Effects of dapagliflozin on congestion assessed by remote pulmonary artery pressure monitoring.

AIMS: To explore the effects of dapagliflozin on congestion through CardioMEMS (Abbott Inc., Atlanta, USA) and Cordella™ pulmonary artery Sensor (Endotronix Inc., Lisle, Il, USA) devices, which are implantable systems that provide real-time remote monitoring of pulmonary artery pressure (PAP). METHODS AND RESULTS: Single-centre open label observational pilot trial, to investigate the short-term effects of dapagliflozin in consecutive heart failure and reduced ejection fraction patients with elevated PAP between October and December 2019, previously implanted with CardioMEMS or Cordella™ Sensor. Changes in PAP were evaluated with an area under the curve methodology to estimate the total sum increase or decrease in pressures (mmHg/day) for 7 days before and after starting dapagliflozin relative to the first day of each period. Nine patients (72 ± 10 years, N-terminal pro b-type natriuretic peptide 1027 ± 510 pg/mL, estimated glomerular filtration rate 45 ± 15 mL/kg/m2, left ventricular ejection fraction 35 ± 10%), all on optimal guideline-directed therapy was included. The mean PAP was reduced from 42 ± 9.16 to 38 ± 9.95 mmHg with dapagliflozin therapy (P < 0.05). The average area under the curve for the week leading to dapagliflozin therapy remained unchanged compared to the drop observed for the week after therapy (P < 0.05). Interestingly, the drop in PAP occurred within the first 2 days of dapagliflozin and remained stable for the week following the start of the therapy. CONCLUSIONS: This is the first study to demonstrate a direct effect of dapagliflozin on achieving effective hemodynamic decongestion, providing further mechanistic data regarding the potential mechanisms of sodium-glucose co-transporter-2 inhibitor benefits on heart failure.

Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction.

BACKGROUND: Sacubitril/valsartan reduced the occurrence of sudden cardiac death in the PARADIGM-HF trial. However, limited information is available about the mechanism. METHODS: Heart failure (HF)-patients receiving sacubitril/valsartan for a class-I indication equipped with an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) with remote tele-monitoring were retrospectively analyzed. Device-registered arrhythmic-events were determined [ventricular tachycardia/fibrillation (VT/VF), appropriate therapy, non-sustained VT (NsVT; > 4beats and < 30 s), hourly premature ventricular contraction (PVC)-burden], following sacubitril/valsartan initiation (incident-analysis) and over an equal time period before initiation (antecedent-analysis). Reverse remodeling to sacubitril/valsartan was defined as an improvement of left ventricular ejection fraction of ≥ 5% between baseline and follow-up. RESULTS: A-total of 151 HF-patients with reduced LVEF (29 ± 9%) were included. Patients were switched from ACE-I or ARB to equal doses of sacubitril/valsartan (expressed as %-target-dose; before = 58 ± 30% vs. after = 56 ± 27%). The mean follow-up of both the incident and antecedent analysis was 364 days. Following the initiation, VT/VF-burden dropped (individual patients with VT/VF pre_n = 19 vs. post_n = 10, total-episodes of VT/VF pre_n = 51 vs. post_n = 14, both p < 0.001), resulting in reduced occurrence of appropriate therapy (pre_n = 16 vs. post_n = 6; p < 0.001). NsVT-burden per patient also dropped (mean episodes pre_n = 7.7 ± 11.8 vs. post_n = 3.7 ± 5.4; p < 0.001). There was no impact on atrial-fibrillation burden. PVC-burden dropped significantly which was associated with an improvement in BiV-pacing in patients with < 90% BiV-pacing at baseline. A higher degree of reverse remodeling was associated with a lower burden of NsVT and PVCs (both p < 0.05). CONCLUSION: Initiation of sacubitril/valsartan is associated with a lower degree of VT/VF, resulting in less ICD-interventions. This beneficial effect on ventricular arrhythmias might be related to cardiac reverse remodeling.

Effects of intravenous home dobutamine in palliative end-stage heart failure on quality of life, heart failure hospitalization, and cost expenditure.

AIMS: In patients with palliative end-stage heart failure, interventions that could provide symptomatic relief and prevent hospital admissions are important. Ambulatory continuous intravenous inotropes have been advocated by guidelines for such a purpose. We sought to determine the effect of intravenous dobutamine on symptomatic status, hospital stay, mortality, and cost expenditure. METHODS AND RESULTS: All consecutive end-stage heart failure patients not amenable for advanced therapies and discharged with continuous intravenous home dobutamine from a single tertiary centre between April 2011 and January 2017 were retrospectively analysed. Dobutamine (fixed dose) was infused through a single-lumen central venous catheter with a small pump that was refilled by a nurse on a daily basis. Symptomatic status was longitudinally assessed as the change in New York Heart Association class and patient global assessment scale. Antecedent and incident heart failure hospitalizations were determined in a paired fashion, and cost impact was assessed. A total of 21 patients (age 77 ± 9 years) were followed up for 869 ± 647 days. At first follow-up (6 ± 1 weeks) after the initiation of dobutamine, patients had a significant improvement in New York Heart Association class (-1.29 ± 0.64; P < 0.001), global assessment scale (<0.001), and N-terminal pro-brain natriuretic peptide (6247 vs. 2543 pg/mL; P = 0.033). Incident heart failure hospitalizations assessed at 3, 6, and 12 months were significantly reduced (P < 0.001 for all) in comparison with antecedent heart failure hospitalizations over the same time period. Cost expenditure was significantly lower at 3 (P < 0.001), 6 (P = 0.005), and 12 months (P = 0.001) after initiation of dobutamine. Mortality rate at 1 year was 48% with 9/12 (75%) patients dying at home, most often from progressive pump failure. CONCLUSIONS: Continuous intravenous home dobutamine in patients with palliative end-stage heart failure is feasible and associated with improved symptomatic status, heart failure hospitalizations, and health-care-related costs. Nevertheless, results should be interpreted in the context of the small and retrospective design. Larger studies are necessary to evaluate the effect of dobutamine in palliative end-stage heart failure.