Phosphodiesterase-5 Inhibitors and Outcomes During Left Ventricular Assist Device Support: A Systematic Review and Meta-Analysis

Kittipibul, Veraprapas; Blumer, Vanessa; Angsubhakorn, Natthapon; Hernandez, Gabriel A.; Chaparro, Sandra; Tedford, Ryan J.; Agarwal, Richa

doi:10.1016/j.cardfail.2020.12.018

Cited by 10 publications

(10 citation statements)

References 38 publications

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“…In some centers, PDE5is are used off-label to mitigate the detrimental impact of PH in advanced HF with reduced ejection fraction (HFrEF) patient prior heart transplantation or LVAD implantation (13)(14)(15). However, there are no randomized clinical trials to support this approach, which is still a subject of debate (4,16,17). In some transplant centers, such as ours, PDE5i may be used acutely for the testing of reversibility of increased PVR (18,19).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Vasculature Responsiveness to Phosphodiesterase-5A Inhibition in Heart Failure With Reduced Ejection Fraction: Possible Role of Plasma Potassium

Monzo

Reichenbach²,

Al‐Hiti³

et al. 2022

Front. Cardiovasc. Med.

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IntroductionPhosphodiesterase-5a inhibition (PDE5i) leads to favorable changes in pulmonary hemodynamic and cardiac output (CO) in patients with advanced heart failure (HF) and reduced ejection fraction (HFrEF). The hemodynamic response to PDE5i could be heterogeneous and the clinical variables associated with these changes are scarcely investigated.Materials and MethodsOf 260 patients with advanced HFrEF referred for advanced therapies [cardiac transplant/left ventricular assist device (LVAD)], 55 had pulmonary hypertension (PH) and fulfilled the criteria for the PDE5i vasoreactivity test. Right heart catheterization (RHC) was performed as a part of clinical evaluation before and after 20-mg intravenous sildenafil. Absolute and relative changes in pulmonary vascular resistance (PVR) were evaluated to assess hemodynamic response to PDE5i. Clinical, biochemical, and hemodynamic factors associated with PVR changes were identified.ResultsSildenafil administration reduced PVR (− 45.3%) and transpulmonary gradient (TPG; − 34.8%) and increased CO (+ 13.6%). Relative change analysis showed a negative moderate association between baseline plasma potassium and changes in PVR (r = − 0.48; p = 0.001) and TPG (r = − 0.43; p = 0.005) after PDE5i. Aldosterone concentration shows a direct moderate association with PVR changes after PDE5i. A significant moderate association was also demonstrated between CO improvement and the severity of mitral (r = 0.42; p = 0.002) and tricuspid (r = 0.39; p = 0.004) regurgitation.ConclusionWe identified plasma potassium, plasma aldosterone level, and atrioventricular valve regurgitations as potential cofounders of hemodynamic response to acute administration of PDE5i. Whether modulation of potassium levels could enhance pulmonary vasoreactivity in advanced HFrEF deserves further research.

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Section: Introductionmentioning

confidence: 99%

Pulmonary Vasculature Responsiveness to Phosphodiesterase-5A Inhibition in Heart Failure With Reduced Ejection Fraction: Possible Role of Plasma Potassium

Monzo

Reichenbach²,

Al‐Hiti³

et al. 2022

Front. Cardiovasc. Med.

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“…In the current meta-analysis, similar to the previous study by Kittipibul et al [ 34 ], a conference abstract was included in the analysis of gastrointestinal bleeding [ 25 ]. Nevertheless, the results were similar after excluding this study from the analysis ( Supplementary Figure S1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Our study incorporates certain strengths compared to the previous meta-analysis by Kittipibul et al [ 34 ]. First of all, we searched three databases compared with the two used in the previous meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the previous meta-analysis performed only three-arm analyses regarding hemocompatibility-related outcomes, while we performed five-arm analyses (for ischemic stroke), four-arm analyses (for pump thrombosis), and eight-arm analyses (for gastrointestinal bleeding), thus providing a significantly higher level of evidence. Lastly, the present meta-analysis included “hard endpoints” (i.e., mortality) that were not investigated in the meta-analysis by Kittipibul et al [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

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Post-Implant Phosphodiesterase-5 Inhibitors in Patients with Left Ventricular Assist Device: A Systematic Review and Meta-Analysis

Xanthopoulos

Magouliotis

Tryposkiadis³

et al. 2022

JCM

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Background: Despite the improvement in left ventricular assist device (LVAD) technology and the advent of third-generation LVADs, hemocompatibility-related events remain a significant issue. Therefore, new pharmacological treatments are necessary to optimize patient management and to further reduce hemocompatibility-related events. The purpose of the present systematic review and meta-analysis was to summarize the existing data regarding the safety and efficacy of post-implant phosphodiesterase-5 inhibitors (PDE-5i) on hemocompatibility-related events. Methods: Among the 258 articles in Pubmed, Scopus, and CENTRAL that were retrieved (1990–2022), 15 studies were included in the qualitative synthesis, and 9 studies were included in the quantitative synthesis. The fixed-effects model was used because it is statistically sound for combining a very small number of studies. The primary endpoint of the study was all-cause mortality, whereas the secondary endpoints were ischemic stroke, pump thrombosis, and gastrointestinal bleeding. Results: Mortality was significantly lower in the PDE-5i group vs. the control group (OR: 0.92 [95% CI: 0.85, 0.98]; p = 0.02). The secondary endpoints ischemic stroke (OR: 0.87 [95% CI: 0.78, 0.98]; p = 0.02) and pump thrombosis (OR: 0.90 [95% CI: 0.82, 0.99]; p = 0.04) were also lower in the PDE-5i group. The incidence of gastrointestinal bleeding was significantly higher in patients with LVAD receiving PDE-5i (OR: 1.26 [95% CI: 1.11, 1.44]; p < 0.01). In the overall analysis, the heterogeneity of outcomes was low, except for pump thrombosis. Conclusions: The use of PDE-5i post-implant was associated with lower mortality and thrombotic events but with a higher risk of gastrointestinal bleeding.

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“…14 Retrospective analyses from a single center of patients receiving PDE5i after LVAD found no impact on time to wean from inotropic support (IS) or survival and noted nonsignificant increases in gastrointestinal bleeding and rehospitalization for heart failure. 15,16 Our previous work from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) and a recent meta-analysis suggest that preimplant PDE5i use is associated with a similar or even higher rate of ERHF, 17,18 but there are no large studies examining the impact of postimplant use on LRHF. The primary aim of this study was to evaluate the association between PDE5i use early after LVAD and the incidence of LRHF, mortality, and major bleeding.…”

mentioning

confidence: 99%

Outcomes With Phosphodiesterase-5 Inhibitor Use After Left Ventricular Assist Device: An STS-INTERMACS Analysis

Grandin

Gulati

Nunez

et al. 2022

Circ: Heart Failure

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Background: Elevated right ventricular afterload following continuous-flow left ventricular assist device (CF-LVAD) may contribute to late right heart failure (LRHF). PDE5i (phosphodiesterase-5 inhibitors) are used to treat pulmonary hypertension and right heart dysfunction after CF-LVAD, but their impact on outcomes is uncertain. Methods: We queried Interagency Registry for Mechanically Assisted Circulatory Support from 2012 to 2017 for adults receiving a primary CF-LVAD and surviving ≥30 days from index discharge. Patients receiving early PDE5i (ePDE5i) at 1 month were propensity-matched 1:1 with controls. The primary outcome was the cumulative incidence of LRHF, defined using prevailing Interagency Registry for Mechanically Assisted Circulatory Support criteria; secondary outcomes included all-cause mortality and major bleeding. Results: Among 9627 CF-LVAD recipients analyzed, 2463 (25.6%) received ePDE5i and 1600 were propensity-matched 1:1 with controls. Before implant, ePDE5i patients had more severe RV dysfunction (13.1% versus 9.6%) and higher pulmonary vascular resistance (2.8±2.7 versus 2.2±2.4 WU), both P <0.001, but clinical factors were well-balanced after propensity-matching. In the unmatched cohort, ePDE5i patients had a higher 3-year cumulative incidence of LRHF, mortality, and major bleeding, but these differences were attenuated in the propensity-matched cohort: LRHF 40.8% versus 35.7% (hazard ratio, 1.14 [95% CI, 0.99–1.32]; P =0.07); mortality 38.6% versus 35.8% (hazard ratio, 0.99 [95% CI, 0.86–1.15]; P =0.93); major bleeding 51.2% versus 46.0% (hazard ratio, 1.12 [95% CI, 0.99–1.27]; P =0.06). Conclusions: Compared with propensity-matched controls, adult CF-LVAD patients receiving ePDE5i had similar rates of LRHF, mortality, and major bleeding. While intrinsic patient risk factors likely account for more adverse outcomes with ePDE5i in the unmatched cohort, there is no obvious benefit of ePDE5i in the LVAD population.

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Phosphodiesterase-5 Inhibitors and Outcomes During Left Ventricular Assist Device Support: A Systematic Review and Meta-Analysis

Cited by 10 publications

References 38 publications

Pulmonary Vasculature Responsiveness to Phosphodiesterase-5A Inhibition in Heart Failure With Reduced Ejection Fraction: Possible Role of Plasma Potassium

Pulmonary Vasculature Responsiveness to Phosphodiesterase-5A Inhibition in Heart Failure With Reduced Ejection Fraction: Possible Role of Plasma Potassium

Post-Implant Phosphodiesterase-5 Inhibitors in Patients with Left Ventricular Assist Device: A Systematic Review and Meta-Analysis

Outcomes With Phosphodiesterase-5 Inhibitor Use After Left Ventricular Assist Device: An STS-INTERMACS Analysis

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