Computed tomography or chest X-ray to assess pulmonary congestion in dyspnoeic patients with acute heart failure.

AIMS: While computed tomography (CT) is widely acknowledged as superior to chest radiographs for acute diagnostics, its efficacy in diagnosing acute heart failure (AHF) remains unexplored. This prospective study included consecutive patients with dyspnoea undergoing simultaneous low-dose chest CT (LDCT) and chest radiographs. Here, we aimed to determine if LDCT is superior to chest radiographs to confirm pulmonary congestion in dyspnoeic patients with suspected AHF. METHODS AND RESULTS: An observational, prospective study, including dyspnoeic patients from the emergency department. All patients underwent concurrent clinical examination, laboratory tests, echocardiogram, chest radiographs, and LDCT. The primary efficacy measure to compare the two radiological methods was conditional odds ratio (cOR). The primary outcome was adjudicated AHF, ascertained by comprehensive expert consensus. The secondary outcome, echo-bnp AHF, was an objective AHF diagnosis based on echocardiographic cardiac dysfunction, elevated cardiac filling pressure, loop diuretic administration, and NT-pro brain natriuretic peptide > 300 pg/mL. Of 228 dyspnoeic patients, 64 patients (28%) had adjudicated AHF, and 79 patients (35%) had echo-bnp AHF. Patients with AHF were older (78 years vs. 73 years), had lower left ventricular ejection fraction (36% vs. 55%), had higher elevated left ventricular filling pressures (98% vs. 18%), and had higher NT-pro brain natriuretic peptide levels (3628 pg/mL vs. 470 pg/mL). The odds to diagnose adjudicated AHF and echo-bnp AHF were up to four times greater using LDCT (cOR: 3.89 [2.15, 7.06] and cOR: 2.52 [1.45, 4.38], respectively). For each radiologic sign of pulmonary congestion, the LDCT provided superior or equivalent results as the chest radiographs, and the interrater agreement was higher using LDCT (kappa 0.88 [95% CI: 0.81, 0.95] vs. 0.73 [95% CI: 0.63, 0.82]). As first-line imaging modality, LDCT will find one additional adjudicated AHF in 12.5 patients and prevent one false-positive in 20 patients. Similar results were demonstrated for echo-bnp AHF. CONCLUSIONS: In consecutive dyspnoeic patients admitted to the emergency department, LDCT is significantly better than chest radiographs in detecting pulmonary congestion.

Remote dielectric sensing to detect acute heart failure in patients with dyspnoea: a prospective observational study in the emergency department.

Aims: Remote dielectric sensing (ReDS) enables quick estimation of lung fluid content. To examine if ReDS is superior to other methods in detecting acute heart failure. Methods and results: We included consecutive patients with dyspnoea from the emergency departments at Bispebjerg Hospital, Copenhagen, and performed ReDS, low-dose chest computed tomography (CT), echocardiogram, lung ultrasound, NT-Pro-brain natriuretic peptide (NT-proBNP), and a Boston score evaluation (chest X-ray and clinical signs). ReDS values >35% were used as a cut-off to diagnose pulmonary congestion. Acute heart failure was adjudicated by experts' review of health records but independently of ReDS values. Sub-analyses investigated ReDS in acute heart failure patients with congestion on CT. We included 97 patients within a median of 4.8 h from admittance: 25 patients (26%) were ReDS-positive and 39 (40%) had adjudicated acute heart failure (21 with and 18 without CT congestion). Heart failure patients had median ReDS 33%, left ventricular ejection fraction 48%, and NT-proBNP 2935 ng/L. A positive ReDS detected heart failure with 46% sensitivity, 88% specificity, and 71% accuracy. The AUC for ReDS was like the Boston score (P = 0.88) and the lung ultrasound score (P = 0.74). CT-congested heart failure patients had higher ReDS values than patients without heart failure (median 38 vs. 28%, P < 0.001). Heart failure patients without CT-congestion had ReDS values like patients without heart failure (mean 30 vs. 28%, P = 0.07). Conclusion: ReDS detects acute heart failure similarly to the Boston score and lung ultrasound score, and ReDS primarily identifies the acute heart failure patients who have congestion on a chest CT.

Chest computed tomography features of heart failure: A prospective observational study in patients with acute dyspnea.

BACKGROUND: Pulmonary congestion is a key component of heart failure (HF) that chest computed tomography (CT) can detect. However, no guideline describes which of many anticipated CT signs are most associated with HF in patients with undifferentiated dyspnea. METHODS: In a prospective observational single-center study, we included consecutive patients ≥ 50 years admitted with acute dyspnea to the emergency department. Patients underwent immediate clinical examination, blood sampling, echocardiography, and CT. Two radiologists independently evaluated all images. Acute HF (AHF) was adjudicated by an expert panel blinded to radiology images. LASSO and logistic regression identified the independent CT signs of AHF. RESULTS: Among 232 patients, 102 (44%) had AHF. Of 18 examined CT signs, 5 were associated with AHF (multivariate odds ratio, 95% confidence interval): enlarged heart (20.38, 6.86-76.16), bilateral interlobular thickening (11.67, 1.78-230.99), bilateral pleural effusion (6.39, 1.98-22.85), and increased vascular diameter (4.49, 1.08-33.92). Bilateral ground-glass opacification (2.07, 0.95-4.52) was a consistent fifth essential sign, although it was only significant in univariate analysis. Eighty-eight (38%) patients had none of the five CT signs corresponding to a 68% specificity and 86% sensitivity for AHF, while two or more of the five CT signs occurred in 68 (29%) patients, corresponding to 97% specificity and 67% sensitivity. A weighted score based on these five CT signs had an 0.88 area under the curve to detect AHF. CONCLUSIONS: Five CT signs seem sufficient to assess the risk of AHF in the acute setting. The absence of these signs indicates a low probability, one sign makes AHF highly probable, and two or more CT signs mean almost certain AHF.

Clinical Applicability of Lung Ultrasound Methods in the Emergency Department to Detect Pulmonary Congestion on Computed Tomography.

BACKGROUND: B-lines on lung ultrasound are seen in decompensated heart failure, but their diagnostic value in consecutive patients in the acute setting is not clear. Chest CT is the superior method to evaluate interstitial lung disease, but no studies have compared lung ultrasound directly to congestion on chest CT. PURPOSE: To examine whether congestion on lung ultrasound equals congestion on a low-dose chest CT as the gold standard. MATERIALS AND METHODS: In a single-center, prospective observational study we included consecutive patients ≥ 50 years of age in the emergency department. Patients were concurrently examined by lung ultrasound and chest CT. Congestion on lung ultrasound was examined in three ways: I) the total number of B-lines, II) ≥ 3 B-lines bilaterally, III) ≥ 3 B-lines bilaterally and/or bilateral pleural effusion. Congestion on CT was assessed by two specialists blinded to all other data. RESULTS: We included 117 patients, 27 % of whom had a history of heart failure and 52 % chronic obstructive pulmonary disease. Lung ultrasound and CT were performed within a median time of 79.0 minutes. Congestion on CT was detected in 32 patients (27 %). Method I had an optimal cut-point of 7 B-lines with a sensitivity of 72 % and a specificity of 81 % for congestion. Method II had 44 % sensitivity, and 94 % specificity. Method III had a sensitivity of 88 % and a specificity of 85 %. CONCLUSION: Pulmonary congestion in consecutive dyspneic patients ≥ 50 years of age is better diagnosed if lung ultrasound evaluates both B-lines and pleural effusion instead of B-lines alone.

P-wave indices as predictors of atrial fibrillation.

BACKGROUND: P-wave duration (PDURATION ) and P-wave area (PAREA ) have been linked to risk of atrial fibrillation (AF), but they do not improve the efficacy of Framingham AF risk score. We suggest the incorporation of both variables in one index, the P-wave area/P-wave duration (PAREA/DURATION ) index, which may be considered an expression of the average amplitude of the P wave that reflects aspects of P-wave morphology. OBJECTIVE: To assess the prognostic value of P-wave area/P-wave duration index (PAREA/DURATION index) in lead II together with other P-wave indices (PWIs) in incidence of AF in the Copenhagen Holter Study. METHODS: The study included 632 men and women, between 55 and 75 years with no apparent heart disease or AF. Baseline standard 12-lead Electrocardiography (ECGs) were analyzed manually. RESULTS: The median follow-up time was 14.7 (14.5;14.9) years. A total of 68 cases of AF and 233 cases of death were recorded. The restricted cubic spline method showed a U-shaped association between PAREA/DURATION and rate of AF. The lowest quintile of PAREA/DURATION index in lead II was associated with increased rate of AF, HR 2.80 (1.64-4.79). The addition of the new index to the Framingham model for AF improved the model in this population. The PAREA in lead II in its lowest quintile was also associated with increased rate of AF, HR 2.16 (1.25-3.75), but did not improve the Framingham model. PDURATION and P-wave terminal force (PTF) were not significantly associated with AF. CONCLUSION: A flat P wave as expressed by a small PAREA/DURATION index in lead II is associated with increased rate of incident AF beyond known AF risk factors.

Echocardiographic subtypes of heart failure in consecutive hospitalised patients with dyspnoea.

Heart failure with preserved ejection fraction (HFpEF) involves half of hospitalised patients with heart failure (HF), but estimates vary due to unclear diagnostic criteria. We performed a prospective observational study of hospitalised patients admitted with dyspnoea. The aim was to apply contemporary guidelines to diagnose HF due to valvular disease (HFvhd), HF due to reduced ejection fraction (HFrEF), HF due to midrange EF (HFmrEF) and HFpEF in relation to presumed cardiac or non-cardiac dyspnoea. Methods: We included consecutive hospitalised patients with presumed HF or dyspnoea and excluded patients with acute coronary syndrome, estimated glomerular filtration rate <30 mL/min/1.73 m² or low NT-proBNP (<296 ng/L). Higher age-adjusted NT-proBNP values excluded patients with presumptive non-cardiac dyspnoea. Contemporary criteria for HFpEF and diastolic dysfunction were assessed, and we adjudicated whether acute decompensated HF (ADHF) had been the primary diagnosis. Results: Of 707 eligible patients, we included 370 patients of whom 75 had non-cardiac dyspnoea. Of these, 10% (38/370) had no cardiac dysfunction. Cardiac dysfunction consisted of 18.4%, HFvhd, 30.1% HFrEF, 10.2% HFmrEF and 41.3% HFpEF. HFpEF was twice as common in presumptive non-cardiac dyspnoea versus cardiac dyspnoea (71% vs 34%, p<0.0001). However, adjudicated ADHF was the primary diagnosis in 80% of HFrEF, 62% of HFmrEF and just 28% of HFpEF. Conclusion: HF according to contemporary criteria applied to 90% of patients admitted with dyspnoea and elevated NT-proBNP irrespective of the presumptive cause of dyspnoea, of whom 10% had HFmrEF and 41% HFpEF. However, significant non-cardiac diagnoses related to 9 out of 10 with HFpEF with pulmonary disease as the predominant adjudicated problem.

Common source of miscalculation and misclassification of P-wave negativity and P-wave terminal force in lead V1.

BACKGROUND: P-wave terminal force (PTF) > 4000 ms·µV and deep terminal negativity (DTN) are ECG markers of left atrial abnormality associated with both atrial fibrillation and stroke. When the precordial lead V1 is placed higher than the correct position in the fourth intercostal space, it may cause increased PTF and DTN. Several studies have documented that electrode misplacement, especially high placement, is common. The influence of electrode misplacement on these novel ECG markers has not previously been quantified. OBJECTIVE: The objective was to assess the influence of electrode misplacement on PTF and DTN. METHOD: 12-Lead ECGs were recorded in 29 healthy volunteers from the Department of Cardiology at the Copenhagen University Hospital of Bispebjerg. The precordial electrode V1 was placed in the fourth, third and second intercostal space, giving a total of 3 ECGs per subject. Continuous variables were compared using Dunnett's post-hoc test and categorical variables were compared using Fischer's exact test. RESULTS: High placement of V1 electrodes resulted in a more than three-fold increase of PTF (IC4 = 2267 ms·µV, IC2 = 7996 ms·µV, p-value < 0.001). There was a similar increase of DTN (IC4 = 0%, IC2 = 28%, p-value < 0.001). P-wave area and amplitude of the negative deflection increased, and P-wave area and amplitude of the positive deflection decreased. The P-wave shape changed from being predominantly positive or biphasic in IC4 to 90% negative in IC2. The PR-duration and P-wave duration were not altered by electrode placement. CONCLUSION: High electrode placement results in significant alteration of PTF and DTN in lead V1.

Rationale and Design of the First Double-Blind, Placebo-Controlled Trial with Allogeneic Adipose Tissue-Derived Stromal Cell Therapy in Patients with Ischemic Heart Failure: A Phase II Danish Multicentre Study.

BACKGROUND: Ischemic heart failure (IHF) has a poor prognosis in spite of optimal therapy. We have established a new allogeneic Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors. It is produced without animal products, in closed bioreactor systems and cryopreserved as an off-the-shelf product ready to use. STUDY DESIGN: A multicentre, double-blind, placebo-controlled phase II study with direct intramyocardial injections of allogeneic CSCC_ASC in patients with chronic IHF. A total of 81 patients will be randomised at 2 : 1 to CSCC_ASC or placebo. There is no HLA tissue type matching needed between the patients and the donors. METHODS: The treatment will be delivered by direct injections into the myocardium. The primary endpoint is change in the left ventricle endsystolic volume at 6-month follow-up. Secondary endpoints are safety and changes in left ventricle ejection fraction, myocardial mass, stroke volume, and cardiac output. Other secondary endpoints are change in clinical symptoms, 6-minute walking test, and the quality of life after 6 and 12 months. CONCLUSION: The aim of the present study is to demonstrate safety and the regenerative efficacy of the allogeneic CSCC_ASC product from healthy donors in a double-blind, placebo-controlled, multicentre study in patients with IHF.

Effects of the glucagon-like peptide-1 receptor agonist liraglutide on 24-h ambulatory blood pressure in patients with type 2 diabetes and stable coronary artery disease: a randomized, double-blind, placebo-controlled, crossover study.

OBJECTIVE: The glucagon-like peptide-1 receptor agonist liraglutide has been shown to reduce blood pressure (BP) in clinical trials using office BP measurements. However, the effects of liraglutide on 24-h BP and on the diurnal variation in BP have not been explored sufficiently. METHODS: Forty-one patients with type 2 diabetes and stable coronary artery disease were randomized to receive liraglutide or placebo to a backbone therapy of metformin in this double-blind, placebo-controlled 12 along with 12 weeks crossover study. Ambulatory blood pressure monitoring (ABPM) was performed at the start and end of each intervention. RESULTS: Twenty-four individuals completed all 24-h BP measurements. Liraglutide, when compared with placebo, did not induce any significant changes in mean 24-h SBP [difference +1.8 mmHg (95% confidence interval, 95% CI: -4.33 to 7.93)] or DBP [+4.2 mmHg (-0.74 to 9.17)]. Twenty-four-hour BP profiles revealed a trend for increase in evening SBP and DBP [+9.2 mmHg (95% CI: 1.1-17.2) and +9.7 mmHg (95% CI: 3.9-15.5), respectively]. Mean heart rate significantly increased after liraglutide [+7.6 bpm (95% CI: 2.56-12.62)]. Liraglutide did not affect the BP variability or the nocturnal BP dipping. CONCLUSIONS: We could not demonstrate any BP-lowering effect of liraglutide when using 24-h ABPM. Liraglutide exhibited diurnal variation in the effect on BP without affecting the BP variability or nocturnal BP dipping.

Point-of-care procalcitonin test to reduce antibiotic exposure in patients hospitalized with acute exacerbation of COPD.

BACKGROUND: This study was conducted to investigate whether point-of-care (POC) procalcitonin (PCT) measurement can reduce redundant antibiotic treatment in patients hospitalized with acute exacerbation of COPD (AECOPD). METHODS: One-hundred and twenty adult patients admitted with AECOPD were enrolled in this open-label randomized trial. Patients were allocated to either the POC PCT-guided intervention arm (n=62) or the control arm, in which antibiotic therapy followed local guidelines (n=58). RESULTS: The median duration of antibiotic exposure was 3.5 (interquartile range [IQR] 0-10) days in the PCT-arm vs 8.5 (IQR 1-11) days in the control arm (P=0.0169, Wilcoxon) for the intention-to-treat population. The proportion of patients using antibiotics for ≥5 days within the 28-day follow-up was 41.9% (PCT-arm) vs 67.2% (P=0.006, Fisher's exact) in the intention-to-treat population. For the per-protocol population, the proportions were 21.1% (PCT-arm) vs 73.9% (P<0.00001, Fisher's exact). Within 28-day follow-up, one patient died in the PCT-arm and two died in the control arm. A composite harm end point consisting of death, rehospitalization, or intensive care unit admission, all within 28 days, showed no apparent difference. CONCLUSION: Our study shows that the implementation of a POC PCT-guided algorithm can be used to substantially reduce antibiotic exposure in patients hospitalized with AECOPD, with no apparent harm.

Reduced cerebral oxygen-carbohydrate index during endotracheal intubation in vascular surgical patients.

Brain activation reduces balance between cerebral consumption of oxygen versus carbohydrate as expressed by the so-called cerebral oxygen-carbohydrate-index (OCI). We evaluated whether preparation for surgery, anaesthesia including tracheal intubation and surgery affect OCI. In patients undergoing aortic surgery, arterial to internal jugular venous (a-v) concentration differences for oxygen versus lactate and glucose were determined from before anaesthesia to when the patient left the recovery room. Intravenous anaesthesia was supplemented with thoracic epidural anaesthesia for open aortic surgery (n = 5) and infiltration with bupivacaine for endovascular procedures (n = 14). The a-v difference for O2 decreased throughout anaesthesia and in the recovery room (1.6 ± 1.9 versus 3.2 ± 0.8 mmol l(-1), mean ± SD), and while a-v glucose decreased during surgery and into the recovery (0.4 ± 0.2 versus 0.7 ± 0.2 mmol l(-1) , P<0.05), a-v lactate did not change significantly (0.03 ± 0.16 versus -0.03 ± 0.09 mmol l(-1)). Thus, OCI decreased from 5.2 ± 1.8 before induction of anaesthesia to 3.2 ± 1.0 following tracheal intubation (P<0.05) because of the decrease in a-v O2 with a recovery for OCI to 4.6 ± 1.4 during surgery and to 5.6 ± 1.7 in the recovery room. In conclusion, preparation for surgery and tracheal intubation decrease OCI that recovers during surgery under the influence of sensory blockade.