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https://www.selleckchem.com/products/Rapamycin.html 156±0.133 versus 0.254±0.166 beats per minute/[isoproterenol ng/mL]; P less then 0.001). Seven of 13 HFpEF subjects had β-receptor sensitivity similar to senior controls but still had lower peak HRs (122±14 versus 156±15 beats per minute; P less then 0.001). CONCLUSIONS Contrary to our hypothesis, patients with HFpEF displayed impaired cardiac β-receptor sensitivity compared with senior controls. In the 7 out of 13 patients with HFpEF with age-appropriate β-receptor sensitivity, peak HR remained low, suggesting impaired sinus node β-receptor function may not fully account for low exercise HR response. Rather in some patients with HFpEF, chronotropic incompetence might reflect premature cessation of exercise before maximal sinus node activation. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT02524145.BACKGROUND Limited progress has been made in the management of cardiogenic shock (CS). Morbidity and mortality of refractory CS remain high. The effects of mechanical circulatory support (MCS) are promising, although many aspects are elusive. We evaluated efficacy and safety of early combined MCS (Impella microaxial pump + venoarterial extracorporeal membrane oxygenation [VA-ECMO]) in refractory CS and aimed to determine factors for decision-making in combined MCS. METHODS AND RESULTS We analyzed 69 consecutive patients with refractory CS from our registry requiring combined MCS. In 12 cases, therapy was actively withdrawn according to patient's will. Patients were severely sick (Survival After Venoarterial ECMO score mean±SD, -8.9±4.4) predicting 30% in-hospital survival; ventilation 94%, dialysis 56%. Impella pumps and VA-ECMO were combined early (duration of combined MCS median 94 hours; interquartile range, 49-150 hours). Early MCS escalation stabilized patients rapidly, reducing number and doses of catecholamines (P less then 0.05 versus baseline) while hemodynamics improved. Reflecting an imp

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