Development Of Heart Failure In Patients Research Articles

N-Terminal Pro-Brain Natriuretic Peptide Plasma Levels Are Associated with Intermediate-Term Follow-Up Cancer in Coronary Patients.

N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels are increased in patients with cancer. In this paper, we test whether NT-proBNP may identify patients who are going to receive a future cancer diagnosis (CD) in the intermediate-term follow-up. We studied 962 patients with stable coronary artery disease and free of cancer and heart failure at baseline. This sample represents a re-analysis of a previous work expanding the sample size and the follow-up. NT-proBNP, galectin-3, monocyte chemoattractant protein-1, high-sensitivity C-reactive protein, high-sensitivity cardiac troponin I (hsTnI), and calcidiol (vitamin D) plasma levels were assessed. The primary outcome was new CD. After 5.40 (2.81–6.94) years of follow-up, 59 patients received a CD. NT-proBNP [HR 1.036 CI (1.015–1.056) per increase in 100 pg/mL; p = 0.001], previous atrial fibrillation (HR 3.140 CI (1.196–8.243); p = 0.020), and absence of previous heart failure (HR 0.067 CI (0.006–0.802); p = 0.033) were independent predictors of receiving a CD in the first three years of follow-up. None of the variables analyzed predicted a CD beyond this time. The number of patients developing heart failure during follow-up was 0 (0.0%) in patients receiving CD in the first three years of follow-up, 2 (6.9%) in those receiving a CD diagnosis beyond this time, and 40 (4.4%) in patients not developing cancer (p = 0.216). These numbers suggest that future heart failure was not a confounding factor. In patients with coronary artery disease, NT-proBNP was an independent predictor of CD in the first three years of follow-up but not later, suggesting that it could be detecting subclinical undiagnosed cancers.

Prospective longitudinal characterisation of the relationship between diabetes and cardiac remodeling

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Clinical Research Training Fellowship and Wellcome Trust Background Cardiovascular disease represents the primary cause of death in patients with type 2 diabetes (T2D). Heart failure (HF) is the commonest initial presentation of cardiovascular disease in T2D. Development of HF in patients with T2D is associated with a 4 to 6-fold increase in mortality, making the prevention of cardiac dysfunction an important goal. The long-term impact of T2D on cardiac function in the absence of cardiovascular disease is unknown. This is the first prospective longitudinal study utilising cardiovascular magnetic resonance (CMR) to evaluate the impact of T2D on cardiac remodeling. Objectives To determine longitudinal changes in the phenotypic expression of heart disease in diabetes over 6 years, and examine the association of baseline blood and imaging biomarkers with remodeling over time in patients who remained free of cardiovascular/clinical events, and to report clinical outcomes in the entire cohort. Methods 100 asymptomatic T2D patients with no history of cardiovascular disease or hypertension were previously studied. Biventricular volumes, function, and myocardial strain were assessed by CMR and blood biomarkers taken. 6-year follow-up CMR was repeated in those without interim cardiovascular events. Results Of the 100 patients, 78 could be contacted for follow-up. 29 participants experienced cardiovascular/clinical events over 6 years. 32 patients who were asymptomatic and without events received follow-up CMR. The major adverse cardiovascular event rate (MI, angina, revascularisation, stroke, death) during the 6-year follow-up period, including the patients with a silent MI, amounted to 25% in this study with an overall clinical event rate of 35%. There were no significant changes in BP, BMI or HBA1c between baseline and follow-up (Table 1). Left ventricular end-diastolic-volume(p = 0.005), mass (p = 0.01), ejection fraction (p = 0.0001), and right ventricular end-diastolic-volume(p = 0.03) and ejection fraction(p = 0.003) reduced over time (Figure 2 and Table 1). Baseline plasma high-sensitivity cardiac-troponin-T (hs-cTnT) (R=-0.44; p = 0.01) was significantly associated with change in left ventricular ejection fraction over time. Conclusions Even in the absence of overt clinical CAD, significant valvular disease, uncontrolled hypertension or change in BMI, T2D results in significant reductions in cardiac size and biventricular systolic function over time. The major adverse cardiovascular event rate (MI, angina, revascularisation, stroke, death) during the 6-year follow-up period was high in diabetes patients (25%). Plasma biomarker hs-cTnT measured at baseline was associated with change in LV systolic function over the 6-year follow-up period. hs-cTnT could potentially have a significant utility as a risk-predicting tool for cardiac dysfunction in T2D patients.

Lymphoma Patients Treated without Anthracyclines Have Negligible Risk of Cardiotoxicity: A Nationwide Cohort Study

▪AbstractObjective: For more than two decades,CHOP (and later R-CHOP) has been the standard frontline treatment for diffuse large b-cell lymphoma (DLBCL). However, anthracycline-based chemotherapy regimens increase risk of cardiotoxicity with congestive heart failure (HF) being the best documented cardiovascular complication of anthracycline use. However, cardiotoxicity has also been associated with other chemotherapeutic drugs. In this nationwide cohort study, we compared the incidence of development of HF in patients with DLBCL or follicular lymphoma (FL) treated with or without anthracyclines.Methods: DLBCL and FL patients > 16 years both receiving anthracycline in the form of R-CHOP/CHOEP or non-anthracycline chemotherapy regiments were identified in the Danish National Lymphoma Registry (LYFO) from 2000-2012. Anthracycline exposed patients were required to receive ≥3 cycles of R-CHOP or R-CHOEP upfront. The non-anthracycline exposed patients consisted of patients receiving non-anthracycline containing chemotherapy (such as CVP, CEOP and Bendamustine). Exclusion criteria were i) treatment with chemo therapy regimens more intensive than R-CHOP/CHOEP, ii) up-front high dose autologous stem cell transplantation and iii) the following heart comorbidities prior to the beginning of the study: HF (ICD-10 code: “I50”), Ischemic Heart Disease (ICD-10 code: “I20-I25”), Arrhythmic Heart Disease (ICD-10 code: “I48-I49”) and Cardiomyopathy (ICD-10 code: “I42”). Information on heart comorbidities in our study population were retrieved from the Danish National Patient Registry. Patient follow-up started from 30 days after ended chemotherapy to minimize confounding by early HF on the planned number of R-CHOP treatments. Follow-up ended when HF occurred, on the day of emigration from Denmark, day of death or the end of the study on 31th. December 2014, whichever came first. Univariate and multivariable cox regression analyses were performed to assess the association between cumulative anthracycline treatments and HF (adjusted analysis included gender, age, Ann Arbor stadium, radiotherapy, comorbidities and type of lymphoma). Cumulative R-CHOP treatments were stratified into groups of “3-5”, “6” and “>6” treatments. Cumulative incidence curves were computed to illustrate risk of HF over time according to number of treatments.Results: The study included 2,696 patients; 2,007 received anthracycline and 689 received non-anthracycline containing chemotherapy. In total, 1979 patients were diagnosed with DLBCL and 717 with follicular lymphoma. Anthracycline users were slightly younger (median age 64.03 vs 65.2 years (p-value <0.01)), received radiotherapy more often (21.03% vs 6.82% (p-value <0.01)) and were more frequently diagnosed with DLBCL (87.94% vs 31.06% (p-value <0.01)) (table 1). For patients not treated with anthracycline, the cumulative risk of HF within 1, 5 and 8 years were 0%, 0.89% and 1.77%, respectively. For patients treated with 3- 5 cycles of R-CHOP/CHOEP, the corresponding cumulative risk were 0.54%, 4.58% and 5.18%. For patients treated with 6 cycles, the cumulative risks were 1.02%, 4.49% and 8.02 % and for patients treated with >6 cycles, the cumulative risks were 4.01 %, 7.86% and 9.33% (fig 1).Compared to patients receiving non-anthracycline containing chemotherapy (reference), patients receiving anthracycline containing chemotherapy had a higher risk of developing HF during follow-up with adjusted hazard ratio (HR) of 3.73 (95% CI 1.38-10.09) for patients receiving 3-5 cycles, 4.38 (95% CI 1.83-10.48) for patients receiving 6 cycles, and 8.22 (95% CI 3.50-19.31) for patients receiving >6 cycles of anthracycline treatment.Conclusion: This present studyconfirms that inclusion of anthracyclines in a multi-agent chemotherapy regimen is responsible for the increased risk of HF observed after treatment for lymphoma and that the rate of HF is correlated to the number of treatment cycles. Patients treated without anthracyclines had a negligible risk of HF supporting the safety of these regimens in patients considered at substantial risk of cardiotoxicity. [Display omitted] DisclosuresJørgensen:Roche: Research Funding. Poulsen:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. El-Galaly:Roche: Other: Travel funding; Takeda: Other: Travel funding.

Lateral Wall Dysfunction Signals Onset of Progressive Heart Failure in Left Bundle Branch Block

ObjectivesThis study sought to investigate if contractile asymmetry between septum and left ventricular (LV) lateral wall drives heart failure development in patients with left bundle branch block (LBBB) and whether the presence of lateral wall dysfunction affects potential for recovery of LV function with cardiac resynchronization therapy (CRT). BackgroundLBBB may induce or aggravate heart failure. Understanding the underlying mechanisms is important to optimize timing of CRT. MethodsIn 76 nonischemic patients with LBBB and 11 controls, we measured strain using speckle-tracking echocardiography and regional work using pressure-strain analysis. Patients with LBBB were stratified according to LV ejection fraction (EF) ≥50% (EFpreserved), 36% to 49% (EFmid), and ≤35% (EFlow). Sixty-four patients underwent CRT and were re-examined after 6 months. ResultsSeptal work was successively reduced from controls, through EFpreserved, EFmid, and EFlow (all p < 0.005), and showed a strong correlation to left ventricular ejection fraction (LVEF; r = 0.84; p < 0.005). In contrast, LV lateral wall work was numerically increased in EFpreserved and EFmid versus controls, and did not significantly correlate with LVEF in these groups. In EFlow, however, LV lateral wall work was substantially reduced (p < 0.005). There was a moderate overall correlation between LV lateral wall work and LVEF (r = 0.58; p < 0.005). In CRT recipients, LVEF was normalized (≥50%) in 54% of patients with preserved LV lateral wall work, but only in 13% of patients with reduced LV lateral wall work (p < 0.005). ConclusionsIn early stages, LBBB-induced heart failure is associated with impaired septal function but preserved lateral wall function. The advent of LV lateral wall dysfunction may be an optimal time-point for CRT.

Association of Mean and Variability of HbA1c with Heart Failure in Patients with Type 2 Diabetes.

Heart failure (HF) is a common presentation in patients with type 2 diabetes mellitus (T2DM). Previous studies revealed that the HbA1c level is significantly associated with HF. However, little is known about the association between HbA1c variability and HF. We aimed to evaluate the association of mean and variability of HbA1c with HF in patients with T2DM. Using Diabetes Share Care Program data, patients with T2DM who had mean HbA1c (HbA1c-Mean), and HbA1c variability (tertiles of HbA1c-SD and HbA1c-adjSD) within 12–24 months during 2001–2008 were included. The cutoffs of HbA1c-Mean were set at <7%, 7–7.9%, and ≥8%. Hazard ratios (HRs) for HF during 2008–2018 were estimated using Cox proportional hazard models. A total of 3824 patients were included, of whom 315 patients developed HF during the observation period of 11.72 years. The associated risk of HF increased with tertiles of HbA1c variability and cutoffs of HbA1c-Mean. In mutually adjusted models, HbA1c-Mean showed a consistent dose-response association with HF, while the association of HbA1c variability with HF disappeared. Among patients with HbA1c-Mean <7%, the associated risk of HF in patients with HbA1c variability in tertile 3 was comparable to patients with HbA1c-Mean ≥8%. In conclusion, mean HbA1c was an independent predictor of HF and not explained by HbA1c variability. In addition to absolute HbA1c level, targeting on stability of HbA1c in patients with good glycemic control was also important for the development of HF in patients with T2DM.

Small Conductance Ca2 +-Activated K+ (SK) Channel mRNA Expression in Human Atrial and Ventricular Tissue: Comparison Between Donor, Atrial Fibrillation and Heart Failure Tissue.

In search of more efficacious and safe pharmacological treatments for atrial fibrillation (AF), atria-selective antiarrhythmic agents have been promoted that target ion channels principally expressed in the atria. This concept allows one to engage antiarrhythmic effects in atria, but spares the ventricles from potentially proarrhythmic side effects. It has been suggested that cardiac small conductance Ca2+-activated K+ (SK) channels may represent an atria-selective target in mammals including humans. However, there are conflicting data concerning the expression of SK channels in different stages of AF, and recent findings suggest that SK channels are upregulated in ventricular myocardium when patients develop heart failure. To address this issue, RNA-sequencing was performed to compare expression levels of three SK channels (KCNN1, KCNN2, and KCNN3) in human atrial and ventricular tissue samples from transplant donor hearts (no cardiac disease), and patients with cardiac disease in sinus rhythm or with AF. In addition, for control purposes expression levels of several genes known to be either chamber-selective or differentially expressed in AF and heart failure were determined. In atria, as compared to ventricle from transplant donor hearts, we confirmed higher expression of KCNN1 and KCNA5, and lower expression of KCNJ2, whereas KCNN2 and KCNN3 were statistically not differentially expressed. Overall expression of KCNN1 was low compared to KCNN2 and KCNN3. Comparing atrial tissue from patients with AF to sinus rhythm samples we saw downregulation of KCNN2 in AF, as previously reported. When comparing ventricular tissue from heart failure patients to non-diseased samples, we found significantly increased ventricular expression of KCNN3 in heart failure, as previously published. The other channels showed no significant difference in expression in either disease. Our results add weight to the view that SK channels are not likely to be an atria-selective target, especially in failing human hearts, and modulators of these channels may prove to have less utility in treating AF than hoped. Whether targeting SK1 holds potential remains to be elucidated.

Use of Hydroxychloroquine and Risk of Heart Failure in Patients With Rheumatoid Arthritis.

To examine the relationship between the use of hydroxychloroquine (HCQ) and risk of developing heart failure (HF) in rheumatoid arthritis (RA). In this nested case-control study, cases were Olmsted County, Minnesota residents with incident RA (based on 1987 American College of Rheumatology criteria) from 1980 to 2013 who developed HF after RA incidence. Each case was matched on year of birth, sex, and year of RA incidence with an RA control who did not develop HF. Data on HCQ use including start and stop dates, as well as dose changes, were reviewed and used to calculate HCQ duration and cumulative dose. Age-adjusted logistic regression models were used to examine the association between HCQ and HF. The study identified 143 RA cases diagnosed with HF (mean age 65.8 yrs, 62% females) and 143 non-HF RA controls (mean age 64.5, 62% female). HCQ cumulative dose was not associated with HF (OR 0.96 per 100-g increase in cumulative dose, 95% CI 0.90-1.03). Likewise, no association was found for patients with a cumulative dose ≥ 300 g (OR 0.92, 95% CI 0.41-2.08). The HCQ duration of intake in years prior to index was not associated with HF (OR 0.98, 95% CI 0.91-1.05). Use of HCQ was not associated with development of HF in patients with RA in this study. Further studies are needed to understand the effect of higher doses of HCQ on the development of HF in RA.

Возможности снижения риска развития хронической сердечной недостаточности у больных артериальной гипертензией с позиций доказательной медицины (фокус на кандесартан)

Arterial hypertension is the main risk factor for the development of cardiovascular complications and makes a significant contribution to cardiovascular morbidity, including chronic heart failure, and mortality, amounting to more than 45%. The leading risk factors for the development of cardiovascular diseases also include a violation of lipid and carbohydrate metabolism. Current treatments for cardiovascular disease include the administration of angiotensin II receptor blockers. This article provides an overview of the literature data on the efficacy, safety profile of candesartan, high adherence to this drug in patients with arterial hypertension, chronic heart failure, impaired carbohydrate and lipid metabolism. The advantages of candesartan in comparison with other representatives of this group of drugs in the prevention of chronic heart failure are emphasized according to large-scale international randomized trials. Keywords: arterial hypertension, atherosclerosis, diabetes mellitus, insulin resistance, chronic heart failure, candesartan, Hyposart For citation: Evdokimova AG, Stryuk RI, Evdokimov VV, Golikova AA. Reducing the risk of chronic heart failure development in patients with arterial hypertension from the position of evidence medicine (focus on candesartan). Consilium Medicum. 2021; 23 (1): 84–92. DOI: 10.26442/20751753.2021.1.200730

Abstract 15524: The Methyltransferase Setd7 Drives Myocardial Ischemic Injury by Modulating the Hippo Pathway: A Study in Mice and Humans

Introduction: Ischemic heart disease is a leading cause of death worldwide. Although revascularization strategies significantly reduce mortality after acute myocardial infarction (MI), a significant number of MI patients develop heart failure. Protein methylation is emerging as a key biological signal implicated in the pathophysiology of cardiovascular (CV) disease. In this regard, the methyltransferase SETD7 was recently shown to methylate proteins relevant to CV homeostasis. Hypothesis: To investigate SETD7 role in myocardial ischemia-reperfusion (I/R) injury. Methods: Experiments were performed in neonatal rat ventricular myocytes (NRVM), SETD7 knockout mice (SETD7 -/- ) undergoing myocardial I/R injury, myocardial samples from patients with and without ischemic heart failure as well as peripheral blood mononuclear cells from patients with ST elevation MI (STEMI, n=25) and age-matched healthy controls (n=20). Results: Glucose deprivation (GD) in NRVM led to upregulation of SETD7 and direct mono-methylation of the Hippo signaling effector YAP. SETD7-dependent methylation of YAP led to its cytosolic retention thus impeding YAP binding to the promoter of pro-survival genes. Selective pharmacological inhibition of SETD7 by (R)-PFI-2 blunted YAP mono-methylation thereby restoring its nuclear retention. We show that YAP binds the promoter of antioxidant genes catalase and superoxide dismutase, thus preventing GD-induced mitochondrial oxidative stress, organelle swelling and apoptosis. Consistently, infarct size, myocardial oxidative stress and left ventricular dysfunction were reduced in SETD7 -/- mice undergoing I/R as compared to wild-type littermates. Of clinical relevance, we found that SETD7/YAP signaling was deregulated in myocardial samples from patients with ischemic heart failure as well as in peripheral blood mononuclear cells from STEMI patients. Conclusions: We demonstrate that SETD7-dependent methylation of YAP is an important mechanism underpinning myocardial oxidative stress, mitochondrial damage and apoptosis during ischemia. Pharmacological modulation of SETD7 by (R)-PFI-2 may represent a potential therapeutic approach to prevent myocardial ischemic damage through modulation of the Hippo pathway.

Mechanisms of COVID-19-induced heart failure: a short review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected more than 42.5 million people globally resulting in the death of over 1.15 million subjects. It has inflicted severe public health and economic hardships across the world. In addition to acute respiratory distress syndrome, respiratory failure, sepsis, and acute kidney injury, COVID-19 also causes heart failure (HF). COVID-19-induced HF is manifested via different mechanisms, including, but not limited to, (1) virus-induced infiltration of inflammatory cells, which could impair the function of the heart; (2) pro-inflammatory cytokines (monocyte chemoattractant protein-1, interleukin-1β; interleukin-6; tumor necrosis factor-α) that could cause necrosis and death of the myocardium; (3) endothelial injury coupled with micro-thrombosis which could damage the endocardium; and (4) acute respiratory distress syndrome and respiratory failure that could lead to heart failure due to severe hypoxia. It is concluded that the etiology of COVID-19-induced HF is multifactorial and mitigation of the development of HF in patients with COVID-19 will require different approaches such as social distancing, drug therapy, and the urgent development of a vaccine to eradicate the disease.

Usefulness of H2FPEF score as an independent predictor of heart failure development in patients with atrial fibrillation

Abstract Background The H2 FPEF score, which based on simple clinical characteristics and echocardiography, enables discrimination of HFpEF from noncardiac causes of dyspnea. Purpose We sought to evaluate whether H2 FPEF score predicts congestive heart failure (CHF) development in patients with atrial fibrillation (AF). Methods Among adult AF patients who underwent transthoracic echocardiography between July 2007 and December 2008, those with preserved left ventricular ejection fraction (LVEF) (≥50%) were included and followed up to new-onset CHF events. Patients with a history of CHF, cardiac surgery, or significant left-sided valvular heart disease were excluded. The H2 FPEF score was calculated from 6 variables (obesity = 2 points, treatment with ≥2 antihypertensive drugs = 1 point, AF = 3 points, echocardiographic pulmonary artery systolic pressure &amp;gt;35 mmHg = 1 point, age &amp;gt;60 years = 1 point, and echocardiographic E/e'ratio &amp;gt;9 = 1 point). CHF was ascertained using Framingham criteria. Cox-proportional hazards modeling was used to assess risk of CHF development. Results Of 562 AF patients, 367 (69±10 year old, 66% men) met all study criteria. Of whom, 37 (10%) developed CHF events during a mean follow–up of 56±43 months. The mean H2 FPEF score was 5.50±1.14, and the number of patients with H2 FPEF score ≥7 was 64 (17%). After adjusting for comorbidities in a multivariate model, H2 FPEF score was significant predictor of new-onset CHF events both as continuous (HR=1.43, 95% CI: 1.05–1.96, P&amp;lt;0.05) or categorical (H2 FPEF score ≥7) (HR=2.32, 95% CI: 1.17–4.63, P&amp;lt;0.05) variables. The Kaplan-Meier estimates of CHF-free survival stratified by H2 FPEF status (≥7 or &amp;lt;7) were shown in Figure. Conclusion H2 FPEF score provides prognostic information for new-onset CHF development in patients with AF. Figure 1 Funding Acknowledgement Type of funding source: None

Risk of heart failure associated with thiazide diuretics compared with calcium channel blockers in patients with type 2 diabetes: a nationwide nested case-control study

Abstract Background Thiazide diuretics and calcium channel blockers (CCB's) are two important and widely used antihypertensive drugs classes among patients with type 2 diabetes (T2D). The risk of developing heart failure (HF) is increased in patients with T2D but whether use of these two drugs are associated with changes in HF risk is unknown. Purpose To examine and compare the association of two different classes of antihypertensive drugs, thiazide diuretics and CCB's, with the development of new onset HF in patients with T2D. Methods The study cohort comprised T2D patients &amp;gt;40 years on metformin and renin-angiotensin system inhibitor (RAS-i) without a history of HF or use of loop diuretics identified in Danish health care registers (period 1995 to 2015). A nested case-control study was conducted by matching all HF cases on sex, age and duration of T2D with 10 controls from the T2D population. Exposure was defined as three redeemed prescriptions of either a thiazide diuretic or a CCB up to 365 days before index, which corresponds to one year of antihypertensive therapy. Conditional logistic regression adjusted for comorbidities (atrial fibrillation, chronic obstructive pulmonary disease and anemia) was used to estimate and compare the treatment effect of thiazide diuretics and CCB's, with patients receiving neither of the two drugs as reference. Results The study population consisted of 170,514 T2D patients using metformin and RAS-i, comprising 13,814 HF cases each matched on sex, age and duration of T2D with 10 controls. The median age was 62 years and 55% were men. T2D patients, who had received antihypertensive treatment with only thiazide diuretics one year prior to index had a significantly lower risk of HF compared to the reference group who did not receive treatment with neither thiazide diuretics or CCB's: Hazard ratio (HR) 0.79 [95% confidence interval (CI) 0.74–0.85]. Patients who had received treatment with only CCB's had a comparable risk of HF: HR 0.98 [95% CI 0.94–1.02]. Patients who had received treatment with both thiazide diuretics and CCB's were not associated with a lower risk of HF: HR 1.01 [95% CI 0.96–1.08]. Conclusion Patients with T2D who received antihypertensive therapy with thiazide diuretics for at least one year had a significantly lower risk of HF compared to those who were not treated with either thiazide diuretics or CCB's. No association between use of CCB's and HF was observed. Use of thiazide diuretics may prevent development of HF in T2D and a randomized clinical trial evaluating diuretics is patients with T2D is warranted. Risk of new onset heart failure Funding Acknowledgement Type of funding source: None

OP0024 USE OF HYDROXYCHLOROQUINE AND RISK OF HEART FAILURE IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background:Hydroxychloroquine (HCQ) is a disease-modifying anti-rheumatic drug (DMARD) used as a long-term treatment for rheumatoid arthritis (RA) patients. Cardiotoxicity is a rare but potentially life-threatening side effect of HCQ and may present as conduction disorders, cardiomyopathy, and resulting heart failure (HF). The evidence of cardiotoxicity associated with the use of HCQ largely relies on case reports and case series while large cohort studies on the subject are lacking.Objectives:To examine the relationship between the use of HCQ and risk of developing HF in RA.Methods:In this nested case-control study, cases were Olmsted county, Minnesota residents with incident RA (based on 1987 ACR criteria) in 1980-2013 who developed HF after RA incidence. Each case was matched on year of birth, sex and year of RA incidence with an RA control who did not develop HF. Each non-HF control was assigned an index date corresponding to the HF diagnosis date of the case. Controls were allowed to later become cases to avoid bias. HF was defined using the Framingham criteria. Data on HCQ use including start and stop dates and dose changes was manually abstracted via medical record review, and used to calculate HCQ duration and cumulative dose. Age-adjusted logistic regression models were used to examine the association between HCQ and HF.Results:From a cohort of 1078 subjects, the study identified 143 RA cases diagnosed with HF (mean age 65.8, 62% females) and 143 non-HF RA controls (mean age 64.5, 62% female). Cases and controls had similar RA duration, proportion of patients positive for rheumatoid factor (RF) and/ or cyclic citrullinated antibody (CCP), body mass index, and smoking status (Table). The duration of HCQ use prior to the diagnosis of HF was 2.8 years in cases and 2.6 years in controls. A total of 71 cases and 69 controls used HCQ at some time before index date. Among these, the median (interquartile range) duration of HCQ use was 2.8 (0.6, 10.0) years for cases and 2.5 (0.7, 8.2) for controls. The median cumulative dose of HCQ was 371 g and 302 g in cases and controls, respectively, with 55% of cases receiving a cumulative dose of ≥ 300 g compared to 54% in controls. HCQ cumulative dose was not associated with HF (Odds Ratio [OR]: 0.96 per 100g increase in cumulative dose, 95% confidence interval [95% CI]: 0.90-1.03). Likewise, no association was found for patients with a cumulative dose ≥300g (OR 0.92, 95% CI 0.41-2.08). The duration of use of HCQ prior to index was not associated with HF (OR 0.98, 95% CI 0.91-1.05). Retinal toxicity rates were similar in cases and controls.Table 1.Characteristics of patients with rheumatoid arthritis with and without heart failure.VariableHFnon-HFAge at RA diagnosis (years)65.8 ± 12.364.5 ± 12.5Female62%62%RA duration at baseline (years)11.3 ± 8.510.3 ± 8.2RF positive66%65%CCP positive46%53%RF/ CCP positive68%66%BMI (at RA diagnosis)28.6 ± 6.527.7 ± 5.4Smoking status at RA incidenceFormer45%41%Current22%22%Conclusion:Use of HCQ was not associated with development of HF in patients with RA in this study. While there was no statistically significant association between the cumulative dose of HCQ and HF, the confidence interval for HCQ dose ≥300 g was wide suggesting that more studies are needed to understand the impact of higher doses of HCQ on development of HF in RA.Disclosure of Interests:Ahmed Sorour: None declared, Youssef Shahin: None declared, Cynthia S. Crowson Grant/research support from: Pfizer research grant, Reto Kurmann: None declared, Sara Achenbach: None declared, Rekha Mankad: None declared, Elena Myasoedova: None declared

Risk of heart failure in type 2 diabetes complicated by incident ischaemic heart disease and end-stage renal disease.

To evaluate the risk of heart failure (HF) in patients with type 2 diabetes (T2D) complicated by development of intercurrent ischaemic heart disease (IHD), end-stage renal disease (ESRD), or both, compared to patients with T2D and no IHD and ESRD. From Danish nationwide registries, we identified all patients with new-onset T2D with no history of HF between 1998 and 2015. Landmark analyses were used to estimate the 5-year absolute risk of HF at several follow-up times, and accounted for the occurrence of IHD and ESRD, identified before HF. The Aalen-Johansen estimator was used to account for censoring and the competing risk of death. A total of 285 024 patients with new-onset T2D were included. During follow-up, 19 960 developed incident HF. Among patients with T2D free of HF 5 years after T2D diagnosis, patients without IHD and ESRD had the lowest 5-year risk of HF [4.02%; 95% confidence interval (CI) 3.90-4.15), those with T2D complicated by IHD [11.51%; relative risk (RR) 2.86; 95% CI 2.72-3.02; P < 0.001] or ESRD (8.11%; RR 2.02; 95% CI 1.39-2.93; P < 0.001) an intermediate risk, and those with both IHD and ESRD (19.76%; RR 4.92; 95% CI 3.43-7.05; P < 0.001) the highest risk. Patients with T2D complicated by development of intercurrent IHD, ESRD, or both, showed a significantly higher risk of HF compared to those who did not develop IHD and ESRD. An effective way to delay or prevent the development of HF in patients with T2D may be to prevent IHD and ESRD.

GATA4-targeted compound exhibits cardioprotective actions against doxorubicin-induced toxicity in vitro and in vivo: establishment of a chronic cardiotoxicity model using human iPSC-derived cardiomyocytes

Doxorubicin is a widely used anticancer drug that causes dose-related cardiotoxicity. The exact mechanisms of doxorubicin toxicity are still unclear, partly because most in vitro studies have evaluated the effects of short-term high-dose doxorubicin treatments. Here, we developed an in vitro model of long-term low-dose administration of doxorubicin utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Moreover, given that current strategies for prevention and management of doxorubicin-induced cardiotoxicity fail to prevent cancer patients developing heart failure, we also investigated whether the GATA4-targeted compound 3i-1000 has cardioprotective potential against doxorubicin toxicity both in vitro and in vivo. The final doxorubicin concentration used in the chronic toxicity model in vitro was chosen based on cell viability data evaluation. Exposure to doxorubicin at the concentrations of 1–3 µM markedly reduced (60%) hiPSC-CM viability already within 48 h, while a 14-day treatment with 100 nM doxorubicin concentration induced only a modest 26% reduction in hiPCS-CM viability. Doxorubicin treatment also decreased DNA content in hiPSC-CMs. Interestingly, the compound 3i-1000 attenuated doxorubicin-induced increase in pro-B-type natriuretic peptide (proBNP) expression and caspase-3/7 activation in hiPSC-CMs. Moreover, treatment with 3i-1000 for 2 weeks (30 mg/kg/day, i.p.) inhibited doxorubicin cardiotoxicity by restoring left ventricular ejection fraction and fractional shortening in chronic in vivo rat model. In conclusion, the results demonstrate that long-term exposure of hiPSC-CMs can be utilized as an in vitro model of delayed doxorubicin-induced toxicity and provide in vitro and in vivo evidence that targeting GATA4 may be an effective strategy to counteract doxorubicin-induced cardiotoxicity.

4:03 PM Abstract No. 59 Risk factors and outcomes for patients developing heart failure after transjugular intrahepatic portosystemic shunt

4:03 PM Abstract No. 59 Risk factors and outcomes for patients developing heart failure after transjugular intrahepatic portosystemic shunt

Increased respiratory disturbance index measured using an advanced device algorithm is associated with heart failure development.

Previous studies suggested that sleep-disordered breathing was associated with cardiovascular diseases such as heart failure (HF). Recently, algorithms of cardiac implantable electronic devices (CIEDs) have been developed to detect advanced sleep apnea (SA); the Apnea Scan (AP Scan) being an example. The purpose of this study was to investigate the association between respiratory disturbance index (RDI) measured using the AP Scan algorithm and HF development. We retrospectively studied consecutive patients with CIEDs equipped with the AP Scan algorithm which were implanted between December 1, 2011 and March 31, 2019. These patients were divided into 2 groups according to the trends of RDI: patients with a continually high RDI > 30 (severe SA group) and those without a continually high RDI (non-severe SA group). There were 16 and 46 patients in the severe and non-severe SA groups, respectively. Increased left ventricular end-diastolic and end-systolic dimensions were observed in the severe SA group. Regarding cardiovascular events, HF was observed in 8 patients (50.0%) in the severe SA group and 1 patient (2.2%) in the non-severe SA group; thus, there was a significantly higher proportion of patients with HF in the severe SA group. In conclusion, continually high RDI was associated with HF development in patients with CIEDs equipped with the AP Scan algorithm. Therefore, an elevated RDI may be a risk factor for the development of HF in patients with CIEDs.

P963 Heart failure development in patients with preserved ejection fraction after STEMI: how frequent is It and can we predict it?

Abstract Data regarding heart failure (HF) development among patients with preserved EF (≥50%) after STEMI are spare. Accurate and early identification of patients at risk might allow timely application of modern therapy targeted for HFpEF. Aim the current study is a sub-study of PREDICT-VT (NCT03263949). Its aim was to determine the incidence and predictors of HFpEF development in STEMI patients treated by pPCI. Methods in 264 consecutive pts enrolled in PREDICT-VT study early echocardiography (5 ± 2 days after pPCI) was done and included multilayer LV deformation analysis with longitudinal (L), radial (R) and circumferential (C) strain (S; %) and strain rate (SR, 1/sec) and rotational LV mechanics. LV index of post systolic shortening for longitudinal strain (PSS LS) and for circumferential strain (PSS CS) were calculated as average of PSS over 18 LV segments. LV diastolic function was assessed according to the current ESC guidelines. Results From 264 patients enrolled in PREDICT-VT study, until now 195 patients completed one-year follow and among them 87 pts (46 %) had EF≥50%. From those patients during one-year follow-up 30 pts (30.3 %) develop HF: 3 pts NYHA class 3/ 4 and 27 pts NYHA class 2. Patients who developed HF (Group HF, n = 30) were older (62 ± 7 vs55 ± 11, p = 0.002), had lower E/A ratio (0.77 ± 0.25 vs 0.94 ± 0.32, p = 0.014), more commonly altered LV diastolic function (83 vs 60%, p = 0.028) compared with pts who remained in NYHA class I (Group none-HF, n = 57). There were no significant differences in LVEF, MI localisation, nor in WMSI between groups. Longitudinal and circumferential myocardial deformations did not differ significantly, except for more pronounced PSS LS on epicardial level in Group –HF (11.5 ±7.5 vs 8.3 ± 7.7%, p = 0.073). Rotation mechanic analysis revealed that Group –HF had increased (14.08 ± 5.5 vs 12.5 ± 5.4°, p = 0.202), but delayed twist (350 ± 69 vs 327 ± 68 ms, p = 0.139) with reduced magnitude of peak untwisting velocities (-88.58 ±34.16 vs -95.20 ± 39.75°/sec, p = 0.488). However, only statistically significant difference was increased magnitude of untwisting velocity during late diastole (-57.53 ± 30.61 vs -42.88 ± 27.78, p = 0.029). Significant univariate predictors of HF development were: older age (Exp (B)=1.08, CI 1.027-1.139, p = 0.03), E/A ratio (Exp (B) =0.130, p = 0.018, 95%CI 0.024-0.700), female gender (Exp (B)=2.933, 95% CI 1.163 -7.397, p = 0.023) and late-diastolic untwisting velocity (Exp (B)=0.983, 95%CI 0.967-0.999, p = 0.033). However, in multivariable analysis only older age (Exp B= 1.09, 95% CI 1.028-1.155, p = 0.004) and female gender (Exp B= 2.80, 95% CI 1.01-7.708, p = 0.046) remained significant predictors. Conclusion HF after STEMI in patients with preserved EF is not rare and probably substantially contributes to the total incidence HF after STEMI. However, its prediction remained challenging, with female gender and older age confirmed as its significant determinants.

P840 A surprising outcome

Abstract Introduction infective endocarditis(IE) is a high morbidity and mortality disease, and heart failure,central nervous system embolization and annular abscess account for common complications.Nevertheless,intracardiac fistula is rare and predicts higher mortality and urgency for surgery. Case 84years old male patient,with an aortic bioprosthesis valve Perimount n23 since 2015,was admitted to internal medicine ward 3months before,due to Enterococcus faecalis bacteremia.at that time,transoesophageal echocardiography(TEE) revealed moderate to severe mitral valve(MV) regurgitation(vena contracta 0.7cm) and trivial tricuspid regurgitation,but did not showed any suggestive images of endocarditis.the patient was treated with 14days of amoxicillin-clavulanate. On the current presentation,due to fadigue to mild physical activity and fever for 2weeks,he was admitted to cardiology ward for further investigation.blood cultures were positive for the previous agent,so antibiotherapy with ampicillin 12g/day and gentamicin 240mg id was started.TEE revealed thickening of aortic bioprosthesis’ leaflets with preserved systolic opening.aortic valve annulus thickening,mainly near the non-coronary cusp,was evident, without characteristic features of peri-annular abscess.on ventricular side of the prosthesis,there was a vegetation(10.7x10.8mm). a small nodule lesion,coherent with a second vegetation,was present on the MV’s posterior leaflet,without regurgitation’s worsening. a third one was observed on the septal leaflet of the tricuspid valve(7.3x6.5mm),which also caused an increasement in severity of the regurgitation,quantified as moderate. On the sixth day,the patient presented with right arm paresis,so a brain CT was performed,showing an ischemic lesion on the left middle cerebral artery.Reevaluation,5days later,owing to new neurological changes,showed multiple acute vertebrobasilar embolic strokes. As a result of poor medical response and embolic strokes,the patient was referred to surgical treatment. however, due to prohibitive surgical risk (euroscore 59%), the patient was refused. After 6weeks of blood culture driven antibiotherapy,a reevaluation TEE revealed a periprosthetic pseudoaneurysm with small aorta-to-right atrium fistula.no vegetations were found. Conclusion rate complication of cardiac fistulae is high,60%of the patients develop heart failure and mortality rate is higher than 40%.although conservative treatment was addressed,after 8months discharge,the patient remains with few heart failure symptoms(NYHA classII).

P5004Peripheral neuropathy and increased risk of heart failure: a population-based longitudinal cohort study

Abstract Background One of the main pathophysiological processes thought to be implicated in the development of diabetic cardiomyopathy is a microvascular disease (MiVD) that is prevalent in type 2 diabetes (T2D). However, the role of MiVD in the development of heart failure (HF) is not known. T2D screening programmes identify three types of MiVD – retinopathy, nephropathy and neuropathy. Both retinopathy and nephropathy have been independently associated with the development of incident HF in observational cohort studies. There is less data on peripheral neuropathy and HF outcomes. This study aimed to determine the independent association of diabetic neuropathy with incident HF events in a large longitudinal population cohort of T2D patients with a detailed clinical follow-up that includes available echocardiographic data. Design This was a population-based longitudinal cohort study from the Genetics of Diabetes Audit and Research in Tayside Scotland study (GoDARTS) from 1996 to 2016. A total of 9,598 patients with T2D were included with data available on hospital admissions, prescribing and other clinical variables including age, gender, smoking history, duration of T2D, body mass index, systolic blood pressure, glycosylated haemoglobin (HbA1c), triglyceride, total LDL and HDL cholesterol levels. Neuropathy cases were identified using a well-validated record linkage method utilising neuropathic drug prescription records to identify cases of neuropathic pain and to monofilament testing that is used to diagnose neuropathy. Results There were 805 HF events. After adjustment for clinical variables, the presence of painful neuropathy related to a 57% increased risk of incident HF (HR 1.57, 95% CI = 1.32–1.89, p&lt;0.001). A similar risk was also observed with diabetic neuropathy identified by monofilament testing with a 52% (HR 1.52, CI = 1.013–1.225, P&lt;0.05) increased risk of incident HF. Conclusions and relevance Peripheral neuropathy, a feature of MiVD, may be pathophysiologically associated with the development of HF in patients with T2D and may be a therapeutic target.