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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

Introduction: Patients(pts) with paroxysmal atrial fibrillation are at risk for developing heart failure with preserved ejection fraction(HFpEF) and often have an impaired exercise capacity. Since left atrial (LA) pressure plays a major role in the exercise intolerance, we aimed to characterize the contribution of resting LA mechanical properties, assessed by two-dimensional speckle tracking echocardiography upon exercise capacity. Purpose: To evaluate relationship between LA mechanics, measured by LA strain (LAS) and parameters of exercise capacity in pts with paroxysmal atrial fibrillation. Methods: The study included 54 pts(64 ± 10years, 76 % males) with dyspnea (NYHA³II), paroxysmal atrial fibrillation and preserved LV ejection fraction (≥50%). The likelihood of HFpEF was estimated using H2FPEF score. During sinus rhythm, all patients underwent speckle tracking echocardiography and cardiopulmonary exercise testing (CPET). Peak oxygen uptake(VO2peak) served as measure of functional capacity and ventilation/carbon dioxide output slope(VE/VCO2) as surrogate of ventilation/perfusion mismatch. Results: LA contractile strain(S) and strain rate(SR) showed significant correlation with VO2peak(both p < 0.05). LA reservoir, conduit and contractile LAS, all had significant relationship with VE/VCO2 slope (all pConclusions: In HFpEF VO2peak and VE/VCO2 are closely related to LA contractile strain, suggesting that abnormalities in LA mechanics may contribute to the blunted exercise capacity. Therefore, we speculate that these markers can be used as an echocardiographic surrogate of functional capacity in HFpEF pts. Further studies are warranted.

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

The additional role of continuous monitoring of filling pressures and impedance in heart failure patients with chronic kidney disease remains undetermined. In this case report, the effects of diuretic therapy and renal replacement therapy by hemodialysis upon right ventricular filling pressures and impedance are described in a patient with end-stage heart failure and end-stage chronic kidney disease (grade 5). We demonstrated that unloading of the heart by hemodialysis partly restored the blunted Frank-Starling relationship.

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)

Cardiac transplant-related vasculopathy remains a leading cause of morbidity and mortality in heart transplant (HTx) recipients. Recently, coronary angiography-derived vessel fractional flow reserve (vFFR) has emerged as a new diagnostic computational tool to functionally evaluate the severity of coronary artery disease. Although vFFR estimates have been shown to perform well against invasive FFR in atherosclerotic coronary artery disease, data on the use of vFFR in heart transplant recipients suffering from cardiac transplant-related arteriopathy are lacking. The aim of the presented study was to validate coronary angiography-derived vessel fractional flow reserve to calculate fractional flow reserve in HTx patients with and without cardiac transplant-related vasculopathy. A prospective, single center study of HTx patients referred for annual check-up, undergoing surveillance coronarography was conducted. Invasive FFR was measured using a motorized device at the speed of 1.0 mm/s in all three major coronary arteries. Angiography-derived pullback FFR was derived from the angiogram and compared with invasive FFR pullback curve. Overall, 18,059 FFR values were extracted from the FFR pullback curves from 23 HTx patients. The mean age was 59.3 ± 9.7 years, the mean time after transplantation was 5.24 years [IQR 1.20, 11.25]. A total of 39 vessels from 23 patients (24 LAD, 11 LCX, 4 RCA) were analyzed. Mean distal vFFR was 0.87 ± 0.14 whereas invasive distal FFR was 0.88 ± 0.17. An excellent correlation was found between invasive distal FFR and vFFR (r = 0.92; p < 0.001). The correlation of the pullback tracing was high, with a correlation coefficient between vFFR and invasive FFR pullback values of 0.72 (95% CI 0.71 to 0.73, p < 0.001). The mean difference between vFFR and invasive FFR pullback values was -0.01 with 0.06 of SD (limits of agreements -0.12 to 0.13). In HTx patients, coronary angiography-derived FFR correlates excellently with invasively measured wire-derived FFR. Therefore, angiography derived FFR could be used as a novel diagnostic tool to quantify the functional severity of graft vasculopathy. ispartof: DIAGNOSTICS vol:11 issue:10 ispartof: location:Switzerland status: published

This study aimed to examine the relationship between corin expression and circulating brain natriuretic peptide in patients with left ventricular (LV) dysfunction.Circulating levels of B-type natriuretic peptide (BNP) can be an indicator of LV dysfunction. The 32-amino-acid BNP is cleaved by corin, a cardiac serine protease, from its108-amino-acid pro-brain natriuretic peptide (proBNP) precursor.This study included 25 patients with idiopathic dilated cardiomyopathy (DCMP) and LV dysfunction and 44 heart transplant recipients with normal LV function who underwent diagnostic left and right heart catheterization. Blood samples were used to determine the ratio of plasma proBNP/BNP levels, and LV endomyocardial biopsies were used to determine the expression of NPPB, which encode BNP and corin, respectively, by quantitative reverse transcription-polymerase chain reaction.Patients with DCMP revealed worse hemodynamic profiles and higher plasma proBNP and BNP levels than those of the transplant recipients. Myocardial NPPB expression was higher and CORIN expression was lower in the DCMP patients than in the transplant recipients. CORIN expression significantly correlated with NPPB expression (r = -0.585; P < 0.001), ejection fraction (EF; r = 0.694; P < 0.01), LV end-diastolic pressure (r = -0.373; P < 0.05), and indexed end-diastolic LV volume (r = -0.452; P < 0.001). In addition, the plasma proBNP/BNP levels inversely correlated with the CORIN expression (r = -0.362; P < 0.005).Decreased myocardial CORIN expression and the corresponding higher levels of circulating unprocessed proBNP in DCMP may partly account for the relative BNP resistance observed in patients with LV dysfunction.

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.

A 53-year-old heart transplant recipient with a past medical history of surgically treated acute type A dissection of the donor aorta 10 years following heart transplantation, presented with a Card...

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.

Purpose A pulmonary wedge pressure >18 mmHg following volume load has been proposed as a partition value for the detection of HFpEF. In both experimental and clinical settings, the hemodynamic changes in filling pressures have been attributed to a nitric oxide(NO)-mediated rightward shift of the pressure-volume relationship. The present study investigates the hemodynamic response to a volume challenge upon diastolic function in heart transplant(HTx) recipients and examines the role of inducible nitric oxide synthase(iNOS) gene expression on diastolic function changes. Methods 36 HTx recipients with normal left ventricular function (ejection fraction[EF]: 61 ± 12%) and without rejection and graft vasculopathy underwent right heart catheterization for the measurement of the degree of hemodynamic response to volume loading after saline infusion of 7 mL/kg over 10 min. Pulmonary capillary wedge pressure(PCWP), right atrial pressure(RAP), and mean pulmonary artery pressure(PA) were measured, following which the PCWP and stroke volume index(SVI) were used for Starling(SVI/PCWP) curve construction. Pts were categorized into the normal (group A, n=20) and abnormal hemodynamics (group B, n=16, PCWP >15 mmHg at rest or >18 mmHg following volume load) groups. For the establishment of the potential role of NO as a mediator of hemodynamic response, the iNOS endomyocardial gene expression level was measured . Results No differences were observed in terms of donor and recipient age, baseline hemodynamic parameters, and EF between both groups. Volume load significantly increased PCWP and PA in both groups, without any significant change in blood pressure or heart rate. Saline infusion was associated with a significant increase in SVI in group A but not group B. Moreover, in group A, the Starling curves revealed a higher SVI at any given PCWP. Group A exhibited significantly higher iNOS gene expression levels than Group B. Conclusion In HTx, rapid saline infusion increases the filling pressure and unmasks the presence of left ventricular diastolic dysfunction. Interestingly, pts with an abnormal hemodynamic response show a blunted Frank-Starling response, as evidenced by the higher PCWP and lack of SVi increase at any given PCWP. The higher iNOS gene expression level in our control group suggests the potential role of NO as a mediator of diastolic function in heart Tx patients.

Post-extrasystolic potentiation (PESP) is a marker of contractile reserve and refers to the augmentation of left ventricular contractility due to preload recruitment and rise in intracellular calcium following a premature beat. In this case report we show that PESP might be a safe and helpful aid to evaluate low flow, low gradient aortic stenosis and contractile reserve in the cathlab, thereby reducing the potential risk of complications associated with intravenous dobutamine evaluation and reducing unnecessary testing.

Background The effect of adherence to cardiac rehabilitation (CR) on outcome is not clear. Therefore, we aimed to assess the impact of drop-out for non-medical reasons of CR on event-free survival in coronary artery disease (CAD). Methods A total of 876 patients who attended CR after acute coronary syndrome (ACS), percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) were included. Drop-out was defined as attending ≤50% of the training sessions. A combined endpoint of all-cause mortality and rehospitalization for a cardiovascular event was used to specify event-free survival. Differences in clinical characteristics were assessed and parameters with p Results A total of 15% died or had a cardiovascular event during a median follow-up period of 33 months (interquartile range 24, 51). Overall, 17% dropped out before finishing half of the program. Patients who withdrew prematurely had a risk twice as high for a cardiovascular event or death (hazard ratio 1.92, 95% confidence interval 1.28–2.90) than those who attended more than half of the sessions. Both ACS (2.36, 1.47–3.58) and PCI (2.20, 1.22–3.96), as primary indicators for CR, were associated with an adverse outcome and also a prior history of chronic heart failure (CHF) remained negatively associated with event-free survival (3.67, 1.24–10.91). Finally, the presence of hyperlipidemia was independently related to a worse outcome (1.48, 1.02–2.16). Conclusions Drop-out for non-medical reasons was independently associated with a negative outcome in CAD. Therefore, underlying factors for drop-out should gain more attention in future research and should be taken into account when organizing CR.

Background: Despite the clear benefits of cardiac rehabilitation (CR), a considerable number of patients drop out early. Objective: Therefore, we wanted to evaluate dropout in CR with a special focus on comorbidities and psychosocial background. Methods: Patients who attended CR after acute coronary syndrome, cardiac surgery, or heart failure (N = 489) were prospectively included. Dropout was defined as attending 50% of the training sessions or less (n = 96 [20%]). Demographic and clinical characteristics, exercise parameters, and psychosocial factors were analyzed according to dropout, and those with a trend toward a significant difference (P G .10) were entered in a multivariate logistic model. Results: The presence of a cerebrovascular accident (4.18 [1.39Y12.52]) involved a higher risk of dropout, and a comparable trend was seen for the presence of chronic obstructive pulmonary disease (2.55 [0.99Y6.54]). Attending the training program only twice per week also implicated a higher risk of an early withdrawal (3.76 [2.23Y6.35]). In contrast, patients on "-blockers were less likely to withdraw prematurely (0.47 [0.22Y0.98]). Singles were more likely to drop out (2.89 [1.56Y5.35]), as well as those patients who were dependent on others to get to CR (2.01 [1.16Y3.47]). Finally, the reporting of severe problems on the anxiety/depression subscale of the EuroQOL-5D questionnaire involved a higher odds for dropout (7.17 [1.46Y35.29]). Conclusions: Neither demographic characteristics nor clinical status or exercise capacity could independently identify patients who were at risk of dropout. The presence of comorbidities and a vulnerable psychosocial background rather seem to play a key role in dropout.

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.

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

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.