Aims
Studies in cardiogenic shock (CS) often have a heterogeneous population of patients, including those with acute myocardial infarction and acute decompensated heart failure (ADHF‐CS). The ...therapeutic profile of milrinone may benefit patients with ADHF‐CS. We compared the outcomes and haemodynamic trends in ADHF‐CS receiving either milrinone or dobutamine.
Methods and results
Patients presenting with ADHF‐CS (from 2014 to 2020) treated with a single inodilator (milrinone or dobutamine) were included in this study. Clinical characteristics, outcomes, and haemodynamic parameters were collected. The primary endpoint was 30 day mortality, with censoring at the time of transplant or left ventricular assist device implantation. A total of 573 patients were included, of which 366 (63.9%) received milrinone and 207 (36.1%) received dobutamine. Patients receiving milrinone were younger, had better kidney function, and lower lactate at admission. In addition, patients receiving milrinone received mechanical ventilation or vasopressors less frequently, whereas a pulmonary artery catheter was more frequently used. Milrinone use was associated with a lower adjusted risk of 30 day mortality (hazard ratio = 0.52, 95% confidence interval 0.35–0.77). After propensity‐matching, the use of milrinone remained associated with a lower mortality (hazard ratio = 0.51, 95% confidence interval 0.27–0.96). These findings were associated with improved pulmonary artery compliance, stroke volume, and right ventricular stroke work index.
Conclusions
The use of milrinone compared with dobutamine in patients with ADHF‐CS is associated with lower 30 day mortality and improved haemodynamics. These findings warrant further study in future randomized controlled trials.
Decreased hepatitis C virus (HCV) clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV) coinfection. The CD4+ T helper cytokines ...interleukin (IL)-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control.
We measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels.
In acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8+ T cells from monoinfected individuals enhanced their function although CD8+ T cells from coinfected individuals were somewhat refractory to the effects of IL-21.
These data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals.
Background: Two randomized controlled trials in 2002 showed that induced hypothermia (32-34°C) had a neuroprotective effect in patients with out-of-hospital cardiac arrest (OHCA) and initial ...shockable rhythm.
Aims
Cardiogenic shock (CS) with variable systemic inflammation may be responsible for patient heterogeneity and the exceedingly high mortality rate. Cardiovascular events have been associated with ...clonal haematopoiesis (CH) where specific gene mutations in haematopoietic stem cells lead to clonal expansion and the development of inflammation. This study aims to assess the prevalence of CH and its association with survival in a population of CS patients in a quaternary centre.
Methods and results
We compared the frequency of CH mutations among 341 CS patients and 345 ambulatory heart failure (HF) patients matched for age, sex, ejection fraction, and HF aetiology. The association of CH with survival and levels of circulating inflammatory cytokines was analysed. We detected 266 CH mutations in 149 of 686 (22%) patients. CS patients had a higher prevalence of CH‐related mutations than HF patients (odds ratio 1.5; 95% confidence interval CI 1.0–2.1, p = 0.02) and was associated with decreased survival (30 days: hazard ratio HR 2.7; 95% CI 1.3–5.7, p = 0.006; 90 days: HR 2.2; 95% CI 1.3–3.9, p = 0.003; and 3 years: HR 1.7; 95% CI 1.1–2.8, p = 0.01). TET2 or ASXL1 mutations were associated with lower survival in CS patients at all time‐points (p ≤ 0.03). CS patients with TET2 mutations had higher circulating levels of SCD40L, interferon‐γ, interleukin‐4, and tumour necrosis factor‐α (p ≤ 0.04), while those with ASXL1 mutations had decreased levels of CCL7 (p = 0.03).
Conclusions
Cardiogenic shock patients have high frequency of CH, notably mutations in TET2 and ASXL1. This was associated with reduced survival and dysregulation of circulating inflammatory cytokines in those CS patients with CH.
Initial mutations in driver genes such as DNMT3A, TET2 and ASXL1 promote a clone expansion of haematopoietic stem cells termed clonal haematopoiesis (CH). CH mutations detected in peripheral blood samples of cardiogenic shock (CS) patients are more frequent than in ambulatory heart failure (HF) patients and are associated with a decreased 3‐year survival. The differently expressed circulating inflammatory cytokines are a new putative mechanism for adverse outcomes associated with specific CH mutations in CS. CI, confidence interval; OR, odds ratio.
Hemodynamic assessment for cardiogenic shock (CS) phenotyping in patients has led to renewed interest in the use of pulmonary artery catheters (PACs).
We included patients admitted with CS from ...January 2014 to December 2020 and compared clinical outcomes among patients who received PACs and those who did not. The primary outcome was the rate of in-hospital mortality. Secondary outcomes included use of advanced heart failure therapies and coronary intensive care unit (CICU) and hospital lengths of stay.
A total of 1043 patients were analysed and 47% received PACs. Patients selected for PAC-guided management were younger and had lower left ventricular function. They also had higher use of vasopressor and inotropes, and 15.2% of them were already supported with temporary mechanical circulatory support (MCS). In-hospital mortality was lower in patients who received PACs (29.3% vs 36.2%; P = 0.02), mainly driven by a reduction in mortality among those in Society for Cardiovascular Angiography and Interventions (SCAI) stages D and E CS. Patients who received PACs were more likely to receive temporary MCS with Impella, durable ventricular assist devices (VADs), or orthotopic heart transplantation (OHT) (P < 0.001 for all analyses). CICU and hospital lengths of stay were longer in patients who used PACs.
Among patients with CS, the use of PACs was associated with lower in-hospital mortality, especially among those in SCAI stages D and E. Patients who received PACs were also more frequently rescued with temporary MCS or received advanced heart failure therapies, such as durable VADs or OHT.
L'évaluation hémodynamique pour le phénotypage du choc cardiogénique (CC) chez les patients a suscité un regain d'intérêt pour l'utilisation des cathéters artériels pulmonaires (CAP).
Nous avons inclus des patients admis pour CC de janvier 2014 à décembre 2020 et avons comparé les résultats cliniques entre les patients ayant reçu des CAP et ceux n'en ayant pas reçu. Le critère d'évaluation principal était le taux de mortalité hospitalière. Les critères d'évaluation secondaires comprenaient l'usage de thérapies avancées pour l'insuffisance cardiaque et la durée des séjours en unité de soins intensifs coronariens (USIC) et à l'hôpital.
Au total, 1043 patients ont fait partie de l'analyse et 47 % ont bénéficié de CAP. Les patients sélectionnés pour une prise en charge guidée par CAP étaient plus jeunes et avaient une fonction ventriculaire gauche plus faible. Ils utilisaient également davantage de vasopresseurs et d'inotropes, et 15,2 % d'entre eux bénéficiaient déjà d'une assistance circulatoire mécanique (ACM) temporaire. La mortalité hospitalière était plus faible chez les patients ayant reçu des CAP (29,3 % contre 36,2 %; P = 0,02), principalement due à une réduction de la mortalité parmi ceux aux stades D et E du CC selon la Society for Cardiovascular Angiography and Interventions (SCAI). Les patients ayant reçu des CAP étaient plus susceptibles de recevoir une ACM temporaire avec Impella, des dispositifs d'assistance ventriculaire (DAV) durables ou une transplantation cardiaque orthotopique (TCO) (P < 0,001 pour toutes les analyses). Les durées de séjour en USIC et à l'hôpital étaient plus longues chez les patients utilisant des CAP.
Chez les patients avec CC, l'utilisation de CAP était associée à une mortalité hospitalière plus faible, en particulier parmi ceux aux stades D et E selon les critères de la SCAI. Les patients ayant reçu des CAP étaient également plus fréquemment soutenus par ACM temporaire ou recevaient des thérapies avancées pour l'insuffisance cardiaque, telles que des DAV durables ou des TCO.
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Abstract
Background
Vasoplegia has been reported in patients receiving angiotensin receptor-neprilysin inhibitors (ARNI) with heart failure with reduced ejection fraction (HFrEF). We present a case ...of vasoplegic shock after initiation of ARNI in a hospitalized 65-year-old man recovering from cardiogenic shock (CS) and acute kidney injury (AKI).
Case summary
A 65-year-old man with HFrEF presented to a community hospital with CS with evidence of poor perfusion with a lactate of 5.6 mmol/L and creatinine (Cr) 125 µmol/L. He was treated with intravenous furosemide infusion. Subsequently, his lactate normalized but he developed an AKI with a Cr of 176 µmol/L. He was then started on ARNI and beta blockers. Over the next 24 h, he developed a vasoplegic shock necessitating multiple vasopressors and a transfer to a tertiary academic centre. With supportive therapy, his vasoplegic shock improved and he was discharged home.
Discussion
PARADIGM-HF found that the introduction of an ARNI in patients with ambulatory symptomatic HFrEF reduces the risk of death and heart failure hospitalization. Most recently, PIONEER-HF showed that ARNI reduced N-terminal pro-B-type natriuretic peptide levels at 4 and 8 weeks, without significantly different rates of medication-related adverse effects. However, thus far, no clinical trials have examined the role of ARNI in CS. Our case report highlights the risk of vasoplegic shock caused by initiation of ARNI in patients hospitalized with CS especially in whom renal and hepatic impairment is present.
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