Haemodynamic forces predicting remodelling and outcome in patients with heart failure treated with sacubitril/valsartan.

AIMS: A novel tool for the evaluation of left ventricular (LV) systo-diastolic function through echo-derived haemodynamic forces (HDFs) has been recently proposed. The present study aimed to assess the predictive value of HDFs on (i) 6 month treatment response to sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) patients and (ii) cardiovascular events. METHODS AND RESULTS: Eighty-nine consecutive HFrEF patients [70% males, 65 ± 9 years, LV ejection fraction (LVEF) 27 ± 7%] initiating sacubitril/valsartan underwent clinical, laboratory, ultrasound and cardiopulmonary exercise testing evaluations. Patients experiencing no adverse events and showing ≥50% reduction in plasma N-terminal pro-B-type natriuretic peptide and/or ≥10% LVEF increase over 6 months were considered responders. Patients were followed up for the composite endpoint of HF-related hospitalisation, atrial fibrillation and cardiovascular death. Forty-five (51%) patients were responders. Among baseline variables, only HDF-derived whole cardiac cycle LV strength (wLVS) was higher in responders (4.4 ± 1.3 vs. 3.6 ± 1.2; p = 0.01). wLVS was also the only independent predictor of sacubitril/valsartan response at multivariable logistic regression analysis [odds ratio 1.36; 95% confidence interval (CI) 1.10-1.67], with good accuracy at receiver operating characteristic (ROC) analysis [optimal cutpoint: ≥3.7%; area under the curve (AUC) = 0.736]. During a 33 month (23-41) median follow-up, a wLVS increase after 6 months (ΔwLVS) showed a high discrimination ability at time-dependent ROC analysis (optimal cut-off: ≥0.5%; AUC = 0.811), stratified prognosis (log-rank p < 0.0001) and remained an independent predictor for the composite endpoint (hazard ratio 0.76; 95% CI 0.61-0.95; p < 0.01), after adjusting for clinical and instrumental variables. CONCLUSIONS: HDF analysis predicts sacubitril/valsartan response and might optimise decision-making in HFrEF patients.

A novel echocardiographic method for estimation of pulmonary artery wedge pressure and pulmonary vascular resistance.

AIMS: This study aimed to evaluate a novel echocardiographic algorithm for quantitative estimation of pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR) in patients with heart failure and pulmonary hypertension (PH) scheduled to right heart catheterization (RHC). METHODS AND RESULTS: In this monocentric study, 795 consecutive patients (427 men; age 68.4 ± 12.1 years) undergoing echocardiography and RHC were evaluated. Multiple regression analysis was performed to identify echocardiographic predictors of PAWP and PVR measured by RHC in the derivation group (the first 200 patients). The diagnostic accuracy of the model was then tested in the validation group (the remaining 595 patients). PH was confirmed by RHC in 507 (63.8%) patients, with 192 (24.2%) cases of precapillary PH, 248 (31.2%) of postcapillary PH, and 67 (8.4%) of combined PH. At regression analysis, tricuspid regurgitation maximal velocity, mitral E/e' ratio, left ventricular ejection fraction, right ventricular fractional area change, inferior vena cava diameter, and left atrial volume index were included in the model (R = 0.8, P < 0.001). The model showed a high diagnostic accuracy in estimating elevated PAWP (area under the receiver operating characteristic curve = 0.97, 92% sensitivity, and 93% specificity, P < 0.001) and PVR (area under the receiver operating characteristic curve = 0.96, 89% sensitivity, and 92% specificity, P < 0.001), outperforming 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations (P < 0.001) and Abbas' equation (P < 0.001). Bland-Altman analysis showed satisfactory limits of agreement between echocardiography and RHC for PAWP (bias 0.7, 95% confidence interval -7.3 to 8.7) and PVR (bias -0.1, 95% confidence interval -2.2 to 1.9 Wood units), without indeterminate cases. CONCLUSIONS: A novel quantitative echocardiographic approach for the estimation of PAWP and PVR has high diagnostic accuracy in patients with heart failure and PH.

Cheyne-Stokes respiration related oscillations in cardiopulmonary hemodynamics in patients with heart failure.

BACKGROUND: Although Cheyne-Stokes respiration (CSR) is an oscillatory phenomenon, the direct effects of cyclical hyperventilation and apnea on cardiopulmonary hemodynamics have been poorly investigated. The aim of the study was to examine the echocardiographic changes associated with CSR phases in a group of patients with systolic heart failure (HF) and daytime CSR. METHODS: 14 HF patients (age 70 ±â€¯9 years, LVEF 24 ±â€¯5) underwent a thorough clinical evaluation, 24-h respiratory polygraphy, chemoreflex evaluation by rebreathing technique and neuro-hormonal assessment. Furthermore, they received a simultaneous echocardiographic and respiratory monitoring embedding the respiratory signal in the echocardiographic machine. RESULTS: All patients had daytime CSR (diurnal apnea-hypopnea index, AHI: 18.5, interquartile range: 15.3-39.5 events/h). Systolic pulmonary artery pressure and pulmonary vascular resistances (PVR) increased from hyperventilation to apnea (H 45.3 ±â€¯11.4 vs A 52.4 ±â€¯13.8 mmHg, p = 0.004, and H 3.3 ±â€¯2.5 vs A 5.1 ±â€¯3.2 Wood units, p = 0.0003, respectively), while acceleration time of the pulmonary artery decreased (H 110.1 ±â€¯19.8 vs A 92.0 ±â€¯19.9 ms, p = 0.001). During apnea a reduction of right and left ventricular outflow tract VTI (H 12.8 ±â€¯4.9 versus A 9.9 ±â€¯3.1, p = 0.002 and H 26.9 ±â€¯8.8 versus A 22.8 ±â€¯7.9 mm, p = 0.006, respectively), and a reduction in tricuspid annular plane systolic excursion (H 15.9 ±â€¯4.4 versus A 14.4 ±â€¯4.1 mm, p = 0.005) were also observed. Notably, PVR variation strongly correlated with chemosensitivity to hypercapnia (R = 0.89, p = 0.0004) and plasma norepinephrine level (R = 0.78, p = 0.003). CONCLUSIONS: In HF patients with CSR, an increase in pulmonary pressure and pulmonary vascular resistances was observed during apnea. Pulmonary vasoconstriction strongly correlated with chemosensitivity to hypercapnia and indexes of adrenergic activation.

N-terminal fragment of B-type natriuretic peptide predicts coexisting subclinical heart and vessel disease.

BACKGROUND: Identification of preclinical cardiovascular disease represents a challenge. We evaluate N-terminal proB-type natriuretic peptides (NT-proBNP) as markers of both cardiac and vascular subclinical disease in a community-based study including asymptomatic middle- aged study participants. METHODS AND RESULTS: In total, 807 study participants without previous cardiovascular disease were recruited. They underwent thorough laboratory assessment (including NT-proBNP), ultrasound examination of heart and evaluation of coronary calcium score and carotid intima-media thickness, by computed tomography and ultrasound, respectively.Cardiac and vascular disease were defined as one among left ventricular (LV) ejection fraction less than 50% (3.1%), E/E' ratio more than 15 (9%), LV mass index more than 115 in men or more than 95 g/m in women (20%), LV end diastolic diameter more than 55 mm (2.5%), coronary calcium score more than 100 AU (13%), or carotid intima-media thickness more than 1.2 mm (21%), respectively. NT-proBNP [OR, 1.275; 95% (confidence interval) CI, 1.007-1.613, P < 0.001], 10-year Framingham risk score (FRS; OR 1.132; 95% CI, 1.058-1.212, P < 0.001) and lower creatinine clearance (OR, 0.983; 95% CI, 0.971-0.994, P < 0.001) predicted cardiac (220, 27%), whereas 10-year Framingham risk score (OR, 1.340; 95% CI, 1.245-1.674, P < 0.001) and NT-proBNP (OR, 1.501; 95% CI, 1.181-1.907, P < 0.001) predicted vascular involvement (215, 26%), at multivariate analysis. In total, 84 study participants (10.1%) had coexisting cardiac and vascular disease. NT-proBNP increased linearly from health study participants to study participants with only cardiac or vascular involvement, up to coexisting cardiovascular disease. CONCLUSION: Coexisting cardiac and vascular involvement in asymptomatic study participants is common. Along with traditional risk factors, NT-proBNP appears a valuable biomarker for global subclinical heart and vessels disease.

N-terminal prob-type natriuretic peptide is a marker of vascular remodelling and subclinical atherosclerosis in asymptomatic hypertensives.

BACKGROUND: Arterial hypertension is a main determinant of arterial remodelling and atherosclerosis. Coronary artery calcium score and carotid intima-media thickness are recognized indices of vascular remodelling. Established biohumoral markers for the diagnosis of atherosclerosis are still lacking in asymptomatic subjects with hypertension. OBJECTIVES: We aimed to test the association of plasma N-terminal pro B-type natriuretic peptide concentrations with either coronary artery calcium score or carotid intima-media thickness in asymptomatic hypertensive subjects. METHODS: We conducted a case-control study on 436 hypertensi.ve and 436 age/sex-matched normotensive subjects from the population of the Montignoso HEart and Lung Project, a community-based study of asymptomatic general population ≥45 years. Subjects underwent N-terminal pro B-type natriuretic peptide measurement, echocardiography and evaluation of coronary artery calcium score and carotid intima-media thickness. RESULTS: Hypertensive subjects had higher median coronary artery calcium score (60 (interquartile range, 30-112) vs. 15 (interquartile range 3-70) Agatson units, p = 0.007), carotid intima-media thickness (8.6 (interquartile range 7.5-9.1) vs. 7.9 (7.1-8.4) µm, p < 0.001) and indexed left ventricular mass (101 (interquartile range 82-126) vs. 87 (63-91) mg/m2, p = 0.03) than controls, with no differences in left ventricular ejection fraction, diameters, E/E', left atrial area. N-terminal pro B-type natriuretic peptide concentrations were higher in hypertensive subjects with either coronary artery calcium score (p = 0.008) or carotid intima-media thickness >75th (p < 0.006) percentile and highest in combined coronary artery calcium score/carotid intima-media thickness >75th percentile (p = 0.021). In multivariable analysis, N-terminal pro B-type natriuretic peptide independently predicted either coronary artery calcium score or carotid intima-media thickness >75th percentile, but only in hypertensive subjects (odds ratio = 1.87, 95% confidence interval 1.30-2.74, p = 0.001 and odds ratio = 1.99, 95% confidence interval 1.43-2.76, p = 0.001). CONCLUSIONS: In asymptomatic subjects with hypertension, N-terminal pro B-type natriuretic peptide is a marker of hypertension-mediated preclinical vascular disease.

Principle of responsibility in medical imaging.

Radiological and medico-nuclear procedures are an essential part of contemporary medicine. They employ ionising energy, differently from other imaging modalities such as echography or magnetic resonance. The use of ionising testing is therefore associated to environmental impact and definite biorisks for the patient and the operator. In many clinical conditions specialty guidelines accept the equivalence of medical information provided by "red" (ionising) and "green" (noionising) techniques. Medical equivalence is translated into physician freedom of choice. However, common sense, guidelines of Radiological Medical Societies and Euratom directive (incorporated in national laws, such as Italian law 187/26 of May 2000) suggest that a "red" technique should be used only when a "green" alternative is not competitive.

Pericardial rather than epicardial fat is a cardiometabolic risk marker: an MRI vs echo study.

BACKGROUND: Several studies using echocardiography identified epicardial adipose tissue (EPI) as an important cardiometabolic risk marker. However, validation compared with magnetic resonance imaging (MRI) or computed tomography has not been performed. Moreover, pericardial adipose tissue (PERI) has recently been shown to have some correlation with cardiovascular disease risk factors. The aims of this study were to validate echocardiographic analyses compared with MRI and to evaluate which cardiac fat depot (EPI or PERI) is the most appropriate cardiovascular risk marker. METHODS: Forty-nine healthy subjects were studied (age range, 25-68 years; body mass index, 21-40 kg/m(2)), and PERI and EPI fat depots were measured using echocardiography and MRI. Findings were correlated with MRI visceral fat and subcutaneous fat, blood pressure, insulin sensitivity, triglycerides, cholesterol, insulin, glucose, and 10-year coronary heart disease risk. RESULTS: Most cardiac fat was constituted by PERI (about 77%). PERI thickness by echocardiography was well correlated with MRI area (r = 0.36, P = .009), and independently of the technique used for quantification, PERI was correlated with body mass index, waist circumference, visceral fat, subcutaneous fat, blood pressure, insulin sensitivity, triglycerides, cholesterol, glucose, and coronary heart disease risk. On the contrary, EPI thicknesses correlated only with age did not correlate significantly with MRI EPI areas, which were found to correlate with age, body mass index, subcutaneous fat, and hip and waist circumferences. CONCLUSIONS: Increased cardiac fat in the pericardial area is strongly associated with features of the metabolic syndrome, whereas no correlation was found with EPI, indicating that in clinical practice, PERI is a better cardiometabolic risk marker than EPI.