Aims Increases in extravascular lung water (EVLW) during exercise contribute to symptoms, morbidity, and mortality in patients with heart failure and preserved ejection fraction (HFpEF), but the mechanisms leading to pulmonary congestion during exercise are not well-understood. Methods and results Compensated, ambulatory patients with HFpEF (n = 61) underwent invasive haemodynamic exercise testing using high-fidelity micromanometers with simultaneous lung ultrasound, echocardiography, and expired gas analysis at rest and during submaximal exercise. The presence or absence of EVLW was determined by lung ultrasound to evaluate for sonographic B-line artefacts. An increase in EVLW during exercise was observed in 33 patients (HFpEFLW+, 54%), while 28 (46%) did not develop EVLW (HFpEFLW−). Resting left ventricular function was similar in the groups, but right ventricular (RV) dysfunction was two-fold more common in HFpEFLW+ (64 vs. 31%), with lower RV systolic velocity and RV fractional area change. As compared to HFpEFLW−, the HFpEFLW+ group displayed higher pulmonary capillary wedge pressure (PCWP), higher pulmonary artery (PA) pressures, worse RV-PA coupling, and higher right atrial (RA) pressures during exercise, with increased haemoconcentration indicating greater loss of water from the vascular space. The development of lung congestion during exercise was significantly associated with elevations in PCWP and RA pressure as well as impairments in RV-PA coupling (area under the curve values 0.76–0.84). Conclusion Over half of stable outpatients with HFpEF develop increases in interstitial lung water, even during submaximal exercise. The acute development of lung congestion is correlated with increases in pulmonary capillary hydrostatic pressure that favours fluid filtration, and systemic venous hypertension due to altered RV-PA coupling, which may interfere with fluid clearance. Clinical trial registration NCT02885636.

BackgroundOptimal methods of mortality risk stratification in patients in the cardiac intensive care unit (CICU) remain uncertain. We evaluated the ability of the Sequential Organ Failure Assessment (SOFA) score to predict mortality in a large cohort of unselected patients in the CICU.Methods and ResultsAdult patients admitted to the CICU from January 1, 2007, to December 31, 2015, at a single tertiary care hospital were retrospectively reviewed. SOFA scores were calculated daily, and Acute Physiology and Chronic Health Evaluation (APACHE)‐III and APACHE‐IV scores were calculated on CICU day 1. Discrimination of hospital mortality was assessed using area under the receiver‐operator characteristic curve values. We included 9961 patients, with a mean age of 67.5±15.2 years; all‐cause hospital mortality was 9.0%. Day 1 SOFA score predicted hospital mortality, with an area under the receiver‐operator characteristic curve value of 0.83; area under the receiver‐operator characteristic curve values were similar for the APACHE‐III score, and APACHE‐IV predicted mortality (P>0.05). Mean and maximum SOFA scores over multiple CICU days had greater discrimination for hospital mortality (P<0.01). Patients with an increasing SOFA score from day 1 and day 2 had higher mortality. Patients with day 1 SOFA score <2 were at low risk of mortality. Increasing tertiles of day 1 SOFA score predicted higher long‐term mortality (P<0.001 by log‐rank test).ConclusionsThe day 1 SOFA score has good discrimination for short‐term mortality in unselected patients in the CICU, which is comparable to APACHE‐III and APACHE‐IV. Advantages of the SOFA score over APACHE include simplicity, improved discrimination using serial scores, and prediction of long‐term mortality.

Background: The use of norepinephrine may be associated with better outcomes in some patients with shock. We sought to determine whether norepinephrine was associated with lower mortality in unselected cardiac intensive care unit (CICU) patients compared with other vasopressors, and whether patterns of vasopressor and inotrope usage in the CICU have changed over time. Methods: We retrospectively evaluated consecutive adult patients admitted to a tertiary care hospital CICU from January 1, 2007 to December 31, 2015. Vasoactive drug doses were quantified using the peak Vasoactive-Inotropic Score (VIS). Temporal trends were assessed using the Cochran–Armitage trends test and multivariable logistic regression was used to determine predictors of hospital mortality. Results: We included 10,004 patients with a mean age of 67 ± 15 years; vasoactive drugs were used in 2,468 (24.7%) patients. Use of norepinephrine increased over time, whereas dopamine utilization decreased (P < 0.001 for trends). After adjustment for illness severity and other variables, the peak VIS was a predictor of hospital mortality across the entire population (unit odds ratio [OR] 1.013, 95% confidence interval [CI], 1.009–1.017, P < 0.001) and among patients receiving vasoactive drugs (OR 1.018, 95% CI, 1.013–1.022, P < 0.001). Among patients receiving vasoactive drugs, norepinephrine was associated with a lower risk of hospital mortality (OR 0.66, 95% CI, 0.49–0.90, P = 0.008) after adjustment for illness severity and peak VIS. Conclusions: Vasoactive drug use in CICU patients has a dose-dependent association with short-term mortality. Use of norepinephrine in CICU patients is associated with decreased odds of death when compared with other vasoactive drugs.

Purpose: To assess trends in life support interventions and performance of the automated Acute Physiology and Chronic Health Evaluation (APACHE) IV model at mortality prediction compared with Oxford Acute Severity of Illness Score (OASIS) in a contemporary cardiac intensive care unit (CICU). Methods and Materials: Retrospective analysis of adults (age ≥18 years) admitted to CICU from January 1, 2007, through December 31, 2015. Temporal trends were assessed with linear regression. Discrimination of each risk score for hospital mortality was assessed with use of area under the receiver operating characteristic curve (AUROC) values. Calibration was assessed with Hosmer-Lemeshow goodness-of-fit test.Results: The study analyzed 10,004 patients. CICU and hospital mortality rates were 5.7% and 9.1%. APACHE IV predicted death had an AUROC of 0.82 (0.81-0.84) for hospital death, compared with 0.79 for OASIS (P<.05). Calibration was better for OASIS than APACHE IV. Increases were observed in CICU and hospital lengths of stay (both P<.001), APACHE IV predicted mortality (P=.007), Charlson Comorbidity Index (P<.001), noninvasive ventilation use (P<.001), and noninvasive ventilation days (P=.02).Conclusions: Contemporary CICU patients are increasingly ill, observed in upward trends in comorbid conditions and life support interventions. APACHE IV predicted death and OASIS showed good discrimination in predicting death in this population. APACHE IV and OASIS may be useful for benchmarking and quality improvement initiatives in the CICU, the former having better discrimination.

BackgroundChimeric antigen receptor (CAR) T-cell-associated cytokine release syndrome (CRS) may present with tachycardia, hemodynamic instability and reduced cardiac function. Pediatric CAR studies examining cardiac toxicity are limited.MethodsWe report on cardiac toxicity observed in children and young adults with hematologic malignancies enrolled in a CD19-28ζ CAR T-cell phase I trial (NCT01593696). All patients had a formal baseline echocardiogram. Real-time studies included echocardiograms on intensive care unit (ICU) transfer, and serial troponin and pro-B-type natriuretic peptide (pro-BNP) in the select patients.ResultsFrom July 2012 to March 2016, 52 patients, with a median age of 13.4 years (range 4.2–30.3) were treated. CRS developed in 37/52 (71%), which was grade 3–4 CRS in nine patients (17%). The median prior anthracycline exposure was 205 mg/m2 (range 70–620 mg/m2) in doxorubicin equivalents. The median baseline left ventricle ejection fraction (LVEF) and baseline LV global longitudinal strain (GLS) were 60% (range 50%–70%) and 16.8% (range 14.1%–23.5%, n=37) respectively. The majority, 78% (29/37), of patients had a reduced GLS <19% at baseline, and 6% (3/52) of patients had baseline LVEF <53%. ICU transfers occurred in 21 patients, with nine requiring vasoactive hemodynamic support and three necessitating >1 vasopressor. Six (12%) patients developed cardiac dysfunction (defined by >10% absolute decrease in LVEF or new-onset grade 2 or higher LV dysfunction, per CTCAE v4), among whom 4 had grade 3–4 CRS. Troponin elevations were seen in 4 of 13 patients, all of whom had low LVEF. Pro-BNP was elevated from baseline in 6/7 patients at the onset of CRS, with higher levels correlating with more severe CRS. Cardiac dysfunction fully resolved in all but two patients by day 28 post-CAR.ConclusionCardiac toxicity related to CD19-28ζ CAR T-cell-associated CRS was generally reversible by day 28 postinfusion. Implementation of more frequent monitoring with formal echocardiograms incorporating systemic analysis of changes in GLS, and cardiac biomarkers (troponin and proBNP) may help to earlier identify those patients at highest risk of severe cardiac systolic dysfunction, facilitating earlier interventions for CRS to potentially mitigate acute cardiac toxicity.