Introduction The pathophysiology of heart failure (HF) is characterized by hemodynamic, neurohormonal and autonomic perturbations. Alterations in receptor activation from this autonomic imbalance may have profound effects on cardiac function and structure. The optimal counteraction of the excessive sympathetic activity is still unclear. An excessive blockade of the sympathetic nervous system may result in adverse outcomes. Evidence from preclinical and human studies reveals that α1-adrenergic receptors mediate adaptive and protective effects in the heart. Midodrine is an α1 receptor agonist exerting its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure without stimulating cardiac beta-adrenergic receptors. Hypothesis Use of midodrine to improve autonomic dysfunction and SBP, thus enabling optimization of life saving medications, has not been evaluated adequately. Methods The goal of the Cardiorenal center is to reduce 30-day hHF, 90-day hHF, optimize GDMT, improve QOL, prevent CKD progression, and enhance survival. A comprehensive, multidisciplinary, nurse-directed, physician guided heart failure management program including those with CKD was started in 2017. The program of intensive face to face weekly or bimonthly encounters demonstrated fewer rehospitalizations and improved QOL. The multicomponent program consists of the INSPIRE HF framework: 1) Identify individualized priorities and nature of multimorbidity, 2) Nutrition intervention, 3) Stabilize fluid status 4) Psychosocial motivational empowerment, 5) Initiate GDMT 6) Revisit comorbidities with biomarker assessments and 7) Education and exercise programs.. A total of 162 patients discharged from the hospital enrolled within a week at the clinic were followed for 30 months on a weekly basis. Sixty patients were identified as having autonomic dysfunction with low SBP Results A total of 60 patients (Men 67 %, F 33 %) were started on midodrine. Mean midodrine dose was 20.7 mg a day .Over a period of 6 weeks, 75% of patients were able to be initiated on beta blockers (p=0.04); 50 % on ARNI (p=0.08) and 33 % on MRA (p Conclusion Cardio-selective α1-AR activation with low doses of agonists such as midodrine appears to be feasible, safe and enables GDMT utilization in patients with autonomic dysfunction and hypotension. Further randomized clinical trial may be beneficial in understanding the role of alpha agonists in patients with heart failure.