Prevalence and Persistence of Breathing Disorders in Chronic Heart Failure Patients: Preliminary Results from Home Telemonitoring in the HHH Study

In this paper we present preliminary results of the European Community multicountry trial HHH (Home or Hospital in Heart Failure), which assessed the prevalence and persistence of nocturnal breathing disorders in mild-to-moderate CHF patients. All subjects (465) carried out a baseline respiratory recording in the hospital, followed by 12 recordings (one per month) at home. The latter were totally self-managed by the patients, and data were transmitted to the referring hospital through telephone lines. We found that 43 % of the patients had a periodic breathing pattern (PB, waxing and waning of ventilation with or without apneas) during the night lasting ≥ 1 hour, and the apnea-hypopnea index (AHI) was ≥ 5 events/hour in 51 % of them. During the 1-year follow-up, a PB ≥ 1 hour and an AHI ≥ 5 events/hour were persistent (i.e., occurred in> 50 % of the recordings) in 43 % and 52 % of the patients. These findings confirm the high prevalence of nocturnal breathing disorders in CHF patients and show that in a large proportion of patients they tend to persist over time. 1

Acute right-sided transcutaneous vagus nerve stimulation improves cardio-vagal baroreflex gain in patients with chronic heart failure

Purpose: The aim of this paper is to investigate the acute effects of short-term transcutaneous vagus nerve stimulation (tVNS) on cardio-vagal baroreflex gain and heart rate variability in patients with chronic heart failure (CHF). Methods: A total of 16 adults with CHF and left ventricular ejection fraction (LVEF) < 50% in sinus rhythm were enrolled (65 ± 8 years, 63% men, LVEF 40 ± 5%, 88% on beta-blockers, 50% on quadruple CHF therapy). Over a single experimental session, after a 10-min baseline recording, each patient underwent two trials of 10-min tVNS (Parasym Device, 200 μs, 30 Hz, 1 mA below discomfort threshold) at either the right or left tragus in a randomized order, separated by a 10-min recovery. Results: Compared with baseline, tVNS did not affect heart rate, blood pressure, and respiratory rate (p > 0.05), and no patients complained of discomfort or any adverse effect. Right-sided tVNS was associated with a significant increase in cardio-vagal baroreflex gain (from 5.6 ± 3.1 to 7.5 ± 3.8 ms/mmHg, ∆ 1.9 ± 1.6 ms/mmHg, p < 0.001), while no change was observed with left-sided tVNS (∆ 0.5 ± 2.0 ms/mmHg, p = 0.914). These findings were independent of stimulation-side order (excluding any carry-over effect) and consistent across sex, LVEF category, and HF etiology subgroups (p-value for interaction > 0.05). Conclusions: Acute right-sided tVNS increases cardio-vagal baroreflex gain in patients with CHF and LVEF < 50%, with no tolerability concerns

Myocardial stress perfusion scintigraphy for outcome prediction in patients with severe left ventricular systolic dysfunction

Abstract: Coronary angiography has been recommended in all patients with suspected chronic coronary syndrome and left ventricular ejection fraction (LVEF) ≤35%. The role of ischemia testing, for example, through stress-rest myocardial perfusion scintigraphy (MPS), for risk prediction is not well established. Methods: We evaluated 1576 consecutive patients referred to MPS and stratified into 3 LV ejection fraction (LVEF) categories: ≤35%, 36–49%, and ≥ 50%. Results: Patients with LVEF ≤35% were oldest, most often men, and with the highest likelihood of prior early (elective or urgent) coronary revascularization. They had also the highest values or summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS), as well as the highest frequency of significant coronary artery disease, and a greater number of diseased vessels. Follow-up: In this subgroup, 32 cardiovascular death or non-fatal myocardial infarction (MI) (21%), 35 all-cause deaths (22%), and 37 cardiovascular deaths, non-fatal MI, or late revascularizations (27%) were recorded with the shortest survival among all LVEF classes. SRS, SSS, and SDS had very low area under the curve values for the prediction of the 3 endpoints, with very high cut-offs, respectively. SRS and SSS cut-offs predicted a worse outcome in Cox regression models including the number of diseased vessels and early revascularization. Conclusions: In patients with LVEF ≤35%, SRS and SSS are less predictive of outcome than in patients with better preserved systolic dysfunction, but their cut-offs retain independent prognostic significance from the number of vessels with significant stenoses and from early revascularization

Discharge FGF23 level predicts one year outcome in patients admitted with acute heart failure

Background: Patients with acute heart failure (AHF) show high levels of fibroblast growth factor-23 (FGF23) on admission. We examined if plasma FGF23 changes during an episode of AHF, and if FGF23 holds prognostic significance in this setting. Methods: Consecutive AHF patients were enrolled. Blood samples were collected on admission and at discharge. Patients were then followed for all-cause death or HF hospitalization. Results: Patients (n = 125; median age 76 years [interquartile interval 71–83], 63% men, left ventricular ejection fraction 35% [25%–56%]) had median admission FGF23 70 ng/L (47–100), N-terminal pro-B-type natriuretic peptide (NT-proBNP) 5844 ng/L (2,503-10,468), high-sensitivity troponin T (hs-TnT) 40 ng/L (25–72), and soluble suppression of tumorigenesis-2 (sST2) 26 ng/mL (17–37). While other biomarkers decreased, FGF23 increased by 15% from admission to discharge (p = 0.033), with a significant correlation with percent changes in estimated glomerular filtration rate (rho = 0.306, p = 0.001). Over a 12-month follow-up, 64 patients (51%) experienced the endpoint. They were more often men, older, with higher systolic pulmonary artery pressure (sPAP), higher NT-proBNP, hs-TnT and discharge FGF23. The best FGF23 cut-off at discharge from receiver operating characteristics analysis was 78 ng/L. Both discharge FGF23 and the 78 ng/L cut-off independently predicted outcome in models including gender, sPAP, age, and 1) admission NT-proBNP, 2) discharge NT-proBNP, 3) admission NT-proBNP and hs-TnT, 4) discharge NT-proBNP and hs-TnT. The 78 ng/L cut-off also refined risk reclassification. Conclusions: During an AHF episode, FGF23 increases from admission to discharge, and patients with higher discharge FGF23 have a higher risk of worse outcome

Omics phenotyping in heart failure:The next frontier

This state-of-the-art review aims to provide an up-to-date look at breakthrough omic technologies that are helping to unravel heart failure (HF) disease mechanisms and heterogeneity. Genomics, transcriptomics, proteomics, and metabolomics in HF are reviewed in depth. In addition, there is a thorough, expert discussion regarding the value of omics in identifying novel disease pathways, advancing understanding of disease mechanisms, differentiating HF phenotypes, yielding biomarkers for diagnosis or prognosis, or identifying new therapeutic targets in HF. The combination of multiple omics technologies may create a more comprehensive picture of the factors and physiology involved in HF than achieved by either one alone and provides a rich resource for predictive phenotype modelling. However, the successful translation of omics tools as solutions to clinical HF requires that the observations are robust and reproducible and can be validated across multiple independent populations to ensure confidence in clinical decision-making.</p

Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure : a pilot study

Altres ajuts: This work was supported in part by Fundació La Marató de TV3 (201516-10, 201502-30), Societat Catalana de Cardiologia, "la Caixa" Banking Foundation.Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor developed for the treatment of heart failure with reduced ejection fraction. Its benefits are achieved through the inhibition of neprilysin (NEP) and the specific blockade of the angiotensin receptor AT1. The many peptides metabolized by NEP suggest multifaceted potential consequences of its inhibition. We sought to evaluate the short-term changes in serum endorphin (EP) values and their relation with patients' physical functioning after initiation of sacubitril/valsartan treatment. A total of 105 patients with heart failure with reduced ejection fraction, who were candidates for sacubitril/valsartan treatment, were included in this prospective, observational, multicentre, and international study. In a first visit, and in agreement with current guidelines, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker was replaced by sacubitril/valsartan because of clinical indication by the responsible physician. By protocol, patients were reevaluated at 30 days after the start of sacubitril/valsartan. Serum levels of α- (α-EP), γ-Endorphin (γ-EP), and soluble NEP (sNEP) were measured using enzyme-linked immunoassays. New York Heart Association (NYHA) functional class was used as an indicator of patient's functional status. Baseline median levels of circulating α-EP, γ-EP, and sNEP were 582 (160-772), 101 (37-287), and 222 pg/mL (124-820), respectively. There was not a significant increase in α-EP nor γ-EP serum values after sacubitril/valsartan treatment (P value = 0.194 and 0.102, respectively). There were no significant differences in sNEP values between 30 days and baseline (P value = 0.103). Medians (IQR) of Δα-EP, Δγ-EP, and ΔsNEP between 30 days and baseline were 9.3 (−34 − 44), −3.0 (−46.0 − 18.9), and 0 units (−16.4 − 157.0), respectively. In a pre-post sacubitril/valsartan treatment comparison, there was a significant improvement in NYHA class, with 36 (34.3%) patients experiencing improvement by at least one NYHA class category. Δα-EP and ΔsNEP showed to be significantly associated with NYHA class after 30 days of treatment (P = 0.014 and P < 0.001, respectively). Δα-EP was linear and significantly associated with NYHA class improvement after 30 days of sacubitril/valsartan treatment. These preliminary data suggest that beyond the haemodynamic benefits achieved with sacubitril/valsartan, the altered cleavage of endorphin peptides by NEP inhibition may participate in patients' symptoms improvement

Prevalence and Correlates of Dilated and Non-Dilated Left Ventricular Cardiomyopathy in Transfusion-Dependent Thalassemia: Data from a National, Multicenter, Observational Registry

We investigated the prevalence, clinical characteristics, and prognostic role of dilated cardiomyopathy (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC) in patients with transfusion-dependent beta-thalassemia (beta-TDT). We retrospectively included 415 beta-TDT patients who underwent cardiovascular magnetic resonance to quantify myocardial iron overload (MIO) and biventricular function parameters and to detect replacement myocardial fibrosis. Demographic and laboratory parameters were comparable among patients with no overt cardiomyopathy (NOCM; n = 294), DCM (n = 12), and NDLVC (n = 109), while cardiac size and systolic function were significantly different. Compared to NOCM patients, DCM and NDLVC patients had a higher prevalence of MIO and replacement myocardial fibrosis. During a mean follow-up of 57.03 +/- 18.01 months, cardiac complications occurred in 32 (7.7%) patients: 15 heart failures, 15 supraventricular arrhythmias, and 2 pulmonary hypertensions. Compared to the NOCM group, both the NDLVC and the DCM groups were associated with a significantly increased risk of cardiac complications (hazard ratio = 4.26 and 8.81, respectively). In the multivariate analysis, the independent predictive factors were age, MIO, and the presence of DCM and NDLVC versus the NOCM phenotype. In beta-TDT, the detection of NDLVC and DCM phenotypes may hold value in predicting cardiac outcomes

Amyloid deposits and fibrosis on left ventricular endomyocardial biopsy correlate with extracellular volume in cardiac amyloidosis

BACKGROUND: The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. METHODS AND RESULTS: We included all patients diagnosed with amyloid light-chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68–81). Lambda-positive AL was found in 14 of 19 AL cases (38%) and kappa-positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%–30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%–23%; range, 5%–60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (r=0.661, P=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (P=0.035) and N-terminal pro-B-type natriuretic peptide (P=0.002) serum levels. CONCLUSIONS: Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone