Multi-modality assessment of congestion in acute heart failure: Associations with left ventricular ejection fraction and prognosis.

BACKGROUND: Integrating clinical examination with ultrasound measures of congestion could improve risk stratification in patients hospitalized with acute heart failure (AHF). AIM: To investigate the prevalence of clinical, echocardiographic and lung ultrasound (LUS) signs of congestion according to left ventricular ejection fraction (LVEF) and their association with prognosis in patients with AHF. METHODS: We pooled the data of four cohorts of patients (N = 601, 74.9±10.8 years, 59 % men) with AHF and analysed six features of congestion at enrolment: clinical (peripheral oedema and respiratory rales), biochemical (BNP/NT-proBNP≥median), echocardiographic (inferior vena cava (IVC)≥21 mm, pulmonary artery systolic pressure (PASP)≥40 mmHg, E/e'≥15) and B-lines ≥25 (8-zones) in those with reduced (<40 %, HFrEF), mildly reduced (40-49 %, HFmrEF and preserved (≥50 %HFpEF) LVEF. RESULTS: Compared to patients with HFmrEF (n = 110) and HFpEF (n = 201), those with HFrEF (N = 290) had higher natriuretic peptides, but prevalence of clinical (39 %), echocardiographic (IVC≥21 mm: 56 %, E/e'≥15: 57 %, PASP≥40 mmHg: 76 %) and LUS (48 %) signs of congestion was similar. In multivariable analysis, clinical (HR: 3.24(2.15-4.86), p < 0.001), echocardiographic [(IVC≥21 mm (HR:1.91, 1.21-3.03, p=0.006); E/e'≥15 (HR:1.54, 1.04-2.28, p = 0.031)] and LUS (HR:2.08, 1.34-3.24, p = 0.001) signs of congestion were significantly associated with all-cause mortality and/or HF re-hospitalization. Adding echocardiographic and LUS features of congestion to a model than included age, sex, systolic blood pressure, clinical congestion and natriuretic peptides, improved prediction at 90 and 180 days. CONCLUSIONS: Clinical and ultrasound signs of congestion are highly prevalent in patients with AHF, regardless of LVEF and their combined assessment improves risk stratification.

Usefulness of Combined Ultrasound Assessment of E/e' Ratio, Pulmonary Pressure, and Cava Vein Status in Patients With Acute Heart Failure.

Congestion is poorly investigated by ultrasound scans during acute heart failure (AHF) and systematic studies evaluating ultrasound indexes of cardiac pulmonary and systemic congestion during early hospital admission are lacking. We aimed to investigate the prevalence of ultrasound cardiac pulmonary and systemic congestion in a consecutive cohort of hospitalized patients with AHF, analyzing the relevance of each ultrasound congestion component (cardiac, pulmonary, and systemic) in predicting the risk of death and rehospitalization. This is a prospective research study of a single center that evaluates patients with an AHF diagnosis who are divided according to the left ventricular ejection fraction in patients with heart failure with preserved ejection fraction or reduced ejection fraction. We performed a complete bedside echocardiography and lung ultrasound analyses within the first 24 hours of hospital admission. The ultrasound congestion score was preliminarily established by measuring the following parameters: cardiac congestion, which was defined as the contemporary presence of E/e' >15 and pulmonary systolic pressure >35 mm Hg and the pulmonary congestion, defined as the total B-line number >25 at the lung ultrasound performed in 8 chest sites; moreover, the systemic congestion was defined if the inferior vena cava (IVC) was >21 mm and if it was associated with a reduced inspiratory collapse >50%. We thoroughly assessed 230 patients and evaluated their results. Of these patients, 135 had heart failure with reduced ejection fraction and there were 95 patients with heart failure with preserved ejection fraction; 122 patients experienced adverse events during the 180-day follow-up. The receiver operating characteristic curve analysis showed that the tricuspid annular peak systolic excursion (TAPSE) (area under the curve [AUC] 0.34 [0.26 to 0.41], p <0.001), E/e' (AUC 0.62 [0.54 to 0.69], p = 0.003), and IVC (AUC 0.70 [0.63 to 0.77], p <0.001) were all significantly related to poor prognosis detection. The univariate Cox regression analysis revealed that cardiac congestion in terms of E/e' and pulmonary systolic pressure (hazard ratio [HR] 1.49 [1.02 to 2.17], p = 0.037), TAPSE (HR 0.90 [0.85 to 0.94], p <0.001), and systemic congestion (HR 2.64 [1.53 to 4.56], p <0.001) were all significantly related to the 180-day outcome. After adjustment for potential confounders, only TAPSE (HR 0.92 [0.88 to 0.98], p = 0.005) and IVC (HR 1.92 [1.07 to 3.46], p = 0.029) confirmed their prognostic role. The multivariable analysis of multiple congestion levels in terms of systemic plus cardiac (HR 1.54 [1.05 to 2.25], p = 0.03), systemic plus pulmonary (HR 2.26 [1.47 to 3.47], p <0.001), and all 3 congestion features (HR 1.53 [1.06 to 2.23], p = 0.02) revealed an incremental prognostic role for each additional determinant. In conclusion, among the ultrasound indexes of congestion, IVC and TAPSE are related to adverse prognosis, and the addition of pulmonary and cardiac congestion indexes increases the risk prediction accuracy. Our data confirmed that right ventricular dysfunction and systemic congestion are the most powerful predictive factors in AHF.

The Conundrum of HFpEF Definition: Non-Invasive Assessment Uncertainties and Alternative Diagnostic Strategies.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome including several morphological phenotypes and varying pathophysiological mechanisms. The conventional classification of HF based on left ventricular ejection fraction (LVEF) has created an oversimplification in diagnostic criteria. Although LVEF is a standardized parameter easy to calculate and broadly applied in the large clinical trials, but it is erroneously considered an index of left ventricular (LV) systolic function. Indeed, it is affected by preload and afterload and it has limitations related to reproducibility, reduced sensitivity and scarce prognostic values especially when above 50%. Notably, additional diagnostic parameters have been recently proposed in order to improve diagnostic accuracy and to homogenize the different HFpEF populations. Unfortunately, these algorithms comprise sophisticated measurements that are difficult to apply in the daily clinical practice. Additionally, the scarce diffusion of these diagnostic criteria may have led to neutral or negative results in interventional phase 3 trials. We propose changes to the current HFpEF diagnostic approach mainly based on LVEF stratification measurement aiming towards a more inclusive model taking into consideration an integrative approach starting from the main diseases responsible for cardiac dysfunction through to cardiac structural and functional alterations. Accordingly, with recent universal HF definitions, a stepwise model could be helpful in recognizing patients with early vs. overt HFpEF by the appraisal of specific Doppler echocardiographic variables. Thus, we would encourage the application of new criteria in order to better identify the different phenotypes and to move towards more personalized medicine.

Non-invasive assessment of acute heart failure by Stevenson classification: Does echocardiographic examination recognize different phenotypes?

Background: Acute heart failure (AHF) presentation is universally classified in relation to the presence or absence of congestion and the peripheral perfusion condition according to the Stevenson diagram. We sought to evaluate a relationship existing between clinical assessment and echocardiographic evaluation in patients with AHF. Materials and methods: This is a retrospective blinded multicenter analysis assessing both clinical and echocardiographic analyses during the early hospital admission for AHF. Patients were categorized into four groups according to the Stevenson presentation: group A (warm and dry), group B (cold and dry), group C (warm and wet), and group D (cold and wet). Echocardiographic evaluation was executed within 12 h from the first clinical evaluation. The following parameters were measured: left ventricular (LV) volumes, LV ejection fraction (LVEF); pattern Doppler by E/e1 ratio, pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion (TAPSE), and inferior cave vein diameter (ICV). Results: We studied 208 patients, 10 in group A, 16 in group B, 153 in group C, and 29 in group D. Median age of our sample was 81 [69-86] years and the patients enrolled were mainly men (66.8%). Patients in groups C and A showed significant higher levels of systolic arterial pressures with respect to groups B and D (respectively, 130 [115-145] mmHg vs. 122 [119-130] mmHg vs. 92 [90-100] mmHg vs. 95 [90-100] mmHg, p < 0.001). Patients in groups A and C (warm) demonstrated significant higher values of LVEF with respect to patients in groups B and D (43 [34-49] vs. 42 [30-49] vs. 27 [15-31] vs. 30 [22-42]%, p < 0.001). Whereas group B experienced significant lower TAPSE values compared with other group (14 [12-17] mm vs. A: 17 [16-21] mm vs. C: 18 [14-20] mm vs. D: 16 [12-17] mm; p = 0.02). Finally, echocardiographic congestion score including PASP ≥ 40 mmHg, ICV ≥ 21, mm and E/e' > 14 did not differ among groups. Follow-up analysis showed an increased mortality rate in D group (HR 8.2 p < 0.04). Conclusion: The early Stevenson classification remains a simple and universally recognized approach for the detection of congestion and perfusion status. The combined clinical and echocardiographic assessment may be useful to better define the patients' profile.

Clinical, Laboratory and Lung Ultrasound Assessment of Congestion in Patients with Acute Heart Failure.

Congestion is the main cause of hospitalization in patients with acute heart failure (AHF), however its precise assessment by simple clinical evaluation remains elusive. The recent introduction of the lung ultrasound scan (LUS) allowed to physicians to more precisely quantify pulmonary congestion. The aim of this study was to compare clinical congestion (CC) with LUS and B-type natriuretic peptide (BNP) in order to achieve a more complete evaluation and to evaluate the prognostic power of each measurement. Methods: All patients were submitted to clinical evaluation for blood sample analysis and LUS at admission and before discharge. LUS protocol evaluated the number of B-lines for each chest zone by standardized eight site protocol. CC was measured following ESC criteria. The mean difference between admission and discharge congestion logBNP and B-lines values were calculated. Combined end points of death and rehospitalization was calculated over 180 days. Results: 213 patients were included in the protocol; 133 experienced heart failure with reduced ejection fraction (HFrEF), and 83 presented with heart failure with preserved ejection fraction (HFpEF). Patients with HFrEF had a more increased level of BNP (1150 (812−1790) vs. 851 (694−1196); p = 0.002) and B lines total number (32 (27−38) vs. 30 (25−36); p = 0.05). A positive correlation was found between log BNP and Blines number in both HFrEF (r = 0.57; p < 0.001) and HFpEF (r = 0.36; p = 0.001). Similarly, dividing B-lines among tertiles the upper group (B-lines ≥ 36) had an increased clinical congestion score. Among three variables at admission only B-lines were predictive for outcome (AUC 0.68 p < 0.001) but not LogBNP and CC score. During 180 days of follow-up, univariate analysis showed that persistent ΔB-lines <−32.3% (HR 6.54 (4.19−10.20); p < 0.001), persistent ΔBNP < −43.8% (HR 2.48 (1.69−3.63); p < 0.001) and persistent ΔCC < 50% (HR 4.25 (2.90−6.21); p < 0.001) were all significantly related to adverse outcome. Multivariable analysis confirmed that persistent ΔB-lines (HR 4.38 (2.64−7.29); p < 0.001), ΔBNP (HR 1.74 (1.11−2.74); p = 0.016) and ΔCC (HR 3.38 (2.10−5.44); p < 0.001 were associated with the combined end point. Conclusions: a complete clinical laboratory and LUS assessment better recognized different congestion occurrence in AHF. The difference between admission and discharge B-lines provides useful prognostic information compared to traditional clinical evaluation.

Pulmonary Congestion Assessment in Heart Failure: Traditional and New Tools.

Congestion related to cardiac pressure and/or volume overload plays a central role in the pathophysiology, presentation, and prognosis of heart failure (HF). Most HF exacerbations are related to a progressive rise in cardiac filling pressures that precipitate pulmonary congestion and symptomatic decompensation. Furthermore, persistent symptoms and signs of congestion at discharge or among outpatients are strong predictors of an adverse outcome. Pulmonary congestion is also one of the most important diagnostic and therapeutic targets in chronic heart failure. The aim of this review is to analyze the importance of clinical, instrumental, and biochemical evaluation of congestion in HF by describing old and new tools. Lung ultrasonography (LUS) is an emerging method to assess pulmonary congestion. Accordingly, we describe the additive prognostic role of chest ultrasound with respect to traditional clinical and X-ray assessment in acute and chronic HF setting.

Mortality Risk Assessment Using CHA(2)DS(2)-VASc Scores in Patients Hospitalized With Coronavirus Disease 2019 Infection.

Early risk stratification for complications and death related to Coronavirus disease 2019 (COVID-19) infection is needed. Because many patients with COVID-19 who developed acute respiratory distress syndrome have diffuse alveolar inflammatory damage associated with microvessel thrombosis, we aimed to investigate a common clinical tool, the CHA(2)DS(2)-VASc, to aid in the prognostication of outcomes for COVID-19 patients. We analyzed consecutive patients from the multicenter observational CORACLE registry, which contains data of patients hospitalized for COVID-19 infection in 4 regions of Italy, according to data-driven tertiles of CHA(2)DS(2)-VASc score. The primary outcomes were inpatient death and a composite of inpatient death or invasive ventilation. Of 1045 patients in the registry, 864 (82.7%) had data available to calculate CHA(2)DS(2)-VASc score and were included in the analysis. Of these, 167 (19.3%) died, 123 (14.2%) received invasive ventilation, and 249 (28.8%) had the composite outcome. Stratification by CHA(2)DS(2)-VASc tertiles (T1: ≤1; T2: 2 to 3; T3: ≥4) revealed increases in both death (8.1%, 24.3%, 33.3%, respectively; p <0.001) and the composite end point (18.6%, 31.9%, 43.5%, respectively; p <0.001). The odds ratios for mortality and the composite end point for T2 patients versus T1 CHA(2)DS(2)-VASc score were 3.62 (95% CI:2.29 to 5.73,p <0.001) and 2.04 (95% CI:1.42 to 2.93, p <0.001), respectively. Similarly, the odds ratios for mortality and the composite end point for T3 patients versus T1 were 5.65 (95% CI:3.54 to 9.01, p <0.001) and 3.36 (95% CI:2.30 to 4.90,p <0.001), respectively. In conclusion, among Italian patients hospitalized for COVID-19 infection, the CHA(2)DS(2)-VASc risk score for thromboembolic events enhanced the ability to achieve risk stratification for complications and death.

Diagnostic utility of contemporary echo and BNP assessment in patients with acute heart failure during early hospitalization.

BACKGROUND: The use of B-type natriuretic peptide (BNP) and echocardiography in acute heart failure (AHF) diagnosis is poorly employed in the Emergency Department. The aim of the present study is to evaluate relation among BNP levels systolic and diastolic dysfunction during early phases of AHF hospitalization. METHODS: We performed contemporary echocardiographic and BNP assessment in 310 patients with AHF within 12h since hospital admission. We studied the correlation among BNP and degree of diastolic dysfunction evaluated by pulsed Doppler transmitral flow and Tissue Doppler flow. Finally we investigated the relation among BNP and the right systolic longitudinal ventricular function (TAPSE) and the systolic pulmonary arterial pressure (PAPs). RESULTS: BNP levels were 1417±1126, 1081±955, 894±901pg/mL, for patients with EF≤25%, EF 25-40% and EF 40-50% (p=0.005), respectively. "BNP levels linearly correlate with the degree of diastolic dysfunction: 582±406pg/mL in altered relaxation pattern, 712±557pg/mL in pseudonormal pattern and 1694±805 in restrictive filling pattern (p<0.001 for all patterns)." BNP levels were significantly increased in patients with right systolic ventricular dysfunction (TAPSE<18mm; p=0.006) and in patients with PAPs≥40mmHg (p=0.001). ROC curve and logistic regression analysis highlighted the power of BNP to detect severe systolic dysfunction, right ventricular (RV) overload and dysfunction and diastolic dysfunction patterns. CONCLUSIONS: BNP levels correlate linearly with LV systolic dysfunction as well as with impaired degree of diastolic dysfunction. Significant PAP increase is a further factor influencing BNP elevation in patients with AHF during early hospitalization phase.

Cardio-renal syndrome: an entity cardiologists and nephrologists should be dealing with collegially.

Heart failure may lead to acute kidney injury and vice versa. Chronic kidney disease may affect the clinical outcome in terms of cardiovascular morbidity and mortality while chronic heart failure may cause CKD. All these disorders contribute to the composite definition of cardio-renal syndromes. Renal impairment in HF patients has been increasingly recognized as an independent risk factor for morbidity and mortality; however, the most important clinical trials in HF tend to exclude patients with significant renal dysfunction. The mechanisms whereby renal insufficiency worsens the outcome in HF are not known, and several pathways could contribute to the "vicious heart/kidney circle." Traditionally, renal impairment has been attributed to the renal hypoperfusion due to reduced cardiac output and decreased systemic pressure. The hypovolemia leads to sympathetic activity, increased renin-angiotensin-aldosterone pathways and arginine-vasopressin release. All these mechanisms cause fluid and sodium retention, peripheral vasoconstriction and an increased congestion as well as cardiac workload. Therapy addressed to improve renal dysfunction, reduce neurohormonal activation and ameliorate renal blood flow could lead to a reduction in mortality and hospitalization in patients with cardio-renal syndrome.

Brain natriuretic peptide and other risk markers for outcome assessment in patients with non-ST-elevation coronary syndromes and preserved systolic function.

Several emerging cardiac markers constitute strong predictors among patients with coronary artery disease. In particular, brain natriuretic peptide (BNP), troponin T (TnT), and C-reactive protein (CRP) are related to increased risk of recurrent ischemic events and death. However, little is known about the utility of these biomarkers in combination. This study examined risk assessment in patients with coronary artery disease and preserved systolic function. We studied 208 consecutive patients (138 men, 70 women) with stable angina, unstable angina, and non-Q-wave myocardial infarction whose plasma BNP, TnT, and CRP levels were measured at hospital admission. All recruited patients underwent echocardiographic examination, and selective coronary angiography was performed. After adjusting for clinical presentation, age, gender, and common risk factors, BNP was demonstrated as a strong predictor of heart failure (6 months, odds ratio [OR] 2.03, 95% confidence interval [CI] 1.24 to 2.9, p <0.01; 12 months, OR 2.65, 95% CI 1.69 to 3.5, p <0.001) and mortality at 3, 6, and 12 months (p <0.001). BNP was also significantly related to extent of coronary artery disease and left anterior descending artery involvement (p <0.01). Patients with a BNP level >80 pg/ml in all 3 groups had a significantly poorer prognosis with increased incidence of heart failure and death. CRP was related to recurrent ischemic events (infarct or recurrent angina, OR 1.4, 95% CI 1.14 to 2.08, p <0.01) and was associated with major cardiac revascularization at 12 months (OR 1.51, 95% CI 1.29 to 1.73, p <0.001). TnT demonstrated a mild correlation with recurrent infarct or angina at 12 months (OR 1.1, 95% CI 0.96 to 1.22, p <0.05) but appeared related to multivessel coronary artery disease (OR 1.47, 95% CI 1.05 to 1.99, p <0.01). In conclusion, BNP appears to be associated with a long-term increased risk of mortality and heart failure in patients with apparently mild risk. BNP is also associated with a larger extent and greater severity of myocardial ischemia. Early BNP measurement could provide incremental information to TnT and CRP, and it may be the strongest independent predictor of cardiac outcome in subjects without left ventricular dysfunction or enlargement.