The management of heart failure cardiogenic shock: an international RAND appropriateness panel.

BACKGROUND: Observational data suggest that the subset of patients with heart failure related CS (HF-CS) now predominate critical care admissions for CS. There are no dedicated HF-CS randomised control trials completed to date which reliably inform clinical practice or clinical guidelines. We sought to identify aspects of HF-CS care where both consensus and uncertainty may exist to guide clinical practice and future clinical trial design, with a specific focus on HF-CS due to acute decompensated chronic HF. METHODS: A 16-person multi-disciplinary panel comprising of international experts was assembled. A modified RAND/University of California, Los Angeles, appropriateness methodology was used. A survey comprising of 34 statements was completed. Participants anonymously rated the appropriateness of each statement on a scale of 1 to 9 (1-3 as inappropriate, 4-6 as uncertain and as 7-9 appropriate). RESULTS: Of the 34 statements, 20 were rated as appropriate and 14 were rated as inappropriate. Uncertainty existed across all three domains: the initial assessment and management of HF-CS; escalation to temporary Mechanical Circulatory Support (tMCS); and weaning from tMCS in HF-CS. Significant disagreement between experts (deemed present when the disagreement index exceeded 1) was only identified when deliberating the utility of thoracic ultrasound in the immediate management of HF-CS. CONCLUSION: This study has highlighted several areas of practice where large-scale prospective registries and clinical trials in the HF-CS population are urgently needed to reliably inform clinical practice and the synthesis of future societal HF-CS guidelines.

Medical therapy of cardiogenic shock: Contemporary use of inotropes and vasopressors.

Cardiogenic shock is a primary cardiac disorder that results in both clinical and biochemical evidence of tissue hypoperfusion and can lead to multi-organ failure and death depending on its severity. Inadequate cardiac contractility or cardiac power secondary to acute myocardial infarction remains the most frequent cause of cardiogenic shock, although its contribution has declined over the past two decades, compared with other causes. Despite some advances in cardiogenic shock management, this clinical syndrome is still burdened by an extremely high mortality. Its management is based on immediate stabilization of haemodynamic parameters so that further treatment, including mechanical circulatory support and transfer to specialized tertiary care centres, can be accomplished. With these aims, medical therapy, consisting mainly of inotropic drugs and vasopressors, still has a major role. The purpose of this article is to review current evidence on the use of these medications in patients with cardiogenic shock and discuss specific clinical settings with indications to their use.

Early beta-blocker therapy improves in-hospital mortality of patients with non-ST-segment elevation myocardial infarction - a meta-analysis.

BACKGROUND: Although current guidelines endorse early beta-blocker therapy in stable patients with STEMI, there is no clear recommendation on the early use of these drugs in patients with NSTEMI. METHODS: Literature search was conducted by 3 independent researchers using PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS. Studies were eligible if (P) patients included were ≥ 18 years of age and had non-ST-segment elevation myocardial infarction (NSTEMI), (I) early (<24 h) treatment with intravenous or oral beta-blockers was compared to (C) no treatment with beta-blockers and data on (O) in-hospital mortality and/or in-hospital cardiogenic shock were depicted. Odds ratios and 95% confidence intervals were calculated using random effects models with the Mantel-Haenszel method. The Hartung-Knapp-Sidik-Jonkman method was used as estimator for τ2. RESULTS: 977 records were screened for eligibility, which led to the inclusion of 4 retrospective, nonrandomized, observational cohort studies comprising a total of N = 184,951 patients. After pooling of the effect sizes, early therapy with beta-blockers resulted in a reduction of in-hospital mortality (OR 0.43 [0.36-0.51], p = 0.0022) despite no significant effect on the prevalence of cardiogenic shock (OR 0.36 [0.07-1.91], p = 0.1196). CONCLUSION: Early treatment with beta-blockers was associated with an attenuation of in-hospital mortality despite no increase in cardiogenic shock. Thus, early therapy with these drugs could elicit beneficial effects on top of reperfusion therapy, similar to the effects seen in STEMI-patients. The low number of studies (k = 4) has to be considered when interpreting the findings of this analysis.

State of Shock: Contemporary Vasopressor and Inotrope Use in Cardiogenic Shock.

Cardiogenic shock is characterized by tissue hypoxia caused by circulatory failure arising from inadequate cardiac output. In addition to treating the pathologic process causing impaired cardiac function, prompt hemodynamic support is essential to reduce the risk of developing multiorgan dysfunction and to preserve cellular metabolism. Pharmacologic therapy with the use of vasopressors and inotropes is a key component of this treatment strategy, improving perfusion by increasing cardiac output, altering systemic vascular resistance, or both, while allowing time and hemodynamic stability to treat the underlying disease process implicated in the development of cardiogenic shock. Despite the use of mechanical circulatory support recently garnering significant interest, pharmacologic hemodynamic support remains a cornerstone of cardiogenic shock management, with over 90% of patients receiving at least 1 vasoactive agent. This review aims to describe the pharmacology and hemodynamic effects of current pharmacotherapies and provide a practical approach to their use, while highlighting important future research directions.

The current and future status of inotropes in heart failure management.

INTRODUCTION: Heart failure (HF) is a complex syndrome with a wide range of presentations and acuity, ranging from outpatient care to inpatient management due to acute decompensated HF, cardiogenic shock or advanced HF. Frequently, the etiology of a patient's decompensation is diminished cardiac output and peripheral hypoperfusion. Consequently, there is a need for use of inotropes, agents that increase cardiac contractility, optimize hemodynamics and ensure adequate perfusion. AREAS COVERED: Inotropes are divided into 3 major classes: beta agonists, phosphodiesterase III inhibitors and calcium sensitizers. Additionally, as data from prospective studies accumulates, novel agents are emerging, including omecamtiv mecarbil and istaroxime. The aim of this review is to summarize current data on the optimal use of inotropes and to provide an expert opinion regarding their current and future use in the management of HF. EXPERT OPINION: The use of inotropes has long been linked to worsening mortality, tachyarrhythmias, increased myocardial oxygen consumption and ischemia. Therefore, individualized and evidence-based treatment plans for patients who require inotropic support are necessary. Also, better quality data on the use of existing inotropes is imperative, while the development of newer and safer agents will lead to more effective management of patients with HF in the future.

Improved mortality and haemodynamics with milrinone in cardiogenic shock due to acute decompensated heart failure.

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.

Cardiogenic shock: a major challenge for the clinical trialist.

PURPOSE OF REVIEW: Cardiogenic shock (CS) results in persistently high short-term mortality and a lack of evidence-based therapies. Several trials of novel interventions have failed to show an improvement in clinical outcomes despite promising preclinical and physiologic principles. In this review, we highlight the challenges of CS trials and provide suggestions for the optimization and harmonization of their design. RECENT FINDINGS: CS clinical trials have been plagued by slow or incomplete enrolment, heterogeneous or nonrepresentative patient cohorts, and neutral results. To achieve meaningful, practice-changing results in CS clinical trials, an accurate CS definition, a pragmatic staging of its severity for appropriate patient selection, an improvement in informed consent process, and the use of patient-centered outcomes are required. Future optimizations include the use of predictive enrichment using host response biomarkers to unravel the biological heterogeneity of the CS syndrome and identify subphenotypes most likely to benefit from individualized treatment to allow a personalized medicine approach. SUMMARY: Accurate characterization of CS severity and its pathophysiology are crucial to unravel heterogeneity and identify the patients most likely to benefit from a tested treatment. Implementation of biomarker-stratified adaptive clinical trial designs (i.e., biomarker or subphenotype-based therapy) might provide important insights into treatment effects.

Association between short-term systemic use of glucocorticoids and prognosis of cardiogenic shock: a retrospective analysis.

OBJECTIVE: To investigate the prescription rate of short-term systemic use of glucocorticoids during hospitalization in patients with cardiogenic shock (CS), and outcomes related with glucocorticoid use. METHODS: We extracted patients' information from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0) database. The primary endpoint was 90-day all-cause mortality. Secondary safety endpoints were infection identified by bacterial culture and at least one episode of hyperglycemia after ICU admission. Propensity score matching (PSM) was used to balance baseline characteristics. The difference in cumulative mortality rate between these treated with and without glucocorticoids was assessed by Kaplan-Meier curve with log-rank test. Independent risk factors for endpoints were identified by Cox or Logistic regression analysis. RESULTS: A total of 1528 patients were enrolled, and one-sixth of these patients received short-term systemic therapy of glucocorticoids during hospitalization. These conditions, including rapid heart rate, the presence of rheumatic disease, chronic pulmonary disease and septic shock, high lactate level, the requirements of mechanical ventilation and continuous renal replacement therapy, were associated with an increase in glucocorticoid administration (all P ≤ 0.024). During a follow-up of 90 days, the cumulative mortality rate in patients treated with glucocorticoids was significantly higher than that in these untreated with glucocorticoids (log-rank test, P < 0.001). Multivariable Cox regression analysis showed that glucocorticoid use (hazard ratio 1.48, 95% confidence interval [CI] 1.22-1.81; P < 0.001) was independently associated with an increased risk for 90-day all-cause mortality. This result was consistent irrespective of age, gender, the presence of myocardial infarction, acute decompensated heart failure and septic shock, and inotrope therapy, but was more evident in low-risk patients as assessed by ICU scoring systems. Additionally, multivariable Logistic regression analysis showed that glucocorticoid exposure was an independent predictor of hyperglycemia (odds ratio 2.14, 95% CI 1.48-3.10; P < 0.001), but not infection (odds ratio 1.23, 95% CI 0.88-1.73; P = 0.221). After PSM, glucocorticoid therapy was also significantly related with increased risks of 90-day mortality and hyperglycemia. CONCLUSIONS: Real-world data showed that short-term systemic use of glucocorticoids was common in CS patients. Importantly, these prescriptions were associated with increased risks of adverse events.

Inotrope versus placebo therapy in cardiogenic shock: Rationale and study design of the CAPITAL DOREMI2 trial.

BACKGROUND: Cardiogenic shock (CS) is a state of end-organ hypoperfusion related to cardiac dysfunction. Current guidelines recommend consideration of inotrope therapy in patients with CS, however no robust data support their use. The purpose of the CAPITAL DOREMI2 trial is to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of patients with CS. METHODS AND DESIGN: This is a multi-center, double-blind, randomized, placebo-controlled trial comparing single-agent inotrope therapy to placebo in patients with CS. A total of 346 participants with Society for Cardiovascular Angiography and Interventions class C or D CS will be randomized in a 1:1 fashion to inotrope or placebo therapy, which will be administered over a 12-hour period. After this period, participants will continue open-label therapies at the discretion of the treating team. The primary outcome is a composite of all-cause in-hospital death, and, as measured during the 12-hour intervention period, any of: sustained hypotension or high dose vasopressor requirements, lactate greater than 3.5 mmol/L at 6 hours or thereafter, need for mechanical circulatory support, arrhythmia leading to emergent electrical cardioversion, and resuscitated cardiac arrest. All participants will be followed for the duration of their hospitalization, and secondary outcomes will be assessed at the time of discharge. IMPLICATION: This trial will be the first to establish the safety and efficacy of inotrope therapy against placebo in a population of patients with CS and has the potential to alter the standard care provided to this group of patients.

[Intensive Care in Heart Surgery - is All Now Different?] / Intensivtherapie in der Herzchirurgie ­ alles anders?

With approximately 100000 operations performed in Germany per year, cardiac surgery is among the surgical specialties that require intensive care tratment most frequently. Although all therapeutic aspects of ICU treatment are of high importance among cardiac surgery patients, there is a focus on hemodynamics with the overarching goal of sufficient oxygen delivery. Patients undergoing cardiac surgery are particularily prone to hemodynamic instability and low cardiac output syndrome, potentially culminating into cardiogenic shock. This article presents an overview of essential elements of intensive care medicine in cardiac surgery, paying special attention to hemodynamic monitoring, low cardiac output syndrome, inotropy, cardiac arrhyhmia, perioperative myocardial infarction, and patient blood management.

A Retrospective Review of Cardiogenic Shock Development in Patients With ST-Elevation Myocardial Infarction and Percutaneous Coronary Intervention Receiving Early Beta-Blockers.

ABSTRACT: Beta-blockers (BBs) have proven to improve morbidity and mortality in patients after an ST elevation myocardial infarction (STEMI). Guidelines suggest initiating a BB within 24 hours, except in those with risk factors for developing cardiogenic shock, although published literature is conflicting regarding the true association of these risk factors with shock. This retrospective cohort study aimed to assess whether the presence of defined risk factors was associated with cardiogenic shock after early BB administration in patients with a STEMI and percutaneous coronary intervention. The primary outcome determined the rate of cardiogenic shock development and secondarily determined any characteristics associated with cardiogenic shock in patients who received beta blockers. The population included 299 patients and cardiogenic shock occurred in 8 patients (2.7%). There were no median (interquartile range) differences in age [63 years (60-71) versus 62 years (52-71); P = 0.4965], systolic blood pressure [110 mm Hg (105-115) versus 109 mm Hg (103-114); P = 0.6027], or heart rate [90 (78-104) versus 76 (64-90); P = 0.0697] before BB administration in patients who developed shock versus those who did not, respectively. Hours to BB administration from arrival [15.6 (6.0-54.8) versus 21.9 (10.6-42; P = 0.6968] and the number (%) with anterior infarction [3 (37.5%) versus 107 (36.8%); P = 1.000] were similar between groups. There was a statistically significant higher median (interquartile range) peak troponin [140 ng/mL (54-304) versus 49 ng/mL (16-132); P = 0.0354] in patients who developed shock. Early initiation of a BB in patients with STEMI and percutaneous coronary intervention with risk factors for cardiogenic shock does not seem to be associated with shock in most patients.

Management, clinical outcomes, and its predictors among heart failure patients admitted to tertiary care hospitals in Ethiopia: prospective observational study.

BACKGROUND: Heart failure is a global pandemic, as it affects approximately 64.34 million people worldwide with a $346.17 billion global economic burden. The prevalence of heart failure has increased from 43.4 to 46.5% in the last 10 years in lower and middle-income countries. Most of the studies conducted in Ethiopia were retrospective cross-sectional, with limited study participants, and conducted in a single setting that commonly addresses the prevalence and pattern of heart failure rather than clinical outcome, associated factors, and specific management in different areas. Hence, this study aimed to assess management, clinical outcomes and their predictors among heart failure patients admitted to tertiary care hospitals in Ethiopia. METHODS: A prospective observational study design was conducted on heart failure patients admitted at two tertiary care hospitals in Ethiopia from September 2020 to May 2021. Using semi-structured questionnaires relevant data were collected from patients' medical records and face-to-face interviewing. Data were analyzed using SPSS version 23.0. A multivariate Cox regression model was performed to identify independent predictors of 90-day all-cause mortality. Variables with P values < 0.05 were considered statistically significant. RESULTS: Out of 283 patients enrolled in this study, 52.3% were male and the mean (± SD) age was 52.4 ± 17.9 years. The most common medications prescribed during hospitalization and discharge were diuretics (98.9% vs 95.6%), angiotensin I converting enzyme inhibitors/angiotensin II receptor blockers (48.8% vs 67.3%), and beta-blockers (46.6% vs 64.7%), respectively. In the present study, the 90-day all-cause mortality was 10.2%. Hypertension (HR = 3.7, 95% CI 1.2-11.6), cardiogenic shock (HR = 8.7, 95% CI 3.2-20.8), alcohol drinking (HR = 2.8, 95% CI 1.1-7.8), absence of angiotensin I converting enzyme inhibitors/angiotensin II receptor blockers (HR = 0.02, 95% CI 0.0-0.2), and reduced ejection fraction (HR = 1.5, 95% CI 1.1-3.8) were predictors of 90-day all-cause mortality. CONCLUSION: High 90-day all-cause mortality was observed among heart failure patients in the present study. In the current study, the majority of heart failure patients were treated with diuretics. Alcohol drinking, hypertension, cardiogenic shock, reduced ejection fraction, and absence of angiotensin I converting enzyme inhibitors/angiotensin II receptor blockers drugs were predictors of poor treatment outcomes for whom restriction of alcohol consumption, early management of hypertension, reduced ejection fraction, cardiogenic shock, and providing angiotensin I converting enzyme inhibitors/angiotensin II receptor blockers drugs for all heart failure patients would be recommended to improve these poor treatment outcomes.

Beneficial effects of levosimendan to wean patients from VA-ECMO: a systematic review and meta-analysis.

INTRODUCTION: Patients with refractory cardiogenic shock can benefit from veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The use of levosimendan in VA-ECMO patients may facilitate weaning and enhance survival. EVIDENCE ACQUISITION: MEDLINE, Scopus, Web of Science, and Cochrane were searched from inception to October 10th, 2021. Eligible clinical trials and observational studies reporting the use of levosimendan in VA-ECMO were searched. Two reviewers extracted data and independently assessed the risk of bias. To integrate the data, a random-effect model was applied. The success of weaning from VA-ECMO was the primary outcome. EVIDENCE SYNTHESIS: Ten observational studies, including a total of 987 patients, were identified. Levosimendan was associated with successful weaning (362/448) compared with controls (328/539) (OR 2.37, 95% CI 1.71-3.28; P=0.01) and reduced mortality (144/433 vs. 258/507) (nine studies, OR 0.53, 95% CI 0.36-0.78; P=0.01) compared with control. CONCLUSIONS: Levosimendan was associated with successful weaning and increased survival in VA-ECMO patients. Randomized trials should confirm these findings.

Short-term effects of levosimendan use for venoarterial extracorporeal membrane oxygenation: A systematic review and meta-analysis.

OBJECTIVE: Levosimendan has been demonstrated to reduce the incidence of cardiogenic shock and facilitate weaning from cardiopulmonary bypass. However, the beneficial effects of levosimendan treatment on hospital outcomes in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) are uncertain. We performed a systematic review and meta-analysis to evaluate the short-term effects of levosimendan use for patients undergoing VA-ECMO. METHODS: We searched PubMed, Embase, and the Cochrane Library for English articles published from inception to July 15, 2021. Observational studies comparing levosimendan versus non- levosimendan for VA-ECMO were considered eligible for the current study. RESULTS: Nine observational studies with 1058 patients were included. In-hospital mortality was 46.3% in the levosimendan group as compared with 50.7% in the control group. Levosimendan significantly reduced in-hospital mortality in patients undergoing VA-ECMO compared with the control group (RR, 0.80; 95% CI, 0.67-0.95; p = 0.013). The incidence of weaning from VA-ECMO was 79.3% in the levosimendan group as compared with 63.4% in the control group. Levosimendan significantly increase the incidence of weaning from VA-ECMO in patients as compared with the control group (RR, 1.20; 95% CI, 1.07-1.34; p = 0.002). In the one-way sensitivity analysis for estimating the effect of each study on mortality or weaning from VA-ECMO, omission of each study did not make a significant difference. CONCLUSIONS: Our study indicates that levosimendan use significantly reduced in-hospital mortality and increase the incidence of weaning in patients undergoing VA-ECMO.