Milrinone vs Dobutamine for the Management of Cardiogenic Shock: Implications of Renal Function and Injury.

Background: Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction. Objectives: This study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function. Methods: In this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m2 and acute kidney injury (AKI). The primary outcome was the composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Results: Baseline eGFR <60 ml/min/1.73 m2 and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m2 did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome (P interaction = 0.02) and death (P interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI. Conclusions: In patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI.

Implications of Myocardial Infarction on Management and Outcome in Cardiogenic Shock.

Background The randomized DOREMI (Dobutamine Compared to Milrinone) clinical trial evaluated the efficacy and safety of milrinone and dobutamine in patients with cardiogenic shock. Whether the results remain consistent when stratified by acute myocardial infarction remains unknown. In this substudy, we sought to evaluate differences in clinical management and outcomes of acute myocardial infarction complicated by cardiogenic shock (AMICS) versus non-AMICS. Methods and Results Patients in cardiogenic shock (n=192) were randomized 1:1 to dobutamine or milrinone. The primary composite end point in this subgroup analysis was all-cause in-hospital mortality, cardiac arrest, non-fatal myocardial infarction, cerebrovascular accident, the need for mechanical circulatory support, or initiation of renal replacement therapy (RRT) at 30-days. Outcomes were evaluated in patients with (n=65) and without (n=127) AMICS. The primary composite end point was significantly higher in AMICS versus non-AMICS (hazard ratio [HR], 2.21; 95% CI, 1.47-3.30; P=0.0001). The primary end point was driven by increased rates of all-cause mortality, mechanical circulatory support, and RRT. No differences in other secondary outcomes including cardiac arrest or cerebrovascular accident were observed. AMICS remained associated with the primary composite outcome, 30-day mortality, and RRT after adjustment for age, sex, procedural contrast use, multivessel disease, and inotrope type. Conclusions AMI was associated with increased rates of adverse clinical outcomes in cardiogenic shock along with increased rates of mortality and initiation of mechanical circulatory support and RRT. Contrast administration during revascularization likely contributes to increased rates of RRT. Heterogeneity of outcomes in AMICS versus non-AMICS highlights the need to study interventions in specific subgroups of cardiogenic shock. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03207165.

The association between mean arterial pressure and outcomes in patients with cardiogenic shock: insights from the DOREMI trial.

AIMS: Cardiogenic shock (CS) is a state of low cardiac output resulting in end-organ hypoperfusion. Despite high in-hospital mortality rates, little evidence exists regarding the optimal mean arterial pressure (MAP) target in CS. We therefore evaluated the relationship between achieved MAP and clinical outcomes in patients with CS. METHODS AND RESULTS: We performed a post hoc analysis of the CAPITAL DOREMI trial: a randomized, double-blind trial comparing dobutamine to milrinone in patients with CS. We divided patients into a high MAP group (average MAP ≥ 70 mmHg over the 36 h following randomization), and a low MAP group (average MAP < 70 mmHg). Our primary outcome included in-hospital all-cause mortality, resuscitated cardiac arrest, need for cardiac transplantation or mechanical circulatory support, non-fatal myocardial infarction, transient ischaemic attack or stroke, or initiation of renal replacement therapy. In total, 71 (37.0%) patients achieved an average MAP < 70 mmHg, and 121 (63.0%) achieved an average MAP ≥ 70 mmHg. The primary outcome occurred in 48 (67.6%) patients in the low MAP group and 51 (42.2%) patients in the high MAP group [adjusted relative risk (aRR) 0.70; 95% confidence interval (CI) 0.53-0.92; P = 0.01]. All-cause mortality occurred in 41 (57.8%) and 35 (28.9%) patients in the low and high MAP groups, respectively (aRR 0.56; 95% CI 0.40-0.79; P < 0.01). There were no significant differences in any secondary outcomes between each group. CONCLUSIONS: In patients with CS treated with inotrope therapy, low MAP is associated with worse clinical outcomes. Randomized data evaluating optimal MAP targets in CS is needed to guide medical therapy.

Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial.

BACKGROUND: Cardiogenic shock (CS) is associated with significant morbidity and mortality. The impact of beta-blocker (BB) use on patients who develop CS remains unknown. We sought to evaluate the clinical outcomes and hemodynamic response profiles in patients treated with BB in the 24 h prior to the development of CS. METHODS: Patients with CS enrolled in the DObutamine compaREd to MIlrinone trial were analyzed. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, need for cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite and hemodynamic response profiles derived from pulmonary artery catheters. RESULTS: Among 192 participants, 93 patients (48%) had received BB therapy. The primary outcome occurred in 47 patients (51%) in the BB group and in 52 (53%) in the no BB group (RR 0.96; 95% CI 0.73-1.27; P = 0.78) throughout the in-hospital period. There were fewer early deaths in the BB group (RR 0.41; 95% CI 0.18-0.95; P = 0.03). There were no differences in other individual components of the primary outcome or in hemodynamic response between the two groups throughout the remainder of the hospitalization. CONCLUSIONS: BB therapy in the 24 h preceding the development of CS did not negatively influence clinical outcomes or hemodynamic parameters. On the contrary, BB use was associated with fewer deaths in the early resuscitation period, suggesting a paradoxically protective effect in patients with CS. Trial registration ClinicalTrials.gov Identifier: NCT03207165.

Simultaneous electrochemical detection of guanine and adenine using reduced graphene oxide decorated with AuPt nanoclusters.

A rapid and sensitive electrochemical sensing platform is reported based on bimetallic gold-platinum nanoclusters (AuPtNCs) dispersed on reduced graphene oxide (rGO) for the simultaneous detection of guanine and adenine using square wave voltammetry (SWV). The synthesis of AuPtNCs-rGO nanocomposite was achieved by a simultaneous reduction of graphene oxide (GO) and metal ions (Au3+ and Pt4+) in an aqueous solution. The developed AuPtNCs-rGO electrochemical sensor with the optimized 50:50 bimetallic (Au:Pt) nanoclusters exhibited an outstanding electrocatalytic performance towards the simultaneous oxidation of guanine and adenine without the aid of any enzymes or mediators in physiological pH. The electrochemical sensor platform showed low detection limits of 60 nM and 100 nM (S/N = 3) for guanine and adenine, respectively, with high sensitivity and an extensive linear range from 1.0 µM to 0.2 mM for both guanine and adenine. The interference from the most common electrochemically active interferents, including ascorbic acid, uric acid, and dopamine, was almost negligible. The simultaneous sensing of guanine and adenine in denatured Salmon Sperm DNA sample was successfully achieved using the proposed platform, showing that the AuPtNCs-rGO nanocomposite could provide auspicious clinical diagnosis and biomedical applications.

Novel cobalt quantum dot/graphene nanocomposites as highly efficient electrocatalysts for water splitting.

A cost-effective, non-noble metal based high-performance electrocatalyst for the oxygen evolution reaction (OER) is critical to energy conversion and storage processes. Here, we report on a facile and effective in situ strategy for the synthesis of an advanced nanocomposite material that is comprised of cobalt quantum dots (Co QDs, ∼3.2 nm), uniformly dispersed on reduced graphene oxide (rGO) as a highly efficient OER electrocatalyst platform. This nanocomposite electrocatalyst afforded a mass activity of 1250 A g(-1) at a low overpotential (η) of 0.37 V, a small Tafel slope of ∼37 mV dec(-1) and a turnover frequency (TOF) of 0.188 s(-1) in 0.1 M KOH, comparing favorably with state-of-the-art RuO2, IrO2 and Pt/C catalysts. The synergy between abundant catalytically active sites through the fine dispersion of Co QDs, and enhanced electron transfer generated from the graphene resulted in first-rate electrocatalytic properties toward the OER. These merits coupled with the higher stability of the nanocomposite hold great promise for triggering breakthroughs in electrocatalysis for water splitting.