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Serial transthoracic echocardiographic (TTE) assessment of LVEF and GLS are the gold standard in screening Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD). Non-invasive left-ventricle (LV) pressure-strain loop (PSL) emerged as a novel method to quantify Myocardial Work (MW). This study aims to describe the temporal changes and longitudinal trajectories of MW indices during cardiotoxic treatment. We included 50 breast cancer patients with normal LV function referred for anthracycline therapy w/wo Trastuzumab. Medical therapy, clinical and echocardiographic data were recorded before and 3, 6, and 12 months after initiation of the chemotherapy. MW indices were calculated through PSL analysis. According to ESC guidelines, mild and moderated CTRCD was detected in 10 and 9 patients, respectively (20% CTRCDmild, 18% CTRCDmod), while 31 patients remained free of CTRCD (62% CTRCDneg). Prior to chemotherapy MWI, MWE and CW were significantly lower in CTRCDmod than in CTRCDneg and CTRCDmild. Overt cardiac dysfunction in CTRCDmod at 6 months was accompanied by significant worse values in MWI, MWE and WW compared to CTRCDneg and CTRCDmild. MW features such as low baseline CW, especially when associated with a rise in WW at follow-up, may identify patients at risk for CTRCD. Additional studies are needed to explore the role of MW in CRTCD. ispartof: JOURNAL OF CLINICAL MEDICINE vol:12 issue:4 ispartof: location:Switzerland status: published

Aims: To describe the baseline characteristics of participants in the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial and compare these with other contemporary diuretic trials in acute heart failure (AHF).Methods and results: ADVOR recruited 519 patients with AHF, clinically evident volume overload, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and maintenance loop diuretic therapy prior to admission. All participants received standardized loop diuretics and were randomized towards once daily intravenous acetazolamide (500 mg) versus placebo, stratified according to study centre and left ventricular ejection fraction (LVEF) (≤40% vs. >40%). The primary endpoint was successful decongestion assessed by a dedicated score indicating no more than trace oedema and no other signs of congestion after three consecutive days of treatment without need for escalating treatment. Mean age was 78 years, 63% were men, mean LVEF was 43%, and median NT-proBNP 6173 pg/ml. The median clinical congestion score was 4 with an EuroQol-5 dimensions health utility index of 0.6. Patients with LVEF ≤40% were more often male, had more ischaemic heart disease, higher levels of NT-proBNP and less atrial fibrillation. Compared with diuretic trials in AHF, patients enrolled in ADVOR were considerably older with higher NT-proBNP levels, reflecting the real-world clinical situation.Conclusion: ADVOR is the largest randomized diuretic trial in AHF, investigating acetazolamide to improve decongestion on top of standardized loop diuretics. The elderly enrolled population with poor quality of life provides a good representation of the real-world AHF population. The pragmatic design will provide novel insights in the diuretic treatment of patients with AHF.

Introduction: Heart failure (HF) is a heterogenous syndrome with complex pathophysiology. Biomarkers and clinical risk scores often fail to capture modifications in the treatment continuity and provide suboptimal patient-level precision in the prognostic stratification. Electronic patient records provide necessary granularity yielding opportunities to develop new artificial intelligence (AI) based strategies for comprehensive prognostic re-stratification. Hypothesis: We assessed the hypothesis that, utilizing longitudinal patient data in an AI approach, yields superior performance predicting all-cause mortality in a cohort of patients hospitalized with a de novo or worsened HF, compared to single observational time point predictions. Methods: In a cohort of 2449 HF patients hospitalized between 2011-2017, we utilized 151 451 patient exams from 422 parameters. Features included clinical phenotyping, medication, ECG, laboratory, echocardiography, catheterization data or percutaneous and surgical interventions gathered on a routine clinical basis reflecting standard of care as captured in individual electronic records. AI models were developed, and their performance on the validation set was compared to industry standard clinical scores. Results: AI models yielded performance ranging from 0.83 to 0.89 AUC on the outcome-balanced validation set in predicting all-cause mortality at 30-, 90-, 180-, 360- and 720-day time-limits. The primary endpoint, 1-year mortality prediction model, recorded 0.85 AUC on the validation set compared to 0.7 AUC (Seattle HF model) and 0.73 AUC (MAGGIC HF Score) respectively. Conclusions: Our findings present a novel, patient-level, AI-based risk prediction approach of all-cause mortality in heart failure utilizing all historical data available in electronic health records. This suggests the potential of AI based predictive models in a point-of-care approach to guide clinical risk stratification.

Introduction: Overexpression of serpin peptidase inhibitor, clade A member 3 (SERPINA3) has been associated with poor prognosis in cancer. Hypothesis: SERPINA3 in a de novo or worsened heart failure (HF) bears a prognostic information alone and in addition to established biomarkers NT-proBNP and ST2 or clinical risk factors. Methods: Circulating SERPINA3 levels were examined in HFpatients who died within 5 years (n=44) and compared with age- and hemodynamically matched survivors (n=39). Prognostic value of circulating SERPINA3 levels alone and in combination with ST2 and NT-proBNP was then analyzed in an independent cohort with a de novo or worsened HF (n=384). Results: Plasma SERPINA3 levels were significantly higher in HF non-survivors compared to survivors (334.7 ± 138.7 vs 228.2 ± 83.1 μg/mL, pde novo or worsened HF (n=384), circulating SERPINA3 levels >316 μg/mL were associated with increased all-cause mortality (HR (95% CI): 2.4 (1.5-3.9), p=0.0002) and its composite with unplanned cardiac admission (HR (95% CI): 2.0 (1.2-3.3), p=0.004). In a multivariate analysis, including established clinical risk factors and ST2 and NT-proBNP, SERPINA3 remained independent predictor of all-cause mortality together with age, ST2, glomerular filtration and pulmonary capillary wedge pressure. Conclusions: Elevated SERPINA3 appears to provide additional prognostic information in models incorporating clinical, hemodynamic and laboratory risk including ST2 and NT-proBNP by identifying a subgroup of heart failure patients at increased mortality risk.

AIMS: We investigated the prognostic relevance of serpin peptidase inhibitor, clade A member 3 (SERPINA3) in patients admitted with a de novo or worsened heart failure (HF). METHODS AND RESULTS: In the first stage, 83 HF-related left ventricular (LV) transcripts were examined in patients with congestive cardiomyopathy (CCMP, n = 44) who died within 5 years and compared with age-matched and haemodynamically matched CCMP survivors (n = 39) and controls with normal LV function (n = 17). Among 14 differentially expressed transcripts, myocardial gene and circulating SERPINA3 levels were up-regulated in non-survivors vs. survivors (2.40 ± 3.66 vs. 0.36 ± 0.22 units, P 316 μg/mL were associated with increased all-cause mortality {hazard ratio [HR] [95% confidence interval (CI)]: 2.4 [1.5-3.9], P = 0.0002} and its composite with unplanned cardiovascular readmission [HR (95% CI): 2.0 (1.2-3.3), P = 0.004]. Patients with elevated SERPINA3 levels and elevated either N-terminal pro brain natriuretic peptide or ST2 showed worse freedom from both endpoints. In a multivariate analysis, including established clinical risk factors, SERPINA3 remained independent predictor of all-cause mortality together with age, gender, ST2, glomerular filtration, and pulmonary capillary wedge pressure. CONCLUSION: In patients with a de novo or worsened HF, increased SERPINA3 levels > 316 μg/mL are associated with increased mortality or unplanned cardiac readmission. Elevated SERPINA3 levels on top of established clinical predictors appear to identify a subgroup of HF patients at higher mortality risk. Prospective studies should further validate its value in prognostic stratification of HF. ispartof: ESC HEART FAILURE vol:8 issue:6 ispartof: location:England status: published

Background Heart failure (HF) is a heterogenous syndrome with complex pathophysiology. Biomarkers and clinical risk scores often fail to provide optimal patient-level precision in the prognostic stratification. As utilizing single observational timepoint, they do not capture the entire care pathway with variations in individual patient management. Electronic patient records provide an opportunity to develop new artificial intelligence (AI) strategies for comprehensive prognostic re-stratification reflecting diagnostic and therapeutic management. Purpose We sought to use deep artificial intelligence (AI) and develop an unbiased predictive algorithm for all-cause mortality in a cohort of patients hospitalized with a de novo or worsened HF. Methods In a cohort of 2449 HF patients hospitalized between 2011–2017, we utilized 151 451 patient exams from 422 parameters. They included clinical phenotyping, medication, ECG, laboratory, echocardiography, catheterization data or percutaneous and surgical interventions gathered on a routine clinical basis reflecting standard of care as captured in individual electronic records. The AI model development consisted of 101 iterations of repeated random subsampling splits into balanced training and validation sets. Results AI models yielded performance ranging from 0.83 to 0.89 AUC on the outcome-balanced validation set in predicting all-cause mortality at 30-, 90-, 180-, 360- and 720-day time-limits (Figure 1). The primary endpoint, 1-year mortality prediction model, recorded an 0.85 AUC accuracy. We observed stable model performance across all HF phenotypes: HFpEF 0.83 AUC, HFmrEF 0.85 AUC and HFrEF 0.86 AUC, respectively). Conclusion Our findings present a novel, patient-level, AI-based risk prediction of all-cause mortality in heart failure with a robust accuracy across its phenotypes. This suggests the potential of AI based predictive models in a point-of-care approach to guide clinical risk stratification. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): VZW Cardiovascular Research Center Aalst

Introduction Breast cancer patients receiving anthracyclines are particularly prone to develop cancer therapeutics-related cardiac dysfunction. Early detection of cardiotoxicity onset is required for optimal timing of cardio protection treatment. The latest guidelines consider a relative reduction of 15% in global longitudinal strain (GLS) from baseline as risk for cardiotoxicity. Nevertheless, the more recent Myocardial Work Index (MWI) offers a load-independent tool for detection of subclinical heart failure (HF). However, data in cancer patients are still scarce. Purpose This study analyses the predictive value of MWI for cardiotoxicity diagnosis after 6 months chemotherapy. Methods The study population consists of breast cancer patients referred for chemotherapy with anthracyclines and taxanes. Patients with a history of HF previous to chemotherapy or depressed LV function at baseline were excluded. Echocardiography was performed before onset of the chemotherapy (baseline) and after 6 months follow-up. LVEF, GLS and MWI were assessed offline using EchoPAC software. The values at baseline and 6 months follow-up were pairwise compared to detect subclinical cardiac dysfunction. LVEF, GLS and MWI means at baseline were taken as cut-off to compare the predictive value of each parameter. Moreover, patients were categorized in one group with GLS reduction >15% (Group 1) and one group with GLS reduction Results From April 2016 to July 2020, 28 women with breast cancer were included (age 54±11 years, LVEF 58±4%, GLS −21±2%, MWI 2160±308 mmHg). All patients underwent the same standard chemotherapy protocol (4xEC, 12xTaxol). No difference in baseline characteristics between group 1 (n=13) and group 2 (n=15) was observed. At 6 months follow up a significant decrease in LVEF (53±8%, p=0.003), GLS (−19±3%, p=0.002) and MWI (1920±391 mmHg, p=0.005) was shown without any change in blood pressure. However, while mean LVEF and GLS at baseline did not predict any significant change, patients with MWI under the mean value at baseline (n=15) presented significant lower LVEF (50±8 vs 57±6% p=0.006), GLS (−17±3 vs −20±2%, p=0.01), MWI (1733±320 vs 2136±362 mmHg, p=0.005) after 6 months. Additionally, both groups had similar MWI at baseline (2148±335 mmHg vs 2170±294 mmHg, p=0.85), whereas those patients with GLS reduction >15% showed significant lower MWI after 6 months (1694±332 mmHg vs 2116±334 mmHg, p=0.003, Figure 1). Conclusions At 6 months follow up, a decline of the LV systolic function as side effect of chemotherapy can be seen. MWI at baseline shows the best predictive value for development of cardiotoxicity, in comparison to LVEF and GLS. Further studies are warranted to better understand the role of MWI for early detection of cardiotoxicity and its clinical relevance. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Onze-Lieve-Vrouw hospital in Aalst (Belgium)

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Cardiovascular Research Center Aalst, (Aalst, Belgium) Introduction Breast cancer patients receiving anthracyclines are particularly prone to develop cancer therapeutics-related cardiac dysfunction (CTRCD). Early detection of cardiotoxicity onset is required for optimal timing of cardio protection treatment. The latest guidelines consider a relative reduction of 15% in global longitudinal strain (GLS) from baseline as risk for cardiotoxicity. Nevertheless, the more recent Myocardial Work Index (MWI) offers a load-independent tool for detection of subclinical heart failure (HF). Data in cancer patients are still scarce. Purpose This study analyses the predictive value of MWI for cardiotoxicity diagnosis after 6 months chemotherapy. Methods The study population consists of breast cancer patients referred for chemotherapy with anthracyclines and taxanes. Patients with a history of HF previous to chemotherapy or depressed LV function at baseline were excluded. Echocardiography was performed before onset of the chemotherapy (baseline) and after 6 months follow-up. LVEF, GLS and MWI were assessed offline using EchoPAC software. The values at baseline and 6 months follow-up were pairwise compared to detect subclinical cardiac dysfunction. Mean LVEF, GLS and MWI at baseline were taken as cut-off value to compare the predictive value of each parameter. Moreover, patients were categorized in one group with GLS reduction >15% (Group 1) and one group with GLS reduction Results From April 2016 to January 2020, 24 women with breast cancer were included (age 54 ± 11 years, LVEF 58 ± 4%, GLS -21 ± 2%, MWI 2181 ± 325 mmHg). All patients underwent the same standard chemotherapy protocol (4xEC, 12xTaxol). No difference in baseline characteristics between group 1 (n = 9) and group 2 (n = 15) was observed. At 6 months follow up a significant decrease in LVEF (53 ± 8%, p = 0.003), GLS (-19 ± 3%, p = 0.002) and MWI (1933 ± 410 mmHg, p = 0.005) was shown without any change in blood systolic pressure. However, while mean LVEF and GLS at baseline did not predict any significant change, patients with MWI under the mean value at baseline (n = 13) presented significant lower LVEF (49 ± 8%, p = 0.006), GLS (-18 ± 4%, p = 0.045), MWI (1753 ± 341 mmHg, p = 0.018) after 6 months. Additionally, both groups had similar MWI at baseline (2199 ± 390 mmHg vs 2170 ± 294 mmHg, p = 0.85), whereas those patients with GLS reduction >15% showed significant lower MWI after 6 months (1626 ± 344 mmHg vs 2116 ± 334 mmHg, p = 0.003, Figure 1). Conclusions At 6 months follow up, a decline of the LV systolic function as side effect of chemotherapy can be seen. In comparison to LVEF and GLS, MWI shows the best predictive value for development of early cardiotoxicity. Further studies are warranted to better understand the role of MWI in predicting CTRCD and its clinical relevance. Abstract Figure. Change in MWI

Introduction: The Sodium Glucose cotransporter (SGLT) and glucose transporters(GLUTs) play a crucial role in cellular glucose transport. Although experimental data have shown differential regulation of GLUT4 and SGLT in diabetic cardiomyopathy, the impact of diabetes mellitus (DM) upon myocardial glucose transporters in humans remains undetermined. Aim: To better understand the impact of elevated glucose levels upon myocardial expression of glucose transporters, the endomyocardial gene expression of GLUT1, GLUT4 and SGLT1 was investigated in heart transplant(HTx) recipients, with and without DM, who received a heart from a DM- donor. Methods: At baseline(BL), immediately after HTx and 12 ± 2 months(FU) later, serial endomyocardial biopsies were procured in 26 Htx pts, free of clinical or histological rejection, at time of routine surveillance biopsy. Patients were categorized in DM+ (n = 13pts) and DM- (n = 13 pts), according to the presence of diabetes mellitus (DM) at FU. Results: Despite similar hemodynamics and HbA1c levels at BL, DM+ pts had higher HbA1c levels (46,00 ± 13,79 vs 38,33 ± 4,88; p < 0,05) at FU. No differences were noted in BL GLUT1, GLUT4 and SGLT gene expression between both groups. In DM- pts SGLT1(0,081 ± 0,080 vs 0,188 ± 0,108; p = 0,0036) , GLUT4(0,076 ± 0,068 vs 0,137 ± 0,065; p = 0,0011 )and GLUT1(0,020 ± 0,021 vs 0,022 ± 0,009; p = 0,043) increased significantly at FU whereas no change was observed in DM+ pts. Conclusion: Similar to experimental data, differential endomyocardial regulation in SGLT1 and GLUT4 was noted between DM+ and DM-pts with a blunted upregulation of glucose transporters at 1 year in DM+ HTx pts. These observations are in line with experimental data and suggest that myocardial glucose uptake is differentially regulated in DM+ HTx pts.

Background. Cardiac allograft vasculopathy (CAV) remains the Achilles’ heel of long-term survival after heart transplantation (HTx). The severity and extent of CAV is graded with conventional coronary angiography (COR) which has several limitations. Recently, vessel“It is very important for the corresponding author to have a linked ORCID (Open Researcher and Contributor ID) account on MTS. To register a linked ORCID account, please go to the Account Update page (http://mts.hindawi.com/update/) in our Manuscript Tracking System and after you have logged in click on the ORCID link at the top of the page. This link will take you to the ORCID website where you will be able to create an account for yourself. Once you have done so, your new ORCID will be saved in our Manuscript Tracking System automatically.”"?> fractional flow reserve (vFFR) derived from COR has emerged as a diagnostic computational tool to quantify the functional severity of coronary artery disease. Purpose. The present study assessed the usefulness of vFFR to detect CAV in HTx recipients. Methods. In HTx patients referred for annual check-up, undergoing surveillance COR, the extent of CAV was graded according to the criteria proposed by the international society of heart and lung transplantation (ISHLT). In addition, three-dimensional coronary geometries were constructed from COR to calculate pressure losses using vFFR. Results. In 65 HTx patients with a mean age of 53.7 ± 10.1 years, 8.5 years (IQR 1.90, 15.2) years after HTx, a total number of 173 vessels (59 LAD, 61 LCX, and 53 RCA) were analyzed. The mean vFFR was 0.84 ± 0.15 and median was 0.88 (IQR 0.79, 0.94). A vFFR ≤ 0.80 was present in 24 patients (48 vessels). HTx patients with a history of ischemic cardiomyopathy (ICMP) had numerically lower vFFR as compared to those with non-ICMP (0.70 ± 0.22 vs. 0.79 ± 0.13, p=0.06). The use of vFFR reclassified 31.9% of patients compared to the anatomical ISHLT criteria. Despite a CAV score of 0, a pathological vFFR ≤ 0.80 was detected in 8 patients (34.8%). Conclusion. The impairment in epicardial conductance assessed by vFFR in a subgroup of patients without CAV according to standard ISHLT criteria suggests the presence of a diffuse vasculopathy undetectable by conventional angiography. Therefore, we speculate that vFFR may be useful in risk stratification after HTx.

Supplemental Digital Content is available in the text., Background. Endothelium-enriched microRNAs (miRs) are involved in the development of cardiac allograft vasculopathy (CAV). Recently, serum-derived miR-126-3p and -5p, known endothelial microRNAs with a crucial function in angiogenesis and re-endothelialization, provided additional predictive power for cardiac allograft vasculopathy in addition to clinical predictors. However, their myocardial expression in and relationship with CAV are still unknown. Our study aim was to investigate the expression of endomyocardial microRNA-126-3p and microRNA-126-5p levels in heart transplant recipients and their relationship with allograft vasculopathy. Methods. We studied 39 heart transplant recipients, 21 with proven allograft vasculopathy (CAV+) and 18 without allograft vasculopathy (CAV−) with serial coronary angiograms. Additionally, 8 patients with end-stage native coronary artery disease (CAD) were added to the study to investigate disease specificity of the microRNA signature. The mRNA levels of miR-126-3p and miR-126-5p were determined by qRT-PCR in the right ventricular endomyocardial biopsies obtained at baseline and during routine follow-up. Results. MiR-126-3p levels were significantly lower in the CAV+ group compared to the CAV− group at follow-up, while miR-126-5p levels were unaltered. This was in stark contrast to native CAD patients in whom miR-126-3p and -5p levels were significantly higher. qPCR levels of miR-126 targets are differentially regulated in CAV versus ischemic cardiomyopathy and are influenced by the administration of immunosuppressive agents in endothelial cells. Conclusions. Our data provide evidence for a distinct microRNA signature in heart transplantation patients with allograft vasculopathy. In contrast to CAD patients, lower miR-126-3p levels coincide with the development of cardiac allograft vasculopathy. Further studies in a larger patient population are warranted to determine if the serial measurement of myocardial microRNA-126 products could help in risk assessment and early detection of CAV.

Background:\ud \ud Prognostic models for patients with chronic heart failure are generally based on a single assessment but treatment is often given with the intention of changing risk; re- evaluation of risk is an important aspect of care. The prognostic value of serial measurements of natriuretic peptides for the assessment of changes in risk is uncertain.\ud \ud Aims:\ud \ud To evaluate the prognostic value of serial measurements of plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) during follow-up of out-patients with chronic heart failure (CHF).\ud \ud Methods:\ud \ud Patients diagnosed with CHF between 2001 and 2014 at a single out-patient clinic serving a local community were included in this analysis. NT-proBNP was measured at the initial visit and serially during follow-up. Only patients who had one or more measurements of NT-proBNP after baseline, at 4, 12 and/or 24 months were included.\ud \ud Results:\ud \ud At baseline, amongst 1998 patients enrolled, the median age was 73 (IQR: 64–79) years, 70% were men, 31% were in NYHA class III/IV, and 77% had NT-proBNP >400 pg/mL. Median follow-up was 4.8 (IQR: 2.5–8.6) years. Serial measurements of NT-proBNP improved prediction of all-cause mortality at 3 years (c- statistic = 0.71) compared with using baseline data only (c-statistic = 0.67; p

Purpose Cardiac transplant-related arteriopathy remains a leading cause of morbidity and mortality in heart transplant (HTx) recipients. Recently, vessel fractional flow reserve (vFFR) derived from coronary angiography has emerged as a new diagnostic computational tool to functionally evaluate the severity of coronary artery disease (CAD). Although vFFR estimates have been shown to perform well against invasive FFR in atherosclerotic CAD, data on the use of vFFR in HTx recipients are lacking. The aim was to validate coronary angiogram-derived FFR to calculate FFR in HTx patients with and without cardiac transplant-related arteriopathy. Methods Prospective, single center study of HTx patients referred for annual check-up, undergoing surveillance coronarography. Invasive FFR was measured using a motorized device at the speed of 1.0 mm/sec in all three major coronary arteries. Angiography-derived pullback FFR was derived from the angiogram and compared with invasive FFR pullback curve. Results Overall, 13634 FFR values were extracted from the FFR pullback curves from 19 HTx patients. The mean age was 60.8 ± 9.10 years, the mean time after transplantation was 5.88 years [IQR 1.10, 12.0]. A total of 29 vessels (19 LAD, 6 LCX, 4 RCA) were analysed. Mean distal vFFR was 0.91 ± 0.05 whereas invasive distal FFR was 0.92 ± 0.07. A good correlation was found between invasive distal FFR and vFFR (r =0.635; p Conclusion In HTx patients coronary angiography-derived FFR correlates well with invasively measured wire-derived FFR. Angiography-derived FFR could be used as a novel diagnostic tool to quantify the functional severity of graft vasculopathy.

Aims: To assess the clinical value of measuring right atrial pressure (RAP) using near-infrared spectroscopy (NIRS) in patients with chronic heart failure (CHF). Methods and results: RAP was measured non-invasively using NIRS over the external jugular vein (Venus 1000, Mespere LifeSciences, Canada) in ambulatory patients with CHF enrolled in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) programme. Comparing 243 patients with CHF (mean age 71 years; mean left ventricular ejection fraction (LVEF) 45%, median NT-proBNP 788 ng/L) to 49 controls (NT-proBNP ≤125 ng/L), RAP was 7 [interquartile range (IQR) 4–11] mmHg vs. 4 (IQR 3–8) mmHg (P < 0.001). Those with RAP ≥10 mmHg (n = 75) were older, had more severe clinical congestion and renal dysfunction, higher plasma NT-proBNP, larger left atrial volume, higher systolic pulmonary pressure and were more often in atrial fibrillation but their LVEF was similar to patients with lower RAP. During a median follow-up of 595 (IQR: 492–714) days, 49 patients (20%) died or were hospitalized for worsening CHF. Compared with patients with RAP ≤5 mmHg, those with RAP ≥10 mmHg had a greater risk of an event (hazard ratio 2.38, 95% confidence interval 1.19–4.75, P = 0.014). RAP measured by NIRS predicted outcome, competing with NT-proBNP in multivariable models. Conclusions: Measuring RAP using NIRS identifies ambulatory patients with CHF who have more severe congestion and a worse outcome. The device might be a useful objective method of monitoring RAP, especially for those inexperienced in eliciting physical signs or when measurement of natriuretic peptides is not immediately available.

Aims The PARADIGM-HF trial showed that sacubitril–valsartan, an ARB–neprilysin inhibitor, is more effective than enalapril for some patients with heart failure (HF). It is uncertain what proportion of patients with HF would be eligible for sacubitril–valsartan in clinical practice. Methods and results Between 2001 and 2014, 6131 patients consecutively referred to a community HF clinic with suspected HF were assessed. The criteria required to enter the randomized phase of PARADIGM-HF, including symptoms, NT-proBNP, and current treatment with or without target doses of ACE inhibitors or ARBs, were applied to identify the proportion of patients eligible for sacubitril–valsartan. Recognizing the diversity of clinical opinion and guideline recommendations concerning this issue, entry criteria were applied singly and in combination. Of 1396 patients with reduced left ventricular ejection fraction (≤40%, HFrEF) and contemporary measurement of NT-proBNP, 379 were on target doses of an ACE inhibitor or ARB at their initial visit and, of these, 172 (45%) fulfilled the key entry criteria for the PARADIGM-HF trial. Lack of symptoms (32%) and NT-proBNP

Purpose A mean pulmonary wedge pressure (mPAP) ≥ 25 mm Hg following volume load or exercise has been proposed as a partition value for detection of HfpEF. However, the hemodynamic response to volume challenge in heart transplant (Tx) recipients has never been studied. Methods 36 heart Tx recipients (Age: 65 years) with normal LV function (EF: 55 ± 7 %) and without rejection and graft vasculopathy underwent right heart catheterization to measure hemodynamic response to volume loading before and after a rapid saline infusion of 7mL/kg over 10 min. PCWP, right atrial pressure (RAP), mean pulmonary artery pressure(PA) were obtained and the PCWP and indexed(i) stroke volume(SV) data were used to construct Starling (SVindex/PCWP) curves. Pts were categorized in those with elevated filling pressures (Group DD, n=10 pts) defined by a PCWP ≥ 15 mm Hg at rest or ≥ 25 mm Hg following volume loading vs those without (Controls, n=26 pts). Results No difference in age of donor and transplant, baseline hemodynamics and EF was noted between both groups. Saline infusion significantly increased PCWP and mean PA in both Groups without any significant change in BP and heart rate. Interestingly saline infusion was associated with a significant rise in SV and SVi in Controls not in DD pts(Fig 1). Moreover, in DD pts the Starling curves revealed a larger SVi at any give PCWP compared to Controls pts. Conclusion In the transplanted heart volume loading increases filling pressures and is able to unmask left ventricular diastolic dysfunction. Interestingly, those with DD are characterized by a blunted Frank Starling response as evidenced by higher PCWP and failure to increase SV for any given PCWP. Further prospective studies are warranted to unravel the underlying mechanisms.

PURPOSE: Cardiac graft vasculopathy (CAV) remains the Achilles' heel of long-term survival after heart transplantation (HTx). The severity and extent of CAV is graded with conventional coronary angiography(COR) which has several limitations. Recently virtual fractional flow reserve (vFFR) derived from COR has emerged as a new diagnostic computational tool to functionally evaluate the extent of coronary artery disease. The present study assessed the usefulness of vFFR to detect CAV in HTx recipients. METHODS: In HTx pts referred for annual check-up, undergoing surveillance COR and normal LV systolic function, the extent of CAV was graded according to the ISHLT guidelines. Three-dimensional coronary geometries were constructed offline and generic boundary conditions for computational fluid dynamics analysis were applied to calculate vFFR. RESULTS: In 49 HTx pts with a mean age of 53.3 ± 11.0 years, 8.6 ± 7.1 years post HTx, a total number of 171 vessels(59 LAD, 60 Cx, 52 RCA) were analyzed. Mean vFFR in all HTx pts was 0.85 ± 0.15, median 0.89 [IQR 0.80, 0.95]. HTx pts with previous history of ischemic cardiomyopathy(ICMP) had significantly lower vFFR as compared to those with non-ICMP. Use of vFFR reclassified 33% of patients compared to the anatomical ISHLT criteria. A vFFR ≤ 0.80 was present in 24 pts (42 vessels). Despite a CAV score of 0, a pathological vFFR ≤ 0.80 was detected in 6 pts (25.0 %). Finally, pts with a vFFR ≤ 0.80 had significantly higher need for revascularization (Figure 1) vs those with normal vFFR (HR 9.18, 95% CI 1.18 to 71.2, p=0.03). CONCLUSION: The impairment of coronary flow assessed by vFFR in a subgroup of pts without CAV according to standard ISHLT criteria, suggests the presence of a diffuse vasculopathy undetectable by conventional COR. Similar to coronary atherosclerosis, a pathological vFFR bears prognostic information as evidenced by a higher need for revascularization when vFFR is low. Therefore, we speculate that vFFR may be a helpfull tool in risk stratification post HTx.

Introduction A pulmonary capillary wedge pressure (PCWP) ≥25 mm Hg following volume load or exercise has been proposed as a partition value for detection of HfpEF. However, the hemodynamic response to volume challenge in heart transplant (Tx) recipients has never been studied. Methods 24 heart Tx recipients (age: 65 years) with normal LV function (55±7%) and without rejection and graft vasculopathy underwent right heart catheterization to measure hemodynamic response to volume loading before and after a rapid saline infusion of 7mL/kg over 10 min. PCWP, right atrial pressure (RAP), mean pulmonary artery pressure (AP) were obtained and the PCWP and indexed (i) stroke volume (SV) data were used to construct Starling (SVindex/PCWP) curves. Pts were categorized in those with elevated filling pressures (Group A, n=13 pts) defined by a PCWP ≥15 mm Hg at rest or ≥25 mm Hg following volume loading vs those without (Group B, n=11 pts). Results No difference in age of donor and transplant heart, baseline hemodynamics and EF was noted between both groups. Saline infusion significantly increased PCWP and mean AP in both Groups (table 1) without any significant change in BP and heart rate. Interestingly saline infusion was associated with a significant rise in SV and SVi in Group B not in Group A pts. Moreover, in Group B pts the Starling curves revealed a larger SVi at any give PCWP compared to Group A pts (Fig.1). Table 1 All (n=24) Group A (n=13) Group B (n=11) Baseline Volume Loading Baseline Volume Loading Baseline Volume Loading RAP (mm Hg) 5.3±4.1 9.2±4.8* 7.6±4.8 11.4±5.2* 3.8±2.5 7.3±1.9* Mean AP 18.4±5.4 24.1±5.9* 21.7±5.1 26.8±6.5** 14.9±2.4 20.8±2.6* PCWP 12.1±4.9 16.8±6.7* 15.0±4.9 19.8±6.5** 8.4±1.9 14.6±3.7* SV 71.4±19.6 72.5±23.6 73.2±6.2 72.4±6.2 69.2±14.6 79.2±3.9 SViml/m2) 37.4±9.2 37.9±11.2 36.7±7.1 38.7±9.9 35.3±6.0 40.5±5.2* *p Figure 1 Conclusions In the transplanted heart volume loading increases filling pressures and is able to unmask left ventricular diastolic dysfunction. Interestingly, those with HFpEF are characterized by a blunted Frank Starling response as evidenced by higher PCWP and failure to increase SV for any given PCWP. Further prospective studies are warranted to unravel the underlying mechanisms.

Diuretic resistance in acute heart failure is a common clinical problem, and it is associated with adverse outcomes. Effective therapies are still lacking. The Doraya catheter, a temporary intravenous flow regulator placed in the inferior vena cava below the level of the renal veins, is a novel device designed to target renal and cardiac congestion, thereby improving diuretic response. A first-in-man clinical study is currently ongoing.

Background Previous studies have shown that xanthine oxidase inhibitors (XOI) might improve outcome for patients with cardiovascular disease. However, more evidence is required. Methods and results We published a meta-analysis of trials conducted before 2014 examining the effects of XOI on mortality in patients with cardiovascular disease. At least two further trials (N = 323 patients) have since been published. Accordingly, we repeated our analysis after a further search for randomized controlled trials of XOI in PubMed/MEDLINE, EMBASE, and Cochrane Databases. We identified eight relevant trials with 1031 patients. The average age of the patients was 61 years and 68% were men (one study did not report gender). There were 57 deaths in these eight trials, 26 in those assigned to XOI, and 31 in those assigned to the control. The updated meta-analysis could not confirm a reduction in mortality for patients assigned to XOI compared with placebo (odds ratio 0.84) but 95% confidence intervals were wide (0.48–1.47). Conclusions This updated meta-analysis does not suggest that XOI exert a large reduction in mortality but also cannot exclude the possibility of substantial harm or benefit.

Cardiac graft vasculopathy (CAV) remains the Achilles’ heel of long-term survival after heart transplantation (HTx). The severity of CAV is graded with coronary angiogram (COR) which has several known limitations. Vessel fractional flow reserve (vFFR) derived from COR has emerged as a new

Objectives This study sought to characterize patients attending a community heart failure (HF) clinic and identified those who were eligible for optimization of beta-blockers (BB) or ivabradine. Background Among patients with HF due to left ventricular systolic dysfunction in sinus rhythm, those with higher resting heart rate have a worse prognosis. Reducing sinus rate to 50 to 60 beats/min might improve outcomes. Methods A total of 1,000 consecutively scheduled HF clinic follow-up appointments over a 6-month period were reviewed. Demographic, clinical, and echocardiographic data were collected for patients who attended (824 unique patients; 555 men). Mean age was 74 ± 11 years, median N-terminal pro–B-type natriuretic peptide levels were 1,002 ng/l (interquartile range: 367 to 2,151 ng/l), and the mean left ventricular ejection fraction (LVEF) was 44 ± 11%. A total of 202 (25%), 252 (31%), and 370 (45%) patients had LVEFs of ≤35%, 36% to 49%, and ≥50%, respectively. Of patients with LVEF ≤35%, 142 (70%) were in sinus rhythm. Results At 70 clinic visits, 58 patients with LVEFs of ≤35% were in sinus rhythm and had heart rates ≥70 beats/min. Of these, 13 patients had their BB dose increased, 20 were potentially eligible for, but did not have, BB uptitration, 15 were already taking target doses of BBs, and 10 patients were reported to be intolerant of higher doses. Thus, 25 patients were potentially eligible for ivabradine according to European Society of Cardiology guidelines; this number dropped to 14 when the United Kingdom National Institute for Health and Care Excellence guidelines were applied. Conclusions Among patients with LVEFs of ≤35%, most are treated with BBs and have a heart rate at rest of

Background: \ud \ud Specialised disease management programmes for heart failure aim to improve care, clinical outcomes and/or reduce healthcare utilisation. Since the last version of this review in 2010, several new trials of structured telephone support and non-invasive home telemonitoring have been published which have raised questions about their effectiveness.\ud Objectives: \ud \ud To review randomised controlled trials (RCTs) of structured telephone support or non-invasive home telemonitoring compared to standard practice for people with heart failure, in order to quantify the effects of these interventions over and above usual care.\ud Search methods: \ud \ud We updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology AsseFssment Database (HTA) on the Cochrane Library; MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index- Science (CPCI-S) on Web of Science (Thomson Reuters), AMED, Proquest Theses and Dissertations, IEEE Xplore and TROVE in January 2015. We handsearched bibliographies of relevant studies and systematic reviews and abstract conference proceedings. We applied no language limits.\ud Selection criteria: \ud \ud We included only peer-reviewed, published RCTs comparing structured telephone support or non-invasive home telemonitoring to usual care of people with chronic heart failure. The intervention or usual care could not include protocol-driven home visits or more intensive than usual (typically four to six weeks) clinic follow-up.\ud Data collection and analysis: \ud \ud We present data as risk ratios (RRs) with 95% confidence intervals (CIs). Primary outcomes included all-cause mortality, all-cause and heart failure-related hospitalisations, which we analysed using a fixed-effect model. Other outcomes included length of stay, health-related quality of life, heart failure knowledge and self care, acceptability and cost; we described and tabulated these. We performed meta-regression to assess homogeneity (the null hypothesis) in each subgroup analysis and to see if the effect of the intervention varied according to some quantitative variable (such as year of publication or median age).\ud Main results: \ud \ud We include 41 studies of either structured telephone support or non-invasive home telemonitoring for people with heart failure, of which 17 were new and 24 had been included in the previous Cochrane review. In the current review, 25 studies evaluated structured telephone support (eight new studies, plus one study previously included but classified as telemonitoring; total of 9332 participants), 18 evaluated telemonitoring (nine new studies; total of 3860 participants). Two of the included studies trialled both structured telephone support and telemonitoring compared to usual care, therefore 43 comparisons are evident.\ud \ud Non-invasive telemonitoring reduced all-cause mortality (RR 0.80, 95% CI 0.68 to 0.94; participants = 3740; studies = 17; I² = 24%, GRADE: moderate-quality evidence) and heart failure-related hospitalisations (RR 0.71, 95% CI 0.60 to 0.83; participants = 2148; studies = 8; I² = 20%, GRADE: moderate-quality evidence). Structured telephone support reduced all-cause mortality (RR 0.87, 95% CI 0.77 to 0.98; participants = 9222; studies = 22; I² = 0%, GRADE: moderate-quality evidence) and heart failure-related hospitalisations (RR 0.85, 95% CI 0.77 to 0.93; participants = 7030; studies = 16; I² = 27%, GRADE: moderate-quality evidence).\ud \ud Neither structured telephone support nor telemonitoring demonstrated effectiveness in reducing the risk of all-cause hospitalisations (structured telephone support: RR 0.95, 95% CI 0.90 to 1.00; participants = 7216; studies = 16; I² = 47%, GRADE: very low-quality evidence; non-invasive telemonitoring: RR 0.95, 95% CI 0.89 to 1.01; participants = 3332; studies = 13; I² = 71%, GRADE: very low-quality evidence).\ud \ud Seven structured telephone support studies reported length of stay, with one reporting a significant reduction in length of stay in hospital. Nine telemonitoring studies reported length of stay outcome, with one study reporting a significant reduction in the length of stay with the intervention. One telemonitoring study reported a large difference in the total number of hospitalisations for more than three days, but this was not an analysis of length of stay per hospitalisation. Nine of 11 structured telephone support studies and five of 11 telemonitoring studies reported significant improvements in health-related quality of life. Nine structured telephone support studies and six telemonitoring studies reported costs of the intervention or cost effectiveness. Three structured telephone support studies and one telemonitoring study reported a decrease in costs and two telemonitoring studies reported increases in cost, due both to the cost of the intervention and to increased medical management. Adherence was rated between 55.1% and 98.5% for those structured telephone support and telemonitoring studies which reported this outcome. Participant acceptance of the intervention was reported in the range of 76% to 97% for studies which evaluated this outcome. Seven of nine studies that measured these outcomes reported significant improvements in heart failure knowledge and self-care behaviours.\ud Authors' conclusions: \ud \ud For people with heart failure, structured telephone support and non-invasive home telemonitoring reduce the risk of all-cause mortality and heart failure-related hospitalisations; these interventions also demonstrated improvements in health-related quality of life and heart failure knowledge and self-care behaviours. Studies also demonstrated participant satisfaction with the majority of the interventions which assessed this outcome.

There is no robust evidence that any treatment can modify the natural history of patients with heart failure and preserved left ventricular ejection fraction (HFpEF), although most agree that diuretics can control congestion and improve symptoms. HFpEF is often complicated by systemic and pulmonary hypertension, atrial fibrillation, obesity, chronic lung and kidney disease, lack of physical fitness, and old age that can complicate both diagnosis and management. Further trials should phenotype patients precisely and create better definitions of HFpEF based on biomarkers.

The brand new 2016 ESC guidelines for the treatment of acute and chronic heart failure continue to give a prominent place to mineralocorticoid receptor antagonists in the treatment of chronic heart failure with reduced ejection fraction (HFrEF). In the prevention of HF hospitalization and death, a class I, level of recommendation A, is given to MRAs for patients with HFrEF, who remain symptomatic despite treatment with an ACE-inhibitor and a beta-blocker and have an LVEF below 35 %. This recommendation is primarily based on two landmark trials, the RALES trial (for spironolactone) and the EMPHASIS-HF trial (for eplerenone). A crucial question is, however, why MRAs are advised only in “third place,” i.e., after optimal up-titration of ACE-inhibitors and beta-blockers. We wonder whether MRAs could not or should not be given earlier in the treatment of HFrEF, namely before or together with the up-titration of ACE-inhibitors and beta-blockers. Several arguments to support this plea are described in this short paper.

IMPORTANCE: Detailed information on the prevalence, associations, and consequences of anemia and iron deficiency in epidemiologically representative outpatients with chronic heart failure (HF) is lacking. OBJECTIVE: To investigate the epidemiology of anemia and iron deficiency in a broad range of patients referred to a cardiology clinic with suspected HF. DESIGN, SETTING, AND PARTICIPANTS: We collected clinical data, including hemoglobin, serum iron, transferrin saturation, and serum ferritin concentrations, on consecutive patients referred with suspected HF to a single outpatient clinic serving a local community from January 1, 2001, through December 31, 2010. Follow-up data were censored on December 13, 2011. Patients underwent phenotyping by echocardiography and plasma N-terminal pro-brain natriuretic peptide measurement and were followed for up to 10 years. MAIN OUTCOME MEASURES: Prevalences of anemia and iron deficiency and their interrelationship, all-cause mortality, and cardiovascular mortality. RESULTS: Of 4456 patients enrolled in the study, the median (interquartile range) age was 73 (65-79) years, 2696 (60.5%) were men, and 1791 (40.2%) had left ventricular systolic dysfunction (LVSD). Of those without LVSD, plasma N-terminal pro-brain natriuretic peptide concentration was greater than 400 pg/mL in 1172 (26.3%), less than 400 pg/mL in 841 (18.9%), and not measured in 652 (14.6%). Overall, 1237 patients (27.8%) had anemia, with a higher prevalence (987 [33.3%]) in patients who met the criteria for HF with or without LVSD. Depending on the definition applied, iron deficiency was present in 270 (43.2%) to 425 (68.0%) of patients with and 260 (14.7%) to 624 (35.3%) of patients without anemia. Lower hemoglobin (hazard ratio 0.92; 95% CI, 0.89-0.95; P < .001) and serum iron (hazard ratio 0.98; 95% CI, 0.97-0.99; P = .007) concentrations were independently associated with higher all-cause and cardiovascular mortality in multivariable analyses. CONCLUSIONS AND RELEVANCE: Anemia is common in patients with HF and often associated with iron deficiency. Both anemia and iron deficiency are associated with an increase in all-cause and cardiovascular mortality and might both be therapeutic targets in this population.

The PARADIGM-HF trial showed that sacubitril-valsartan, an ARB-neprilysin inhibitor, is more effective than enalapril for some patients with heart failure (HF). It is uncertain what proportion of patients with HF would be eligible for sacubitril-valsartan in clinical practice.Between 2001 and 2014, 6131 patients consecutively referred to a community HF clinic with suspected HF were assessed. The criteria required to enter the randomized phase of PARADIGM-HF, including symptoms, NT-proBNP, and current treatment with or without target doses of ACE inhibitors or ARBs, were applied to identify the proportion of patients eligible for sacubitril-valsartan. Recognizing the diversity of clinical opinion and guideline recommendations concerning this issue, entry criteria were applied singly and in combination. Of 1396 patients with reduced left ventricular ejection fraction (≤40%, HFrEF) and contemporary measurement of NT-proBNP, 379 were on target doses of an ACE inhibitor or ARB at their initial visit and, of these, 172 (45%) fulfilled the key entry criteria for the PARADIGM-HF trial. Lack of symptoms (32%) and NT-proBNP600 ng/L (49%) were common reasons for failure to fulfil criteria. A further 122 patients became eligible during follow-up (n = 294, 21%). However, if background medication and doses were ignored, then 701 (50%) were eligible initially and a further 137 became eligible during follow-up.Of patients with HFrEF referred to a clinic such as ours, only 21% fulfilled the PARADIGM-HF randomization criteria, on which the ESC Guidelines are based; this proportion rises to 60% if background medication is ignored.

Purpose: To assess the effect of routine use of home telemonitoring on the risk of re-admission to hospital amongst patients with heart failure. Context: Heart failure is a common reason for hospitalizations, which often recur. Telemonitoring might detect early decompensation allowing intervention to prevent re-admission. A systematic review concluded that telehealth reduced heart failure related hospitalizations by almost 30 % [1]. In Europe, the use of telehealth has primarily been limited to studies, pilots and small programs; it has not yet become routine in clinical practice. Accordingly, we assessed the effects of a telemonitoring service on unplanned re-admissions to hospital at 90 days and one year. Methods: OPERA-HF is an ongoing prospective observational study, enrolling patients hospitalized with worsening heart failure to the Hull & East Yorkshire Hospitals NHS Trust, UK. All patients enrolled in the study are followed subsequent to discharge. The primary outcome for this analysis was unplanned all-cause readmission. Patients were referred to telehealth by the hospital discharge team if aged >18 years and registered with a Hull-based primary care physician. To remove imbalances in baseline characteristics between patients on telehealth and those not, propensity matching was used to estimate effectiveness. A logistic regression model was used to determine the propensity score (probability of being selected for telehealth) for each patient. The calculated propensity scores were applied to a weighted logistic regression to account for selection assignment differences between patients on telehealth and on standard care. Propensity scores were calculated by controlling for age, number of severe comorbidities, New York Heart Association (NYHA) class at admission, emergency heart failure hospitalizations in prior 6 months, total daily pill count, heart rate and NT-proBNP at discharge. Results and discussion: Of 546 patients enrolled, 89 received telehealth. Table 1 shows their baseline characteristics. Patients selected for telehealth had fewer unplanned readmissions at both 90 days (OR: 0.66; 95% CI: 0.45 to 0.97; P Characteristic w/o Telehealth (N=457) with Telehealth (N=89) All (N= 546) Valid N Summary Valid N Summary Valid N Summary Age, year 457 77 [68 – 83] 89 73 [66 – 80] 546 76 [68 – 82] Number of severe comorbidities, sum 457 1 [1 -2] 89 2 [1 -2] 546 1 [1 - 2] More than one unplanned HF hospitalizations in prior 6 months, yes 457 70 (15%) 89 14 (16%) 546 84 (15%) Total daily pill count at discharge, sum 386 11 [9 -16] 84 13 [9 -16] 470 12 [9 - 16] NYHA at admission: Class I/II, yes NYHA at admission: Class III, yes NYHA at admission: Class IV, yes 307 40 (13%) 199 (65%) 68 (22%) 80 7 (9%) 52 (65%) 21 (26%) 387 47 (12%) 251 (65%) 89 (23%) Heart Rate at discharge, bpm 283 75 [66 – 89] 68 75 [68 – 82] 351 75 [67 – 88] NT-proBNP at discharge, pg/mL 340 4828[1972- 10710] 67 5097 [2930 - 8714] 407 4891 [2112 - 10500 ] 90 day unplanned readmission, yes 457 151 (33%) 89 25 (28%) 546 176 (32%) 1 year unplanned readmission, yes 396 221 (56%) 78 41 (53%) 474 262 (55%) Table 1 Baseline characteristics stratified by being on Tele health or not. Characteristics are summarized by their count and fraction (N (%)) for categorical or their median and interquartile range (Median [25th – 75th]) for continuous variables, respectively References: [1] Inglis SC, Clark RA, Dierckx R, Prieto-Merino D, Cleland JGFet al., 2015, Structured telephone support or non-invasive telemonitoring for patients with heart failure, COCHRANE DATABASE OF SYSTEMATIC REVIEWS, ISSN: 1469-493X

Jugular venous distension is a classical sign of heart failure (HF) but it can be difficult to assess clinically.Outpatients with HF and control subjects were assessed. Internal jugular vein diameter (JVD) was measured using a linear high-frequency ultrasound probe (10 MHz) at rest, after a Valsalva manoeuvre and during deep inspiration. JVD ratio was calculated as the maximum diameter during Valsalva to that measured at rest. 311 patients (mean age 71 years, mean left ventricular EF 42%, median (IQR) amino-terminal pro-brain natriuretic peptide 979 (441-2007) ng/L) and 66 controls were included. JVD (median and IQR range) at rest was smaller in controls (0.16 (0.14-0.20) cm) than in patients with HF (0.23 (0.17-0.33) cm; p0.001) but similar during Valsalva (1.03 (0.90-1.16) cm vs 1.08 (0.90-1.25) cm; p=0.28). Consequently, JVD ratio was greater in controls (6.3 (4.9-7.6)) than in patients (4.5 (2.9-6.1); p0.001). During a median follow-up of 516 (IQR 335-622) days, 48 patients (15%) with HF died or were hospitalised for HF. In multivariable models, among clinical, echocardiographic or biochemical variables, only increasing NT-proBNP and ultrasound assessment of internal jugular vein were independently associated with prognosis. Comparing top and bottom tertiles of JVD ratio (2.3 (IQR 1.7-2.9) versus 6.8 (6.1-7.7)), the tertile with lower values had a 10-fold greater risk of an adverse event (HR 10.05, 95% CI 3.07 to 32.93).Ultrasound assessment of the internal jugular vein identifies outpatients with HF who have a higher risk of an adverse outcome.NCT01872299.

To investigate, in a ‘real-world’ setting, the impact of home telemonitoring (HTM) compared to usual care on achieved dose of guideline-recommended medication, hospitalisation rate and mortality in patients with heart failure (HF). Methods: We retrospectively analyzed data on 333 patients with HF referred to a HTM service supported by a nurse-specialist (mean age 71±12 years, mean left ventricular ejection fraction (LVEF) 36 ± 11% and median N-Terminal pro B-type Natriuretic Peptide (NT-proBNP) 2,972 ng/L (interquartile range (IQR): 1,447–7,801 ng/L)). Most patients (n = 278) accepted HTM (HTM-group) but 55 refused and received usual care (UC-group). In the HTM-group, weight, heart rate, blood pressure and symptom severity were measured daily. Results: At referral, respectively 90%, 90%, 67% and 94% of patients with LVEF ≤40% (n = 229) were treated with β-blockers (BB), angiotensin converting enzyme-inhibitors (ACE-I) or angiotensin receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA) and diuretics, with rates similar between groups. After 6 months, prescription of BB (92% vs 83%), ACE-I/ARB (92% vs 90%) and MRA (68% vs 67%) did not differ significantly between groups. The proportions of patients who achieved ≥50% and ≥100% of target doses of BB, ACE-I/ARB and MRA were also similar in each group. However, during a median follow-up of 1094 days (IQR 767–1419) fewer patients who chose HTM died (33% vs 49%; P = 0.002). Conclusion: Patients who choose HTM have a better prognosis than those who do not but this does not appear to be mediated through greater prescription of key HF medications.

This study sought to characterize patients attending a community heart failure (HF) clinic and identified those who were eligible for optimization of beta-blockers (BB) or ivabradine.Among patients with HF due to left ventricular systolic dysfunction in sinus rhythm, those with higher resting heart rate have a worse prognosis. Reducing sinus rate to 50 to 60 beats/min might improve outcomes.A total of 1,000 consecutively scheduled HF clinic follow-up appointments over a 6-month period were reviewed. Demographic, clinical, and echocardiographic data were collected for patients who attended (824 unique patients; 555 men). Mean age was 74 ± 11 years, median N-terminal pro-B-type natriuretic peptide levels were 1,002 ng/l (interquartile range: 367 to 2,151 ng/l), and the mean left ventricular ejection fraction (LVEF) was 44 ± 11%. A total of 202 (25%), 252 (31%), and 370 (45%) patients had LVEFs of ≤35%, 36% to 49%, and ≥50%, respectively. Of patients with LVEF ≤35%, 142 (70%) were in sinus rhythm.At 70 clinic visits, 58 patients with LVEFs of ≤35% were in sinus rhythm and had heart rates ≥70 beats/min. Of these, 13 patients had their BB dose increased, 20 were potentially eligible for, but did not have, BB uptitration, 15 were already taking target doses of BBs, and 10 patients were reported to be intolerant of higher doses. Thus, 25 patients were potentially eligible for ivabradine according to European Society of Cardiology guidelines; this number dropped to 14 when the United Kingdom National Institute for Health and Care Excellence guidelines were applied.Among patients with LVEFs of ≤35%, most are treated with BBs and have a heart rate at rest of 70 beats/min; 12% of these patients might be eligible for ivabradine.

Heart failure is one of the most important medical problems facing societies in developed economies and its prevalence is predicted to rise inexorably in the next few decades as longevity increases. Worsening heart failure leading to hospitalization is associated with a poor prognosis and imposes a substantial burden on health care resources and budgets. Interventions that can stabilize patients should reduce the need for hospitalization and improve prognosis. This might be facilitated by frequent self-monitoring of clinical and physiological variables by patients themselves at home. Rising pulmonary artery pressure is an early sign of cardiac decompensation that may be more sensitive than conventional methods of patient assessment and thus allow early adjustment of medical therapy to avoid hospitalizations and improve patient outcomes. Remote monitoring of pulmonary artery pressure is now possible using devices that can be implanted percutaneously. This innovative technology could become a routine part of the management of heart failure in the next few decades.

Heart failure (HF) is a leading cause of hospitalisations in older people. Several strategies, supported by novel technologies, are now available to monitor patients’ health from a distance. Although studies have suggested that remote monitoring may reduce HF hospitalisations and mortality, the study of different patient populations, the use of different monitoring technologies and the use of different endpoints limit the generalisability of the results of the clinical trials reported, so far. In this review, we discuss the existing home monitoring modalities, relevant trials and focus on future directions for telemonitoring.

Purpose: Several reports suggest that Home Telemonitoring (HTM) may reduce mortality and possibly hospitalizations for heart failure (HF) but others have not confirmed this. Whether HTM is more or less effective in clinical practice than in clinical trials is uncertain. This analysis investigated variations in outcome of patients with Chronic Heart Failure (CHF) receiving HTM in a clinical service compared to those receiving conventional care. Purpose: Several reports suggest that Home Telemonitoring (HTM) may reduce mortality and possibly hospitalizations for heart failure (HF) but others have not confirmed this. Whether HTM is more or less effective in clinical practice than in clinical trials is uncertain. This analysis investigated variations in outcome of patients with Chronic Heart Failure (CHF) receiving HTM in a clinical service compared to those receiving conventional care. Methods: As part of the local heart failure service provision for the City of Kingston-upon-Hull (population circa 288,000), 225 patients were enrolled in the HTM service between April 2008 and May 2012 during which time 1822 patients had been registered in an out-patient service. A literature review was carried out, and this together with recommendations from clinicians and completeness of data resulted in 54 features that were chosen as candidate covariates for the calculation of propensity scores (PS). Key co-variates included age, sex, weight, NT-proBNP, Blood pressure, Creatinine, Urea, Heart rate, Diabetic, Hypertension, Beta blocker, etc. Outcomes of interest were (time to first International Congress on Telehealth and Telecare 2013, London, July 01-03, 2013. 2 International Journal of Integrated Care –Volume 13, 20 November –URN:NBN:NL:UI:10-1-115718– http://www.ijic.org/ event) all-cause hospitalization or death, cardiovascular (CV) hospitalization or death, all-cause mortality and CV mortality. Results: Before PS matching, there were 645 patients in the control group and 106 patients in the HTM group, who had an ECG, Echo, blood test, medication and physical examination during a specified time window. PS was calculated using a non-parsimonious multivariable logistic regression model and 80 pairs of patients with a similar PS (to two decimal places) were matched. Risks of the four types of outcomes were then analysed using Kaplan-Meier methods and are plotted. At two year, all-cause hospitalization or death was 37.3% in the HTM group and 59.5% in the control group (p = 0.008); CV hospitalization or death was 34.2% in the HTM group and 51.8% in the control group (p = 0.046); all-cause mortality was 23.4% in the HTM group and 21.2% in the control group (p = 0.531); CV mortality was 16.2% in the HTM group and in 13.9% in the control group (p = 0.629). Conclusions: In this analysis, HTM was associated with a lower incidence of (all-cause or CV) hospitalisation or death but not all-cause or CV mortality.

Although pericardial effusion is a well-known feature of Churg-Strauss syndrome, cardiac tamponade has rarely been encountered. The present report describes a case of Churg-Strauss syndrome that presented as an acute cholecystitis and was complicated by tamponade. Histopathological exam of both pericardium and gall bladder was conclusive for Churg-Strauss syndrome.