Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction

Pilgrim, Thomas; Vollenbroich, René; Deckarm, Sarah; Gräni, Christoph; Dobner, Stephan; Stark, Anselm W.; Erne, Sophie A.; Bosombo, Flora Babongo; Fischer, Kady; Stortecky, Stefan; Reusser, Nicole; Fürholz, Monika; Siontis, George C.M.; Heg, Dik; Hunziker, Lukas; Windecker, Stephan; Lanz, Jonas

doi:10.1001/jamacardio.2021.2247

Cited by 11 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The participants of this study were enrolled in the CARE-AMI trial (clinical trial unique identifier: NCT03274752) ( 8 ). Detailed in- and exclusion criteria have been reported previously.…”

Section: Methodsmentioning

confidence: 99%

“…Detailed in- and exclusion criteria have been reported previously. In brief, patients presenting with anterior STEMI and reduced LVEF (i.e., ≤ 45%), who underwent primary percutaneous coronary intervention (PCI) within 24 h were eligible for inclusion and underwent baseline CMR after PCI ( 8 ). Exclusion criteria consisted of previous myocardial infarction (MI) or primary percutaneous intervention along with contraindications to CMR ( 8 ) (see Figure 1 ).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Diagnostic performance of cardiac magnetic resonance segmental myocardial strain for detecting microvascular obstruction and late gadolinium enhancement in patients presenting after a ST-elevation myocardial infarction

Gräni

Stark

Fischer

et al. 2022

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

BackgroundMicrovascular obstruction (MVO) and Late Gadolinium Enhancement (LGE) assessed in cardiac magnetic resonance (CMR) are associated with adverse outcome in patients with ST-elevation myocardial infarction (STEMI). Our aim was to analyze the diagnostic performance of segmental strain for the detection of MVO and LGE.MethodsPatients with anterior STEMI, who underwent additional CMR were enrolled in this sub-study of the CARE-AMI trial. Using CMR feature tracking (FT) segmental circumferential peak strain (SCS) was measured and the diagnostic performance of SCS to discriminate MVO and LGE was assessed in a derivation and validation cohort.ResultsForty-eight STEMI patients (62 ± 12 years old), 39 (81%) males, who underwent CMR (i.e., mean 3.0 ± 1.5 days) after primary percutaneous coronary intervention (PCI) were included. All patients presented with LGE and in 40 (83%) patients, MVO was additionally present. Segments in all patients were visually classified and 146 (19%) segments showed MVO (i.e., LGE+/MVO+), 308 (40%) segments showed LGE and no MVO (i.e., LGE+/MVO–), and 314 (41%) segments showed no LGE (i.e., LGE–). Diagnostic performance of SCS for detecting MVO segments (i.e., LGE+/MVO+ vs. LGE+/MVO–, and LGE–) showed an AUC = 0.764 and SCS cut-off value was –11.2%, resulting in a sensitivity of 78% and a specificity of 67% with a positive predictive value (PPV) of 30% and a negative predictive value (NPV) of 94% when tested in the validation group. For LGE segments (i.e., LGE+/MVO+ and LGE+/MVO– vs. LGE–) AUC = 0.848 and SCS with a cut-off value of –13.8% yielded to a sensitivity of 76%, specificity of 74%, PPV of 81%, and NPV of 70%.ConclusionSegmental strain in STEMI patients was associated with good diagnostic performance for detection of MVO+ segments and very good diagnostic performance of LGE+ segments. Segmental strain may be useful as a potential contrast-free surrogate marker to improve early risk stratification in patients after primary PCI.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Diagnostic performance of cardiac magnetic resonance segmental myocardial strain for detecting microvascular obstruction and late gadolinium enhancement in patients presenting after a ST-elevation myocardial infarction

Gräni

Stark

Fischer

et al. 2022

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this manuscript, we wanted to investigate why paroxetine could have failed to improve LV remodeling in STEMI patients with LVEF < 45% in a recent trial ( 4 ), despite the very interesting pre-clinical findings studies ( 5 ), attributed to the inhibition of GRK2.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study found that paroxetine has no beneficial effects on LV remodeling in patients with STEMI and LV ejection fraction ≤ 45%. Specifically, paroxetine treatment was not associated with a recovery in LV ejection fraction compared to placebo ( 4 ). The rationale behind this trial was that paroxetine relieves LV remodeling when administered as a stand-alone medication to mice with MI ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

The Potential Anti-remodeling Effect of Paroxetine After Myocardial Infarction May Be Blunted by Beta-Blockers

Iborra‐Egea

Aimo

Mondaini

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundLeft ventricular (LV) remodeling consists in maladaptive changes in cardiac geometry and function following an insult such as ST-segment elevation myocardial infarction (STEMI). Interventions able to prevent LV remodeling after a STEMI are expected to improve the outcome of this condition. Paroxetine has inhibitory effects on GRK2, also known as beta-adrenergic receptor kinase 1 (ADRBK1). This drug does not yield beneficial effects on LV remodeling in patients with STEMI and LV ejection fraction ≤ 45%.MethodsWe compared the molecular effects of paroxetine and drugs for neurohormonal antagonism (beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists), using a bioinformatic approach integrating transcriptomic data in a swine model of post-MI and available evidence from the literature and massive public databases.ResultsAmong standard therapies for MI, beta-blockers are the only ones acting directly upon GKR2, but the mechanism of action overlaps with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers with respect to the AT2R-mediated anti-hypertensive response. Moreover, beta-blockers could have anti-fibrotic and anti-inflammatory effects through the regulation of myocyte-specific enhancer factors, endothelins and chemokines.ConclusionThe additive benefit of paroxetine on the background of the standard therapy for STEMI, which includes beta-blockers, is expected to be limited. Nonetheless, paroxetine becomes particularly interesting when a beta-blocker is contraindicated (for example, in hypotensive individuals) or poorly tolerated.

show abstract

“…In the Original Investigation titled “Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction: A Randomized Clinical Trial,” published online July 14, 2021, in JAMA Cardiology , there were errors in Table 2, Limitations, and the Visual Abstract. In Table 2, Week 18 under Placebo should be Week 12, and the number of participants for that column should be 18.…”

mentioning

confidence: 99%

Errors in Table 2, Limitations, and Visual Abstract

2021

JAMA Cardiol

View full text Add to dashboard Cite

In the Original Investigation titled "Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction: A Randomized Clinical Trial," 1 published online July 14, 2021, in JAMA Cardiology, there were errors in Table 2, Limitations, and the Visual Abstract. In Table 2, Week 18 under Placebo should be Week 12, and the number of participants for that column should be 18.In the Limitations, a parenthetical explanation was inadvertently included in the text during manuscript editing. In the Visual Abstract, the article was incompletely cited. This article was corrected online.

show abstract

Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction

Cited by 11 publications

References 10 publications

Diagnostic performance of cardiac magnetic resonance segmental myocardial strain for detecting microvascular obstruction and late gadolinium enhancement in patients presenting after a ST-elevation myocardial infarction

Diagnostic performance of cardiac magnetic resonance segmental myocardial strain for detecting microvascular obstruction and late gadolinium enhancement in patients presenting after a ST-elevation myocardial infarction

The Potential Anti-remodeling Effect of Paroxetine After Myocardial Infarction May Be Blunted by Beta-Blockers

Errors in Table 2, Limitations, and Visual Abstract

Contact Info

Product

Resources

About