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.

Modes of Death in Patients with Cardiogenic Shock in the Cardiac Intensive Care Unit: A Report from the Critical Care Cardiology Trials Network.

BACKGROUND: There are limited data on how patients with cardiogenic shock (CS) die. METHODS: The Critical Care Cardiology Trials Network is a research network of cardiac intensive care units coordinated by the Thrombolysis In Myocardial Infarction (TIMI) Study Group (Boston, MA). Using standardized definitions, site investigators classified direct modes of in-hospital death for CS admissions (October 2021 to September 2022). Mutually exclusive categories included 4 modes of cardiovascular death and 4 modes of noncardiovascular death. Subgroups defined by CS type, preceding cardiac arrest (CA), use of temporary mechanical circulatory support (tMCS), and transition to comfort measures were evaluated. RESULTS: Among 1068 CS cases, 337 (31.6%) died during the index hospitalization. Overall, the mode of death was cardiovascular in 82.2%. Persistent CS was the dominant specific mode of death (66.5%), followed by arrhythmia (12.8%), anoxic brain injury (6.2%), and respiratory failure (4.5%). Patients with preceding CA were more likely to die from anoxic brain injury (17.1% vs 0.9%; P < .001) or arrhythmia (21.6% vs 8.4%; P < .001). Patients managed with tMCS were more likely to die from persistent shock (P < .01), both cardiogenic (73.5% vs 62.0%) and noncardiogenic (6.1% vs 2.9%). CONCLUSIONS: Most deaths in CS are related to direct cardiovascular causes, particularly persistent CS. However, there is important heterogeneity across subgroups defined by preceding CA and the use of tMCS.

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.

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.

Escalation strategies, management, and outcomes of acute myocardial infarction-cardiogenic shock patients receiving percutaneous left ventricular support.

BACKGROUND: There are limited national-level data on the contemporary practices of mechanical circulatory support (MCS) use in acute myocardial infarction-cardiogenic shock (AMI-CS). METHODS: We utilized the Healthcare Cost and Utilization Project-National/Nationwide Inpatient Sample data (2005-2017) to identify adult admissions (>18 years) with AMI-CS. MCS devices were classified as intra-aortic balloon pump (IABP), percutaneous left ventricular assist devices (pLVAD), or extracorporeal membrane oxygenation (ECMO). We evaluated trends in the initial device used (IABP alone, pLVAD alone or ≥2 MCS devices), device escalation, bridging to durable LVAD/heart transplantation, and predictors of in-hospital mortality and device escalation. RESULTS: Among 327,283 AMI-CS admissions, 131,435 (40.2%) had an MCS device placed with available information on timing of placement. IABP, pLVAD, and ≥2 MCS devices were used as initial device in 120,928 (92.0%), 8202 (6.2%), and 2305 (1.7%) admissions, respectively. Most admissions were maintained on the initial MCS device with 1%-1.5% being escalated (IABP to pLVAD/ECMO, pLVAD to ECMO). Urban, medium, and large-sized hospitals and acute multiorgan failure were significant independent predictors of MCS escalation. In admissions receiving MCS, escalation of MCS device was associated with higher in-hospital mortality (adjusted odds ratio: 1.56, 95% confidence interval:  1.38-1.75; p < 0.001). Admissions receiving durable LVAD/heart transplantation increased over time in those initiated on pLVAD and ≥2 MCS devices, resulting in lower in-hospital mortality. CONCLUSIONS: In this 13-year study, escalation of MCS in AMI-CS was associated with higher in-hospital mortality suggestive of higher acuity of illness. The increase in number of durable LVAD/heart transplantations alludes to the role of MCS as successful bridge strategies.

Critical Care Cardiology Trials Network (CCCTN): a cohort profile.

AIMS: The 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 RESULTS: The 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. CONCLUSION: The 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.

Oxacillin plus ertapenem rapidly clears persistent left ventricular assist device-related methicillin-susceptible Staphylococcus aureus bacteremia.

There is an increasing use of left ventricular assist devices (LVADs) as bridge to transplantation or permanent destination therapy in the heart failure patient population. Infection remains a common complication in LVADs, with Gram-positive skin flora as predominant pathogens implicated, including Staphylococcus aureus. While there is emerging evidence for synergistic antibiotic combinations with methicillin resistant S. aureus, there remains a significant gap in the literature for persistent methicillin susceptible S. aureus bacteremia. In this article, we describe the first successful treatment of persistent LVAD-related bacteremia with salvage oxacillin plus ertapenem. The salvage therapy described here must be balanced by the risks for toxicity, impact on resistance, microbiota disruption, drug shortages, and patient costs. This combination warrants further evaluation in the clinical setting to better establish its role in our expanding patient population.

Gone, but not Forgotten.

The global health and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has rocked our communities and way of life. With millions infected around the globe, and hundreds of thousands of lives lost, there has been a paradigm shift in how clinicians evaluate and care for patients in multiple different types of healthcare settings. Many patients are reluctant to seek medical attention for cardiovascular illnesses, and late presentations of acute cardiac issues are raising the morbidity and mortality for treatable cardiac conditions. In this expert opinion, the authors canvas the many challenges in the diagnosis, treatment and delivery of care to patients with congestive heart failure and acute coronary syndromes during the COVID-19 pandemic.

Tumor Thrombus From Urothelial Carcinoma of Renal Pelvis.

We present a case report of an unfortunate 67-year-old man. He developed symptoms of thromboembolic disease in the immediate post-operative period after nephroureterectomy with recurrent pulmonary embolism in spite of being on several different anticoagulation regimens. He was later found to have tumor thrombus in the pulmonary artery secondary to urothelial tumor extension.

Evolution of a Geriatric Syndrome: Pathophysiology and Treatment of Heart Failure with Preserved Ejection Fraction.

The majority of older adults who develop heart failure (HF), particularly older women, have a preserved left ventricular ejection fraction (HFpEF). The prevalence of this syndrome is increasing, and the prognosis is not improving, unlike that of HF with reduced ejection fraction (HFrEF). Individuals with HFpEF have severe symptoms of effort intolerance, poor quality of life, frequent hospitalizations, and greater likelihood of death. Despite the importance of HFpEF, there are numerous major gaps in our understanding of its pathophysiology and management. Although it was originally viewed as a disorder due solely to abnormalities in left ventricular diastolic function, our understanding has evolved such that HFpEF is now understood as a systemic syndrome involving multiple organ systems, and it is likely that it is triggered by inflammation and other as-yet-unidentified circulating factors, with important contributions of aging and multiple comorbidities, features generally typical of other geriatric syndromes. We present an update on the pathophysiology, diagnosis, management, and future directions in this disorder in older persons.

Emerging Collaboration Between Palliative Care Specialists and Mechanical Circulatory Support Teams: A Qualitative Study.

CONTEXT: Despite national requirements mandating collaboration between palliative care specialists and mechanical circulatory support (MCS) teams at institutions that place destination therapy ventricular assist devices, little is known about the nature of those collaborations or outcomes for patients and families. OBJECTIVES: To assess how Centers for Medicare & Medicaid Services' regulations have changed collaboration between palliative care and MCS teams and how this collaboration is perceived by MCS team members. METHODS: After obtaining verbal consent, members of MCS teams were interviewed using semistructured telephone interviews. Interviews were transcribed, and content was coded and analyzed using qualitative methods. RESULTS: Models for collaboration varied widely between institutions. Several expected themes emerged from interviews: 1) improvements over time in the relationship between palliative care specialists and MCS teams, 2) palliative care specialists as facilitators of advance care planning, and 3) referral to hospice and ventricular assist device deactivation as specific areas for collaboration. Several unexpected themes also emerged: 4) the emergence of dedicated heart failure palliative care teams, 5) palliative care specialists as impartial voices in decision making, 6) palliative care specialists as extra support for MCS team members, and 7) the perception of improved patient and family experiences with palliative care team exposure. CONCLUSION: Although the structure of collaboration varies between institutions, collaboration between MCS teams and palliative care specialists is increasing and often preceded the Centers for Medicare & Medicaid Services requirement. Overall impressions of palliative care specialists are highly positive, with perceptions of improved patient and family experience and decreased burden on MCS team members.

Malnutrition and Cachexia in Heart Failure.

Heart failure is a growing public health concern. Advanced heart failure is frequently associated with severe muscle wasting, termed cardiac cachexia This process is driven by systemic inflammation and tumor necrosis factor in a manner common to other forms of disease-related wasting seen with cancer or human immunodeficiency virus. A variable degree of malnutrition is often superimposed from poor nutrient intake. Cardiac cachexia significantly decreases quality of life and survival in patients with heart failure. This review outlines the evaluation of nutrition status in heart failure, explores the pathophysiology of cardiac cachexia, and discusses therapeutic interventions targeting wasting in these patients.

Depression predicts repeated heart failure hospitalizations.

OBJECTIVE: Management of depression, if it is independently associated with repeated hospitalizations for heart failure (HF), offers promise as a viable and cost-effective strategy to improve health outcomes and reduce health care costs for HF. The objective of this study was to assess the association between depression and the number of HF-related hospitalizations in patients with low-to-moderate systolic or diastolic dysfunction, after controlling for illness severity, socioeconomic factors, physician adherence to evidence-based medications, patient adherence to HF drug therapy, and patient adherence to salt restrictions. METHODS AND RESULTS: The Heart Failure Adherence and Retention Trial (HART) was a randomized behavioral trial to evaluate whether patient self-management skills coupled with HF education improved patient outcomes. Depression was measured at baseline with the Geriatric Depression Scale (GDS). The number of hospitalizations was analyzed with a negative binomial regression model that included an offset term to account for the differential duration of follow-up for individual subjects. The average unadjusted number of hospitalizations per year was 0.40 in the depressed group (GDS ≥10) and 0.33 in the nondepressed group (GDS <10). Depression was a strong predictor (incident rate ratio 1.45; P = .006) after adjusting for physician adherence to evidence-based medication use, patient adherence to HF drug therapy, patient adherence to salt restriction, illness severity, HF severity (6-minute walk <620 feet), and socioeconomic factors. CONCLUSIONS: Depression is a strong psychosocial predictor of repeated hospitalizations for HF. Compared with nondepressed individuals, those with depression were hospitalized for HF 1.45 times more often, even after controlling for physician adherence to evidence-based medications and patient adherence to HF drug therapy and salt restrictions. This finding suggests that clinicians should screen for depression early in the course of HF management.

Heart transplantation in a patient with chloroquine-induced cardiomyopathy.

We present the first report of a patient who underwent heart transplantation (HT) after endomyocardial biopsy (EMB) and revealed chloroquine-induced cardiomyopathy (CIC). This patient, who was treated with chloroquine for 6 years, developed a restrictive cardiomyopathy that progressed to congestive heart failure (CHF) resistant to medical management.

Increase in atrial size in long-term survivors of heart transplant.

Atrial size in recipients of orthotopic heart transplant (OHTX) who have long-term survival is not well described in the literature. We reviewed 2-dimensional echocardiograms of 14 recipients of OHTX who survived at least 5 years. Apical 4-chamber images were used for measurements starting at 1-year post-OHTX. The recipients of OHTX were 8 (57%) men and 6 (43%) women with a mean age of 43.6 +/- 12.1 (20-60) years and mean survival of 9.5 +/- 2.6 (5.8-14.4) years. All chambers increased with time post-OHTX (r > 0.83, P <.002). The changes in left atrium (LA) and right atrium (RA), remnants of donor LA and RA, and remnants of recipients' LA areas correlated inversely with patient survival post-OHTX (r > 0.83, P <.002). The change in RA recipient remnant area did not correlate with survival (r = 0.58, P =.06). In recipients of OHTX with long-term survival, there is a significant correlation between the echocardiographic size of LA and RA, and donor and recipient remnants with time and survival.

Prevention of osteoporosis in cardiac transplant recipients.

Osteoporosis is a leading cause of pretransplant and posttransplant morbidity. The need for early detection by measuring bone mineral density, even before transplant, must be emphasized. Preventive measures are not comparable. The use of calcium and vitamin D supplements, although recommended, is inadequate for the prevention of bone loss and complications such as vertebral fractures. Bisphosphonates have been shown to attenuate the bone loss and reduce fractures associated with steroid-induced osteoporosis. Small studies in transplant recipients suggest similar results. Other preventive measures such as hormone replacement therapy are also helpful. There are limited data on the administration of nasal calcitonin in transplant recipients.