SGLT2 inhibitor therapy and pulmonary artery pressure in patients with chronic heart failure—further evidence for improved hemodynamics by continuous pressure monitoring

Abstract

SGLT2 inhibitors were designed as drugs for patients with diabetes that interfere with renal glucose and sodium reabsorption. The EMPEROR-reduced and DAPA-HF trials showed that SGLT2i treatment led to a significant reduction in the combined endpoint of cardiovascular death and hospitalizations in patients with heart failure with a reduced ejection fraction independent of diabetes status [1, 2]. However, the mechanisms responsible for these effects remain largely unexplored and clinical observations assessing heart function or hemodynamic status of those patients remain scarce. A key feature of heart failure is inadequate cardiac output resulting in congestion and secondary pulmonary hypertension [3]. Higher pulmonary artery pressures predict HF symptoms, unplanned hospitalizations and mortality [4, 5]. Therefore, we analyzed the effect of SGLT2i on PA pressures in patients with severe heart failure regardless of ejection fraction. For this purpose, we analyzed data recorded by the CardioMEMS system, a remote sensor which transmits ambulatory recorded pulmonary artery pressures. This was a retrospective case-series of ambulatory HFrEF or HFpEF patients who had previously received a CardioMEMS device, in whom either Dapagliflozin or Empagliflozin was initiated at the discretion of the treating physician. Hemodynamic data were abstracted from the medical record. PAP readings were collected daily starting 4 weeks prior to SGLT2i initiation for up to 10 weeks following initiation of treatment with SGLT2i. Patient records were audited to verify that other interventions that might have influenced PAP measurements (e.g., addition of new diuretic drugs and change in diuretic dose) had not occurred during the observation period. All patients were on stable guideline-directed medical therapy for at least three months prior to SGLT2i treatment initiation. Adjustment of standard therapies was permitted if clinically indicated. Patients were excluded if they had initiation of β-blockers, angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, or valsartan/sacubitril within three months before SGLT2i initiation. Hemodynamic data pre and post SGL2 initiation were compared via Wilcoxon signed-rank testing and linear regression analysis was employed. All patients provided written informed consent for participation in this single center registry (NCT03020043). The study complies with the Declaration of Helsinki and was approved by the local ethics committee. Statistical significance was assumed if P < 0.05. Statistical analysis was performed with Graph Pad Prism Vers. 8.2.0. In the present cohort, 17 patients with advanced chronic heart failure were analyzed. All patients underwent implantation of a CardioMEMS system between 2015 and 2020. SGLT2 inhibitors were initiated either as diabetes therapy or as a heart failure drug. 8 of 17 patients had diabetes. 13 patients received dapagliflozin (1 × 10 mg/d), four patients were treated with empagliflozin (1 × 10 mg/d). Baseline characteristics and medication of all patients are shown in Table1. PAP values were recorded on a daily base in the 30-day period prior to initiation of SGL2i treatment until 70 days (10 weeks) after start of SGLT2 intake. After 10 weeks, we observed significant reductions of systolic PAP (− 3.59 ± 1.55 mmHg; P = 0.034), mean PAP * Sebastian Cremer [email protected]