Fatal Heart Failure Research Articles

S3508 A Rare Case of Juvenile Hemochromatosis

INTRODUCTION: Juvenile hemochromatosis is a rare phenomenon seen in patients who have a severe overload of iron in the first three decades in life. It is the most severe form of hereditary hemochromatosis and can cause further clinical complications of cardiomyopathy, hypogonadism, and liver fibrosis. The disease process can progress and cause signs of fatal heart failure. Both male and female populations are equally represented. Lab studies usually reveal elevated serum ferritin and transferrin saturation and gene transformation for HFE mutation is often positive. Phlebotomy is pursued in order to achieve iron depletion which greatly reduces morbidity and mortality. We present a 19 year old male who arrived at an outpatient hematologist office for evaluation of his fatigue. CASE DESCRIPTION/METHODS: This is a 19 year African American old male with no PMH history who arrived at an outpatient hematologist office after having routine blood work for his symptoms of fatigue. Referral labs indicated a ferritin of 1322 associated with an elevated total bilirubin of 3.5 and direct bilirubin that was mostly indirect. On physical examination, the patient had mild scleral icterus but a benign examination. Outpatient lab work revealed a total bilirubin of 5.2, direct bilirubin less than 0.2, Combs test negative, ferritin 1301, haptoglobin at 18. Hemoglobin electrophoresis showed a decreased MCV secondary to a beta thalassemia trait. A hemochromatosis DNA analysis revealed that the patient had a homozygous trait of C2827 locus further indicating a diagnosis of hemochromatosis. A MRI of the liver demonstrated increased iron overload and tiny gallstones. The patient proceeded with an outpatient cholecystectomy and liver biopsy. He was started on a regular phlebotomy program every 2 weeks with the goal of getting his serum ferritin level below 100. DISCUSSION: Juvenile hemochromatosis is a rare inherited autosomal recessive manner. Juvenile hemochromatosis shares numerous features with adult hemochromatosis, but iron deposition occurs at an accelerated rate. It is important to note that there is no gender disparity. Clinicians should refer to an outpatient hepatologist for further management and seek early treatment with phlebotomy as it can prevent and even reverse secondary complications of organ damage. In our particular case, the patient was identified early in the disease course and significantly improved his outcomes.

SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials

Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) trials showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes. However, neither trial was powered to assess effects on cardiovascular death or all-cause death or to characterise effects in clinically important subgroups. Using study-level published data from DAPA-HF and patient-level data from EMPEROR-Reduced, we aimed to estimate the effect of SGLT2 inhibition on fatal and non-fatal heart failure events and renal outcomes in all randomly assigned patients with HFrEF and in relevant subgroups from DAPA-HF and EMPEROR-Reduced trials. We did a prespecified meta-analysis of the two single large-scale trials assessing the effects of SGLT2 inhibitors on cardiovascular outcomes in patients with HFrEF with or without diabetes: DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin). The primary endpoint was time to all-cause death. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of cardiovascular death or hospitalisation for heart failure. These subgroups were based on type 2 diabetes status, age, sex, angiotensin receptor neprilysin inhibitor (ARNI) treatment, New York Heart Association (NYHA) functional class, race, history of hospitalisation for heart failure, estimated glomerular filtration rate (eGFR), body-mass index, and region (post-hoc). We used hazard ratios (HRs) derived from Cox proportional hazard models for time-to-first event endpoints and Cochran's Q test for treatment interactions; the analysis of recurrent events was based on rate ratios derived from the Lin-Wei-Yang-Ying model. Among 8474 patients combined from both trials, the estimated treatment effect was a 13% reduction in all-cause death (pooled HR 0·87, 95% CI 0·77-0·98; p=0·018) and 14% reduction in cardiovascular death (0·86, 0·76-0·98; p=0·027). SGLT2 inhibition was accompanied by a 26% relative reduction in the combined risk of cardiovascular death or first hospitalisation for heart failure (0·74, 0·68-0·82; p<0·0001), and by a 25% decrease in the composite of recurrent hospitalisations for heart failure or cardiovascular death (0·75, 0·68-0·84; p<0·0001). The risk of the composite renal endpoint was also reduced (0·62, 0·43-0·90; p=0·013). All tests for heterogeneity of effect size between trials were not significant. The pooled treatment effects showed consistent benefits for subgroups based on age, sex, diabetes, treatment with an ARNI and baseline eGFR, but suggested treatment-by-subgroup interactions for subgroups based on NYHA functional class and race. The effects of empagliflozin and dapagliflozin on hospitalisations for heart failure were consistent in the two independent trials and suggest that these agents also improve renal outcomes and reduce all-cause and cardiovascular death in patients with HFrEF. Boehringer Ingelheim.

Abstract 365: Ponatinib Triggers Cardiac Inflammation by STAT-3 Dependent Immune Checkpoint Blockade

Background: Ponatinib is a potent anticancer tyrosine kinase inhibitor (TKI) with considerable cardiotoxicity. The manifestation of cardiovascular adverse events, including fatal myocardial infarction and congestive heart failure, has hampered its clinical use. Therefore, a better understanding of the mechanism by which ponatinib exerts cardiotoxicity is urgently warranted to efficiently counteract treatment-related adversities. Methods: Wild type C57BL/6, comorbidity mouse model ApoE -/- , and pressure overload (PO) mouse model were used to investigate the cardiotoxic mechanism of ponatinib. Echocardiography was performed to assess cardiac function. Flow cytometry analysis was performed to assess the dynamics of inflammation. Results: We observed that high-fat diet (HFD) fed ApoE -/- mice develop cardiac dysfunction within 2 weeks of ponatinib treatment. An unbiased RNA-Seq analysis revealed significant upregulation of inflammatory genes (CCR1, CCR5, CCL6, CCL8, CCL9, CXCL4) in ponatinib treated hearts. Since ApoE -/- background, and HFD are known confounder of inflammation signal, we validated this observation in naïve C57BL/6 mice. Despite the lack of cardiac dysfunction in ponatinib treated naïve C57BL/6 mice, comprehensive immune profiling depicted upregulation of myocardial inflammation as evident by infiltrated immune cells (CD45 + TNFα + , CD45 + CD11b + F4/80 + Ly6C + CCR2 + , CD45 + Gal1 + ). Interestingly, we also demonstrated the downregulation of immune checkpoints over T cells (TCRαβ + CTLA4 + , TCRαβ + PD1 + ) in ponatinib treated hearts. Next, in the PO mouse model, ponatinib treated mice showed significant cardiac dysfunction with myocardial inflammation as reflected by increased frequencies of inflammatory parameters (TNFα + , IL1β + , IL6 + , MCP1 + , CXCL9 + ). Mechanistically, we demonstrated that ponatinib potentially suppresses PD-L1 expression over cardiomyocytes via inhibition of STAT3, subsequently leading to immune cells mediated myocardial inflammation. Conclusions: These findings uncover a novel mechanism of ponatinib induced cardiac inflammation leading to adverse cardiac function. It also suggests that strategies to attenuate inflammation may be an effective therapy to prevent ponatinib induced cardiac adverse events.

Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the URic acid Right for heArt Health study.

To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension. The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders. A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole database: SUA more than 5.34 mg/dl (confidence interval 4.37-5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78-5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284-2.109, P < 0.0001) for all heart failure and 1.645 (1.284-2.109, P < 0.0001) for fatal heart failure, respectively. The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).

ECMO FOR THE TREATMENT OF MODS DUE TO ORAL SCORPION TOXICOSIS: A CASE REPORT

TYPE: Abstract Publication TOPIC: Cardiovascular Disease PURPOSE: Scorpion sting poisoning kills 3,000 people worldwide every year. However, multiple organ dysfunction syndrome (MODS) induced by oral scorpion venom is rarely reported. Using extracorporeal membrane oxygenation (ECMO) as a treatment for scorpion poisoning has not been reported. METHODS: The purpose of this report was to describe a case of oral scorpion toxicosis observed in Shanghai, China, in a 64-year-old man with "arthritis". The patient rapidly developed toxic myocarditis, liver injury, renal injury and polyserositis due to the neurotoxic activity of the venom. Cardiomyopathy that can lead to fatal acute heart failure is a risk after scorpion toxicosis. Decreased blood pressure, pulmonary wedge pressure >20 mmHg, cardiac index <2.0 L/min/m2, urine output <20 ml/h, metabolic acidosis, and hyperlactacidaemia, even if not improved with large-dose positive vasoactive agents, all indicate severe scorpion toxicosis, and the condition requires close patient monitoring and symptomatic treatment using ECMO. Notably, plasmapheresis treats progressive bilirubin elevation, and continuous renal replacement therapy treats acute renal failure. With aggressive medical management, the patient recovered within a few days. RESULTS: We presented this case because of its unusual clinical presentation, unexpected complications, and prompt resolution. CONCLUSIONS: It is particularly important to clarify the medical history, diagnosis and use of multiple organ support treatment for scorpion poisoning as soon as possible to reduce the death rate. CLINICAL IMPLICATIONS: It is particularly important to clarify the medical history, diagnosis and use of multiple organ support treatment for scorpion poisoning as soon as possible to reduce the death rate. DISCLOSURE: No significant relationships. KEYWORDS: ECMO, MODS, scorpion toxicosis

Atrial fibrillation and the risk of cardiovascular disease and mortality in the Hypertension in the Very Elderly Trial

To assess the prognostic value of electrocardiographic atrial fibrillation in older hypertensive people in the randomized, placebo-controlled Hypertension in the Very Elderly Trial. Hypertension in the Very Elderly Trial randomized 3845 hypertensive people aged 80 years and over, 3273 with electrographic data on the presence or absence of atrial fibrillation at baseline and without established cardiovascular disease. Multivariate Cox proportional hazard models were used to estimate hazard ratios with 95% confidence intervals (CIs) for all-cause mortality, incident fatal and nonfatal major cardiovascular events, all-stroke and all-heart failure. The mean follow-up time was 2.1 years. Baseline prevalence of atrial fibrillation was 5.8%. Compared with people without atrial fibrillation at baseline, after adjustments the presence of atrial fibrillation was associated with increased risk of mortality (hazard ratio = 2.49, 95% CI = 1.80-3.44, P < 0.001), of nonfatal and fatal cardiovascular events (hazard ratio = 2.47, 95% CI = 1.71-3.55, P < 0.001), all-stroke (hazard ratio = 2.47, 95% CI = 1.34-4.56, P = 0.004) and all-heart failure (hazard ratio 2.33, 95% CI = 1.10-4.93, P = 0.027). Atrial fibrillation is an important risk factor to consider when assessing older hypertensive adults as it is associated with increased risk of mortality, nonfatal and fatal cardiovascular events, stroke and heart failure.

Abstract MP39: Incident Heart Failure Within Five Years of Delivery Among Women With Hypertensive Disorders of Pregnancy or Pre-pregnancy Hypertension in a Diverse Population

Introduction: Hypertensive disorders of pregnancy (HDP) and pre-pregnancy hypertension are associated with increased morbidity and mortality for the mother, with potential long-term implications. We investigated the relationships between HDP and pre-pregnancy hypertension with fatal and nonfatal incident maternal heart failure (HF) within five years of delivery, and examined racial/ethnic differences. Methods: A retrospective population-based study was conducted among 433,636 women aged 13-49 (58.7% non-Hispanic white [NHW], 31.8% non-Hispanic black [NHB], 9.5% Hispanic) with a live, singleton birth in South Carolina between 2004-2016. HDP were defined as pre-eclampsia, eclampsia, or gestational hypertension based on hospitalization/emergency department (ED) visit data, or HDP on birth certificates. Pre-pregnancy hypertension was based on hospitalization/ED visit data or birth certificates. Incident HF was defined by hospital/ED visit and death certificate data. Cox proportional hazards models adjusted for sociodemographic, behavioral, and clinical characteristics. Results: Eighteen percent of women were diagnosed with HDP in ≥1 pregnancy (n=78,317; 53.5% NHW, 40.8% NHB, 5.7% Hispanic). Of the 433,636 women, 2.3% had pre-pregnancy hypertension with superimposed HDP, 15.7% had no pre-pregnancy hypertension with HDP, 0.4% had pre-pregnancy hypertension without superimposed HDP and 81.6% had neither condition. Compared to those without pre-pregnancy hypertension or HDP, incident HF risk was increased for women with: no pre-pregnancy hypertension with HDP (HR=4.35; 95% CI: 4.01-4.71), pre-pregnancy hypertension without superimposed HDP (HR=5.07; 95% CI: 3.52-7.29), and pre-pregnancy hypertension with superimposed HDP (HR=6.66; 95% CI: 5.91-7.51). The table shows race/ethnic specific estimates of incident HF risk. Discussion: Women with HDP and pre-pregnancy hypertension were at higher risk for HF or HF death within five years of delivery and the risk varied across racial/ethnic groups.

Humoral factors in serum of rats with chronic heart failure induce cardiomyocyte hypertrophy and reduce viability

Myocardial infarction (MI) is one of the leading causes of global mortality. Over the last decade, acute MI mortality has significantly decreased; however, fatal heart failure remains a common complication for post-MI survivors.[1][1] Lack of oxygen due to MI causes cardiac tissue necrosis and, as a

Hydrogen Sulfide as a Potential Alternative for the Treatment of Myocardial Fibrosis.

Harmful, stressful conditions or events in the cardiovascular system result in cellular damage, inflammation, and fibrosis. Currently, there is no targeted therapy for myocardial fibrosis, which is highly associated with a large number of cardiovascular diseases and can lead to fatal heart failure. Hydrogen sulfide (H2S) is an endogenous gasotransmitter similar to nitric oxide and carbon monoxide. H2S is involved in the suppression of oxidative stress, inflammation, and cellular death in the cardiovascular system. The level of H2S in the body can be boosted by stimulating its synthesis or supplying it exogenously with a simple H2S donor with a rapid- or slow-releasing mode, an organosulfur compound, or a hybrid with known drugs (e.g., aspirin). Hypertension, myocardial infarction, and inflammation are exaggerated when H2S is reduced. In addition, the exogenous delivery of H2S mitigates myocardial fibrosis caused by various pathological conditions, such as a myocardial infarct, hypertension, diabetes, or excessive β-adrenergic stimulation, via its involvement in a variety of signaling pathways. Numerous experimental findings suggest that H2S may work as a potential alternative for the management of myocardial fibrosis. In this review, the antifibrosis role of H2S is briefly addressed in order to gain insight into the development of novel strategies for the treatment of myocardial fibrosis.

Late Diagnosis of Takayasu Disease in a 50-Year-Old African Black Woman with Repeated Episodes of Heart Failure: Seeing the Forest through the Trees—A Case Report

Background: First described in 1908, TAK has now been recognized as a non-specific inflammatory disease of unknown etiology, predominantly affecting young females. Sometimes, it progresses into relatively rare and potentially fatal scenarios such heart failure. Case Presentation: Here, we present the case of a 50-year sub-saharan female suffering from acute heart failure related to TAK. Despite constitutional symptoms (fever, malaise, weight loss) and more characteristic features such claudication of lower extremities, carotydinia, and pulseless syndrome, diagnosis of TAK was delayed since main presentation was heart failure. Immunosuppressive and anticoagulant therapies have induced improvement in cardiac manifestations. Conclusion: Early diagnosis and proper treatment can protect the patient from dangerous complications such heart failure.

Long-Term Prognosis of Suspected Myocarditis and Cardiomyopathy Associated with Viral Infection of the Myocardial Tissue: A Meta-Analysis of Cohort Studies.

Aim Myocarditis and cardiomyopathy impose a substantial economic burden on society. Many studies have examined the effects of various predictors on the prognosis of these diseases, such as the left ventricular systolic function, the New York Heart Association glomerular filtration rate, the QT interval, and the presence of viruses. In the present study, we conducted a meta-analysis of cohort studies to investigate the significance of the presence of viruses in the myocardial tissue on the prognosis of these diseases. Methods The Embase, PubMed, and Cochrane library databases were searched for relevant literature that had been published between January 1, 1964 and August 14, 2018. The inclusion criteria were patients over 18 years of age, suspected myocarditis or dilated cardiomyopathy, accepted myocardial biopsy, and the detection of virus in the myocardial tissue. Results In total, 10 studies met the inclusion criteria. These studies included 1006 patients with suspected myocarditis or idiopathic heart disease for whom the primary endpoint was all-cause death, heart transplant, or re-hospitalization due to fatal arrhythmia and heart failure. There was no significant difference in the prognosis of virus-positive and virus-negative patients with myocarditis or dilated cardiomyopathy confirmed by endomyocardial biopsy (EMB) [hazard ratio (HR) = 1.40, 95% confidence interval (CI) = 0.93–2.12, P = 0.11]. However, virus-negative patients had a better prognosis following nonspecific treatment (HR = 1.40, 95% CI = 1.06–1.86, P = 0.02) and right ventricular biopsy (HR = 2.08, 95% CI = 1.07–4.04, P = 0.03). Conclusions The presence of a virus did not worsen the long-term prognosis of patients with suspected myocarditis or dilated cardiomyopathy. However, virus-positive patients who did not undergo specific treatment or who underwent right ventricular biopsy did have a worse prognosis. Thus, the early diagnosis of the presence of viral infection in the myocardium will improve the prognosis of patients.

Wild-type ATTR amyloidosis may be associated with unexpected death among the elderly.

Wild-type ATTR amyloidosis (ATTR-wt) is characterized by the accumulation of amyloid in the heart, leading to fatal heart failure and arrhythmia. In this study, we investigated the amyloid deposits in the heart from 556 forensic autopsy cases over 60 years of age. The prevalence of ATTR-wt was 5.8% (32 of the 556), with the prevalence increasing as a function of age. We identified an ATTR-wt-specific morbidity rate of 12.3% for patients over 80 years of age, while the prevalence among individuals over 90 years of age was 34.9%. In none of these 32 cases had a clinical diagnosis of ATTR-wt been made. In 29 of the 32 cases found to be ATTR-wt positive, an obvious extraneous cause of death was identified and included burning, drowning, hypothermia, suicide, and traffic accident. On the other hand, heart failure due to ATTR-wt was confirmed as the cause of death in 3 of the 32 cases. It is suggested that ATTR-wt may be associated with unexpected death among the elderly.

Longitudinal Associations Between Income Changes and Incident Cardiovascular Disease

Higher income is associated with lower incident cardiovascular disease (CVD). However, there is limited research on the association between changes in income and incident CVD. To examine the association between change in household income and subsequent risk of CVD. The Atherosclerosis Risk In Communities (ARIC) study is an ongoing, prospective cohort of 15 792 community-dwelling men and women, of mostly black or white race, from 4 centers in the United States (Jackson, Mississippi; Washington County, Maryland; suburbs of Minneapolis, Minnesota; and Forsyth County, North Carolina), beginning in 1987. For our analysis, participants were followed up until December 31, 2016. Participants were categorized based on whether their household income dropped by more than 50% (income drop), remained unchanged/changed less than 50% (income unchanged), or increased by more than 50% (income rise) over a mean (SD) period of approximately 6 (0.3) years between ARIC visit 1 (1987-1989) and visit 3 (1993-1995). Our primary outcome was incidence of CVD after ARIC visit 3, including myocardial infarction (MI), fatal coronary heart disease, heart failure (HF), or stroke during a mean (SD) of 17 (7) years. Analyses were adjusted for sociodemographic variables, health behaviors, and CVD biomarkers. Of the 8989 included participants (mean [SD] age at enrollment was 53 [6] years, 1820 participants were black [20%], and 3835 participants were men [43%]), 900 participants (10%) experienced an income drop, 6284 participants (70%) had incomes that remained relatively unchanged, and 1805 participants (20%) experienced an income rise. After full adjustment, those with an income drop experienced significantly higher risk of incident CVD compared with those whose incomes remained relatively unchanged (hazard ratio, 1.17; 95% CI, 1.03-1.32). Those with an income rise experienced significantly lower risk of incident CVD compared with those whose incomes remained relatively unchanged (hazard ratio, 0.86; 95% CI, 0.77-0.96). Income drop over 6 years was associated with higher risk of subsequent incident CVD over 17 years, while income rise over 6 years was associated with lower risk of subsequent incident CVD over 17 years. Health professionals should have greater awareness of the influence of income change on the health of their patients.

Two cases of congestive heart failure during osimertinib treatment for EGFR mutant NSCLC

Abstract We herein report two case of fatal congestive heart failure during osimertinib treatment for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Case1: A 66-year-old woman presented with progressive palpitation and dyspnea two months after starting osimertinib for the treatment of EGFR T790M-positive NSCLC. An echocardiogram demonstrated severe decreased left ventricular systolic function. She was diagnosed with fatal congestive heart failure caused by osimertinib treatment. Her general condition deteriorated, and she died three months after starting osimertinib. Case2: A 84-year-old woman was treated for recurrent EGFR mutant NSCLC after lobectomy, and osimertinib was administered. Severe exertional dyspnea appeared one month after starting osimertinib. She was also diagnosed with fatal congestive heart failure caused by osimertinib, and died for a few days. The causal relationship between osimertinib and cardiotoxicity has so far received little attention and thus remains unclear. Osimertinib inhibits HER2 (ERBB2) in addition to EGFR (ERBB1), thereby potentially causing cardiotoxicity.

P1566Identification of the cardiovascular threshold limit for serum uric acid. Analysis from a general Italian population

Abstract Background Serum uric acid (SUA) is increasingly recognised as an important predictor of cardiovascular disease (CVD) and total mortality. However, the levels of SUA that discriminate across the different strata of risk for CVD and total mortality remain unknown, complicating the identification of subjects at high or low mortality risk for SUA in clinical practice. Purpose In this study we used a large Italian population comprising &gt;3ehz748.0326 subjects to assess the threshold of SUA that increases the risk of total and CVD mortality. Methods The URic Acid Right for heArt Health (URRAH) study is a regional-basis multicentre cohort study which collected data from prospective studies and databases from different hypertension centres, including subjects with at least one measure of SUA and a follow-up of about 20 years. Total mortality was defined as mortality for any causes, cardiovascular mortality as death due to fatal myocardial infraction, stroke or heart failure. Multivariate dichotomic logistic and Cox regression models were used to confirm the relationship between SUA and mortality status both from cardiovascular and any causes, while ROC curves were used to identify the threshold of SUA that better discriminated people at higher or lower mortality risk. Results A total of 22.275 subjects had SUA and mortality information. Logistic regression identified a direct and strong association between SUA and an increased risk of total (OR 1.176, 95% CI 1.127–1.227) and CVD (OR 1.147, 95% CI 1.093–1.203) mortality, independently of other CVD risk factors (age, BMI, LDL cholesterol, diagnosis of diabetes, hypertension, chronic kidney disease, alcohol consumption and smoking). Cox models confirmed the presence of an independent association between SUA and any causes (HR 1.123, 95% CI 1.090–1.567) and CVD (HR 1.124, 95% CI 1.081–1.169) mortality. ROC curve analysis identified a cut-off value od SUA [(4.79 mg/dL (95% CI 4.7–5.4 mg/dl)] able to discriminate total mortality status, and a different one [(5.60 mg/dL (95% CI 5.09–5.89 mg/dl)] able to identify CVD mortality status. Multivariate Cox analysis adjusted for confounders confirmed that subjects with SUA &gt;4.79 mg/dl had a significantly higher total mortality (HR 1.293, 95% CI 1.181–1.416) compared to those with SUA &lt;4.79 mg/dl, independently of covariables. Similarly, subjects with SUA &gt;5.60 mg/dl had a significantly higher CVD mortality (HR 1.428, 95% CI 1.273–1.600) than those with SUA &lt;5.60 mg/dl after adjustment for the same confounders. Conclusion Levels of SUA that increase the risk of total and CVD mortality are significantly lower than those commonly used for the definition of hyperuricemia in clinical practice. Our data provide the first large evidence of a level of “cardiovascular” SUA that might be used in clinical practice to identify subjects at greater risk of total and CVD mortality.

Hypopharyngeal cancer patient with autoimmune myositis and myasthenia gravis emerged after nivolumab administration

Abstract Background The immune checkpoint inhibitor(ICI) was approved for head and neck cancer refractory to cDDP, thereafter promptly its survival benefit had been demonstrated. Synergistic effect by combination of SBRT regarded as in situ vaccination and immunotherapy is theoretically expected, but simultaneously an increase in the incidence of irAE by ICI is also concerned. Case A 78-year-old man with T4aN2bM0 hypopharyngeal squamous cell carcinoma of posterior wall type underwent SBRT, which resulted in CR. Afterwards bilateral cervical lymph node metastasis and lung metastasis appeared (rT0N2cM1) and were hit by SBRT, but the right upper deep cervical lesion gradually increased. Then chemotherapy (TXT/CDGP) was performed, which resulted in reduction of pulmonary (MR), but right cervical metastasis was SD, then nivolumab was started. After third course, general fatigue and dysphagia associated with a rise in CK/CKMB appeared. Autoimmune myositis as irAE was suspected and the patient was hospitalized. Mild right ptosis was also observed which was considered at first as Horner symptom since AchR antibody was negative, but tensilon test proved positive, which lead to the diagnosis of autoimmune myositis associated with myasthenia gravis. PSL 1 mg / kg was administrated and gradually decreased every week, then the CK/CKMB value improved remarkably and clinical symptoms were also relieved. The right upper deep neck lesion shrank remarkably on the onset of irAE, but pulmonary metastasis was SD. CR of the neck lesion has persisted to date but the right middle lung field metastatic lesion tended to grow and was submitted to SBRT. Discussion The onset of autoimmune myositis and myasthenia gravis has the risk of leading to fatal heart failure, thus it is mandatory to immediately discontinue treatment and to cope with, regardless of the anti-tumor effect. Regular CK measurement and careful observation are essential on nivolumab administration.

P1728Cardiogenic shock patients: those with and those without out-of-hospital cardiac arrest are different clinical entities

Abstract Introduction Cardiogenic shock (CS) due to myocardial infarction (MI) carries 30-day mortality rates as high as 50%. The vast majority of study cohorts assessing mortality in CS comprise both patients presenting with and without out-of-hospital cardiac arrest (OHCA). Patients with and without OHCA are likely to represent two distinctive entities, which may be problematic to combine in an intervention trial. Purpose The aim of the study was to compare CS due to MI patients presenting with and without OHCA in terms of patient characteristics and outcome. Methods In the period from 2010–2017 all patients admitted at two tertiary heart centres in Denmark with CS following MI were individually identified and validated through patient records. The two centres have a catchment area of 3.9 million citizens corresponding to two-thirds of the Danish population. Results A total of 1716 CS patients were identified, of which 42% presented with OHCA. OHCA patients were younger (mean 63 vs 67 years), more frequently male (85 vs 67%), had higher lactate concentration (median 6.2 vs 5.0 mmol/L) on admission and higher left ventricular ejection fraction (median 30 vs 25%) compared to patients without OHCA (p&lt;0.0001 for all). Patients presenting with OHCA had lower 30-day mortality compared to patients without OHCA (49% vs. 57%, respectively, plogrank&lt;0.0001, Figure). Cause of in hospital death differed markedly between the two groups. Not surprisingly, anoxic brain damage was the leading cause of in hospital death in the OHCA group (56%) and only seen in 4% of patients without OHCA. In contrast, cardiac failure was the main cause of death in hospital death among patients without OHCA (60%), compared to 27% in patients with OHCA (p&lt;0.0001). Figure 1 Conclusion Among patients with CS due to MI, overall 30-day mortality was significantly lower in patients presenting with OHCA. Anoxic brain damage was the main cause of in hospital death among OHCA patients, whereas fatal heart failure prevailed in patients without OHCA. Combining these two groups in a single trial with one specific intervention seems inappropriate and likely to cause an imbalance in the signal-to-noise ratio. Acknowledgement/Funding The Danish Heart Foundation and a research grant from Abiomed

Incidence of heart failure after pacemaker implantation: a nationwide Danish Registry-based follow-up study.

The objective of the current study is to investigate the risk of heart failure (HF) after implantation of a pacemaker (PM) with a right ventricular pacing (RVP) lead in comparison to a matched cohort without a PM and factors associated with this risk. All patients without a known history of HF who had a PM implanted with an RVP lead between 2000 and 2014 (n = 27704) were identified using Danish nationwide registries. An age- and gender-matched control cohort (matched 1:5, n = 138520) without PM and HF was identified to compare the risk. Outcome was the cumulative incidence of HF including fatal HF within the first 2 years of PM implantation, with all-cause mortality and myocardial infarction (MI) as competing risks. Due to violation of proportional hazards, the follow-up period was divided into three time-intervals: <30 days, 30-180 days, and >180 days-2 years. The cumulative incidence of HF including fatal HF was observed in 2937 (10.6%) PM patients. Risks for the three time-intervals were <30 days [hazard ratio (HR) 5.98, 95% CI 5.19-6.90], 30-180 days (HR 1.84, 95% CI 1.71-1.98), and >180 days (HR 1.11, 95% CI 1.04-1.17). Among patients with a PM device, factors associated with increased risk of HF were male sex (HR 1.33, 95% CI 1.24-1.43), presence of chronic kidney disease (CKD) (HR 1.64, 95% CI 1.29-2.09), and prior MI (1.77, 95% 1.50-2.09). Pacemaker with an RVP lead is strongly associated with risk of HF specifically within the first 6 months. Patients with antecedent history of MI and CKD had substantially increased risk.

Outbreaks of nutritional cardiomyopathy in pigs in Brazil

ABSTRACT: Dilated cardiomyopathy (DCM) is a condition that affects the myocardium, seldom reported in pigs. The DCM is characterized by ventricular dilation, which results in systolic and secondary diastolic dysfunction and can lead to arrhythmia and fatal congestive heart failure. This study described the clinical, pathological, chemical and toxicological findings of nutritional dilated cardiomyopathy (DCM) in nursery pigs through natural and experimental studies. Naturally occurring cases of DCM in three swine farms were investigated through necropsy (fourteen pigs), microscopic, virological, chemical and toxicological exams for the detection of the etiology. The experimental study was conducted with nine 40 days-old piglets, which were divided into three groups of three piglets each. Group 1 was fed with the suspected diet of the naturally occurring cases, Group 2 with half of the suspected diet and half of a control diet, and Group 3 received only the control diet. Clinical signs were recorded. All pigs were submitted of euthanized, necropsie and collection sample for laboratories exams, after 15 days of experiment onset. At the necropsy, all naturally occurring cases had bilateral cardiac dilatation associated to hepatic enhanced lobular pattern (nutmeg liver) and lungs edema. Microscopically, the heart revealed severe hypertrophy and vacuolization of cardiomyocytes, as well as myofiber disarray. Feed analysis revealed low-quality standard soybean meal. After the suspected feed was replaced, clinically ill pigs recovered, and mortality ceased. At the experimental study, two piglets from Group 1 had cough, dyspnea and diarrhea. At the necropsy, these animals had similar gross and microscopic lesions to the natural cases. The nutritional DCM in pigs may be associated to the diet with low-quality soybean meal, as it was further confirmed through an experimental study.

SERUM URIC ACID, INDEPENDENTLY OF ARTERIAL HYPERTENSION, PREDICTS FATAL HEART FAILURE IN A LARGE COHORT OF MEN AND WOMEN. SEARCH FOR A CUT-OFF VALUE

Objective: Searching for a prognostic cut-off value of serum uric acid (SUA) in predicting incident heart failure (HF) in a large regional-based Italian cohort of men and women in the frame of the URRAH study (URic Acid Right for heArt Health). Design and method: The ongoing large database URRAH collects data from studies and cohorts from hypertension centres and epidemiological laboratories including subjects with at least 1 measure of SUA and a follow-up of ∼20 years. Incident HF was defined in 23,475 subjects on the basis of ICD10 codes and double-checked with general practitioners and hospital files. Multivariate dichotomic Cox regression models having fatal and morbid HF as dependent variables, adjusted for arterial hypertension (AH), age, sex, diabetes, hematocrit, LDL-cholesterol, smoking and chronic renal disease were used to search for an association between SUA as a continuous variable and HF. Two prognostic cut-off values (one for fatal and one for morbid HF), identified by means of receiver operating curves (ROC) and able to discriminate between subjects doomed to develop the event, were then used as independent predictors to divide people into those <cut-off and >cut-off in further multivariate Cox models adjusted for the confounders. Results: In Cox analysis, SUA as a continuous variable was a significant predictor of fatal [odds ratio, OR 1.101 (1.011–1.200), p = 0.028] and morbid [OR 1.179 (1–031–1.349), p = 0.016] incident HF, independently of AH. Diuretics reduced the risk of fatal HF only [OR 0.448 (0.259–0.774), p = 0.005]. ROC showed that >5.70 mg/dl (CI 4.40 to 6.77, sensitivity 42.67, specificity 71.15, p < 0.0001) was the univariate prognostic cut-off value for fatal HF, and >4.20 mg/dl (CI 3.36 to 6.05, sensitivity 75.06, specificity 31.14, p < 0.003) for non-fatal HF. Nevertheless, only the cut-off for fatal HF was accepted as multivariate predictor in Cox analysis, the hazard ratios being 1.645 (1.284 - 2.109, p < 0.0001), with diuretic acting as a protective factor (p = 0.007), while that for morbid HF was rejected (p = 0.4). Conclusions: In conclusion, a clear prognostic cut-off value of SUA for fatal HF exists (>5.70 mg/dl) also after adjustment for confounders including AH, while SUA did not predict morbid HF.