Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study.

OBJECTIVES: Systemic thrombolysis improves outcomes in patients with pulmonary embolism (PE) but is associated with the risk of hemorrhage. The data on efficacy and safety of reduced-dose alteplase are limited. The study objective was to compare the characteristics, outcomes, and complications of patients with PE treated with full- or reduced-dose alteplase regimens. DESIGN: Multicenter retrospective observational study. SETTING: Tertiary care hospital and 15 community and academic centers of a large healthcare system. PATIENTS: Hospitalized patients with PE treated with systemic alteplase. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pre- and post-alteplase hemodynamic and respiratory variables, patient outcomes, and complications were compared. Propensity score (PS) weighting was used to adjust for imbalances of baseline characteristics between reduced- and full-dose patients. Separate analyses were performed using the unweighted and weighted cohorts. Ninety-eight patients were treated with full-dose (100 mg) and 186 with reduced-dose (50 mg) regimens. Following alteplase, significant improvements in shock index, blood pressure, heart rate, respiratory rate, and supplemental oxygen requirements were observed in both groups. Hemorrhagic complications were lower with the reduced-dose compared with the full-dose regimen (13% vs. 24.5%, p = 0.014), and most were minor. Major extracranial hemorrhage occurred in 1.1% versus 6.1%, respectively ( p = 0.022). Complications were associated with supratherapeutic levels of heparin anticoagulation in 37.5% of cases and invasive procedures in 31.3% of cases. The differences in complications persisted after PS weighting (15.4% vs. 24.7%, p = 0.12 and 1.3% vs. 7.1%, p = 0.067), but did not reach statistical significance. There were no significant differences in mortality, discharge destination, ICU or hospital length of stay, or readmission after PS weighting. CONCLUSIONS: In a retrospective, PS-weighted observational study, when compared with the full-dose, reduced-dose alteplase results in similar outcomes but fewer hemorrhagic complications. Avoidance of excessive levels of anticoagulation or invasive procedures should be considered to further reduce complications.

Echocardiographic parameters and hemodynamic instability at the initiation of continuous kidney replacement therapy.

OBJECTIVE: Investigate the association of echocardiographic parameters with hemodynamic instability after initiating continuous kidney replacement therapy (CKRT) in a cohort of intensive care unit (ICU) patients requiring CKRT. METHODS: Historical cohort study of consecutive adults admitted to the ICU at a tertiary care hospital from December 2006 through November 2015 who underwent CKRT and had an echocardiogram done within seven days before CKRT initiation. The primary outcome was hypotension within one hour of CKRT initiation. RESULTS: We included 980 patients, 804 (82%) with acute kidney injury (AKI) and 176 (18%) with end-stage kidney disease (ESKD). Median patient age was 63 (± 14) years, and median Sequential Organ Failure Assessment (SOFA) score on the day of CKRT initiation was 12 (IQR 10-14). Multivariable analysis showed that Left (OR 2.01, 95% CI 1.04-3.86), and Right (OR 1.5, 95% CI 1.04-2.25) moderate and severe ventricular enlargement, Vasoactive-Inotropic Score (VIS) one hour before CKRT initiation (OR 1.18 per 10 units increase, 95% CI 1.09-1.28) and high bicarbonate fluid replacement (OR 2.52, 95% CI 1.01-6.2) were associated with hypotension after CKRT initiation. CONCLUSION: Right and left ventricular enlargement are risk factors associated with hypotension after CKRT initiation.

Doppler-derived haemodynamics performed during admission echocardiography predict in-hospital mortality in cardiac intensive care unit patients.

AIMS: Cardiac point-of-care ultrasound (CV-POCUS) has become a fundamental part for the assessment of patients admitted to cardiac intensive care units (CICU). We sought to refine the practice of CV-POCUS by identifying 2D and Doppler-derived measurements from bedside transthoracic echocardiograms (TTEs) performed in the CICU that are associated with mortality. METHODS AND RESULTS: We retrospectively included Mayo Clinic CICU patients admitted from 2007 to 2018 and assessed the TTEs performed within 1 day of CICU admission, including Doppler and 2D measurements of left and right ventricular function. Logistic regression and classification and regression tree (CART) analysis were used to determine the association between TTE variables with in-hospital mortality. A total of 6957 patients were included with a mean age of 68.0 ± 14.9 years (37.0% females). A total of 609 (8.8%) patients died in the hospital. Inpatient deaths group had worse biventricular systolic function [left ventricular ejection fraction (LVEF) 48.2 ± 16.0% vs. 38.7 ± 18.2%, P < 0.0001], higher filling pressures, and lower forward flow. The strongest TTE predictors of hospital mortality were left ventricular outflow tract velocity-time integral [LVOT VTI, adjusted OR 0.912 per 1 cm higher, 95% confidence interval (CI) 0.883-0.942, P < 0.0001] followed by medial mitral E/e' ratio (adjusted OR 1.024 per 1 unit higher, 95% CI 1.010-1.039, P = 0.0011). Classification and regression tree analysis identified LVOT VTI <16 cm as the most important TTE predictor of mortality. CONCLUSIONS: Doppler-derived haemodynamic TTE parameters have a strong association with mortality in the CICU, particularly LVOT VTI <16 cm or mitral E/e' ratio >15. The incorporation of these simplified Doppler-derived haemodynamics into admission CV-POCUS facilitates early risk stratification and strengthens the clinical yield of the ultrasound exam.

Echocardiographic left ventricular stroke work index: An integrated noninvasive measure of shock severity.

BACKGROUND: Echocardiographic findings vary with shock severity, as defined by the Society for Cardiovascular Angiography and Intervention (SCAI) shock stage. Left ventricular stroke work index (LVSWI) measured by transthoracic echocardiography (TTE) can predict mortality in the cardiac intensive care unit (CICU). We sought to determine whether LVSWI could refine mortality risk stratification by the SCAI shock classification in the CICU. METHODS: We included consecutive CICU patients from 2007 to 2015 with TTE data available to calculate the LVSWI, specifically the mean arterial pressure, stroke volume index and medial mitral E/e' ratio. In-hospital mortality as a function of LVSWI was evaluated across the SCAI shock stages using logistic regression, before and after multivariable adjustment. RESULTS: We included 3635 unique CICU patients, with a mean age of 68.1 ± 14.5 years (36.5% females); 61.1% of patients had an acute coronary syndrome. The LVSWI progressively decreased with increasing shock severity, as defined by increasing SCAI shock stage. A total of 203 (5.6%) patients died during hospitalization, with higher in-hospital mortality among patients with lower LVSWI (adjusted OR 0.66 per 10 J/m2 higher) or higher SCAI shock stage (adjusted OR 1.24 per each higher stage). A LVSWI <33 J/m2 was associated with higher adjusted in-hospital mortality, particularly among patients with shock (SCAI stages C, D and E). CONCLUSIONS: The LVSWI by TTE noninvasively characterizes the severity of shock, including both systolic and diastolic parameters, and can identify low-risk and high-risk patients at each level of clinical shock severity.

Braden Skin Score Subdomains Predict Mortality Among Cardiac Intensive Care Patients.

BACKGROUND: The Braden Skin Score (BSS) is a bedside nursing assessment that may be a measure of frailty and predicts mortality among patients in the cardiac intensive care unit (CICU). We examined the association between each of the 6 individual BSS subscores with hospital mortality in patients in the CICU. We hypothesized that BSS subscores reflecting patient frailty would have a stronger association with outcomes. METHODS: Retrospective cohort study of unique adult patients admitted to the Mayo Clinic CICU from 2007 to 2018 with BSS documented on admission. Primary outcome was all-cause hospital mortality. Odds ratios (ORs) were determined using multivariable logistic regression. RESULTS: The 11,954 included patients had a mean age of 67.4 ± 15.2 years (37.8% women). Each individual BSS subscore was lower among patients who died in the hospital (all P < .001). The total BSS was inversely associated with in-hospital mortality across admission diagnoses and among patients with coma or mechanical ventilation; each individual subscore was inversely associated with in-hospital mortality. On multivariable regression, all subscores were inversely associated with hospital mortality after full adjustment. Shear had the strongest association (adjusted OR 0.59), followed by nutrition (adjusted OR 0.67), skin moisture (adjusted OR 0.76), mobility (adjusted OR 0.76), sensory perception (adjusted OR 0.82), and activity level (adjusted OR 0.85). CONCLUSION: BSS can serve as a rapid noninvasive screening tool for identifying poor outcomes in patients in the CICU. BSS subdomains that are more strongly associated with mortality appear to reflect physical frailty. Insofar as the BSS and its subscores measure frailty, a low BSS may identify frail patients.

Outcomes Associated With Cardiac Arrest in Patients in the Cardiac Intensive Care Unit With Cardiogenic Shock.

Cardiac arrest (CA) is common and has been associated with adverse outcomes in patients with cardiogenic shock (CS). We sought to determine the prevalence, patient characteristics, and outcomes of CA in cardiovascular intensive care unit patients with CS. We queried cardiovascular intensive care unit admissions from 2007 to 2018 with an admission diagnosis of CS and compared patients with and without CA. Temporal trends were assessed using linear regression. The primary and secondary outcomes of in-hospital and 1-year mortality were analyzed using logistic regression and Cox proportional-hazards analysis, respectively. We included 1,498 patients, and CA was present in 510 patients (34%), with 258 (50.6% of patients with CA) having ventricular fibrillation (VF). Mean age was 68 ± 14 years, and 37% were females. The prevalence of CA decreased over time (from 43% in 2007 to 24% in 2018, p <0.001). Hospital mortality was 33.3% and decreased over time in patients without CA (from 30% in 2007 to 22% in 2018, p = 0.05), but not in patients with CA (p = 0.71). CA was associated with a higher risk of hospital mortality (51.0% vs 24.2%, adjusted odds ratio 2.15, 95% confidence interval [CI] 1.52 to 3.05, p <0.001), with no difference between VF CA and non-VF CA (p = 0.64). CA was associated with higher 1-year mortality (adjusted hazard ratio 1.53, 95% CI 1.24 to 1.89, p <0.001). In conclusion, CA is present in 1 of 3 of CS hospitalizations and confers a substantially higher risk of hospital and 1-year mortality with no improvement during our 12-year study period contrary to prevailing trends.

Epidemiology and outcomes of pulmonary hypertension in the cardiac intensive care unit.

AIMS: Pulmonary hypertension (PH) has been consistently associated with adverse outcomes in hospitalized patients. Limited epidemiologic data exist regarding PH in the cardiac intensive care unit (CICU) population. Here, we describe the prevalence, aetiology, and outcomes of PH in the CICU. METHODS AND RESULTS: Cardiac intensive care unit patients admitted from 2007 to 2018 who had right ventricular systolic pressure (RVSP) measured via transthoracic echocardiography near CICU admission were included. PH was defined as RVSP >35 mmHg, and moderate-to-severe PH as RVSP ≥50 mmHg. Predictors of in-hospital mortality were determined using multivariable logistic regression. Among 5042 patients (mean age 69.4 ± 14.8 years; 41% females), PH was present in 3085 (61%). The majority (68%) of patients with PH had left heart failure, and 29% had lung disease. In-hospital mortality occurred in 8.3% and was more frequent in patients with PH [10.9% vs. 4.2%, adjusted odds ratio (OR) 1.40, 95% confidence interval (CI) 1.03-1.92, P = 0.03], particularly patients with moderate-to-severe PH (14.4% vs. 6.2%, adjusted OR 1.65, 95% CI 1.27-2.14, P < 0.001). In-hospital mortality increased incrementally as a function of higher RVSP (adjusted 1.18 per 10 mmHg increase, 95% CI 1.09-1.28, P < 0.001). Patients with higher RVSP or moderate-to-severe PH had increased in-hospital mortality across admission diagnoses (all P < 0.05). CONCLUSIONS: Pulmonary hypertension is very common in the CICU population and appears to be independently associated with a higher risk of death during hospitalization, although the strength of this association varies according to the underlying admission diagnosis. These data highlight the importance of PH in patients with cardiac critical illness.

Laboratory Markers of Acidosis and Mortality in Cardiogenic Shock: Developing a Definition of Hemometabolic Shock.

BACKGROUND: Acidosis and higher lactate predict worse outcomes in cardiogenic shock (CS) patients. We sought to determine whether overall acidosis severity on admission predicted in-hospital mortality in CS patients. METHODS: This retrospective descriptive analysis included CS patients admitted to a single academic tertiary cardiac intensive care unit from 2007 to 2015. Admission arterial pH, base excess, and anion gap values were used to generate a Composite Acidosis Score (range 0-5, with a score ≥2 defining Severe Acidosis). Adjusted in-hospital mortality was analyzed using multivariable logistic regression. RESULTS: We included 1,065 patients with median age of 68.9 (59.0, 77.2) years (36.4% females). Concomitant diagnoses included cardiac arrest in 38.1% and acute coronary syndrome in 59.1%. Severe Acidosis was present in 35.2%, and these patients had worse shock and more organ failure. In-hospital mortality occurred in 34.1% and was higher among patients with Severe Acidosis (54.9% vs. 22.4%, adjusted odds ratio [OR] 2.01, 95% CI 1.43-2.83, P < 0.001). Increasing Composite Acidosis Score was associated with higher in-hospital mortality (adjusted OR 1.25 per point, 95% CI 1.11-1.40, P < 0.001). Severe Acidosis was associated with higher hospital mortality at every level of shock severity and organ failure (all P < 0.05). Admission lactate level had equivalent discrimination for in-hospital mortality as the Composite Acidosis Score (0.69 vs. 0.66; P = 0.32 by De Long test). CONCLUSION: Given its incremental association with higher in-hospital mortality among CS patients beyond shock severity and organ failure, we propose Severe Acidosis as a marker of hemometabolic shock. Lactate levels performed as well as a composite measure of acidosis for predicting mortality.

Biventricular Function and Shock Severity Predict Mortality in Cardiac ICU Patients.

BACKGROUND: Ventricular function, including left ventricular systolic dysfunction (LVSD), right ventricular systolic dysfunction (RVSD), and biventricular dysfunction (BVD), contribute to shock in cardiac ICU (CICU) patients, but the prognostic usefulness remains unclear. RESEARCH QUESTION: Do patients with ventricular dysfunction have higher mortality at each Society for Cardiovascular Angiography and Intervention (SCAI) shock stage? STUDY DESIGN AND METHODS: We identified patients in the CICU admitted with available echocardiography data. LVSD was defined as left ventricular ejection fraction < 40%, RVSD as moderate or greater systolic dysfunction by semiquantitative measurement, and BVD as the presence of both. Multivariate logistic regression determined the relationship between ventricular dysfunction and adjusted in-hospital mortality as a function of SCAI stage. RESULTS: The study population included 3,158 patients with a mean ± SD age of 68.2 ± 14.6 years, of which 51.8% had acute coronary syndromes. LVSD was present in 22.3%, RVSD in 11.8%, and BVD in 16.4%. After adjustment for SCAI shock stage, no difference in in-hospital mortality was found between patients with LVSD or RVSD and those without ventricular dysfunction (P > .05), but BVD was associated independently with higher in-hospital mortality (adjusted hazard ratio, 1.815; 95% CI, 1.237-2.663; P = .0023). The addition of ventricular dysfunction to the SCAI staging criteria increased discrimination for hospital mortality (area under the receiver operating characteristic curve, 0.784 vs 0.766; P < .001). INTERPRETATION: Among patients admitted to the CICU, only BVD was associated independently with higher hospital mortality. The addition of echocardiography assessment to the SCAI shock criteria may facilitate improved clinical risk stratification.

Echocardiographic Correlates of Mortality Among Cardiac Intensive Care Unit Patients With Cardiogenic Shock.

BACKGROUND: Prior studies have shown worse outcomes in patients with cardiogenic shock (CS) who have reduced left ventricular ejection fraction (LVEF), but the association between other transthoracic echocardiogram (TTE) findings and mortality in CS patients remains uncertain. We hypothesized that Doppler TTE measurements would outperform LVEF for risk stratification. METHODS: Retrospective analysis of cardiac intensive care unit patients with an admission diagnosis of CS and a TTE within 1 day of admission. Hospital survivors and inpatient deaths were compared, and multivariable logistic regression was used to analyze the associations between TTE variables and hospital mortality. RESULTS: We included 1,085 patients, with a median age of 69.5 (59.6, 77.5) years; 37% were females and 62% had an acute coronary syndrome. Most patients (66%) had moderate or severe left ventricular (LV) systolic dysfunction, and 48% had moderate or severe right ventricular (RV) systolic dysfunction. Hospital mortality occurred in 31%, and inpatient deaths had a lower median LVEF (29% vs. 35%, P < 0.001). Patients with mild or no LV or RV dysfunction were at lower risk of adjusted hospital mortality (P < 0.01). The LV outflow tract (LVOT) velocity-time integral (VTI) was the single best predictor of hospital mortality. After multivariable adjustment, both the LVEF and LVOT VTI remained strongly associated with hospital mortality (P < 0.001). CONCLUSIONS: Early comprehensive Doppler TTE can provide important prognostic insights in CS patients, highlighting its potential utility in clinical practice. The LVOT VTI, reflecting forward flow, is an important measurement to obtain on bedside TTE.

Myocardial contraction fraction by echocardiography and mortality in cardiac intensive care unit patients.

BACKGROUND: The myocardial contraction fraction (MCF) is proposed as an improved measure of left ventricular (LV) systolic function that overcomes important limitations of the left ventricular ejection fraction (LVEF). We sought to determine whether a low MCF was associated with higher mortality in cardiac intensive care unit (CICU) patients. METHODS: We retrospectively analyzed unique Mayo Clinic CICU patients from 2007 to 2018 with MCF calculated as the ratio of the stroke volume to the left ventricular myocardial volume from a transthoracic echocardiogram within 1 day of CICU admission. Multivariable logistic regression analyzed the association between MCF and hospital mortality, after adjustment for LVEF and clinical variables. RESULTS: We included 4794 patients with a mean age of 68.0 ± 14.8 years (37.1% females). The mean MCF was 0.41 ± 0.16, and was lower in the 6.6% of patients who died in the hospital (0.32 ± 0.14 versus 0.42 ± 0.16, p < 0.001). On multivariable analysis, higher MCF remained associated with lower hospital mortality (adjusted OR 0.78 per 0.1 higher, 95% CI 0.69-0.89, p < 0.001), whereas LVEF was not significantly associated with hospital mortality (unadjusted OR 0.91 per 10% higher, OR 95% CI 0.82-1.02, p = 0.09). Patients with MCF <0.2 had the highest in-hospital mortality, and those with MCF ≥0.5 had the lowest in-hospital mortality, irrespective of admission diagnosis or LVEF. CONCLUSIONS: MCF demonstrated a strong, inverse relationship with hospital mortality in CICU patients, even after adjusting for LVEF and clinical variables. MCF can be used to identify prognostically-relevant myocardial dysfunction at the bedside, even among patients with preserved LVEF.

Diamond-Forrester classification using echocardiography haemodynamic assessment in cardiac intensive care unit patients.

AIMS: We sought to determine whether the Diamond-Forrester classification using non-invasive haemodynamic measurements by 2-D and Doppler echocardiography would predict hospital mortality in cardiac intensive care unit (CICU) patients. METHODS AND RESULTS: We retrospectively analysed unique patients admitted to the CICU at Mayo Clinic Rochester from 2007 to 2018. Doppler-derived cardiac index (CI) and ratio of mitral valve E velocity to medial mitral annulus e' velocity (E/e' ratio) were used to classify patients into four profiles: Profile I (warm/dry), Profile II (warm/wet), Profile III (cold/dry), and Profile IV (cold/wet). Logistic regression was used to determine predictors of hospital mortality, and Cox proportional-hazards analysis was used to determine predictors of mortality during one year of follow-up. We included 4563 patients with a mean age of 68.3 ± 14.3 years, including 36.2% female patients. The distribution of each profile was as follows: I, 47.4%; II, 36.2%; III, 7.9%; IV, 8.5%. A total of 5.8% patients died during hospitalization, and 18.1% died by 1 year. Patients with either low CI or elevated E/e' ratio had higher in-hospital and 1 year mortality. Patients with elevated E/e' ratio (i.e. Profiles II and IV) had an increased risk of death during hospitalization and at 1 year after multivariate adjustment (adjusted hazard ratio 1.72 and 2.17 for 1 year mortality, respectively, compared with Profile I, P < 0.01). CONCLUSIONS: Simple Doppler echocardiographic assessment can be used to identify haemodynamic profiles defined by the Diamond-Forester classification in patients admitted in CICU. These profiles predict outcomes and may be used to guide therapy in critically ill patients.

Integrated Multiorgan Bedside Ultrasound for the Diagnosis and Management of Sepsis and Septic Shock.

Despite decades of research, the mortality rate of sepsis and septic shock remains unacceptably high. Delays in diagnosis, identification of an infectious source, and the challenge of providing patient-tailored resuscitation measures routinely result in suboptimal patient outcomes. Bedside ultrasound improves a clinician's ability to both diagnose and manage the patient with sepsis. Indeed, multiple point-of-care ultrasound (POCUS) protocols have been developed to evaluate and treat various subsets of critically ill patients. These protocols mostly target patients with undifferentiated shock and have been shown to improve clinical outcomes. Other studies have shown that POCUS can improve a clinician's ability to identify a source of infection. Once a diagnosis of septic shock has been made, serial POCUS exams can be used to continuously guide resuscitative efforts. In this review, we advocate that the patient with suspected sepsis or septic shock undergo a comprehensive POCUS exam in which sonographic information across organ systems is synthesized and used in conjunction with traditional data gleaned from the patient's history, physical exam, and laboratory studies. This harmonization of information will hasten an accurate diagnosis and assist with hemodynamic management.