Chronic Heart Research Articles

Abstract 16458: Trends in Treatment and Outcomes of Cardiogenic Shock in the Adult Congenital Heart Disease Population: A Nationwide Analysis From 2007-2017

Introduction: Heart failure (HF) is common in the adult congenital heart disease (ACHD) population. We sought to assess outcomes of cardiogenic shock (CS) and assess the trends of utilization of mechanical circulatory support (MCS) in these patients. Methods: Using the nationwide inpatient sample (NIS) database for the years 2007-2017, adult patients with a primary discharge diagnosis of HF, and a co-diagnosis of CS were identified. They were divided into 2 groups - patients with ACHD and those without ACHD. Statistical significance was assigned at p<.05. Results: Out of the 114420 patients with HF who developed CS, 2572 (2.3%) patients had ACHD, and demonstrated an increasing yearly trend (Figure 1). Patients with ACHD were younger (55 vs 64.7 years, p<.01), and had lower rates of comorbidities like hypertension (24.8 vs 38.3 %, p<.01), diabetes mellitus (15.9 vs 27.5 %, p<.01) and chronic ischemic heart disease (27.1 vs 42.1 %, p<.01). Utilization of temporary MCS (25.9 vs 14.8 %, p<.01), Left ventricular assist device (LVAD) (28.4 vs 7.6 %, p<.01), and orthotopic heart transplantation (OHT) (8.0 vs 2.9 %, p<.01) was higher in the ACHD group. Yearly trends are shown in Figure 2. Patients with ACHD had lower in-hospital mortality (16.6 vs 23.7 %, p<.01) and lower adjusted odds of death [0.79 (CI 0.62,0.99), p<.04], but had longer length of stay (22.6 vs 14.6 days, p<.01) and total charges during hospitalization ($444007 vs $212972, p<.01). Conclusion: Although low, the rates of CS in ACHD patients is increasing, however, these patients had a lower mortality, likely driven by lower age, fewer comorbidities, and increased utilization of MCS and heart transplantation.

Abstract 14574: Assessing Cardiovascular, Thrombotic and Bleeding Outcomes in Patients With Chronic Liver Disease Undergoing Left Ventricular Assist Device Implantation: Analysis of the National Inpatient Sample Database

Introduction: Coagulopathy and hematologic abnormalities are major concerns in patients with chronic liver disease (CLD) and refractory heart failure which combined with the use of anticoagulation or anti-platelet therapy, may affect perioperative outcomes in patients undergoing left ventricular assist device (LVAD) implantation. Methods: The National Inpatient Sample Database was queried from 2012 to 2017 for relevant International Classification of Diseases (ICD)-9 and ICD-10 procedural and diagnostic codes. Baseline characteristics and in-hospital outcomes were compared in patients with chronic liver disease and those without, who underwent LVAD implantation. Results: A total of 23,435 patients underwent LVAD implantation, 2,200 patients with CLD and 20,755 patients without CLD. See Table 1 for baseline characteristics. All-cause inpatient mortality (14.8% vs. 11.1%, p<0.001), major bleeding (34.3% vs. 30.2%, p<0.001), transfusion of platelets (18.0% vs. 14.0%, p<0.001), and the occurrence of a subarachnoid hemorrhage (1.6% vs. 0.7%, p<0.001) were greater in patients with CLD. LVAD thrombosis (6.6% vs. 9.4%, p<0.001) and post-operative ischemic stroke (3.4% vs. 6.1%, p<0.001) occurred less in patients with CLD. Using a multivariate logistic regression model to adjust for confounding factors, revealed that CLD was predictive of increased mortality in patients undergoing LVAD implantation (odds ratio: 1.29, 95% confidence interval [CI]; 1.06 to 1.56, p=0.010). Conclusions: We demonstrated between 2012 to 2017, given the clinical paradox of pro- and anticoagulant risks in patients with CLD and advanced HF, LVAD implantation was associated with increased mortality, major bleeding with increased utilization of platelet products and yet increased thrombotic complications. Further studies are needed to evaluate both thrombotic and bleeding risks in this population, along with mitigating factors without compromising either outcome.

Abstract 17267: Outcomes of Patients With Non-ST-Segment Elevation Myocardial Infarction and High Degree Atrioventricular Block Treated With Early vs Delayed Invasive Strategy

Introduction: High degree atrioventricular block (HDAVB) is an uncommon complication of non-ST-segment elevation myocardial infarction (NSTEMI), frequently necessitating pacemaker implantation. Hypothesis: This contemporary analysis compares the need for pacemaker implantation based on the timing of intervention in acute NSTEMI complicated by HDAVB. Methods: We used 2016-2017 National Inpatient Sample (NIS) database to identify all admissions with NSTEMI. Those without HDAVB were excluded from the study. Time to coronary intervention from initial admission was used to segregate the admissions into two groups: early invasive strategy (EIS) (<24 hours) and delayed invasive strategy (DIS)(>24 hours). A multivariate logistic and linear regression analysis was performed to compare in-hospital outcomes among both groups. Results: Out of 949,984 NSTEMI related admissions, coexistent HDAVB was present in 0.7% (n=6725) patients which were subsequently included in the study. Amongst those, 55.61% (n=3740) hospitalization included invasive intervention (EIS=1320, DIS=2420) (Figure1). Patients treated with EIS were younger (69.95 vs 72.38, p= <0.05) and had a concomitant cardiogenic shock. Contrarily the prevalence of chronic kidney disease (CKD), heart failure (HF), and pulmonary hypertension was higher in DIS group. EIS was associated with lower length of stay and total hospitalization cost. Although statistical significance was not achieved, a trend towards higher in-hospital mortality and lower pacemaker implantation rates were seen in hospitalizations involving EIS (Table1). Conclusions: HDAVB is a rare complication of NSTEMI and it is associated with significant mortality. The timing of revascularization does not appear to influence the rate of pacemaker placement in NSTEMI complicated by HDAVB. Further studies are needed to assess if all patients presenting with HDAVB should be treated with an early invasive strategy.

Abstract 13401: Prothymosin Alpha (Protα) Associates With Pathogenesis and Sex Predisposition in Rheumatic Heart Valve Disease

Introduction: Acute rheumatic fever (ARF) results from autoimmune responses to group A streptococcus. ARF can cause chronic rheumatic heart valve disease (RHVD), a major public health burden in low- and middle-income countries. Although ARF affects both sexes equally, females have a higher prevalence of RHVD. We identified a target protein, ProTα, that may contribute to pathophysiology of and gender predisposition in RHVD. Estradiol regulates ProTα, which influences transcriptional activity of the estrogen receptor (ER). Methods: Human heart valves (n=120) obtained from heart transplantation and valve replacement surgeries, including non-diseased mitral and aortic valves (NDMV and NDAV, n=17/group), rheumatic mitral and aortic valves (RMVD, n=45; RAVD, n=8) and calcifying valves from patients with calcific aortic valve disease (CAVD, n=33) underwent proteomic and network analyses, and immunohistochemical assessment of CD68, CD4, CD8 and ProTα. ProTα levels were measured in plasma and peripheral mononuclear cells (PBMCs) from RHVD patients and healthy donors (n=14/group) by ELISA and flow cytometry. Results: A comparison of proteomes from NDMV and NDAV established the baseline differences between valve types. 12 proteins were enriched (q<0.05) in NDMV that may indicate the mitral valve predisposition to RVHD. Proteome analysis of non-diseased and diseased valves (NDMV vs RMVD, NDAV vs RAVD) identified a total of 213 proteins enriched in RHVD (q<0.05). The expression of the 12 NDMV-enriched proteins were evaluated across the 213 proteins enriched in diseased valves, resulting in the identification of ProTα common to both the RMVD and RAVD proteomes, but absent in CAVD. Additional KEGG pathway enrichment analyses linked 6 among 213 proteins with the estrogen signaling pathway (p<0.05). Immunoreactive ProTα colocalized with T CD8 cells in RHVD. ProTα and ERα also correlated strongly in circulating T CD8 cells in RHVD (p<0.05). ProTα plasma levels were higher in RHVD patients than healthy individuals (2 fold, p<0.05). Conclusion: We propose that ProTα is a novel contributor to the immunopathogenesis of RHVD and may regulate sex predisposition in this disease.

Abstract 16640: Neutrophil Expansion is Essential for Adverse Left Ventricular Remodeling and Dysfunction in Chronic Ischemic Heart Failure

Chronic inflammation contributes significantly to disease progression in heart failure (HF), and is characterized by expansion of activated macrophages, dendritic cells, and T cells in the failing heart. Neutrophils play a well-known role as the initial drivers of inflammatory response to myocardial infarction (MI), thereby providing the platform for the subsequent recruitment of macrophages and T cells. However, whether and how neutrophils contribute to inflammation and adverse LV remodeling in chronic HF are unknown. We tested the hypothesis that activated neutrophils are required for tissue remodeling and disease progression in HF. Male C57Bl/6 mice were studied 4 and 8 weeks after left coronary artery ligation during established ischemic HF (sham-operated controls). As assessed by flow cytometry, CD11b + Ly6G + neutrophils were expanded in the peripheral blood (4 w post-MI), and in the bone marrow, spleen, and heart at 8 w post-MI. Immunostaining revealed that in the failing heart, neutrophils were primarily localized to the MI border zone, but also augmented in remote zone myocardium. CXCL1 and CXCL5 chemokine expression was increased in the failing heart, consistent with chemotactic signals for myocardial neutrophil recruitment. Isolated naïve neutrophils also exhibited increased chemotaxis in response to plasma from HF mice (versus plasma from naïve mice), as assessed by time-lapse video microscopy. Moreover, blood neutrophils isolated from HF mice exhibited significantly increased neutrophil extracellular trap (NET) production as compared to control neutrophils, whereas plasma NETs (histone-DNA complexes) were increased in HF mice. Finally, the in vivo role of neutrophils in chronic HF (8 w post-MI) was determined via depletion studies using genetic (Ly6G-diptheria toxin receptor mice) and antibody (1A8) based approaches. In both models, 2 and 4 w of neutrophil depletion, respectively, significantly improved LV systolic function and reduced end systolic volume. 1A8 treated HF mice also exhibited reduced remote zone fibrosis. We conclude: neutrophil expansion and activation are important components of the chronic inflammatory response in HF, and play an obligatory role in the progression of LV remodeling in ischemic cardiomyopathy.

Acute kidney injury with cardiorenal syndrome; experience from a tertiary care renal unit in Pakistan

Introduction: Acute kidney injury (AKI) is a commonly recognized clinical problem after many morbid conditions related to heart like congenital heart disease surgery, acute or chronic congestive heart failure, acute myocardial infarction, infective endocarditis or cardiomyopathies. Cardio-renal syndrome (CRS) includes a spectrum of disorders involving both the heart and kidneys simultaneously; here acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other. Objectives: To report here, case series of patients with AKI developing in association with CRS. We aim to report different causes of CRS and outcome of patients in this group of patients. Patients and Methods: Subjects for the study reported here comprised a cohort of 34 patients coming to this institution with AKI in association of CRS. AKI was defined according to KDIGO guidelines and CRS based on consensus conference of ADQI in 2012. Type 1or type2 CRS are included in the study. All patients had normal size kidneys on ultrasonography. Results: Thirty-four patients with AKI and CRS were brought to this institute from January 1990 to December 2014; this was contributing 1% to medical causes of total AKI. Among these 25 were males and 9 females; mean age of these patients was 54.06±14.106 years. Causes of CRS were acute myocardial infarction (ST elevated), congestive cardiac failure, infective endocarditis and dilated cardiomyopathy. More than two third of patients were either oliguric or anuric on presentation. Fluid replacement and/or inotropic support required in 79%. Renal replacement therapy in form of hemodialysis was conducted in 64.7% and intermittent peritoneal dialysis in one patient. Complete renal recovery was observed in 19 (56%) patients, while 12 (35%) died during acute phase of illness. CKD-V developed in one patient, 2 patients lost long term follow up, but became dialysis free and renal functions were in improving trends, they were labeled as partial recovery. Secondary insults like hypotension, aggressive diuresis, and volume loss from gastro-intestinal tract or infection were evaluated for any co-relation with outcome but statistically no significant difference was found. Conclusion: CRS can be severe life-threatening condition especially when patients present with circulatory collapse. Diuretics must be used cautiously in patients with congestive cardiac failure. Infective endocarditis with acute right heart failure can lead to CRS.

COVID-19 in lung transplant recipients: A multicenter study.

This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.

Gender differences in association between air pollution and daily mortality in Green Lungs of Poland – population-based study with almost 3,000,000 person-years of observation

Abstract Introduction Air pollution is considered to be one of the main risk factors for public health, in particular its impact on the disorders of the pulmonary and cardiovascular system and the related mortality. Purpose This study was carried out to assess the influence of the atmospheric conditions and air pollutants on mortality in the population of the big city in the eastern Poland. Materials and methods Based on the data from the Central Statistical Office, the number and causes of the deaths of the city residents in the period 2008–2017 were analyzed. The study utilized the data recorded by the Provincial Inspectorate for Environmental Protection station and the Institute of Meteorology and Water Management during the analysis period. Multivariate Poisson regression was used for statistical analysis. Results A total of 34,005 deaths had been recorded, in which women accounted for 47.5%. The proportion of cardiovascular-related deaths was 48% (N=16,370). The main causes of deaths in the female population were chronic ischemic heart disease (N=1683; 10.42%) and cerebral infarction (N=1617; 10.01%), while in the male population, in addition to chronic ischemic heart disease (N=1530; 8.57%), deaths were caused mainly by malignant neoplasm of the bronchus and lung (N=1555; 8.71%). During the analysis, it was observed that the 1-day norm of sulfur dioxide (SO2) recommended by the World Health Organization (WHO) guidelines was sporadically exceeded (N=18, 0.50% of analyzed days), while the daily norm for the particulate matter with a diameter of 2.5 μm or less (PM2.5) was exceeded on 688 days (23.60% of analyzed days). In the female group, excluding the seasonal impact, an increase of SO2 concentration by 1-μg/m3 (RR 1.05, 95% confidence interval (CI) 1.01–1.10; P=0.009) and a 10°C decrease of temperature (RR 1.04, 95% CI 1.02–1.07; P=0.003) were related to an increase in the number of daily deaths. In the male group, a stronger effect of SO2concentration on mortality was noted; the RR for 1-μg/m3 increase of SO2 was 1.10 (95% CI 1.04–1.18; P=0.002). In the subgroup analysis of cardiovascular deaths, the main pollutant that was found to have an effect on daily mortality was PM2.5; the RR for 10-μg/m3 increase of PM2.5 was 1.07 (95% CI 1.02–1.12; P=0.01). Conclusions Air quality and atmospheric conditions had an impact on the mortality of Białystok residents, and this effect was more pronounced in the male population. The main air pollutants that influenced the rate of mortality were SO2and PM2.5. In the female population, an additional factor that influenced the total mortality and mortality due to cardiovascular diseases was temperature. It is worth emphasizing that the impact of SO2 on mortality was clear within “safe” range recommended by WHO. More research on that topic is necessary, but our results bring questions whether the recommended norms should be stricter, or is there a safe concentration of SO2 in the air at all. Funding Acknowledgement Type of funding source: None

Risk factors for mortality within one-year after implantable cardioverter defibrillator implantation: a nationwide study

Abstract Background Current guidelines do not recommend implantable cardioverter defibrillator (ICD) implantation in patients with an estimated survival probability of less than one year. There is still an unmet need to identify patients who are unlikely to benefit from an ICD. Purpose We determined one-year mortality after ICD implantation and associated risk factors of one-year mortality. Methods Using Danish nationwide registries from 2000–2016, we identified patients ≥18 years old undergoing first-time ICD implantation for primary or secondary prevention. Patients were followed for up to one-year from time of ICD implantation. Risk factors associated with one-year mortality after time of ICD implantation were evaluated in multivariable logistic regression models. Results A total of 13,344 patients underwent first-time ICD implantation (median age: 66 years [25th-75th percentile 58–72 years], male=81.3%, secondary prevention=54.6%), of which 647 died (4.8%) within one year of follow-up. Compared with ICD patients who survived for one year, those who died were significantly older (72 years vs. 66 years, p<0.001) and had more comorbidities, including congestive heart failure (70.8% vs. 63.4%), atrial fibrillation (36.6% vs. 23.6%), diabetes (30.8% vs. 19.9%), chronic obstructive pulmonary disease (COPD) (17.0% vs. 8.2%), chronic renal disease (13.0% vs. 4.4%), malignancy (9.9% vs. 5.4%), and dialysis (7.3% vs. 2.4%) (p<0.001 for all). Results from the multivariable logistic regression model are depicted in the Figure. There was a graded relationship between age and one-year mortality, with a greater risk of all-cause mortality with increasing age. In addition, dialysis, chronic renal disease, COPD, malignancy, diabetes, and congestive heart failure were strongly associated with increased risk of one-year all-cause mortality. However, ischaemic heart disease was associated with a lower risk of all-cause mortality (Figure). The one-year risk of death was 13.2% for both patients receiving dialysis and patients with chronic renal disease, respectively. The majority of deaths within one year were attributed to cardiovascular causes (408/647, 63.1%) of which chronic ischaemic heart disease (68/647, 10.5%), acute myocardial infarction (50/647, 7.7%), and atherosclerosis (40/647, 6.2%) were the most common. The most common non-cardiovascular cause of death was malignancy (10.5%). Conclusion In patients with a first-time ICD implantation, 95% survived for more than one year after implantation. While low mortality rates are indicative of relevant patient selection for ICD implantation, advanced age, dialysis, and several comorbidities were all strongly associated with increased one-year mortality, whereas ischaemic heart disease was associated with a lower risk of one-year mortality. Potential benefit of an ICD in such patients should be carefully evaluated before implantation. Funding Acknowledgement Type of funding source: None

Prognostic value of NT-proBNP and best cut-offs for risk prediction in obese patients with chronic systolic heart failure

Abstract Background N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) is a strong predictor of outcome in chronic systolic heart failure (CHF). Although plasma NT-proBNP has been reported to display an inverse correlation with body-mass-index (BMI), its prognostic value in obese patients has been poorly investigated so far. Objectives To evaluate the prognostic value and the best cut-offs for risk prediction of NT-proBNP in obese individuals from a multinational cohort of patients with systolic CHF. Methods We analyzed data from the BIOS (Biomarkers In Heart Failure Outpatient Study) Consortium. Patients with left ventricular ejection fraction (LVEF) ≤50% were selected and classified as nonobese (BMI <30 kg/m2), mildly obese (BMI 30–35 kg/m2), moderately obese (BMI 35–40 kg/m2), or severely obese (BMI ≥40 kg/m2), according to standard nomenclature. Clinical and bio-humoral data, including NT-proBNP testing, were retrieved, and 5-year cardiac and all-cause mortality status were considered as primary and secondary outcome, respectively. The independent prognostic role of NT-proBNP was evaluated through Cox regression analysis, adjusting the model for age, gender, New York Heart Association class, ischaemic aetiology, LVEF, and estimated glomerular filtration rate (eGFR). Results The study population included 11,574 patients (age 65±12 years, LVEF 30±9%, males 78%). Most of patients were nonobese (n=8,937, 77%), while mildly, moderately, and severely obese patients were 1,887 (16%), 499 (4%), and 251 (3%), respectively. Median values of plasma NT-proBNP were progressively lower from nonobese to mildly, moderately, and severely obese patients (1455 ng/L, 903 ng/L, 767 ng/L, 660 ng/L, respectively) and BMI was predictive of NT-proBNP independently from age, LVEF, and eGFR (r=−0.152, p<0.001). The best NT-proBNP cut-offs to predict 5-year cardiac mortality were significantly lower in mildly [1044 ng/L; AUC 0.663 (Sen 66%; Spe 59%), p<0.001] moderately [736 ng/L; AUC 0.670 (Sen 76%; Spe 52%), p<0.001]), and severely [1060 ng/L; AUC 0.635 (Sen 57%; Spe 69%), p=0.021] obese patients compared to nonobese individuals [2034 ng/L; AUC 0.714 (Sens. 65%; Spec. 66%), p<0.001]. Further, NT-proBNP independently predicted 5-year cardiac death in nonobese, mildly and moderately obese patients (all p<0.001), but not in severely obese patients (p=0.457). Similar findings were observed for the secondary endpoint of 5-year all-cause mortality. Conclusions Compared to nonobese CHF patients, obese patients have lower circulating NT-proBNP levels, which retain independent prognostic significance for cardiac and all-cause mortality across most categories of obesity. BMI-adjusted NT-proBNP cut-offs might be considered for prognostic stratification in obese patients with CHF. Funding Acknowledgement Type of funding source: None

The graduate school of medicine and palliative care: good news, but it's still not enough.

The recent establishment of palliative care and medicine as a medical specialty to be taught in postgraduate courses starting from the 2021/2022 academic year in Italy is certainly good news. Some doubts arise, anyway, if the academic programs will be limited to the postgraduate area instead of involving every university in the undergraduate courses. The risk is to maintain the reductionism of future physicians receiving a kind of education centered on the biomedical paradigm only. Since at least thirty years we know that there should not be a definite time marking a clear break between previous active treatments for the disease and subsequent palliative ones. Mainly in very old people affected by multiple chronic disorders a simultaneous presence of both forms of treatment should be scheduled, with increasing weight of palliation as the disease progresses and the probability of responding to active treatments becomes less and less. Unfortunately the reality of assistance in the last thirty days of life of patients suffering from cancer and/or chronic heart or lung diseases is increasingly centered on hospital settings, while the proportion of patients who are referred for hospice/palliative care in the last month of life is marginal, especially for non-cancer patients. We are going on with a health system that responds to the needs of the chronicities with the structures and pathways that are suitable for acute care: a completely different model would be needed. For over ten years palliative care in Italy has a specific regulatory reference such as that of law 38/2010, reaffirmed by the most recent law 219/2017: yet, although training is expressly provided for in these laws, we are still far from having made it, except for some sporadic cases. Now it seems that we are about to accomplish such provisions, even if starting from the roof instead of the foundations; as palliative care means multiprofessional and multidisciplinary teams a specific training program dedicated also to nurses, psychologists and physiotherapists is mandatory.

One-year outcome of the rule-out group according to the 0-h /1-hour algorithm with suspected myocardial infarction in Asian countries

Abstract Background/Introduction; A rapid rule-out or rule-in protocol based on the 0-h/1-hour algorithm using high-sensitivity cardiac troponin T (hs-cTnT) is recommended by the European Society of Cardiology (ESC). Around 40–50% were stratified into “rule-out” group, and their 30-days prognosis was excellent. However, the one-year prognosis is uncertain. We aimed to better characterize these patients. Methods This study was a prospective, multi-center, observational study of patients with suspected non-ST elevation acute coronary syndrome (NSTE-ACS) admitted to 5 hospitals in Japan and Taiwan from 2014 November to 2018 December, respectively. All patients underwent a clinical assessment the included medical history, physical examination, 12-lead ECG, standard blood test, chest radiography. Exclusion criteria were ST elevated myocardial infarction, chronic kidney disease (serum creatinine more than 3 mg/dL) and congestive heart failure, arrhythmia, or infection disease. The patients were divided into three groups according to the algorithm; “rule-out”, “observe” and “rule-in”. The final diagnosis was then adjudicated by 2 independent cardiologists using all available information, including coronary angiography, coronary computed tomography, stress electrocardiography and follow-up data. The presence of acute myocardial infarction (AMI) was defined according to the Fourth Universal Definition of Myocardial Infarction. After hospital discharge patients were follow after one-year b telephone or in written form. Major adverse cardiovascular events (including death myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention (PCI)) were recorded by establishing contact with the patient and the family physicians. The primary prognosis end point was all-cause mortality. Results Of the 1,187 patients were analyzed after exclusion. The prevalence rate of AMI was 16.1%. According to the algorithm, 42% (n=493) of patients were assigned to “rule-out” group and had no AMI nor death. The most common final adjudicated diagnoses were atypical chest pain (80%), gallstone attack (3%) and vasospastic angina pectoris (2%). All patients with unstable angina (4.7%) underwent PCI. Conclusion(s) Our findings suggest that the “rule-out” group patients according to ESC 0-h/1-hour algorithm provides very high safety and efficacy for the triage toward AMI. Funding Acknowledgement Type of funding source: None

The impact of stem cell therapy in chronic ischaemic heart disease and congestive heart failure: an updated cochrane systematic review and meta-analysis of randomised controlled trials

Abstract Introduction Controversies in stem cell research (Anversa retractions) have led many to question the validity of clinical cell therapy research. There is however consistent data supporting the use of cell therapy for chronic IHD. Purpose To update the clinical evidence for the safety and efficacy of autologous adult bone marrow-derived stem/progenitor cells as a treatment for chronic IHD and CHF. Methods A full Cochrane review of relevant trials up to 21st November 2018 was performed. Randomised controlled trials comparing autologous adult stem/progenitor cells with no cells in participants with chronic IHD and CHF were deemed eligible. Trials that involved acute myocardial infarction were excluded. Results In total 41 randomised controlled trials and 2397 patients are included in the meta-analysis. This updated Cochrane review shows a statistically significant reduction in mortality (RR 0.51; 95% CI, 0.37 to 0.68; p≤0.00001) and MACE (RR 0.66; CI 0.55 to 0.80; p<0.00001) seen with cell therapy. This is associated with a significant improvement in symptoms (exercise tolerance, NYHA, CCS) and ejection fraction. Conclusions Cell therapy may be effective for this patient group both for cardiovascular outcomes and symptom control. This conclusion therefore warrants further testing of cell therapy in prospective clinical trials assessing meaningful clinical endpoints. Stem cell therapy and risk of all-cause Funding Acknowledgement Type of funding source: None

Patient-reported health and 1-year mortality in patients with ischemic heart disease – findings from the Denheart study

Abstract Background Though survival has improved markedly in ischemic heart disease (IHD), it remains a leading cause of death worldwide. Screening tools to identify patients at risk are ever in demand. Large-scale studies exploring the association between patients' self-reported mental and physical health and mortality are lacking. Purpose (i) to describe patient-reported outcomes (PROs) at discharge in IHD patients deceased and alive at one year, (ii) to investigate the discriminant predictive performance of PRO instruments on mortality, (iii) to investigate differences in time to death among survey responders/non-responders and among three diagnostic sub-groups (chronic ischemic heart disease/stable angina, non-STEMI/unstable angina and STEMI), and (iv) to investigate predictors of one-year mortality among sociodemographic, clinical and self-reported factors. Methods Data from the national DenHeart survey with register-data linkage was used. A total of 14,115 adults with IHD were discharged during one year. Eligible (n=13,476) were invited to complete a questionnaire and 7,167 (53%) responded. Questionnaires included the Health survey short form 12-items (SF-12), Hospital Anxiety and Depression Scale (HADS), EuroQoL-5-dimensions (EQ-5D), HeartQoL, Edmonton Symptom Assessment Scale (ESAS) and ancillary questions. Clinical and demographic characteristics were obtained from registries as were data on one-year mortality. Comparative analyses investigated differences in PROs, and discriminant PRO-performance was explored by Receiver Operating Characteristics (ROC) curves. Kaplan-Meier survival analysis explored differences in time to death across sub-groups. Predictors of mortality were explored using multifactorially adjusted cox regression analyses with time to death as underlying timescale. Results Highly significant and clinically important differences in PROs were found between those alive and those deceased at one year. The best discriminant performance was observed for the physical component scale of the SF-12 (Area Under the Curve (AUC) 0.706) (Figure 1). One-year mortality among responders and non-responders was 2% and 7%, respectively. Significant differences in time to death was observed between responders and non-responders (p<0.001) and among diagnostic subgroups (p<0.001). Strongest predictors of one-year mortality included STEMI (hazard ratio (HR) 2.9 95% confidence interval (CI) 2.3–3.7), Tu comorbidity index score 3+ (HR 3.6, 95% CI 2.7–4.8) and patient-reported feeling unsafe about returning home from hospital (HR 2.07, 95% CI 1.2–3.61). Conclusions One-year post-discharge mortality was expectedly low, however notably higher in certain subgroups. Though clinical predictors may be difficult to modify, factors such as feeling unsafe about returning home should be addressed at discharge. PRO-performance estimates may guide clinicians and researchers in choosing appropriate predictive patient-reported outcome tools. Figure 1. PRO instruments ROC curves Funding Acknowledgement Type of funding source: None

Increased 5-year risk of stroke, atrial fibrillation, acute coronary syndrome and heart failure in out-of-hospital cardiac arrest survivors relative to population controls: a nationwide register-based

Abstract Background Out-of-hospital cardiac arrest (OHCA) survivors are a selected group of patients with younger age and less comorbid conditions relative to non-survivors. Long-term risk of stroke, atrial fibrillation or flutter (AF), acute coronary syndrome (ACS) and heart failure (HF) in OHCA survivors not diagnosed with any of these conditions as part of the cardiac arrest is unknown. Purpose To examine 5-year risk of stroke, AF, ACS and HF in 30-day OHCA survivors relative to age- and sex-matched population controls. Methods OHCA 30-day survivors and age- and sex-matched population controls not previously diagnosed with stroke, AF, ACS or HF or during the first 30 days after cardiac arrest were included using Danish Cardiac Arrest Registry data from 2001–2015 as well as the Danish Civil Registration System. Characteristics are compared using totals and percentages for categorical data and median and 25–75% percentiles for continuous data. Five-year outcomes are compared using cumulative incidence plots as well as Shared Frailty Cox regression modeling, unadjusted and adjusted for potential confounders including age, sex, hypertension, diabetes, chronic obstructive pulmonary disease (COPD), peripheral arterial disease (PAD), chronic ischemic heart disease (IHD), transient ischemic attack (TIA), thyroid disease, cholesterol-lowering, antiplatelet and anticoagulant agents. Results Of 4362 30-day survivors, 1063 were stroke-, AF-, ACS- and HF-naïve and 1051 were matched to population controls using age, sex and time of OHCA event as matching variables. The figure depicts the risk of stroke beyond day 30 to 5 years of follow-up was 4.7% versus 1.7% for OHCA survivors vs. controls. Risks of AF, ACS and HF were 7.0% vs. 2.1%, 4.7% versus 1.2% and 12.2% vs. 1.0%, respectively. OHCA 30-day survivors were significantly more likely to have PAD relative to controls, 4.9% vs. 1.1%. Differences in IHD (22.0% vs. 1.7%), hypertension (28.1% vs. 14.6%), diabetes (9.5% vs. 4.1%), lipid-lowering agents (27.6% vs. 9.5%), COPD (11.3% vs. 2.2%) were also significant. When adjusting for these comorbidities as well as for thyroid diseases, chronic kidney disease, cancer, antiplatelet and anticoagulant therapy, differences remained highly significant: HR stroke 3.33 [95% CI 2.21–5.02], HR AF 3.26 [2.28–4.66], HR ACS 3.36 [2.14–5.27] and HR HF 11.50 [8.02–16.48]. Conclusion We demonstrate an increased five-year risk of stroke, atrial fibrillation or flutter, acute coronary syndrome and heart failure in out-of-hospital cardiac arrest survivors without prior existence of any of these conditions. These results indicate that OHCA survivors continue to remain high-risk patients for cardiovascular events and prevention intervention is warranted. Funding Acknowledgement Type of funding source: None

Long term prognostic impact of gender in patients with stable coronary disease: an analysis of the CICCOR registry, a seventeen years, prospective, monocentric, cohort study

Abstract Purpose Women and men with stable coronary artery disease (sCAD) have different clinical features and management, but 1-year prognosis has been reported to be similar in large observational registries. The objective of the present study was to investigate the impact of female sex in the prognosis of the disease in the very long-term. Methods The CICCOR registry (“Chronic ischaemic heart disease in Cordoba”) is a prospective, monocentric, cohort study. From February 1, 2000 to January 31, 2004, all consecutive patients with sCAD attended at two outpatient cardiology clinics in a city of the south of Spain were included in the study and prospectively followed. Differential clinical features of women and men were described and the impact of female sex in long term prognosis was investigated. Results The study sample included 1268 patients, 337 women (27%) and 931 men (73% male). Women were older than men (70±9 versus 65±11 years, p<0.0005), more likely to have hypertension (72% versus 49%, p<0.0005) and diabetes (45% versus 26%), and less likely to be ex-smoker/active smoker (5%/2% versus 49%/9%, p<0.0005). They had more frequently angina in functional class ≥II (22% versus 17%, p=0.04) and atrial fibrillation (8% versus 5%, p=0.04), but had received less frequently coronary revascularization (32% versus 44%, p<0.0005). Prescription of statins (64% versus 68%, p=0.22), antiplatelets (89% versus 93%, p=0.07) and betablockers (67% versus 63%, p=0.28) at first visit was similar than men, but women received more frequently nitrates (78% versus 64%, p<0.0005), angiotensin-conversing enzyme inhibitors or receptor antagonists (56% versus 47%, p=0.004) and diuretics (41% versus 22%, p<0.0005). After up to 17 years of follow-up (median 11 years, IQR 4–15 years, with a total of 12612 patients-years of observation), probabilities of acute myocardial infarction (12% versus 14%, p=0.55) or stroke (14% versus 12%, p=0.40) at median follow up were similar for women and men. However, the risks of hospital admission for heart failure (22% versus 13%, p<0.0005) or cardiovascular death (35% versus 24%, p<0.0005) were significantly higher for women, with a non-significant trend to higher overall mortality (45% versus 39%, p=0.07). After multivariate adjustment, the risks of most events were similar for women and men (Hazard Ratios [95% confidence intervals]: 0.79 [0.55–1.14], p=0.21 for acute myocardial infarction; 0.89 [0.61–1.29], p=0.54 for stroke; 1.13 [0.82–1.57], p=0.46 for admission for heart failure; and 0.92 [0.73–1.16], p=0.48 for cardiovascular death), with a non-significant trend to lower overall mortality (0.83 [0.67–1.02], p=0.08). Conclusion Although women and men with sCAD presents a different clinical profile, and crude rates of hospital admissions for heart failure and cardiovascular death were higher in women, female sex was not an independent prognostic factor in this observational study with up to 17 years of follow-up. Funding Acknowledgement Type of funding source: None

18F-FDG PET/CT brain glucose metabolism as a marker of different types of depression comorbidity in chronic systolic heart failure patients

Abstract Background/Introduction Depression comorbidity is an important issue in heart failure (HF) disease. Results from the recent prospective randomized trial MOOD-HF did not provide a rationale for the indiscriminate use of antidepressants in depressed HF patients. Purpose The study investigated whole-brain and regional-brain glucose metabolism in HF patients with 18F-FDG PET/CT and its association with depression comorbidity. Methods Twenty-nine hospitalized patients with symptomatic systolic HF disease (LVEF<40%), NYHA class II-IV and mean age of 55.5±12.0 years participated in the study. All patients had echocardiography, blood sampling, HF-adapted and psychometric questionnaires before discharge and a brain 18F-FDG PET/CT scan after discharge. Semi-automated PET/CT image analysis was performed on all patients and 30 matched controls. The metabolic index SUVmean was calculated for the whole-brain and three brain regions (prefrontal cortex, amygdala and hippocampus), implicated in depression pathogenesis. A standardized SUVmean was also estimated by dividing depression-related regional-brain SUVmean with the whole-brain SUVmean. Results HF patients had lower average whole-brain SUVmean (3.90±1.49 vs 5.10±1.35, p=0.001), average regional-brain SUVmean (4.57±2.31 vs 9.96±3.58, p<0.001) and average standardized SUVmean (1.28±0.60 vs 2.07±1.32, p<0.001) compared to controls. Whole-brain SUVmean had a statistically significant correlation to patient age (r=−0.39, p=0.031), NYHA class (p=0.027), LVEF in the major group of 21 NYHA III-IV patients (p=0.018), diabetes comorbidity (p=0.001), creatinine levels (r=−0.49, p=0.005) and depression (r=−0.36, p=0.049). Regional-brain SUVmean was correlated to whole-brain SUVmean (r=0.53, p=0.002) and depression (r=0.46, p=0.011). The standardized SUVmean, in particular, was found to be a robust index that could differentiate HF patients with “epiphenomenal” (>0.93) or “real” (≤0.93) depression. Conclusion HF patients with more severe disease showed whole-brain and regional-brain hypometabolism in 18F-FDG PET/CT scan, which is consistent with impaired cerebral perfusion. Depressed HF patients (Beck Depression Inventory score >13) exhibited different metabolic patterns that could be used to differentiate between “epiphenomenal” and “real” depression. Namely, presence of whole-brain hypometabolism suggested “epiphenomenal” depression. Absence of whole-brain hypometabolism suggested “real” depression. When the pattern of whole-brain hypometabolism included significant relative, depression-related regional hypometabolism (standardized SUVmean ≤0.93), “real” depression was the most likely diagnosis. The distinction is important, as different types of comorbid depression suggest different treatment approach. Summarizing figure Funding Acknowledgement Type of funding source: None

Evaluation of the Autonomic Nervous System in Chronic Chagasic Cardiopathy: A Systematic Review of the Literature

Abstract Background The importance of regional sympathetic denervation in the pathophysiology and prognosis of Chagas disease has been recognized. Objective To conduct a review of studies that have assessed dysautonomia in chronic Chagas heart disease. Methods The search was performed on the Medline, Pubmed, Lilacs and SciELO databases. The inclusion criteria were: original articles published in full; studies on individuals with Chagas disease, that used diagnostic methods for chagasic cardiomyopathy, and had clear inclusion and exclusion criteria. Duplicate studies, studies [...]

Manejo endovascular de la estenosis de la arteria renal en el trasplante renal

INTRODUCCIÓN: La estenosis de la arteria renal es la complicación vascular más frecuente del trasplante renal y una de las principales causas de pérdida del injerto y muerte prematura en los pacientes trasplantados. A pesar de ser potencialmente tratable, es frecuentemente infradiagnosticada, por lo que su diagnóstico precoz y manejo terapéutico adecuado resulta fundamental para evitar la pérdida de función renal. MATERIAL Y MÉTODOS: Analizamos retrospectivamente el caso de dos pacientes de 72 años trasplantados en nuestro centro en 2017. Ambos pacientes, con antecedentes de hipertensión arterial, cardiopatía isquémica crónica y enfermedad renal crónica terminal secundaria a nefroangioesclerosis y glomerulonefritis membranosa, respectivamente; presentaron un empeoramiento de la creatinina en el postoperatorio inmediato del trasplante renal. Ante este hallazgo y la evidencia de velocidades pico sistólicas >200 cm/s en la ecografía-doppler se sospechó una estenosis de la arteria del injerto, posteriormente confirmada con angiografía y angio-TC, respectivamente. Por lo que se realizó una revascularización percutánea e implante de stent. RESULTADOS: Se realizó la angioplastia con balón y colocación de stent, bajo anestesia local, obteniendo un buen resultado morfológico, sin complicaciones inmediatas. Tras el procedimiento ambos pacientes presentaron una mejoría progresiva de la función renal manteniendo un buen ritmo de diuresis, siendo dados de alta a los 8 y 11 días del mismo. Desde entonces, la función renal de ambos pacientes se ha mantenido estable presentando a los 12 meses un filtrado glomerular alrededor de 67 mL/min/1.73m2 y 60 mL/min/1.73m2, respectivamente. Sin evidencia de complicaciones tras 14 meses del procedimiento. CONCLUSIONES: La angioplastia con balón y colocación de stent en la estenosis de la arteria renal en el trasplante es una técnica segura y efectiva. Sin embargo, es necesaria una elevada experiencia para disminuir el número de complicaciones y optimizar los resultados de esta técnica. Palabras clave: trasplante renal, estenosis arterial, manejo mínimamente invasivo, cirugía endovascular.

A Multicenter Prospective Observational Cohort Study to Investigate the Effectiveness and Safety of Rivaroxaban in Japanese Venous Thromboembolism Patients (The J'xactly Study).

There is insufficient real-world data on the current status of Japanese patients with venous thromboembolism (VTE) or its treatment and prevention with rivaroxaban. In this multicenter, prospective, observational study conducted in Japan, 1,039 patients with acute symptomatic/asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) with or without DVT prescribed rivaroxaban were enrolled at 152 institutions and observed for a median of 21.3 months. Mean age was 68.0±14.7 years, mean body weight was 60.3±14.1 kg, 59.0% were females, and 19.0% had active cancer. Incidences of recurrence or aggravation of symptomatic VTE (primary effectiveness outcome) and major bleeding (principal safety outcome) were 2.6% and 2.9% per patient-year, respectively. These outcomes did not differ between patients with DVT and those with PE (primary effectiveness outcome: 2.6% vs. 2.5% per patient-year, P=0.810; principal safety outcome: 3.5% vs. 2.4% per patient-year, P=0.394). The incidence of composite clinically relevant events, including recurrence or aggravation of symptomatic VTE, acute coronary syndrome, ischemic stroke, all-cause death, or major bleeding events, was 9.2% per patient-year. Multivariate analysis revealed that male sex, being underweight, having active cancer, chronic heart and lung disease, and previous stroke were independent determinants for composite clinically relevant events. In Japanese clinical practice, a single-drug approach with rivaroxaban was demonstrated to be a valuable treatment for a broad range of VTE patients.