Predictors of heart failure readmission and all-cause mortality in patients with acute heart failure.

BACKGROUND: Predischarge risk stratification of patients with acute heart failure (AHF) could facilitate tailored treatment and follow-up, however, simple scores to predict short-term risk for HF readmission or death are lacking. METHODS: We sought to develop a congestion-focused risk score using data from a prospective, two-center observational study in adults hospitalized for AHF. Laboratory data were collected on admission. Patients underwent physical examination, 4-zone, and in a subset 8-zone, lung ultrasound (LUS), and echocardiography at baseline. A second LUS was performed before discharge in a subset of patients. The primary endpoint was the composite of HF hospitalization or all-cause death. RESULTS: Among 350 patients (median age 75 years, 43% women), 88 participants (25%) were hospitalized or died within 90 days after discharge. A stepwise Cox regression model selected four significant independent predictors of the composite outcome, and each was assigned points proportional to its regression coefficient: NT-proBNP ≥2000 pg/mL (admission) (3 points), systolic blood pressure < 120 mmHg (baseline) (2 points), left atrial volume index ≥60 mL/m2 (baseline) (1 point) and ≥ 9 B-lines on predischarge 4-zone LUS (3 points). This risk score provided adequate risk discrimination for the composite outcome (HR 1.48 per 1 point increase, 95% confidence interval: 1.32-1.67, p < 0.001, C-statistic: 0.70). In a subset of patients with 8-zone LUS data (n = 176), results were similar (C-statistic: 0.72). CONCLUSIONS: A four-variable risk score integrating clinical, laboratory and ultrasound data may provide a simple approach for risk discrimination for 90-day adverse outcomes in patients with AHF if validated in future investigations.

Dapagliflozin vs. metolazone in heart failure resistant to loop diuretics.

BACKGROUND AND AIMS: To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide. METHODS AND RESULTS: A multi-centre, open-label, randomized, and active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 h). The primary endpoint was a diuretic effect, assessed by change in weight (kg). Secondary endpoints included a change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score. 61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 h was 977 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 h was 3.0 (2.5) kg with dapagliflozin compared to 3.6 (2.0) kg with metolazone [mean difference 0.65, 95% confidence interval (CI) -0.12,1.41 kg; P = 0.11]. Loop diuretic efficiency was less with dapagliflozin than with metolazone [mean 0.15 (0.12) vs. 0.25 (0.19); difference -0.08, 95% CI -0.17,0.01 kg; P = 0.10]. Changes in pulmonary congestion and volume assessment score were similar between treatments. Decreases in plasma sodium and potassium and increases in urea and creatinine were smaller with dapagliflozin than with metolazone. Serious adverse events were similar between treatments. CONCLUSION: In patients with heart failure and loop diuretic resistance, dapagliflozin was not more effective at relieving congestion than metolazone. Patients assigned to dapagliflozin received a larger cumulative dose of furosemide but experienced less biochemical upset than those assigned to metolazone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04860011.

Trajectory and correlates of pulmonary congestion by lung ultrasound in patients with acute myocardial infarction: insights from PARADISE-MI.

AIM: PARADISE-MI examined the efficacy of sacubitril/valsartan in acute myocardial infarction (AMI) complicated by reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both. We sought to assess the trajectory of pulmonary congestion using lung ultrasound (LUS) and its association with cardiac structure and function in a pre-specified substudy. METHODS AND RESULTS: Patients without prior heart failure (HF) underwent eight-zone LUS and echocardiography at baseline (±2 days of randomization) and after 8 months. B-lines were quantified offline, blinded to treatment, clinical findings, time point, and outcomes. Among 152 patients (median age 65, 32% women, mean LVEF 41%), B-lines were detectable in 87% at baseline [median B-line count: 4 (interquartile range 2-8)]. Among 115 patients with LUS data at baseline and follow-up, B-lines decreased significantly from baseline (mean ± standard deviation: -1.6 ± 7.3; P = 0.018). The proportion of patients without pulmonary congestion at follow-up was significantly higher in those with fewer B-lines at baseline. Adjusted for baseline, B-lines at follow-up were on average 6 (95% confidence interval: 3-9) higher in patients who experienced an intercurrent HF event vs. those who did not (P = 0.001). A greater number of B-lines at baseline was associated with larger left atrial size, higher E/e' and E/A ratios, greater degree of mitral regurgitation, worse right ventricular systolic function, and higher tricuspid regurgitation velocity (P-trend <0.05 for all). CONCLUSION: In this AMI cohort, B-lines, indicating pulmonary congestion, were common at baseline and, on average, decreased significantly from baseline to follow-up. Worse pulmonary congestion was associated with prognostically important echocardiographic markers.

Health-related quality of life in acute heart failure: association between patient-reported symptoms and markers of congestion.

AIMS: The aim of this study was to examine the association between patient-reported symptoms and the extent of pulmonary congestion in acute heart failure (AHF). METHODS AND RESULTS: In this prospective, observational study, patient-reported symptoms were assessed at baseline using the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) (range 0-100; 0 worst) in patients hospitalized for AHF. In a subset, patient-reported dyspnoea at rest and on exertion was examined (range 0-10; 10 worst) at baseline. In addition, 4-zone lung ultrasound (LUS) was performed at baseline at the time of echocardiography. B-lines were quantified offline, blinded to clinical findings, by a core laboratory. Chest X-ray (CXR) and physical examination findings were collected from the medical records. Among 322 patients (mean age 72, 60% men, mean left ventricular ejection fraction 39%) with AHF, the median KCCQ-TSS score was 33 (interquartile range 18-48). Worse KCCQ-TSS was associated with worse New York Heart Association class, dyspnoea at rest and on exertion, and peripheral oedema (p trend <0.001 for all). However, KCCQ-TSS was not associated with the extent of pulmonary congestion, as assessed by the number of B-lines on LUS, or findings on CXR, or physical examination (p trend >0.25 for all). Similarly, KCCQ-TSS was not significantly associated with echocardiographic markers of left ventricular filling pressure, pulmonary pressure or with N-terminal pro-B-type natriuretic peptide level. CONCLUSIONS: Among patients hospitalized for AHF, at baseline, KCCQ-TSS was not associated with pulmonary congestion assessed by LUS, CXR, or physical examination. These findings suggest that the profound reduction in KCCQ-TSS in patients with AHF may not be solely explained by pulmonary congestion.

Temporal Changes in Electrolytes, Acid-Base, QTc Duration, and Point-of-Care Ultrasound during Inpatient Hemodialysis Sessions.

Background: Of the more than 550,000 patients receiving maintenance hemodialysis (HD) in the United States, each has an average of 1.6 admissions annually (>880,000 inpatient HD sessions). Little is known about the temporal changes in laboratory values, ECGs, and intravascular and extravascular volume during inpatient HD sessions. Methods: In this prospective cohort study of hospitalized HD patients, we assessed intradialytic laboratory values (metabolic panels, blood gases, ionized calcium levels), ECGs, and sonographic measures of volume status. Results: Among 30 participants undergoing HD (mean age 62 years; 53% men, 43% Black) laboratory values had the largest changes in the first hour of HD. There was no significant change in ionized calcium levels pre- to post-HD (change: -0.01±0.07, P=0.24); 12 of 30 and 17 of 30 patients had levels below the lower reference limit at the beginning and end of HD, respectively. The mean pH increased pre- to post-HD (change: 0.06±0.04, P<0.001); 21 of 30 had a pH above the upper reference limit post-HD. There was a trend toward longer median QTc duration from pre- to post-HD (change: 7.5 msec [-5 msec, 19 msec], P=0.07). The sum of B lines on lung ultrasound decreased from pre- to post-HD (median decrease: 3 [1, 7], P<0.01). The collapsibility index of the inferior vena cava increased pre- to post-HD (median increase: 4.8% [1.5%, 13.4%], P=0.01), whereas internal jugular vein diameter did not change (P=0.24). Conclusions: Among hospitalized patients undergoing HD, we found dynamic changes in laboratory values, QTc duration, and volume status. Further research is required to assess whether HD prescriptions can be tailored to alter these variations to potentially improve patient outcomes.

Lung ultrasound findings following COVID-19 hospitalization: A prospective longitudinal cohort study.

BACKGROUND: Lung ultrasound (LUS) is a useful tool for diagnosis and monitoring in patients with active COVID-19-infection. However, less is known about the changes in LUS findings after a hospitalization for COVID-19. METHODS: In a prospective, longitudinal study in patients with COVID-19 enrolled from non-ICU hospital units, adult patients underwent 8-zone LUS and blood sampling both during the hospitalization and 2-3 months after discharge. LUS images were analyzed blinded to clinical variables and outcomes. RESULTS: A total of 71 patients with interpretable LUS at baseline and follow up (mean age 64 years, 61% male, 24% with acute respiratory distress syndrome (ARDS)) were included. The follow-up LUS was performed a median of 72 days after the initial LUS performed during hospitalization. At baseline, 87% had pathologic LUS findings in ≥1 zone (e.g. ≥3 B-lines, confluent B-lines or subpleural or lobar consolidation), whereas 30% had pathologic findings at follow-up (p < 0.001). The total number of B-lines and LUS score decreased significantly from hospitalization to follow-up (median 17 vs. 4, p < 0.001 and 4 vs. 0, p < 0.001, respectively). On the follow-up LUS, 28% of all patients had ≥3 B-lines in ≥1 zone, whereas in those with ARDS during the baseline hospitalization (n = 17), 47% had ≥3 B-lines in ≥1 zone. CONCLUSION: LUS findings improved significantly from hospitalization to follow-up 2-3 months after discharge in COVID-19 survivors. However, persistent B-lines were frequent at follow-up, especially among those who initially had ARDS. LUS seems to be a promising method to monitor COVID-19 lung changes over time. GOV ID: NCT04377035.

Prevalence and Dynamic Changes in Lung Ultrasound Findings among Adults with Uncomplicated Malaria and Controls in the Amazon Basin, Brazil.

Malaria patients are at risk of cardiopulmonary complications but diagnosis and management can be difficult in resource-limited settings. B-lines on lung ultrasound (LUS) mark changes in lung density; however, little is known about their role in malaria. We aimed to examine the prevalence of B-lines in adults with malaria at baseline and follow-up compared with controls in the Amazon Basin. We also examined the relationship between B-lines and left ventricular ejection fraction. We performed eight-zone LUS, echocardiography, and blood smears in 94 adults (mean age 40 years, 54% men) with uncomplicated malaria and 449 controls without heart failure, renal insufficiency or lung disease (mean age 41 years, 38% men). Examinations of adults with malaria were repeated after antimalarial treatment, corresponding to a median of 30 days (interquartile range [IQR] 27-39). Adults with malaria suffered from Plasmodium vivax (N = 70, median 2,823 [IQR 598-7,698] parasites/µL) or P. falciparum (N = 24, median 1,148 [IQR 480-3,128] parasites/µL). At baseline, adults with malaria more frequently had ≥ 3 B-lines (summed across eight zones) compared with controls (30% versus 2%, P value < 0.001), indicating higher lung density. When examinations were repeated, only 6% of adults with malaria had ≥ 3 B-lines at follow-up, which was significant lower compared with baseline (median reduction 3 B-line; P value < 0.001). B-lines were not significantly associated with left ventricular ejection fraction in adults with malaria. In conclusion, B-lines detected by LUS were more frequent in adults with uncomplicated malaria compared with controls and decreased after completed antimalarial treatment.

Global and regional wall motion abnormalities and incident heart failure in the general population.

BACKGROUND: Wall Motion Score Index (WMSI) is a simple method to quantify global and regional systolic function on echocardiography. We sought to investigate the prognostic importance of global and regional WMSI for the development of incident heart failure (HF) in the general population. METHODS: We included adults without HF or ischemic heart disease from the 4th Copenhagen City Heart Study (2001-2003). At baseline, participants underwent an echocardiography and physical examination and completed a self-administered health questionnaire. WMSI was assessed by conventional echocardiography using a 16-segment model obtaining WMSI assessments for the anterior, lateral, inferior, septal, and posterior left ventricular (LV) walls and calculating a global WMSI. The primary endpoint was incident HF. RESULTS: Among 3415 participants (mean age 58 years, 42% male, 45% with hypertension), 83 (2.4%) had hypo-, a-, or dyskinesia of at least one LV wall segment at baseline. During a median follow-up of 15.4 years, 297 (8.7%) participants developed HF. After adjusting for important clinical variables, LV ejection fraction and E/A, hypo-, a- or dyskinesia of at least one segment in any of the LV regional walls was associated with a higher risk of incident HF (HR 3.63, 95% CI 2.15-6.12, p < 0.001). Similarly, global WMSI was independently associated with a higher risk of HF (HR 1.38 per 0.1 increase, 95%CI 1.22-1.56, p < 0.001). CONCLUSION: Wall motion abnormalities in any regional LV wall and global WMSI were associated with incident HF in this general population cohort independent of various baseline clinical data, LV ejection fraction and E/A.

Acute Heart Failure in the 2021 ESC Heart Failure Guidelines: a scientific statement from the Association for Acute CardioVascular Care (ACVC) of the European Society of Cardiology.

The current European Society of Cardiology (ESC) Heart Failure Guidelines are the most comprehensive ESC document covering heart failure to date; however, the section focused on acute heart failure remains relatively too concise. Although several topics are more extensively covered than in previous versions, including some specific therapies, monitoring and disposition in the hospital, and the management of cardiogenic shock, the lack of high-quality evidence in acute, emergency, and critical care scenarios, poses a challenge for providing evidence-based recommendations, in particular when by comparison the data for chronic heart failure is so extensive. The paucity of evidence and specific recommendations for the general approach and management of acute heart failure in the emergency department is particularly relevant, because this is the setting where most acute heart failure patients are initially diagnosed and stabilized. The clinical phenotypes proposed are comprehensive, clinically relevant and with minimal overlap, whilst providing additional opportunity for discussion around respiratory failure and hypoperfusion.

Left atrial inflow propagation velocity derived by color M-mode Doppler in acute heart failure.

Left atrial (LA) inflow propagation velocity from the pulmonary vein (LAIF-PV) has been proposed as a novel measure of LA reservoir function and is associated with pulmonary capillary wedge pressure in critically ill patients. However, data on LAIF-PV in acute heart failure (AHF) are lacking. We sought to examine the feasibility of measuring LAIF-PV and evaluate clinical and echocardiographic correlates of LAIF-PV in AHF. In a prospective cohort study of adults hospitalized for AHF, we used color M-mode Doppler of the pulmonary veins to obtain LAIF-PV in systole. Among 142 patients with appropriate images and no more than moderate mitral regurgitation, LAIF-PV measures were feasible in 76 patients (54%) aged 71 ± 14 years, including 68% men with left ventricular ejection fraction (LVEF) 38% ± 13. Mean LAIF-PV was 24.2 ± 5.9 cm/s. In multivariable regression analysis adjusted for age, sex, systolic blood pressure, heart rate, body mass index, New York Heart Association class, LA volume and LVEF, the only independent echocardiographic predictors of LAIF-PV were right ventricular (RV) S' [ß 0.46 cm/s per cm/s (95% CI 0.01-0.91), p = 0.045] and tricuspid annular plane systolic excursion (TAPSE) [ß 0.28 cm/s per mm (95% CI 0.02-0.54), p = 0.039]. Notably, LAIF-PV was not significantly correlated with measures of LV function, LA function or E/e'. In conclusion, LAIF-PV was measurable in 54% of patients with AHF, and lower values were associated with measures of impaired RV systolic function but not LV or LA function.

Layer-specific and whole wall global longitudinal strain predict major adverse cardiovascular events in patients with stable angina pectoris.

Global longitudinal strain (GLS) has proven to be a powerful prognostic marker in various patient populations, but the prognostic value of layer-specific GLS has not yet been investigated in patients with suspected stable angina pectoris (SAP). We sought to investigate the prognostic value of layer-specific and whole wall GLS in patients with suspected SAP. From September 2008 to March 2011, 296 consecutive patients with clinically suspected SAP, normal ejection fraction, and no previous cardiac history were enrolled in a prospective cohort study. Patients underwent echocardiography including two-dimensional speckle tracking at rest, exercise stress test, and coronary angiography. The end-point was a composite of incident heart failure, acute myocardial infarction, and cardiovascular death (MACE). Out of the 285 included patients (mean age 61 years, 50% male), 24 (8%) developed MACE during a median follow-up of 3.5 years. Both endocardial [hazard ratio (HR) 1.21, 95% CI 1.08-1.35, p = 0.001], epicardial (HR 1.29, 95% CI 1.12-1.50, p = 0.001) and whole wall GLS (HR 1.25, 1.10-1.42, p = 0.001) were significantly associated with an increased risk of developing MACE during follow-up in univariable Cox regression analysis. In multivariable analysis, only epicardial (HR 1.23, 95% CI 1.00-1.51, p = 0.046) and whole wall GLS (HR 1.20, 95% CI 1.00-1.43, p = 0.049) remained significantly associated with an increased risk of MACE independent of various baseline clinical variables, left ventricular ejection fraction (LVEF), E/e' and Duke Score. Layer-specific and whole wall GLS were significant predictors of MACE in this cohort of patients with suspected SAP independent of various baseline clinical variables, LVEF, E/e' and Duke Score.

Measures of left atrial function predict incident heart failure in a low-risk general population: the Copenhagen City Heart Study.

AIMS: This study investigated left atrial (LA) parameters as measured on transthoracic echocardiography as predictors of incident heart failure (HF) in a community cohort. METHODS AND RESULTS: In a large general population study (n = 2221), participants underwent a health examination with echocardiography. The maximum and minimum LA volumes indexed to body surface area (LAVImax and LAVImin) were measured and the LA emptying fraction (LAEF) and LA expansion index (LAEI) were calculated. Among 1951 participants without atrial fibrillation or significant valve disease, the mean age was 59 ± 16 years and 58% were women. At baseline, 1% (n = 16) had a left ventricular ejection fraction of <50%, 44% had hypertension, and 10% had diabetes. During follow-up (median 15.8 years, interquartile range: 11.3-16.2 years), 187 (10%) participants were diagnosed with incident HF. Participants who were diagnosed with HF during follow-up had a larger LAVImax and LAVImin and a lower LAEF and LAEI compared to participants without HF. In unadjusted analysis, LAVImax, LAVImin, LAEF and LAEI were predictors of incident HF. After multivariable adjustment for clinical and echocardiographic parameters, only LAVImin remained an independent predictor of incident HF (hazard ratio per 1 standard deviation increase: 1.22 [95% confidence interval 1.01-1.47], p = 0.038). CONCLUSION: In the general population, LAVImin is an independent predictor of incident HF. LAVImax, currently the only LA measure in a routine echocardiographic examination, was not an independent predictor of incident HF.

Lung ultrasound findings in hospitalized COVID-19 patients in relation to venous thromboembolic events: the ECHOVID-19 study.

PURPOSE: Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE). METHODS: A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores). RESULTS: Median time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses. CONCLUSION: In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating. GOV ID: NCT04377035.

Lung Ultrasound Findings Associated With COVID-19 ARDS, ICU Admission, and All-Cause Mortality.

BACKGROUND: As lung ultrasound (LUS) has emerged as a diagnostic tool in patients with COVID-19, we sought to investigate the association between LUS findings and the composite in-hospital outcome of ARDS incidence, ICU admission, and all-cause mortality. METHODS: In this prospective, multi-center, observational study, adults with laboratory-confirmed SARS-CoV-2 infection were enrolled from non-ICU in-patient units. Subjects underwent an LUS evaluating a total of 8 zones. Images were analyzed off-line, blinded to clinical variables and outcomes. A LUS score was developed to integrate LUS findings: ≥ 3 B-lines corresponded to a score of 1, confluent B-lines to a score of 2, and subpleural or lobar consolidation to a score of 3. The total LUS score ranged from 0-24 per subject. RESULTS: Among 215 enrolled subjects, 168 with LUS data and no current signs of ARDS or ICU admission (mean age 59 y, 56% male) were included. One hundred thirty-six (81%) subjects had pathologic LUS findings in ≥ 1 zone (≥ 3 B-lines, confluent B-lines, or consolidations). Markers of disease severity at baseline were higher in subjects with the composite outcome (n = 31, 18%), including higher median C-reactive protein (90 mg/L vs 55, P < .001) and procalcitonin levels (0.35 µg/L vs 0.13, P = .033) and higher supplemental oxygen requirements (median 4 L/min vs 2, P = .001). However, LUS findings and score did not differ significantly between subjects with the composite outcome and those without, and were not associated with outcomes in unadjusted and adjusted logistic regression analyses. CONCLUSIONS: Pathologic findings on LUS were common a median of 3 d after admission in this cohort of non-ICU hospitalized subjects with COVID-19 and did not differ among subjects who experienced the composite outcome of incident ARDS, ICU admission, and all-cause mortality compared to subjects who did not. These findings should be confirmed in future investigations. The study is registered at Clinicaltrials.gov (NCT04377035).