Teuteberg, Jeffrey J.

ImportanceThe advanced ambulatory heart failure (HF) population comprises patients who have progressed beyond the pillars of recommended stage C HF therapies but can still find meaningful life-years ahead. Although these patients are commonly encountered in practice, national databases selectively capture the small groups accepted for heart transplant listing or left ventricular assist devices. The epidemiology, trajectories, and therapies for other ambulatory patients with advanced HF are poorly understood.ObservationsIn December 2022, the National Heart, Lung and Blood Institute convened a team of experts to identify knowledge gaps and research priorities for the ambulatory population with limiting daily symptoms and transition toward refractory end-stage D HF, designated as stage C2D. This article summarizes the findings from that 3-day workshop. Workshop participants surveyed the initial challenges and knowledge gaps for (1) recognition of ambulatory C2D HF, (2) estimation of the magnitude of the affected population and identifiable subpopulations, and (3) physiologic phenotypes, such as low cardiac output, right HF, cardiorenal syndromes, congestive hepatopathy and frailty, which offer distinct targets for existing and emerging therapies. Social drivers of HF and patient preferences for quality/length of survival were highlighted as essential modifiers for personalization of therapies.Conclusions and RelevanceTen key points summarized workshop findings, with target cohorts for study proposed as a crucial next step. This workshop summary is intended as a call for action to address knowledge gaps and develop new strategies to improve outcomes in the large ambulatory population with C2D HF.

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; P trend <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 ( P trend <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]; P interaction <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.

Abstract 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.

Background: Algorithmic application of the 2019 Society of Cardiovascular Angiography and Intervention (SCAI) shock stages effectively stratifies mortality risk for patients with cardiogenic shock. However, clinician assessment of SCAI staging may differ. Moreover, the implications of the 2022 SCAI criteria update remain incompletely defined. Methods: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units (CICUs). Between 2019 and 2021, participating centers (n=32) contributed at least a 2-month snapshot of consecutive medical CICU admissions. In-hospital mortality was assessed across 3 separate staging methods: clinician assessment, Critical Care Cardiology Trials Network algorithmic application of the 2019 SCAI criteria, and a revision of the Critical Care Cardiology Trials Network application using the 2022 SCAI criteria. Results: Of 9612 admissions, 1340 (13.9%) presented with cardiogenic shock with in-hospital mortality of 35.2%. Both clinician and algorithm-based staging using the 2019 SCAI criteria identified a stepwise gradient of mortality risk (stage C–E: 19.0% to 83.7% and 14.6% to 52.2%, respectively; P trend <0.001 for each). Clinician assignment of SCAI stages identified higher risk patients compared with algorithm-based assignment (stage D: 49.9% versus 29.3%; stage E: 83.7% versus 52.2%). Algorithmic application of the 2022 SCAI criteria, with incorporation of the vasoactive-inotropic score, more closely approximated clinician staging (mortality for stage C-E: 21.9% to 70.5%; P trend <0.001). Conclusions: Both clinician and algorithm-based application of the 2019 SCAI stages identify a stepwise gradient of mortality risk, although clinician-staging may better allocate higher risk patients into advanced SCAI stages. Updated algorithmic staging using the 2022 SCAI criteria and vasoactive-inotropic score further refines risk stratification.

AbstractAimsThe aims of the Critical Care Cardiology Trials Network (CCCTN) are to develop a registry to investigate the epidemiology of cardiac critical illness and to establish a multicentre research network to conduct randomised clinical trials (RCTs) in patients with cardiac critical illness.Methods and resultsThe CCCTN was founded in 2017 with 16 centres and has grown to a research network of over 40 academic and clinical centres in the United States and Canada. Each centre enters data for consecutive cardiac intensive care unit (CICU) admissions for at least 2 months of each calendar year. More than 20 000 unique CICU admissions are now included in the CCCTN Registry. To date, scientific observations from the CCCTN Registry include description of variations in care, the epidemiology and outcomes of all CICU patients, as well as subsets of patients with specific disease states, such as shock, heart failure, renal dysfunction, and respiratory failure. The CCCTN has also characterised utilization patterns, including use of mechanical circulatory support in response to changes in the heart transplantation allocation system, and the use and impact of multidisciplinary shock teams. Over years of multicentre collaboration, the CCCTN has established a robust research network to facilitate multicentre registry-based randomised trials in patients with cardiac critical illness.ConclusionThe CCCTN is a large, prospective registry dedicated to describing processes-of-care and expanding clinical knowledge in cardiac critical illness. The CCCTN will serve as an investigational platform from which to conduct randomised controlled trials in this important patient population.

OBJECTIVES: Cardiogenic shock presents with variable severity. Categorizing cardiogenic shock into clinical stages may improve risk stratification and patient selection for therapies. We sought to determine whether a structured implementation of the 2019 Society for Cardiovascular Angiography and Interventions clinical cardiogenic shock staging criteria that is ascertainable in clinical registries discriminates mortality in a contemporary population with or at-risk for cardiogenic shock. DESIGN: We developed a pragmatic application of the Society for Cardiovascular Angiography and Interventions cardiogenic shock staging criteria—A (at-risk), B (beginning), C (classic cardiogenic shock), D (deteriorating), or E (extremis)—and examined outcomes by stage. SETTING: The Critical Care Cardiology Trials Network is an investigator-initiated multicenter research collaboration coordinated by the TIMI Study Group (Boston, MA). Consecutive admissions with or at-risk for cardiogenic shock during two annual 2-month collection periods (2017–2019) were analyzed. PATIENTS: Patients with or at-risk for cardiogenic shock. MEASUREMENTS AND MAIN RESULTS: Of 8,240 CICU admissions reviewed, 1,991 (24%) had or were at-risk for cardiogenic shock. Distributions across the five stages were as follows: A: 33%; B: 7%; C: 16%; D: 23%; and E: 21%. Overall in-hospital mortality among patients with established cardiogenic shock was 39%; however, mortality varied from only 15.8% to 32.1% to 62.5% across stages C, D, and E (Cochran-Armitage p trend < 0.0001). The Society for Cardiovascular Angiography and Interventions stages improved mortality prediction beyond the Sequential Organ Failure Assessment and Intra-Aortic Balloon Pumpin Cardiogenic Shock II scores. CONCLUSIONS: Although overall mortality in cardiogenic shock remains high, it varies considerably based on clinical stage, identifying stage C as relatively lower risk. We demonstrate a pragmatic adaptation of the Society for Cardiovascular Angiography and Interventions cardiogenic shock stages that effectively stratifies mortality risk and could be leveraged for future clinical research.

Background: Temporary mechanical circulatory support (MCS) devices provide hemodynamic assistance for shock refractory to pharmacological treatment. Most registries have focused on single devices or specific etiologies of shock, limiting data regarding overall practice patterns with temporary MCS in cardiac intensive care units. Methods: The CCCTN (Critical Care Cardiology Trials Network) is a multicenter network of tertiary CICUs in North America. Between September 2017 and September 2018, each center (n=16) contributed a 2-month snapshot of consecutive medical CICU admissions. Results: Of the 270 admissions using temporary MCS, 33% had acute myocardial infarction-related cardiogenic shock (CS), 31% had CS not related to acute myocardial infarction, 11% had mixed shock, and 22% had an indication other than shock. Among all 585 admissions with CS or mixed shock, 34% used temporary MCS during the CICU stay with substantial variation between centers (range: 17%–50%). The most common temporary MCS devices were intraaortic balloon pumps (72%), Impella (17%), and veno-arterial extracorporeal membrane oxygenation (11%), although intraaortic balloon pump use also varied between centers (range: 40%–100%). Patients managed with intraaortic balloon pump versus other forms of MCS (advanced MCS) had lower Sequential Organ Failure Assessment scores and less severe metabolic derangements. Illness severity was similar at high- versus low-MCS utilizing centers and at centers with more advanced MCS use. Conclusions: There is wide variation in the use of temporary MCS among patients with shock in tertiary CICUs. While hospital-level variation in temporary MCS device selection is not explained by differences in illness severity, patient-level variation appears to be related, at least in part, to illness severity.