Higher Risk Of Heart Failure Research Articles

Death of a child and the risk of heart failure: a population-based cohort study from Denmark and Sweden.

We aimed to investigate whether the death of a child, one of the most severe stressors, is associated with the risk of heart failure (HF). We conducted a population-based cohort study involving parents of live-born children recorded in the Danish and Swedish Medical Birth Registers during 1973-2016 and 1973-2014, respectively (n=6 717 349). We retrieved information on child death, HF diagnosis and sociodemographic characteristics of the parents from several nationwide registries. We performed Poisson regression models to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for HF in relation to bereavement. A total of 129 829 (1.9%) parents lost at least one child during the follow-up. Bereaved parents had a 35% higher risk of HF than the non-bereaved (IRR 1.35, 95% CI 1.29-1.41; p < 0.001). The increased HF risk was observed not only when the child died due to cardiovascular or other natural causes, but also when the loss was due to unnatural causes. The association tended to be U-shaped when we categorized the exposed parents by the number of remaining live children at loss or by the age of the deceased child. We found that the death of a child was associated with an increased risk of HF. The finding that not only cardiovascular and other natural deaths, but also unnatural deaths were associated with HF suggests that stress-related mechanisms may contribute to the development of HF.

Abstract 9820: WATCH-DM Risk Score is Associated with Functional Capacity and Prognosis in Diabetic Patients with Heart Failure with Preserved Ejection Fraction

Introduction: The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF) is frequent and associated with a higher mortality. WATCH-DM risk score is recently developed to predict the risk of HF among patients with T2DM using a machine learning approach (Segar et al, Diabetes Care 2019). Hypothesis: We hypothesized that WATCH-DM risk score would be associated with functional capacity and clinical outcomes in diabetic patients with HF with preserved ejection fraction (HFpEF). Methods: The PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study is a multicenter registration of patients hospitalized for acute decompensated HFpEF. Among 1095 patients registered between 2016 and 2020, 418 patients (38.2%) had T2DM (male gender 49.5%, age 80±9 years, HbA1c 6.8±1.0%). WATCH-DM risk score was calculated in each patient, using BMI, age, systolic/diastolic blood pressure, serum creatinine, HDL-C, fasting plasma glucose, QRS duration, history of myocardial infarction or coronary bypass graft, and patients were divided as the low to average (≤10 points), high (11-13 points) and very high (≥14 points) risk groups. We measured 6 minute walk distance (6MWD) and NT-proBNP before discharge. We followed the study patients for median of 386 days (IQR 221 to 729 days) to observe the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke). Results: The WATCH-DM score in the study patients were 12.8±3.1 points, and 108 patients (25.8 %) had low-average, 147 patients (35.2%) high, and 163 patients (39.0%) very high HF risk. There was significant difference in 6MWD (p=0.004) among the groups, and the low-average risk group had significantly longer 6MWD than the high risk group (p=0.049). NT-proBNP was lower in the low-average risk group than in other 2 groups. Cox proportional hazard model selected the WATCH-DM score as an independent predictor for MACE (p=0.006). Kaplan-Meier curve demonstrated that patients with the low-average risk had significantly lower incidence of MACE than the others (p=0.049). Conclusions: The WATCH-DM risk score predicted functional capacity and prognosis in diabetic patients with HFpEF.

Abstract 12150: Incorporation of Natriuretic Peptides With Clinical Risk-Scores to Predict Heart Failure Among Individuals With Dysglycemia

Introduction: The WATCH-DM score can predict risk of heart failure (HF) in patients with diabetes. Hypothesis: Addition of natriuretic peptide (NP) levels will improve WATCH-DM performance in individuals with dysglycemia. Methods: Adults with diabetes/pre-diabetes free of HF at baseline from 4 cohort studies (ARIC, CHS, FHS, and MESA) were included. The integer- [WATCH-DM(i)] and machine learning-based [WATCH-DM(ml)] scores were used to estimate the 5-year risk of incident HF. Discrimination was assessed by Harrell's concordance index (C-index) and calibration by the Greenwood-Nam-D'Agostino (GND) statistic. Improvement in model performance with the addition of NP-levels was assessed by C-index, Brier score, and continuous net reclassification improvement (NRI). Results: Of the 8,938 participants included, 3,554 (39.8%) had diabetes and 432 (4.8%) developed HF within 5-years. Among 5,384 (60.2%) participants with pre-diabetes, 647 (12.0%) developed incident HF. The WATCH-DM(ml) and (i) scores demonstrated high discrimination for predicting HF risk in diabetes (C-indices=0.76 and 0.69), pre-diabetes (0.83 and 0.72), and overall cohort (0.80 and 0.71), respectively, with no evidence of miscalibration (GND=P &gt;0.10). A greater improvement in C-index was observed with the addition of NP-levels at lower WATCH-DM(i) scores with degradation of risk discrimination at higher scores (Fig. A). Calibration was also improved with addition of NP-levels at lower compared to higher WATCH-DM(i) scores (Fig. B). A greater improvement in reclassification was observed by combing WATCH-DM(i) score with selected NP-levels assessment in low (score&lt;13) vs. high-risk (≥13) participants (NRI=0.45 vs. 0.17; p-value&lt;0.001). Conclusions: The WATCH-DM risk score can accurately predict incident HF risk in community-based individuals with dysglycemia. The addition of NP-levels improves risk prediction among adults with low/intermediate but not high HF risk.

Abstract 12257: The Utility of PREDICT-HF Score in High-Risk Asian Heart Failure Patients Receiving Sacubitril/Valsartan Treatment

Introduction: Although the efficacy and safety of sacubitril/valsartan (Sac/val) for treating patients with heart failure and reduced ejection fraction (HFrEF) have been shown in global clinical trials, long-term tolerability and effectiveness data from Asian patients are limited. Hypothesis: The aim of this study was to investigate the effectiveness and tolerability of Sac/val in clinical practice and the utility of PREDICT-HF score for outcome prediction in Asian heart failure patients with difference risk profiles. Methods: The TAROT-HF study was a multicenter, single-arm, observational study. Totally 1,187 outpatients with HFrEF treated with Sac/val were enrolled and categorized by: (1) high-risk group with one or more of the following three risk factors: old age (≥80 years), low baseline systolic blood pressure (&lt;100mmHg), and renal impairment (eGFR &lt;30ml/min/1.73 m2), and (2) standard-risk group, those who did not have any risk factors. Clinical outcomes were assessed using the PREDICT-HF risk model. Results: A total of 305 (25.7%) patients matched the criteria for the high-risk group. The event rates of cardiovascular death or first unplanned heart failure hospitalization (HFH) among the overall population, high-risk, and standard-risk groups were 13.7, 24.9, and 10.8 events per 100 patient-years, respectively. The C statistics for the PREDICT-HF model in the overall cohort and high-risk group for cardiovascular death or first unplanned HFH at 2 years were 0.73 (95% CI 0.70-0.76) and 0.71 (95% CI 0.65-0.76), respectively. Conclusions: Real-world outcomes of the TAROT-HF study showed good tolerability of Sac/val. Although the current study enrolled high-risk patients not included in the PARADIGM-HF trial, the PREDICT-HF model performed well in real-world Asian HFrEF patients. Three easily detected clinical profiles of age, renal function, and systolic BP could help to identify patients at risk before initiating Sac/val therapy.

RNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patients

BackgroundHeart failure (HF) is one of the most common complications of cardiovascular diseases (CVDs) and among the leading causes of death in the US. Many other CVDs can lead to increased mortality as well. Investigating the genetic epidemiology and susceptibility to CVDs is a central focus of cardiology and biomedical life sciences. Several studies have explored expression of key CVD genes specially in HF, yet new targets and biomarkers for early diagnosis are still missing to support personalized treatment. Lack of gender-specific cardiac biomarker thresholds in men and women may be the reason for CVD underdiagnosis in women, and potentially increased morbidity and mortality as a result, or conversely, an overdiagnosis in men. In this context, it is important to analyze the expression and enrichment of genes with associated phenotypes and disease-causing variants among high-risk CVD populations.MethodsWe performed RNA sequencing focusing on key CVD genes with a great number of genetic associations to HF. Peripheral blood samples were collected from a broad age range of adult male and female CVD patients. These patients were clinically diagnosed with CVDs and CMS/HCC HF, as well as including cardiomyopathy, hypertension, obesity, diabetes, asthma, high cholesterol, hernia, chronic kidney, joint pain, dizziness and giddiness, osteopenia of multiple sites, chest pain, osteoarthritis, and other diseases.ResultsWe report RNA-seq driven case–control study to analyze patterns of expression in genes and differentiating the pathways, which differ between healthy and diseased patients. Our in-depth gene expression and enrichment analysis of RNA-seq data from patients with mostly HF and other CVDs on differentially expressed genes and CVD annotated genes revealed 4,885 differentially expressed genes (DEGs) and regulation of 41 genes known for HF and 23 genes related to other CVDs, with 15 DEGs as significantly expressed including four genes already known (FLNA, CST3, LGALS3, and HBA1) for HF and CVDs with the enrichment of many pathways. Furthermore, gender and ethnic group specific analysis showed shared and unique genes between the genders, and among different races. Broadening the scope of the results in clinical settings, we have linked the CVD genes with ICD codes.ConclusionsMany pathways were found to be enriched, and gender-specific analysis showed shared and unique genes between the genders. Additional testing of these genes may lead to the development of new clinical tools to improve diagnosis and prognosis of CVD patients.

Screening for Heart Failure in Diabetes: A Way to Reduce Its Prevalence? A Proof of Concept of a Risk Assessment Tool

Background: Heart failure (HF) is underdiagnosed among patients with diabetes. Awareness is required to improve its management and to reduce its impact. Objectives: To suggest a risk assessment tool that could facilitate the early diagnosis of HF and even reduce its incidence by facilitating individualised management plans. Methods: Assess current medical literature, searching for parameters that indicate a higher risk of HF among the diabetic population. Results: Twenty-four parameters were found that could be the potential basis for a risk stratification tool. Conclusion: The concept of a risk stratification tool is presented. Work on validating will be required. It has the potential to affect the future management of patients with diabetes and to reduce the incidence and prevalence of HF in this population.

Metabolomics of the tryptophan–kynurenine degradation pathway and risk of atrial fibrillation and heart failure: potential modification effect of Mediterranean diet

The tryptophan-kynurenine pathway is linked to inflammation. We hypothesize that metabolites implicated in this pathway may be associated with the risk of heart failure (HF) or atrial fibrillation (AF) in a population at high risk of cardiovascular disease. We aimed to prospectively analyze the associations of kynurenine-related metabolites with the risk of HF and AF and to analyze a potential effect modification by the randomized interventions of the PREDIMED (Prevención con Dieta Mediterránea) trial with Mediterranean diet (MedDiet). Two case-control studies nested within the PREDIMED trial were designed. We selected 324 incident HF cases and 502 incident AF cases individually matched with ≤3 controls. Conditional logistic regression models were fitted. Interactions with the intervention were tested for each of the baseline plasma metabolites measured by LC-tandem MS. Higher baseline kynurenine:tryptophan ratio (OR for 1 SD: 1.20; 95% CI: 1.01, 1.43) and higher levels of kynurenic acid (OR: 1.19; 95% CI: 1.01, 1.40) were associated with HF. Quinolinic acid was associated with AF (OR: 1.15; 95% CI: 1.01, 1.32) and HF (OR: 1.25; 95% CI: 1.04, 1.49). The MedDiet intervention modified the positive associations of kynurenine (Pinteraction=0.006), kynurenic acid (Pinteraction=0.008), and quinolinic acid (Pinteraction=0.033) with HF and the association between kynurenic acid and AF (Pinteraction =0.02). We found that tryptophan-kynurenine pathway metabolites were prospectively associated with higher HF risk and to a lesser extent with AF risk. Moreover, an effect modification by MedDiet was observed for the association between plasma baseline kynurenine-related metabolites and the risk of HF, showing that the positive association of increased levels of these metabolites and HF was restricted to the control group.

Comparison between Emergency Severity Index plus Capnometer and Emergency Severity Index in the dyspneic patients with Chronic Heart Failure

Background: The Emergency Severity Index (ESI) may not recognize high-risk patients with Heart Failure efficiently.Aim: The goal of this work was to compare the diagnostic validity and mistriage rates of the ESI plus the Capnometer (Capno) and ESI among dyspneic patients with heart failure (HF).Methods: This study was a quasi-experimental group (random assignment) conducted from April 2019 to February 2020. Patients randomly assigned to the ESI+Capno or ESI groups. Triage levels, resources used, disposition and door to ECG and physician visit were compared among patients admitted to the Cardiac Care Unit (CCU), the Cardiac Unit (CU), or discharged from the ED. Interobserver agreement (Kappa) was used to assess reliability of the ESI.Results: Sixty-five HF patients were assigned to the ESI+Capno (n=36) and ESI (n=29) groups. The under-triage rates were 0% and 10%, the over-triage rates were 10% and 31% in the ESI+Capno and ESI groups, respectively. Sensitivity, specificity, accuracy to recognize high-risk HF patients were 100%, 60%, 90% and 62.5%, 42.86%, 48.36% for ESI+Capno and ESI groups, respectively.Implication for Practice: Addition of Capnometer to the ESI increases validity of triage decisions to recognize high-risk HF patients compared to ESI alone. It is recommended that decision to triage HF patients be made after an End-tidal Co2 is considered into decision-making process.

Early and short-term intensive management after discharge for patients hospitalized with acute heart failure: a randomized study (ECAD-HF).

Hospitalization for acute heart failure (HF) is followed by a vulnerable time with increased risk of readmission or death, thus requiring particular attention after discharge. In this study, we examined the impact of intensive, early follow-up among patients at high readmission risk at discharge after treatment for acute HF. Hospitalized acute HF patients were included with at least one of the following: previous acute HF < 6 months, systolic blood pressure ≤ 110 mmHg, creatininaemia ≥ 180 µmol/L, or B-type natriuretic peptide ≥ 350 pg/mL or N-terminal pro B-type natriuretic peptide ≥ 2200 pg/mL. Patients were randomized to either optimized care and education with serial consultations with HF specialist and dietician during the first 2-3 weeks, or to standard post-discharge care according to guidelines. The primary endpoint was all-cause death or first unplanned hospitalization during 6-month follow-up. Among 482 randomized patients (median age 77 and median left ventricular ejection fraction 35%), 224 were hospitalized or died. In the intensive group, loop diuretics (46%), beta-blockers (49%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (39%) and mineralocorticoid receptor antagonists (47%) were titrated. No difference was observed between groups for the primary endpoint (hazard ratio 0.97; 95% confidence interval 0.74-1.26), nor for mortality at 6 or 12 months or unplanned HF rehospitalization. Additionally, no difference between groups according to age, previous HF and left ventricular ejection fraction was found. In high-risk HF, intensive follow-up early post-discharge did not improve outcomes. This vulnerable post-discharge time requires further studies to clarify useful transitional care services.

Intersection Between Diabetes and Heart Failure: Is SGLT2i the "One Stone for Two Birds" Approach?

Purpose of ReviewDiabetes mellitus (DM) is a major comorbidity of heart failure (HF). Comparing the similarities and differences in disease characteristics and treatment between the HF patients with and without DM, this review was to investigate whether and how the novel class of sodium-glucose transport protein 2 inhibitors (SGLT2i) would benefit both populations.Recent FindingsDespite the obviously different clinical profiles, patients of HF with reduced ejection fraction (HFrEF) should be treated the same with guideline directed medical therapy, irrespective of DM status. Upon the mounting evidence that supported its use in diabetic patients at high risk of HF, recent large clinical trials demonstrated that SGLT2i could further reduce HF hospitalization or cardiovascular mortality and improve quality of life in diabetic and non-diabetic HFrEF patients who were optimally managed.SummarySGLT2i expands the foundation of HFrEF therapy. Whether it is equally effective in HF with preserved ejection fraction awaits more evidence.

Prognosis of diabetes mellitus and timing of heart failure in patients with acute myocardial infarction. An analysis of a French nationwide hospital database

Abstract Background Diabetes mellitus (DM) is a factor of increased mortality in patients with acute myocardial infarction (AMI). DM is also associated with a higher risk of heart failure (HF) in patients with coronary artery disease as in the general population. The aim of the present study was to assess the incidence of HF developing at the acute stage of MI and of HF occurring in the year following hospital discharge, according to presence of DM. We also assessed the association between DM, HF and long-term mortality in this AMI population. Methods We used the French administrative hospital-discharge database, including all patients without history of HF admitted for AMI between 2010 and 2019 (n=797,212, mean age 69 years, 66% male). Among them, 520,258 patients (65%) had ST-segment elevation myocardial infarction (STEMI), 276,954 (35%) had non-STEMI, 192,456 patients (24%) had a history of DM. Occurrence of HF during the initial hospital stay was analysed in the whole population. In patients without HF during the index hospitalisation, discharged and alive at day 8 (n=535,813), we collected all hospitalisations for HF occurring during the year after discharge and analysed subsequent long-term mortality in those alive at one year (n=270,534) (length of follow-up 2.0±2.5 years, median 0.9, IQR 0.1–3.5). Results Overall, DM patients were older than non-DM patients (71±12 vs 67±15 years) and had more frequent comorbidities. At the acute stage, DM was associated with a higher risk of HF (28.7% vs 20.5% adjusted OR 1.40, 1.38–1.42, p&amp;lt;0.0001). In patients without HF at the acute stage and discharged alive at day 8, DM was associated with a higher risk of being hospitalised with HF in the first year (5.6% vs 2.8%, adjusted HR 1.52, 1.49–1.56, p&amp;lt;0.0001). In patients alive at one year, rates of all-cause death per year during subsequent follow-up were 2.2% in those without DM or HF during the first year (reference), 3.4% in those with DM and no HF during the first year (adjusted HR 1.22, 1.18–1.25, p&amp;lt;0.0001), 7.7% in those without DM and with HF during the first year (adjusted HR 1.92, 1.83–2.02, p&amp;lt;0.0001) and 8.9% in those with DM hospitalised with HF during the first year (adjusted HR 2.23, 2.09–2.37, p&amp;lt;0.0001) (see figure). Conclusion After AMI, patients with diabetes are at increased risk of heart failure both at the acute stage and in the year following myocardial infarction, compared with non-diabetic patients. Non-fatal HF developing in the year following discharge is associated with noticeably higher subsequent mortality, and the combination of DM and HF is particularly at risk. Improved management is needed in diabetic patients following an AMI to avoid development of heart failure and its longer-term consequences. Funding Acknowledgement Type of funding sources: None.

Death of a child and the risk of heart failure: a population-based cohort study from Denmark and Sweden

Abstract Background Increasing evidence suggests that the death of a child is associated with increased risks of ischemic heart diseases and atrial fibrillation and the association is in part attributable to stress-related mechanisms. However, knowledge regarding the risk of heart failure (HF) after the death of a child is very limited. Purpose To study the association between the death of a child and the parents' risk of HF. Methods We conducted a population-based cohort study involving parents of live-born children recorded in the Danish and Swedish Medical Birth Registers during 1973–2016 and 1973–2014, respectively (n=6,717,531). We retrieved information on child death, HF diagnosis and parents' sociodemographic characteristics from several nationwide registries. We performed Poisson regression models to estimate incidence rate ratio (IRR) and 95% confidence intervals (CI) for HF. Results A total of 129,829 (1.9%) parents lost at least one child during the follow-up. Bereaved parents had a 35% higher risk of HF than non-bereaved parents [IRR (95% CI): 1.35 (1.29–1.41)]. The association was present not only if the child died due to cardiovascular or other natural causes [IRR (95% CI): 1.48 (1.25–1.75) and 1.35 (1.27–1.44), respectively], but also in case of unnatural deaths [IRR (95% CI): 1.32 (1.24–1.42)]. There was a trend toward a U-shaped association according to the deceased child's age at loss and the risk of HF. Bereaved parents who lost their only child or had three or more remaining live children at the time of loss had higher HF risk than those with one or two live children at the time of loss. We found no clear evidence for a difference in the association of interest over time. Conclusions The death of a child was associated with an increased risk of HF. The finding that not only cardiovascular and other natural deaths, but also unnatural deaths were associated with HF suggests that stress-related mechanisms may contribute to the development of HF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Council for Working Life and Social Research and Karolinska Institutet's Research Foundation

Mortality and heart failure in patients with severe tricuspid regurgitation. Risk stratification based on TR severity by CMR

Abstract Background Tricuspid regurgitation (TR) is related to poor prognosis independently of the etiology. A new scale classification has been proposed to better characterize the grading of more than severe TR. Massive and torrential TR seem to have worse prognosis based on echocardiographic studies. Purpose To stratify patients' risk based on TR severity by CMR Methods Consecutive patients in stable clinical condition evaluated in the Heart Valve Clinic with significant TR (severe, massive or torrential TR) with a contemporaneous echo and CMR were included. TR severity was evaluated by vena contracta (VC) and ERO method, using EPIQ system (Phillip Medical system Andover, Massachusets) and by TR regurgitant fraction (TRF) using a 1.5 Tesla CMR Philips scanner. A combined endpoint of hospital admission due to right heart failure and cardiovascular mortality was defined. Results 75 patients were included in this study (age 75±8 years, 75% female, 91% functional TR). According to echocardiography 75% were severe, 15% were massive and 10% were torrential TR. Patients with massive and torrential TR showed higher RV end-diastolic volume and lower RVEF. A TRF &amp;gt;50% held the best accuracy to define massive / torrential TR. During a median follow-up of 3 years (IQR: 1.4 – 3.9 years), 39% of the patients (n=29) experienced the combined endpoint. After adjusting for age and LVEF in a multivariate Cox proportional model, TRF was independently associated with cardiovascular mortality and heart failure (hazard ratio per 1%=1.05, [1.02–1.08], p&amp;lt;0.001). Patients were stratified in 3 groups according to TR severity. Patients with TRF ≤40% showed the lowest incidence of events and those with TRF ≥50% experienced the worse prognosis (log rank=0.001, figure) Conclusion Patients with massive/torrential TR are populations at higher risk of heart failure and mortality. Risk stratification strategies may identify the patients who benefit the most of intensive therapeutic treatments and intervention on the tricuspid valve. New classification scheme should be included in CMR grading scales. Funding Acknowledgement Type of funding sources: None. Kaplan Meier curve. Risk stratification

Severe tricuspid regurgitation worsens prognosis outcome after edge-to-edge mitral valve repair

Abstract Introduction MitraClip has been well established for treatment of severe mitral regurgitation (MR). MR and tricuspid regurgitation (TR) often occur simultaneously and symptoms of biventricular heart failure can overlap. While it has been shown that TR grade regression can be achieved through repair of MR1, presence of moderate to severe TR can increase all-cause mortality after MitraClip2. There is currently no consensus on the management of combined MR and TR. We evaluated the impact of TR on echocardiographic and functional outcome after MitraClip. Methods 370 patients underwent MitraClip for moderate to severe MR at our center from 2010 to 2018. Patients were dichotomized into low grade TR (grade &amp;lt;I - I (trace - mild)) and high grade TR (grade III - V (severe - torrential)). Moderate TR (grade II) was excluded. After MitraClip for MR, patients were followed up for 12 months and their echocardiographic and functional outcome was evaluated. Use of diuretic drugs throughout 12 month follow-up was registered. Results Low grade TR (&amp;lt;I - I) occurred in 225 patients (67.0%), high grade TR (III - V) was present in 111 patients (33.0%). 34 patients (9.2%) with moderate TR (II) were excluded. Patients with high grade TR had an increased morbidity (higher age, worse renal function, higher prevalence of atrial fibrillation, higher levels of natriuretic peptides, increased left atrial and right heart diameters, higher TR gradient). These patients also received significantly higher doses of torasemid (33.5±36.7 mg vs. 21.6±20.9 mg, p=0.003) and furosemid (163.4±155.5 mg vs. 75.8±72.3 mg, p=0.01). Average grade of MR at baseline was similar in both groups (2.9±0.46 vs. 2.8±0.5, p=0.66). Procedural success of MR repair was achieved similarly in both groups (96.4% vs. 96.9%, p=0.82) and residual MR grade immediately after device implantation was comparable (p=0.61). However, recurrent MR in the high grade TR group increased during follow up, while MR further decreased in the low grade TR group (3 months: 1.24±0.7 vs. 1.16±0.7, p=0.5; 12 months: 1.46±0.93 vs. 1.12±0.61, p=0.04). Accordingly, use of diuretic drugs after 12 months rose in the high grade TR group while it did not change or even decreased in the low grade TR group (torasemid: 40.2±48.4 mg vs. 24.1±30.0 mg, p=0.04; furosemid: 197.5±251.0 mg vs. 67.1±81.8 mg, p=0.22). Kaplan-Meier-Analysis showed significantly higher mortality (24.9 vs. 14.1%, p=0.01), higher risk for heart failure induced rehospitalisation (25,4 vs. 12,5%, p=0.005) and for major adverse cardiac and cerebrovascular events (MACCE: 42.3 vs. 29.1%, p=0.008) in the high grade TR group after 12 months. Conclusion MitraClip patients for MR with concomitant high grade TR (≥ III) had an increased morbidity at baseline compared to low grade TR patients. By MitraClip comparable reduction of MR was achieved. However, during 12 month follow-up in the high grade TR group recurrent MR occurred more often while use of diuretics increased. Funding Acknowledgement Type of funding sources: None.

Real-world clinical outcomes and anticoagulant therapy in elderly non-valvular atrial fibrillation patients with heart failure: sub-analysis of the ANAFIE Registry

Abstract Background Atrial fibrillation (AF) and heart failure (HF) are bidirectionally correlated; the more severe the NYHA classification, the higher the incidence rate of atrial fibrillation, and vice versa. HF is included in the items of CHA2DS2-VASc score used to calculate stroke risk in patients with AF, and is itself a risk factor for thromboembolism in such patients. Anticoagulant management in AF patients with HF is thus a key concern that remains to be sufficiently examined, especially in elderly patients aged ≥75 y. Purpose The All Nippon Atrial Fibrillation In the Elderly (ANAFIE) Registry enrolled more than 30,000 elderly (≥75 y) patients with non-valvular AF (NVAF), aiming to produce real-world data on their clinical status and prognosis. This sub-analysis of the ANAFIE Registry assessed the 2-year outcomes and status of anticoagulant treatment in elderly NVAF patients with HF. Methods A total of 32,275 patients from the ANAFIE Registry were divided into two groups according to whether they had HF (HF group and reference group). The incidence rates and adjusted hazard ratios (HR) of clinical outcomes were determined using Kaplan-Meier analysis and the Cox proportional-hazards model, respectively. Results A total of 20,159 (62.5%) patients were included in the reference group, and 12,116 (37.5%) in the HF group. Compared with the reference group, the HF group had higher mean age (82.4 vs 80.9 y), female ratio (46.6% vs 40.4%), non-paroxysmal AF (69.8% vs 50.8%), and had lower mean CrCL (43.3 vs 51.6 mL/min). In the HF group, the rate control drugs were frequently used (50.1% vs 35.8%), and the rhythm control drugs were less used (14.2% vs 22.7%) than in the reference group. More patients in the HF group were using anticoagulants (93.9% vs 91.6%; warfarin (WF), 29.6% vs 23.0%; direct oral anticoagulants (DOAC), 64.2% vs 68.5%) than those in the reference group. The HF group had a numerically higher incidence of stroke or systemic embolic events (SEE) (3.28% vs 2.84%, HR 0.96, p=0.558) and major bleeding (2.35% vs 1.79%, HR 1.14, p=0.130) than the reference group, but the differences were not statistically significant. The HF group had a significantly higher incidence rate of HF requiring hospitalization (12.99% vs 4.59%, HR 1.94, p&amp;lt;0.001) and all-cause mortality (9.83% vs 5.21%, HR 1.32, p&amp;lt;0.001). In the HF group, patients receiving DOAC had significantly lower incidence rates for major bleeding, HF requiring hospitalization, and all-cause mortality than those receiving WF, while there was no difference for stroke/SEE between both groups. Conclusions Elderly NVAF patients with HF had higher risk of HF requiring hospitalization and mortality than those without. Differences were seen in the incidence rates of major bleeding, HF requiring hospitalization, and all-cause mortality between patients on DOAC and those on WF. This study will explore relevant factors affecting clinical outcomes in elderly NVAF patients with HF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Co., Ltd.

Clinical Implications of the Amyloidogenic V122I Transthyretin Variant in the General Population

BackgroundThe V122I variant in transthyretin (TTR) is the most common amyloidogenic mutation worldwide. The aim of this study is to describe the cardiac phenotype and risk for adverse cardiovascular outcomes of young V122I TTR carriers in the general population. Methods and ResultsTTR genotypes were extracted from whole-exome sequence data in participants of the Dallas Heart Study. Participants with African ancestry, available V122I TTR genotypes (N = 1818) and either cardiac magnetic resonance imaging (n = 1364) or long-term follow-up (n = 1532) were included. The prevalence of V122I TTR carriers (45 ± 10 years) was 3.2% (n/N = 59/1818). The V122I TTR carriers had higher baseline left ventricular wall thickness (8.52 ± 1.82 vs 8.21 ± 1.62 mm, adjusted P = .038) than noncarriers, but no differences in other cardiac magnetic resonance imaging measures (P > .05 for all). Although carrier status was not associated with amino terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline (P = .79), V122I TTR carriers had a greater increase in NT-proBNP on follow-up than noncarriers (median 28.5 pg/mL, interquartile range 11.4–104.1 pg/mL vs median 15.9 pg/mL, interquartile range 0.0–43.0 pg/mL, adjusted P = .018). V122I TTR carriers were at a higher adjusted risk of heart failure (hazard ratio 3.82, 95% confidence interval 1.80–8.13, P < .001), cardiovascular death (hazard ratio 2.65, 95% confidence interval 1.14–6.15, P = .023), and all-cause mortality (hazard ratio 1.95, 95% confidence interval 1.08–3.51, P = .026) in comparison with noncarriers. ConclusionsV122I TTR carrier status was associated with a greater increase in NT-proBNP, slightly greater left ventricular wall thickness, and a higher risk for heart failure, cardiovascular death, and all-cause mortality. These findings suggest the need to develop amyloidosis screening strategies for V122I TTR carriers.

Ankle-brachial index and subsequent risk of incident and recurrent cardiovascular events in older adults: The Atherosclerosis Risk in Communities (ARIC) study

Background and aimsThe ankle-brachial index (ABI) is a diagnostic test for screening and detecting peripheral artery disease (PAD), as well as a risk enhancer in the AHA/ACC guidelines on the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, our understanding of the association between ABI and cardiovascular risk in contemporary older populations is limited. Additionally, the prognostic value of ABI among individuals with prior ASCVD is not well understood. MethodsAmong 5,003 older adults at ARIC visit 5 (2011–2013) (4,160 without prior ASCVD [median age 74 years, 38% male], and 843 with ASCVD [median age 76 years, 65% male]), we quantified the association between ABI and the risk of heart failure (HF), and composite coronary heart disease and stroke (CHD/stroke) using multivariable Cox regression models. ResultsOver a median follow-up of 5.5 years, we observed 400 CHD/stroke events and 338 HF cases (242 and 199 cases in those without prior ASCVD, respectively). In participants without a history of ASCVD, a low ABI ≤0.9 (relative to ABI 1.11–1.20) was associated with both CHD/stroke and HF (adjusted hazard ratios 2.40 [95% CI: 1.55–3.71] and 2.23 [1.40–3.56], respectively). In those with prior ASCVD, low ABI was not significantly associated with CHD/stroke, but was with HF (7.12 [2.47–20.50]). The ABI categories of 0.9–1.2 and > 1.3 were also independently associated with increased HF risk. Beyond traditional risk factors, ABI significantly improved the risk discrimination of CHD/stroke in those without ASCVD and HF, regardless of baseline ASCVD. ConclusionsLow ABI was associated with CHD/stroke in those without prior ASCVD and higher risk of HF regardless of baseline ASCVD status. These results support ABI as a risk enhancer for guiding primary cardiovascular prevention and suggest its potential value in HF risk assessment for older adults.

Prevalence and Prognostic Implications of Diabetes With Cardiomyopathy in Community-Dwelling Adults

BackgroundDiabetes is associated with abnormalities in cardiac remodeling and high risk of heart failure (HF). ObjectivesThe purpose of this study was to evaluate the prevalence and prognostic implications of diabetes with cardiomyopathy (DbCM) among community-dwelling individuals. MethodsAdults without prevalent cardiovascular disease or HF were pooled from 3 cohort studies (ARIC [Atherosclerosis Risk In Communities], CHS [Cardiovascular Health Study], CRIC [Chronic Renal Insufficiency Cohort]). Among participants with diabetes, DbCM was defined using different definitions: 1) least restrictive: ≥1 echocardiographic abnormality (left atrial enlargement, left ventricle hypertrophy, diastolic dysfunction); 2) intermediate restrictive: ≥2 echocardiographic abnormalities; and 3) most restrictive: elevated N-terminal pro–B-type natriuretic peptide levels (>125 in normal/overweight or >100 pg/mL in obese) plus ≥2 echocardiographic abnormalities. Adjusted Fine-Gray models were used to evaluate the risk of HF. ResultsAmong individuals with diabetes (2,900 of 10,208 included), the prevalence of DbCM ranged from 67.0% to 11.7% in the least and most restrictive criteria, respectively. Higher fasting glucose, body mass index, and age as well as worse kidney function were associated with higher risk of DbCM. The 5-year incidence of HF among participants with DbCM ranged from 8.4%-12.8% in the least and most restrictive definitions, respectively. Compared with euglycemia, DbCM was significantly associated with higher risk of incident HF with the highest risk observed for the most restrictive definition of DbCM (HR: 2.55 [95% CI: 1.69-3.86]; least restrictive criteria HR: 1.99 [95% CI: 1.50-2.65]). A similar pattern of results was observed across cohort studies, across sex and race subgroups, and among participants without hypertension or obesity. ConclusionsRegardless of the criteria used to define cardiomyopathy, DbCM identifies a high-risk subgroup for developing HF.

VCAM1 expression in the myocardium is associated with the risk of heart failure and immune cell infiltration in myocardium

Ischemic heart disease (IHD) and dilated cardiomyopathy (DCM) are the two most common etiologies of heart failure (HF). Both forms share common characteristics including ventricle dilation in the final stage. Immune mechanisms in HF are increasingly highlighted and have been implicated in the pathogeneses of IHD and DCM. A better understanding of adhesion molecule expression and correlated immune cell infiltration could enhance disease detection and improve therapeutic targets. This study was performed to explore the common mechanisms underlying IHD and DCM. After searching the Gene Expression Omnibus database, we selected the GSE42955, GSE76701, GSE5406, GSE133054 and GSE57338 datasets for different expressed gene (DEGs) selection and new cohort establishment. We use xcell to calculate immune infiltration degree, ssGSEA and GSEA to calculate the pathway and biological enrichment score, consensus cluster to identify the m6A modification pattern, and LASSO regression to make risk predicting model and use new combined cohort to validate the results. The screening stage revealed that vascular cell adhesion molecule 1 (VCAM1) play pivotal roles in regulating DEGs. Subsequent analyses revealed that VCAM1 was differentially expressed in the myocardium and involved in regulating immune cell infiltration. We also found that dysregulated VCAM1 expression was associated with a higher risk of HF by constructing a clinical risk-predicting model. Besides, we also find a connection among the m6A RNA modification ,expression of VCAM1 and immune regulation. Those connection can be linked by the Wnt pathway enrichment alternation. Collectively, our results suggest that VCAM-1 have the potential to be used as a biomarker or therapy target for HF and the m6A modification pattern is associated with the VCAM1 expression and immune regulation.

Identifying risk patterns in older adults with atrial fibrillation by hierarchical cluster analysis: A retrospective approach based on the risk probability for clinical events.

Older adults with atrial fibrillation (AF) have highly diverse risk levels for mortality, heart failure (HF), thromboembolism (TE), and major bleeding (MB), thus an integrated risk-pattern algorithm is warranted. We analyzed 573 AF patients aged≥75years from our single-center cohort (Shinken Database 2010-2018). The 3-year risk scores (risk probability) for mortality (M-score), HF (HF-score), TE (TE-score), and MB (MB-score) were estimated for each patient by logistic regression analysis. Using the four risk scores, cluster analysis was performed with Ward's linkage hierarchical algorithm. Three clusters were identified: Clusters 1 (n=429, 74%), 2 (n=24, 5%), and 3 (n=120, 21%). The clusters were characterized as standard risk (Cluster 1), high TE- and MB-risk (Cluster 2), and high M- and HF-risk (Cluster 3). Oral anticoagulants were prescribed for over 80% of the patients in each cluster. Catheter ablation for AF was performed only in Cluster 1 (8.9%). Compared with Cluster 1, Cluster 2 was more closely associated with males, asymptomatic AF, history of cerebral infarction or transient ischemic attack, history of intracranial hemorrhage, high HAS-BLED score (≥3), and low body mass index (<18.0kg/m2). Cluster 3 was more closely associated with old age, heart failure, and low estimated creatinine clearance (<30mL/min). The cluster analysis identified those at a high risk for all-cause death and HF or a high risk for TE and MB and could support decision making in older adults with AF.