There is disclosed a method for administration of a formulation of resiniferatoxin (RTX) to provide cardiac sympathetic afferent denervation when applied in an amount and concentration sufficient to chemically denervate vanilloid 1 receptor (TRPV1)-expressing CSAR (cardiac sympathetic afferent reflex) afferents. There is further disclosed a method for treating heart failure or hypertension and its related indications selected from the group consisting of increased sympatho-excitation, cardiac hypertrophy, increased left ventricular end diastolic pressure (LVEDP), lung edema, and combinations thereof, comprising administering an effective amount of RTX directly to a tissue site selected from the group consisting of epicardium, a T1-T4 dorsal root ganglion and intrathecally to the T1-T4 region of the spinal column.