall of the left atrium is more susceptible to atrial remodeling associated with hypertension compared with other regions of the left atrium.In the left ventricle,subendocardium is more susceptible to fibrosis associated with hypertension and hyperlipidemia compared with other regions of left ventricular walls.SCS could reduce blood pressure in HFpEF pigs,without any change in cardiac diastolic function.