Early Serial Assessment of Aggregate Vasoactive Support and Mortality in Cardiogenic Shock: Insights From the Critical Care Cardiology Trials Network Registry.

BACKGROUND: Associations of early changes in vasoactive support with cardiogenic shock (CS) mortality remain incompletely defined. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units. Patients admitted with CS (2018-2023) had vasoactive dosing assessed at 4 and 24 hours from cardiac intensive care unit admission and quantified by the vasoactive-inotropic score (VIS). Prognostic associations of VIS at both time points, as well as change in VIS from 4 to 24 hours, were examined. Interaction testing was performed based on mechanical circulatory support status. RESULTS: Among 3665 patients, 82% had a change in VIS <10, with 7% and 11% having a ≥10-point increase and decrease from 4 to 24 hours, respectively. The 4 and 24-hour VIS were each associated with cardiac intensive care unit mortality (13%-45% and 11%-73% for VIS <10 to ≥40, respectively; Ptrend <0.0001 for each). Stratifying by the 4-hour VIS, changes in VIS from 4 to 24 hours had a graded association with mortality, ranging from a 2- to >4-fold difference in mortality comparing those with a ≥10-point increase to ≥10-point decrease in VIS (Ptrend <0.0001). The change in VIS alone provided good discrimination of cardiac intensive care unit mortality (C-statistic, 0.72 [95% CI, 0.70-0.75]) and improved discrimination of the 24-hour Sequential Organ Failure Assessment score (0.72 [95% CI, 0.69-0.74] to 0.76 [95% CI, 0.74-0.78]) and the clinician-assessed Society for Cardiovascular Angiography and Interventions shock stage (0.72 [95% CI, 0.70-0.74] to 0.77 [95% CI, 0.75-0.79]). Although present in both groups, the mortality risk associated with VIS was attenuated in patients managed with versus without mechanical circulatory support (odds ratio per 10-point higher 24-hour VIS, 1.36 [95% CI, 1.23-1.49] versus 1.84 [95% CI, 1.69-2.01]; Pinteraction <0.0001). CONCLUSIONS: Early changes in the magnitude of vasoactive support in CS are associated with a gradient of risk for mortality. These data suggest that early VIS trajectory may improve CS prognostication, with the potential to be leveraged for clinical decision-making and research applications in CS.

Interhospital Variation in Admissions Managed With Critical Care Therapies or Invasive Hemodynamic Monitoring in Tertiary Cardiac Intensive Care Units: An Analysis From the Critical Care Cardiology Trials Network Registry.

BACKGROUND: Wide interhospital variations exist in cardiovascular intensive care unit (CICU) admission practices and the use of critical care restricted therapies (CCRx), but little is known about the differences in patient acuity, CCRx utilization, and the associated outcomes within tertiary centers. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of tertiary and academic CICUs in the United States and Canada that captured consecutive admissions in 2-month periods between 2017 and 2022. This analysis included 17 843 admissions across 34 sites and compared interhospital tertiles of CCRx (eg, mechanical ventilation, mechanical circulatory support, continuous renal replacement therapy) utilization and its adjusted association with in-hospital survival using logistic regression. The Pratt index was used to quantify patient-related and institutional factors associated with CCRx variability. RESULTS: The median age of the study population was 66 (56-77) years and 37% were female. CCRx was provided to 62.2% (interhospital range of 21.3%-87.1%) of CICU patients. Admissions to CICUs with the highest tertile of CCRx utilization had a greater burden of comorbidities, had more diagnoses of ST-elevation myocardial infarction, cardiac arrest, or cardiogenic shock, and had higher Sequential Organ Failure Assessment scores. The unadjusted in-hospital mortality (median, 12.7%) was 9.6%, 11.1%, and 18.7% in low, intermediate, and high CCRx tertiles, respectively. No clinically meaningful differences in adjusted mortality were observed across tertiles when admissions were stratified by the provision of CCRx. Baseline patient-level variables and institutional differences accounted for 80% and 5.3% of the observed CCRx variability, respectively. CONCLUSIONS: In a large registry of tertiary and academic CICUs, there was a >4-fold interhospital variation in the provision of CCRx that was primarily driven by differences in patient acuity compared with institutional differences. No differences were observed in adjusted mortality between low, intermediate, and high CCRx utilization sites.

Medical and Mechanical Circulatory Support of the Failing Right Ventricle.

PURPOSE OF REVIEW: To describe medical therapies and mechanical circulatory support devices used in the treatment of acute right ventricular failure. RECENT FINDINGS: Experts have proposed several algorithms providing a stepwise approach to medical optimization of acute right ventricular failure including tailored volume administration, ideal vasopressor selection to support coronary perfusion, inotropes to restore contractility, and pulmonary vasodilators to improve afterload. Studies have investigated various percutaneous and surgically implanted right ventricular assist devices in several clinical settings. The initial management of acute right ventricular failure is often guided by invasive hemodynamic data tracking parameters of circulatory function with the use of pharmacologic therapies. Percutaneous microaxial and centrifugal extracorporeal pumps bypass the failing RV and support circulatory function in severe cases of right ventricular failure.

Prognostic significance of haemodynamic parameters in patients with cardiogenic shock.

AIMS: Invasive haemodynamic assessment with a pulmonary artery catheter is often used to guide the management of patients with cardiogenic shock (CS) and may provide important prognostic information. We aimed to assess prognostic associations and relationships to end-organ dysfunction of presenting haemodynamic parameters in CS. METHODS AND RESULTS: The Critical Care Cardiology Trials Network is an investigator-initiated multicenter registry of cardiac intensive care units (CICUs) in North America coordinated by the TIMI Study Group. Patients with CS (2018-2022) who underwent invasive haemodynamic assessment within 24 h of CICU admission were included. Associations of haemodynamic parameters with in-hospital mortality were assessed using logistic regression, and associations with presenting serum lactate were assessed using least squares means regression. Sensitivity analyses were performed excluding patients on temporary mechanical circulatory support and adjusted for vasoactive-inotropic score. Among the 3603 admissions with CS, 1473 had haemodynamic data collected within 24 h of CICU admission. The median cardiac index was 1.9 (25th-75th percentile, 1.6-2.4) L/min/m2 and mean arterial pressure (MAP) was 74 (66-86) mmHg. Parameters associated with mortality included low MAP, low systolic blood pressure, low systemic vascular resistance, elevated right atrial pressure (RAP), elevated RAP/pulmonary capillary wedge pressure ratio, and low pulmonary artery pulsatility index. These associations were generally consistent when controlling for the intensity of background pharmacologic and mechanical haemodynamic support. These parameters were also associated with higher presenting serum lactate. CONCLUSION: In a contemporary CS population, presenting haemodynamic parameters reflecting decreased systemic arterial tone and right ventricular dysfunction are associated with adverse outcomes and systemic hypoperfusion.

Hemodynamic effects of COVID-19 vaccination in hospitalized patients awaiting heart transplantation.

Background: The hemodynamic effects of pre-transplant vaccination against COVID-19 among heart transplant candidates hospitalized for advanced heart failure remains unknown. Methods: A retrospective chart review was conducted at a high-volume transplant center from January through December 2021. 22 COVID-19 vaccination events occurred among patients hospitalized for decompensated heart failure while awaiting transplantation. Primary outcomes included inotrope and vasopressor dosages. Secondary outcomes included vital signs, pulmonary artery catheter measurements, diuretic dosages, and renal function. Data were extracted 24 h before through 72 h after vaccination. Results: One of 22 vaccination events was associated with hemodynamic changes requiring increased inotropic and vasopressor support post-vaccination. In all other cases, transient hemodynamic changes occurred without need for escalated therapy. Conclusions: COVID-19 vaccination can be administered safely to most critically ill patients with advanced heart failure including those awaiting transplantation. All patients should be monitored closely as some may be susceptible to significant hemodynamic changes.

Challenges in the development and implementation of a healthcare system based extracorporeal cardiopulmonary resuscitation (ECPR) program for the treatment of out of hospital cardiac arrest.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) can treat cardiac arrest refractory to conventional therapies. Many institutions are interested in developing their own ECPR program. However, there may be challenges in logistics and implementation. AIMS: The aim of our protocol was to demonstrate that an ECPR team was feasible within our healthcare system and that the identification of UPMC Presbyterian as a receiving center allowed for successful treatment within 30 min from EMS dispatch. METHODS: We developed out of hospital cardiac arrest (OHCA) ECPR protocols for Emergency Medical Services (EMS), EMS communications, and our in-hospital ECPR team. Inclusion criteria indentified patients with a potentially reversible arrest etiology and high probability of recoverable brain injury using a simple checklist: witnessed collapse, layperson CPR, initial shockable rhythm, and age 18-60 years. We trained local EMS crews to screen patients and reviewed the criteria with a Medic Command Physician prior to transport to our hospital. RESULTS: From October 2015 to March 31st 2018, EMS treated 1165 EMS OHCA cases, transported 664 (57%) to a local hospital, and transported 120 (10%) to our institution. Of these, five (4.1%) patients underwent ECPR. Among excluded cases, 64 (53%) had nonshockable rhythms, 48 (40%) were unwitnessed arrests, 50 (42%) were over age 60 and the remaining 20 (17%) had no documented reasons for exclusion. For ECPR cases, median pre-hospital CPR duration was 26 [IQR 25-40] min. Four patients (80%) received mechanical CPR. Interval from arrest to arrival on scene was 5 [IQR 4-6] min and interval from radio call to activation of ECPR was 13 [IQR 7-21] min. Interval from EMS dispatch to departure from scene was 20 [IQR 19-21] min. Time from EMS dispatch to initiation of ECPR was 63 [IQR 59-69] min. CONCLUSIONS: ECPR is an infrequent occurrence in EMS practice. Most apparently eligible patients did not get ECPR, highlighting the need for ongoing programmatic development, provider education, and qualitative work exploring barriers to implementation.

Intra-Arrest Administration of Cyclosporine and Methylprednisolone Does Not Reduce Postarrest Myocardial Dysfunction.

OBJECTIVE: To determine whether the administration of intra-arrest cyclosporine (CCY) and methylprednisolone (MP) preserves left ventricular ejection fraction (LVEF) and cardiac output (CO) after return of spontaneous circulation (ROSC). METHODS: Eleven, 25-30kg female swine were randomized to receive 10mg/kg CCY + 40mg MP or placebo, anesthetized and given a transthoracic shock to induce ventricular fibrillation. After 8 minutes, standard CPR was started. After two additional minutes, the experimental agent was administered. Animals with ROSC were supported for up to 12h with norepinephrine as needed. Echocardiography was performed at baseline, and 1, 2, 6 and 12h post-ROSC. Analysis was performed using generalized estimating equations (GEE) after downsampling continuously sampled data to 5 minute epochs. RESULTS: Eight animals (64%) achieved ROSC after a median of 7 [IQR 5-13] min of CPR, 2 [ IQR 1-3] doses of epinephrine and 2 [IQR 1-5] defibrillation shocks. Animals receiving CCY+MP had higher post ROSC MAP (GEE coefficient -10.2, P = <0.01), but reduced cardiac output (GEE coefficient 0.8, P = <0.01) compared to placebo. There was no difference in LVEF or vasopressor use between arms. CONCLUSIONS: Intra-arrest cyclosporine and methylprednisolone decreased post-arrest cardiac output and increased mean arterial pressure without affecting left ventricular ejection fraction.

The Use of ECMO for the Treatment of Refractory Cardiac Arrest or Postarrest Cardiogenic Shock Following In-Hospital Cardiac Arrest: A 10-Year Experience.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the treatment of refractory cardiac arrest (extracorporeal cardiopulmonary resuscitation [ECPR]) and postarrest cardiogenic shock (PACS). Our primary objective was to determine the 1-year survival of patients who were treated with ECMO for PACS or in ECPR. METHODS: We conducted a retrospective analysis of hospitalized patients in a tertiary care facility who underwent treatment with ECMO for ECPR or PACS. Between January 2004 and December 2013, patients were prospectively entered into an institutional registry. One-year follow-up was assessed by electronic medical record or social security death index if clinical follow-up was unavailable. RESULTS: Fifty-one patients were treated with ECMO during the study period. The mean age was 54.0 ± 10.9 years; the majority of patients were men (80.4%). The most common etiology of arrest was acute myocardial infarction (51.0%). Overall, 13 (25.4%) patients survived for at least 1 year. Preexisting coronary artery disease, hypertension, and hyperlipidemia were associated with reduced likelihood of survival. We observed a significant improvement in 1-year mortality in patients treated for PACS when compared to ECPR, 46.7% versus 16.7%, respectively. CONCLUSION: The use of ECMO for treatment of refractory cardiac arrest or cardiogenic shock may be a suitable treatment in a very select cohort of patients. Our results support a significantly higher 1-year survival in patients with PACS compared to refractory cardiac arrest.

Echo-Doppler determinants of outcomes in patients with unoperated significant mitral regurgitation in current era.

OBJECTIVE: One-half of patients with severe symptomatic mitral regurgitation (MR) do not undergo surgery due to comorbidities. We evaluated prognosticators of outcomes in patients with unoperated significant MR. METHODS: In this observational study, we retrospectively evaluated medical records of 75 consecutive patients with unoperated significant MR. RESULTS: All-cause mortality was 39% at 5 years. Non-survivors (n=29) versus survivors (n=46) were: older (77±9.8 vs 68±14, p=0.006), had higher New York Heart Association (NYHA) class (2.7±0.8 vs 2.3±0.8, p=0.037), higher brain natriuretic peptide (1157±717 vs 427±502 pg/mL, p=0.024, n=18), more coronary artery disease (61% vs 35%, p=0.031), more frequent left ventricular ejection fraction <50% (20.7% vs 4.3%, p=0.026), more functional MR (41% vs 22%, p=0.069), higher mitral E/E(') (12.7±4.6 vs 9.8±4, p=0.008), higher pulmonary artery systolic pressure (PASP; 52.6±18.7 vs 36.7±14, p <0.001), more ≥3+ tricuspid regurgitation (28% vs 4%, p=0.005) and more right ventricular dysfunction (26% vs 6%, p=0.035). Significant predictors of 5-year mortality were PASP (p=0.001) and E/E(') (p=0.011) using multivariate regression analysis. CONCLUSIONS: Patients with unoperated significant MR have high mortality. Elevated PASP and mitral E/E(') were the most significant predictors of 5-year survival in patients with unoperated significant MR. Current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines provide a limited incorporation of echo-Doppler parameters in the preoperative risk stratification of patients with severe MR.

Echocardiographic left ventricular systolic dysfunction early after resuscitation from cardiac arrest does not predict mortality or vasopressor requirements.

BACKGROUND/AIMS: Echocardiographic abnormalities are common after resuscitation from cardiac arrest. The association between echocardiographic findings with vasopressor requirements and mortality are not well described. We sought to determine the associations between echocardiographic abnormalities and mortality, vasopressor requirements and organ failure after cardiac arrest. METHODS: We prospectively evaluated 55 adult subjects undergoing transthoracic echocardiography within 24h after resuscitation from cardiac arrest. We evaluated the association between 2D echocardiographic and Doppler measurements and mortality, Sequential Organ Failure Assessment (SOFA) scores and vasopressor requirements. RESULTS: Inpatient mortality was 60%. Mean left ventricular ejection fraction (LVEF) was 43.6%; LVEF was <40% in 36% of subjects. None of the measured echocardiographic parameters (including LVEF) was significantly associated with inpatient mortality (all p>0.1). Subjects with LVEF <40% more often had shockable arrest rhythms and patients resuscitated from shockable rhythms had lower mean LVEF (36.2% vs. 52.3%, p=0.001). There was no correlation between markers of right and left ventricular systolic or diastolic function (including LVEF and Doppler parameters) with vasopressor requirements, lactate levels or SOFA scores. CONCLUSION: Echocardiographic parameters (including LVEF) were not associated with inpatient mortality after cardiac arrest. Vasopressor requirements and organ failure severity were not associated with multiple echocardiographic markers of systolic function.

Myocardial Dysfunction and Shock after Cardiac Arrest.

Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies.