Title: Use of Guideline Directed Medical Therapy and Safety in Patients with Cardiogenic Shock
Authors: Thomas Thielbar, Kelly Dunton, Pujan Patel, Laila Handshaw
Background: Heart failure with reduced ejection fraction (HFrEF) clinical practice guidelines currently recommend the use of guideline directed medical therapy (GDMT) to improve survival, decrease hospitalizations, and improve symptoms in patients with HFrEF. Several studies have demonstrated that early initiation of GDMT during hospitalization, once hemodynamically stable, to be safe and clinically beneficial. This study aims to assess the current ordering practices and safety of GDMT in American Heart Association (AHA) stage D / New York Heart Association (NYHA) class IV heart failure (HF) patients hospitalized for acute decompensated heart failure (ADHF).
Methods: This single-site, retrospective, cohort study included patients age ≥18 years, hospitalized at AdventHealth Orlando, admitted with ADHF (defined as having signs and symptoms of congestion, actively receiving inotropes, and/or temporary mechanical circulatory support [MCS]), classified as AHA stage D / NYHA class IV HF, and underwent an advanced HF evaluation. Exclusion criteria include history of durable left-ventricular assist device (LVAD), type 1 diabetes, history of diabetic ketoacidosis (DKA) or euglycemic DKA, history of angioedema associated with GDMT, and pregnant women. The primary endpoint is percentage of patients on GDMT including angiotensin-converting enzyme inhibitor (ACEi) / angiotensin II receptor blocker (ARB) / angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker (BB), mineralocorticoid receptor antagonist (MRA), and sodium-glucose cotransporter 2 inhibitors (SGLT2i) at three points including day of admission, 72 hours post inotrope or MCS initiation, and day of discharge (defined as hospital discharge, in-hospital mortality, left-ventricular assist device implant or heart transplant). Secondary safety endpoints include incidence of genitourinary infections, acute kidney injury or need for renal replacement therapy, hypotension, bradycardia, hyperkalemia, hypoglycemia, DKA, and angioedema assessed at admission, within 72 hours post inotrope or MCS initiation, and discharge. Additional secondary endpoints include number of patients on each individual medication and their doses from primary endpoint, MCS use, inotrope use and dose, vasopressor use, and VIS score at admission, within 72 hours post inotrope or MCS initiation, and discharge. Exploratory safety endpoints include in-hospital mortality, hospital length of stay, ICU length of stay, implant of LVAD, heart transplant, and actively on heart transplant waitlist. Study endpoints were analyzed utilizing descriptive statistics.
Results: A total of 129 encounters, encompassing 108 patients were screened for inclusion in which 27 encounters were excluded. The final study population included 102 encounters, encompassing 84 patients with a median age of 57 (IQR 48-65) years old, predominantly white (43.1%) males (72.5%) with past medical history significant for type 2 diabetes (52.9%), chronic kidney disease (52.9%), and arrhythmias (66.7%). The primary cause of HF was non-ischemic cardiomyopathy. Only 20.6% of patients were on all four GDMT medication classes prior to admission. SGLT2i and MRA were the most commonly prescribed GDMT at all three time points. Incidence of SGLT2i was 43.1%, 61.8%, and 78.1% at admission, 72 hours post inotrope or MCS initiation, and discharge respectively. Incidence of MRA was 49%, 80.4%, and 87.5% at admission, 72 hours post inotrope or MCS initiation, and discharge respectively. For secondary endpoints, administration of any GDMT did not increase incidence of any associated adverse effect.
Conclusion: We observed that in this patient population, SGLT2i and MRA were most commonly ordered and did not increase the incidence of any safety outcomes assessed. This study illustrates that it is safe to optimize GDMT in this patient population, however, further studies are needed to assess efficacy on a larger scale.