Higher Rates Of Cardiovascular Death Research Articles

EFFECT OF DAPAGLIFLOZIN ON CARDIOVASCULAR OUTCOMES IN HFREF PATIENTS: IMPACT OF DIABETES MELLITUS TYPE 2 STATUS

Dapagliflozin has shown promise in the treatment of heart failure with reduced ejection fraction (HFrEF), but its effects in patients with and without diabetes remain unclear. Objective: This study aimed to assess the effects of dapagliflozin in HFrEF patients, both with and without diabetes. Methods: From January to July 2023, a six-month case-control study was conducted in the cardiology department of a Tertiary Care Hospital in Peshawar, Pakistan. All patients received an additional dose of dapagliflozin (10 mg) alongside their usual treatment plans. The primary outcome was a composite of heart failure exacerbation or cardiovascular death. Data analysis was performed using SPSS version 22. Results: Patients with diabetes mellitus type 2 (DMT2) exhibited a higher rate of cardiovascular death (22%) and hospitalization for heart failure (14.4%) compared to those without diabetes. The hospitalisation rate for heart failure was also higher in the DMT2 group (12.21%) than in the non-diabetic group (8.6%). Over the trial period, cardiovascular death occurred in 12.44% of patients with DMT2 compared to 7.30% in those without DMT2. Patients with diabetes experienced a significantly higher number of first and recurrent hospitalizations for heart failure and cardiovascular death compared to those without diabetes (32.45% vs. 19.20%, p=0.021). Conclusion: Dapagliflozin therapy in HFrEF patients demonstrated varying effects between those with and without diabetes. The study underscores the importance of personalised management strategies considering comorbid medical conditions. Despite dapagliflozin treatment, patients with both heart failure and diabetes continued to experience cardiovascular complications, highlighting the need for individualised treatment plans that account for a patient's complete medical profile.

GDF-15 is associated with worse ischemic and bleeding outcomes in the acute phase and during follow-up in patients with acute coronary syndrome: insights from the TRACER trial

Abstract Introduction Growth differentiating factor-15 (GDF-15) is a stress responsive cytokine that increases with age. GDF-15 has been associated with mortality, myocardial infarction (MI), heart failure and bleeding in patients with acute coronary syndrome (ACS) and stable coronary artery disease. Purpose The aim of this study was to evaluate the levels of GDF-15 and their associations with risk of cardiovascular events and bleeding in patients with ACS in the acute setting and after one month. Methods Venous blood samples were obtained at the index event in 6800 patients and again after one month in 5313 patients with non-ST-segment elevation ACS (NSTE-ACS) randomized to vorapaxar vs placebo on top of dual antiplatelet treatment in the TRACER study. The GDF-15 level was centrally measured by the ROCHE ELISA assay in stored plasma aliquots. The main cardiovascular (CV) endpoint in this substudy was the composite of CV death, MI and ischemic stroke and main safety endpoint was non-procedural major or minor bleeding according to Thrombolysis in Myocardial Infarction (TIMI) classification. Cox-regression models were used to estimate unadjusted and adjusted associations between log-transformed GDF-15 and outcomes. Adjustments were made for study treatment and well-established clinical CV risk factors. All corresponding models but without the biomarker was fitted and a concordance index (c-index) calculated. A likelihood-ratio test was used to test for differences between the two c-indices. Results Median concentration of GDF-15 at baseline and after one month were 1226 ng/L and 1181 ng/L, respectively. The correlation between GDF-15 concentrations at baseline and after one month was r=0.80 (Figure 1). The levels of GDF-15 were independently associated with older age, presence of diabetes mellitus, renal dysfunction and smoking. GDF-15 levels both at baseline and after one month were independently associated with higher rate of CV death, MI and ischemic stroke and with non-procedural TIMI major or minor bleeding (Figure 2). At baseline the addition of GDF-15 levels to the multivariable model for subsequent CV death, MI or ischemic stroke increased the c-index from 0.656 to 0.668 (P<0.001), and for bleeding from 0.715 to 0.719 (P=0.037). At one month adding GDF-15 levels increased the c-index from 0.711 to 0.722 (P<0.001) for CV death, MI or ischemic stroke and from 0.735 to 0.783 (P<0.001) for bleeding. Conclusions In patients with NSTE-ACS levels of GDF-15 are independently associated with CV death, MI or ischemic stroke and non-procedural bleeding and contribute prognostic information both at the index event and after one month. Levels of GDF-15 remain stable over time and provide similar prognostic information in the acute and follow-up setting.Fig.1 Correlation GDF-15 baseline and 1mFig.2 Non-linear cox-regression

Thrombotic profile of East Asian and Western ACS patients and relationship to cardiovascular outcomes

Abstract Background East Asian patients compared to Westerners, have a lower risk of ischemic heart disease and a higher risk of bleeding with antithrombotic medications. The underlying mechanisms are incompletely understood. Genetic differences may underlie lower coagulant and inflammation levels in EA compared to W populations. Objectives We sought to compare thrombotic profiles of East Asian and Western patients with myocardial infarction (MI) and relate these to cardiovascular outcomes. Methods In a 2 centre, prospective, observational study in the U.K. and Korea, blood samples from patients (n=515) with ST- or non-ST-elevation MI (STEMI and NSTEMI) were assessed using the Global Thrombosis Test, measuring thrombotic occlusion (OT) and endogenous fibrinolysis (LT) times. In STEMI patients, blood samples were taken immediately upon arrival, whilst in NSTEMI patients, blood samples were taken after DAPT loading. Patients were followed for 1 year for major adverse cardiovascular events and major bleeding. Results Major adverse cardiovascular events occurred significantly more frequently in Western than in East Asian patients (6.27% vs. 1.92%, p=0.014), driven by a higher rate of cardiovascular death (3.53% vs. 0.38%, p=0.01), with minimal major bleeding events (0.39% vs. 0.38%, p=1.0). East Asian patients showed reduced platelet reactivity (longer OT) compared to Western patients (646s [470-818] vs. 436s [320-580], p<0.001), with similar LT. In STEMI, OT (588s [440-759] vs. 361s [274-462], p<0.001) and LT (1854s [1389-2729] vs. 1338s [1104-1788], p<0.001) were longer in East Asian patients than Westerners. In NSTEMI, OT was longer (OT 734s [541-866] vs. 580s [474-712], p<0.001) and LT shorter (1519s [1058-2508] vs. 1898s [1614-2806], p=0.004) in East Asian than Western patients. While OT was unrelated, LT was a strong independent predictor of MACE after adjustment for risk factors (HR 3.70, 95% CI 1.43-9.57, p=0.007), predominantly in Western patients, and more so in STEMI than NSTEMI. Conclusion East Asian patients exhibit different global thrombotic profiles to Westerners, associated with a lower rate of cardiovascular events. The lower platelet reactivity in East Asian STEMI patients, even before antiplatelet therapy, may explain contribute to the lower risk of subsequent adverse ischaemic events.

GARFIELD-AF: risk profiles, treatment patterns and 2-year outcomes in patients with atrial fibrillation in Germany, Austria and Switzerland (DACH) compared to 32 countries in other regions worldwide.

The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is a worldwide non-interventional study of stroke prevention in patients with non-valvular AF. 52,080 patients with newly diagnosed AF were prospectively enrolled from 2010 to 2016. 4121 (7.9%) of these patients were recruited in DACH [Germany (n = 3567), Austria (n = 465) and Switzerland (n = 89) combined], and 47,959 patients were from 32 countries in other regions worldwide (ORW). Hypertension was most prevalent in DACH and ORW (85.3% and 75.6%, respectively). Diabetes, hypercholesterolaemia, carotid occlusive disease and vascular disease were more prevalent in DACH patients vs ORW (27.6%, 49.4%, 5.8% and 29.0% vs 21.7%, 40.9%, 2.8% and 24.5%). The use of non-vitamin K antagonist oral anticoagulants (NOACs) increased more in DACH over time. Management of vitamin K antagonists was suboptimal in DACH and ORW (time in therapeutic range of INR ≥ 65% in 44.6% and 44.4% of patients or ≥ 70% in 36.9% and 36.0% of patients, respectively). Adjusted rates of cardiovascular mortality and MI/ACS were higher in DACH while non-haemorrhagic stroke/systemic embolism was lower after 2-year follow-up. Similarities and dissimilarities in AF management and clinical outcomes are seen in DACH and ORW. The increased use of NOAC was associated with a mismatch of risk-adapted anticoagulation (over-and-undertreatment) in DACH. Suboptimal control of INR requires educational activities in both regional groups. Higher rates of cardiovascular death in DACH may reflect the higher risk profile of these patients and lower rates of non-haemorrhagic stroke could be associated with increased NOAC use.

Association of Eligibility for a Sodium-Glucose Cotransporter 2 Inhibitor and Cardiovascular Events in Patients With Atrial Fibrillation.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce heart failure (HF) in a broad range of populations, but they have not been studied specifically in patients with atrial fibrillation (AF). We aimed to examine the association between SGLT2i eligibility and cardiovascular events in patients with AF to evaluate the potential utility of SGLT2is for AF management. We pooled data from 2 randomized controlled trials (RCTs) of patients with AF (RE-LY and ACTIVE-W). Among patients assigned to anticoagulation arms, those meeting the enrollment criteria from at least 1 of the phase 3 SGLT2i RCTs were classified as "SGLT2i eligible" and the remainder as "SGLT2i ineligible." The primary outcome was the composite of HF hospitalization or cardiovascular death. A total of 21,484 patients with AF (mean age: 71.2 ± 8.8, 36.1% women, median CHA2DS2-VASc Score= 3) were included. The proportion of patients with AF eligible for SGLT2i was 41.2%. SGLT2i-eligible patients had higher rates of cardiovascular death or hospitalization for HF (5.8 vs 3.2 per 100 person-years, Plog-rank < 0.001), cardiovascular death (3.9 vs 1.5 per 100 person-years, Plog-rank <0.001), and hospitalization for HF (2.5 vs 1.9 per 100 person-years, Plog-rank < 0.001). The age- and sex-adjusted model showed that SGLT2i-eligible patients were at a higher risk of cardiovascular death and hospitalization for HF (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.79-2.17; P < 0.001), cardiovascular death (HR, 2.75; 95% CI, 2.41-3.13; P < 0.001), and hospitalization for HF (HR, 1.41; 95% CI, 1.23-1.62; P < 0.001) than ineligible patients. Most patients with AF do not currently have indications for SGLT2is but still have substantial risk of cardiovascular events. Future randomized trials should evaluate the efficacy of SGLT2is in patients with AF.

Cardiovascular outcomes in patients with chronic kidney disease and COVID-19: a multi-regional data-linkage study.

BackgroundData describing cardiovascular outcomes in patients with COVID-19 and chronic kidney disease (CKD) are lacking. We compared cardiovascular outcomes of patients with and without COVID-19, stratified by CKD status.MethodsThis retrospective, multi-regional data-linkage study utilised individual patient-level data from two Scottish cohorts. All patients tested for SARS-CoV-2 in Cohort 1 between 01/02/2020 and 31/03/2021, and in Cohort 2 between 28/02/2020 and 08/02/2021, were included.ResultsOverall, 86 964 patients were tested for SARS-CoV-2. There were 36 904 patients (61±21 years, 58.1% women, 15.9% CKD, 10.1% COVID-19 positive) in Cohort 1 and 50 060 patients (63±20 years, 62.0% women, 16.4% CKD, 9.1% COVID-19 positive) in Cohort 2. In CKD patients, COVID-19 increased the risk of cardiovascular death by more than two-fold within 30 days (cause-specific hazard ratio [csHR] meta-estimate 2.34, 95% confidence interval [CI] 1.83–2.99), and by 57% at the end of follow-up (csHR meta-estimate 1.57, 95% CI 1.31–1.89). Similarly, the risk of all-cause death in COVID-19 positive versus negative CKD patients was greatest within 30 days (HR 4.53, 95% CI 3.97–5.16). Compared to patients without CKD, those with CKD had a higher risk of testing positive (11.5% versus 9.3%). Following a positive test, CKD patients had higher rates of cardiovascular death (11.1% versus 2.7%), cardiovascular complications, and cardiovascular hospitalisations (7.1% versus 3.3%) than those without CKD.ConclusionsCOVID-19 increases the risk of cardiovascular and all-cause death in CKD patients, especially in the short-term. CKD patients with COVID-19 are also at a disproportionate risk of cardiovascular complications than those without CKD.

Cardiovascular Outcomes associated with Oral Anticoagulants, Antiplatelets and No-Treatment after Atrial Fibrillation Ablation: A Nationwide Cohort Study

Objective: We investigated the long-term cardiovascular outcomes associated with direct oral anticoagulants (DOACs), antiplatelets and No-Treatment compared to warfarin beyond 90-days after atrial fibrillation (AF) catheter ablation. Methods: We identified 12,010 AF patients undergoing first-time ablation in Denmark (2002-2018) and analyzed stroke, serious bleeding, cardiovascular death and the composite of these three endpoints (MACE) by incidence rates (IR) per 1000 person-years and Cox proportional-hazard models. Results: The median age was 62 years (interquartile range [IQR]: 54-68 years); 28.8% were female, 7225 (60.2%) patients were younger than 65-years, and 6927 (57.7%) patients had CHA2DS2-VASc score≥2. Over a total of 65,990 person-years follow-up commencing 90-days after first-time ablation, warfarin, DOACs, antiplatelets and ‘No-treatment’ exposures covered 30,877 (46.8%), 9,452 (14.3%), 6,003 (9.1%) and 19,657 (29.8%) person-years, respectively. There was no difference between DOACs vs warfarin (HR 1.04 [0.77-1.42]95%CI) while antiplatelets (HR 1.50 [1.11-2.05]95%CI) and No-Treatment (HR 1.50 [1.15-1.94]95%CI) were associated with a significantly higher rate of stroke. DOACs (HR 0.70 [0.54-0.92]95%CI), antiplatelets (HR 0.58 [0.41-0.82]95%CI) and No-Treatment (HR 0.52 [0.39-0.69]95%CI) were associated with a significantly lower rate of serious bleeding compared with warfarin. We found no difference between DOACs and warfarin (HR 0.87 [0.61-1.25]95%CI) while Antiplatelets (HR 1.42 [1.04-1.94]95%CI) and No-treatment (HR 2.77 [2.16-3.56]95%CI) were associated with a significantly higher rate of cardiovascular death. We observed no difference with DOACs (HR 0.86 [0.70-1.05]95%CI), antiplatelets (HR 1.04 [0.84-1.27]95%CI) or No-Treatment (HR 1.10 [0.93-1.31]]95%CI) compared to warfarin in multivariable analyses regarding the composite endpoint of MACE. Conclusions: Our study indicates a better bleeding risk profile associated with DOACs than warfarin in patients undergoing AF ablation, but no difference for the endpoints of stroke, cardiovascular death, or the composite endpoint of MACE. Despite the favourable bleeding risk, antiplatelets and No-Treatment compared with warfarin appear hazardous due to a higher rate of stroke and cardiovascular death.

Association between distance to tertiary hospital and cardiovascular outcomes in coronary artery disease patients

Abstract Background The impact of distance from residence to Tertiary Referral Hospital and cardiovascular (CV) outcomes in patients with coronary artery disease (CAD) is unknow. Despite longer travel distances hinder access to healthcare and may worsen CV outcomes, we hypothesize that Mediterranean lifestyle and behaviors in distant rural areas may be associated with a reduced risk of CV death and events. Purpose To investigate the association between travel distance to Tertiary Hospital and mid-term cardiovascular outcomes in a population of CAD patients in Southern Spain. Methods Retrospective study including all patients discharged after percutaneous coronary intervention (PCI) at a high-volume center in Southern Spain during 2018. Those belonging to another healthcare area were excluded. One-way driving distances from residence to hospital were computed using Google Maps Distance Matrix API with R package “gmapsdistance”. Patients were stratified into tertiles according to travel distance (short, STD; intermediate, ITD; and long, LTD). Kaplan-Meier (KM) and Multivariable Cox regression (adjusted for age, sex, atrial fibrillation, cancer history, prior revascularization and clinical presentation) were used to assess the impact of travel distance on CV death and a composite outcome of MACE (Myocardial Infarction, unplanned PCI and CV death). Results Of 1005 patients discharged after PCI during the study period, 966 met the selection criteria. Flowchart and baseline characteristics by distance groups are presented in Figure 1. Median travel distance tertiles were 6.1 (STD), 41.7 (ITD) and 78.4 (LTD). During a median follow-up of 31 (IQR 28–35) months, 50 cardiovascular deaths [STD 27 (8.4%), ITD 13 (4%), LTD 10 (3.1%), p=0.006)] and 63 MACE occurred [STD 45 (13.9%), ITD 37 (11.5%), LTD 26 (8.1%), p=0.060)]. KM curves for the three distance groups are shown in Figure 2. In univariable and multivariable Cox models, longer travel distances were associated with better outcomes, as for every 10 Km increase, there was a 11% and 7% decrease in the hazards of CV death (HR adj: 0.89, CI 0.82–0.98, p=0.029) and of MACE (HR adj: 0.93, CI 0.87–0.99, p=0.025), respectively. Conclusion Travel distance was inversely associated with CV events in a population of CAD patients in Southern Spain. Patients in the first tertile of distance had a higher rate of CV death. Multicenter studies involving other Mediterranean regions are needed to confirm these findings and to look for explanations. Funding Acknowledgement Type of funding sources: None. Flowchart and baseline characteristicsSurvival curves by distance groups

ACE Insertion/Deletion gene polymorphism aassociations in STEMI Patients

Abstract Objective ACE Insertion/deletion (I/D) polymorphism has been reported to be associated with various cardiovascular conditions, however its impact in patients with AHF remains controversial. This study aimed to analyze ACE I/D distribution, rate of acute heart failure (AHF) and survival in ST segment elevation myocardial infarction (STEMI) patients. Methods Genomic DNA from 245 STEMI patients and 87 healthy control subjects were analyzed by single polymerase chain reaction method. Based on the ACE I/D genotype STEMI patients were divided with AHF/no AHF, and then - for preserved/reduced ≤40% left ventricle (LV) ejection fraction (EF) to investigate the frequency of the mutant allele D. Results ACE gene polymorphism analyses revealed that D allele had been found more often in STEMI patients than in controls (84.1 vs. 72.4%). The frequency of II, ID, and DD genotypes in STEMI patients was 27.6%, 52.9% and 19.5% compared to 15.9%, 54.3% and 29.8%, respectively in controls with a significant difference in mutant homozygous genotype. Distribution of I/D ACE gene variants among AHF cases vs no AHF, showed similar frequency of II allele (15.8 vs 13.5%), ID allele (54.9 vs 52.8%) and DD allele (29.3 vs 33.7% respectively). In patients with preserved EF there was not statistical significance among different alleles with and without AHF. However, ACE DD polymorphism has been found in AHF patients with reduced EF significantly more often (50.0 vs 30.5%; p&amp;lt;0.05) in compare to AHF patients with preserved EF. Finally, cardiovascular death among all STEMI patients during 3-year follow up was more frequent in patients with DD allele (17.7% vs 5.7% with II and vs 9.9% with ID allele). Conclusion Presented results confirmed ACE DD polymorphism to be associated with higher rate of cardiovascular death and presence of AHF with reduced LV EF in STEMI patients. Future studies are needed to evaluate importance of ACE DD polymorphism in order to find optimal treatment strategies and to prevent negative outcomes in those patients. Funding Acknowledgement Type of funding sources: None.

Clinical Impact of Intraprocedural Stent Thrombosis During Percutaneous Coronary Intervention in Patients Treated With Potent P2Y12 inhibitors - a VALIDATE-SWEDEHEART Substudy.

BackgroundThe clinical importance of intraprocedural stent thrombosis (IPST) during percutaneous coronary intervention in the contemporary era of potent oral P2Y12 inhibitors is not established. The aim of this study was to assess IPST and its association with clinical outcome in patients with myocardial infarction undergoing percutaneous coronary intervention with contemporary antithrombotic medications.Methods and ResultsThe VALIDATE‐SWEDEHEART study (Bivalirudin Versus Heparin in ST‐Segment and Non–ST‐Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) included 6006 patients with myocardial infarction, treated with potent P2Y12 inhibitors during percutaneous coronary intervention. IPST, defined as a new or worsening thrombus related to a stent deployed during the procedure, was reported by the interventional cardiologist in 55 patients (0.9%) and was significantly associated with ST‐segment elevation myocardial infarction presentation, longer stents, bailout glycoprotein IIb/IIIa inhibitors, and final Thrombolysis in Myocardial Infarction flow <3. The primary composite end point included cardiovascular death, myocardial infarction, out‐of‐laboratory definite stent thrombosis and target vessel revascularization within 30 days. Secondary end points were major bleeding and the individual components of the primary composite end point. Patients with versus without IPST had significantly higher rates of the primary composite end point (20.0% versus 4.4%), including higher rates of cardiovascular death, target vessel revascularization, and definite stent thrombosis, but not myocardial infarction or major bleeding. By multivariable analysis, IPST was independently associated with the primary composite end point (hazard ratio, 3.82; 95% CI, 2.05–7.12; P<0.001).ConclusionsIPST is a rare but dangerous complication during percutaneous coronary intervention, independently associated with poor prognosis, even in the current era of potent antiplatelet agents. Future treatment studies are needed to reduce the rate of IPST and to improve the poor outcome among these patients.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.

Relationship Between the Eosinophil/Monocyte Ratio and Prognosis in Decompensated Heart Failure: A Retrospective Study.

PurposeThe aim of this study was to assess the value of the eosinophil/monocyte ratio (EMR) for predicting the prognosis of decompensated heart failure (HF).Patients and MethodsThis was a retrospective cohort study. We included adults (≥18 years old) diagnosed with decompensated HF for whom EMR data were available. The patients were divided into three groups according to EMR tertiles (T1 [EMR≤0.15], T2 [0.15<EMR≤0.32], and T3 [EMR>0.32]). The primary endpoint was the composite outcome of cardiovascular death or HF rehospitalization.ResultsInitially, the records of 2264 patients with decompensated HF were screened; 1883 of these patients had EMR data and were therefore included in the study. There were 627 patients in the T1 group, 628 in the T2 group, and 628 in the T3 group. The risk of cardiovascular death or HF rehospitalization was significantly different among the three groups (Log rank test, P=0.007). Compared with the T3 group, both the T1 group (hazard ratio [HR]: 1.50, 95% confidence interval [CI]: 1.16–1.94, P=0.002) and the T2 group (HR: 1.34, 95% CI: 1.03–1.74, P=0.030) had significantly higher rates of cardiovascular death or HF rehospitalization. A Cochran-Armitage test for trend showed a positive correlation between the EMR and the composite outcome of cardiovascular death or HF. There was a significant difference between the three groups in terms of cardiovascular death (Log rank test, P<0.001) and HF rehospitalization (Log rank test, P=0.03).ConclusionThe EMR is positively correlated with the risk of cardiovascular death or HF rehospitalization in patients with decompensated HF. Specifically, the lower the EMR, the higher the risk of cardiovascular death or HF rehospitalization.

Neutrophil Gelatinase-Associated Lipocalin Contributes to Increased Risk of Cardiovascular Death After Acute Coronary Syndrome.

BackgroundNeutrophil gelatinase-associated lipocalin (NGAL) has been suggested to reflect early renal dysfunction. We investigated the predictive significance of serum NGAL in predicting cardiovascular (CV) death in an old-age population with coronary heart disease (CHD).MethodsIn total, 633 CHD patients with a stable clinical condition were enrolled. The measurements of serum NGAL and other laboratory indices were performed within 24 hours after admission. Adjusted analysis was used to assess relationships between serum NGAL and CV death during the 10-year follow-up period.ResultsMultivariate logistic regression analysis demonstrated that elevated NGAL levels were related to a higher prevalence of CV disease history [quartile 4, 2.41 (1.60–4.59), P-trend <0.001]. The Kaplan–Meier curve indicated that patients with high NGAL levels tended to have a higher rate of CV death than patients with low NGAL levels. A multivariate Cox model suggested that increased levels of NGAL were independently linked with elevated risk of CV death (HR=2.62, 95% CI 1.51–4.96, P<0.001) during the 10-year follow-up period, after adjusting for related confounding factors using sensitivity analysis. Furthermore, the receiver operating characteristics (ROC) curve demonstrated that serum NGAL (AUC=0.917, 95% CI 0.895–0.940, P<0.001) had an ideal predictive value in predicting CV death.ConclusionSerum levels of NGAL were elevated in patients with CHD and may be a new parameter that could independently predict CV death in these patients, which may strengthen its potential application in clinical practice.

International Observational Analysis of Evolution and Outcomes of Chronic Stable Angina: The Multinational CLARIFY Study.

Although angina is common in patients with stable coronary artery disease, limited data are available on its prevalence, natural evolution, and outcomes in the era of effective cardiovascular drugs and widespread use of coronary revascularization. Using data from 32 691 patients with stable coronary artery disease from the prospective observational CLARIFY registry (Prospective Observational Longitudinal Registry of Patients with Stable Coronary Artery Disease), anginal status was mapped each year in patients without new coronary revascularization or new myocardial infarction. The use of medical interventions in the year preceding angina resolution was explored. The effect of 1-year changes in angina status on 5-year outcomes was analyzed using multivariable analysis. Among 7212 (22.1%) patients who reported angina at baseline, angina disappeared (without coronary revascularization) in 39.6% at 1 year, with further annual decreases. In patients without angina at baseline, 2.0% to 4.8% developed angina each year. During 5-year follow-up, angina was controlled in 7773 patients, in whom resolution of angina was obtained with increased use of antianginal treatment in 11.1%, with coronary revascularization in 4.5%, and without any changes in medication or revascularization in 84.4%. Compared to patients without angina at baseline and 1 year, persistence of angina and occurrence of angina at 1 year with conservative management were each independently associated with higher rates of cardiovascular death or myocardial infarction (adjusted hazard ratio, 1.32 [95% CI, 1.12-1.55] for persistence of angina; adjusted hazard ratio, 1.37 [95% CI, 1.11-1.70] for occurrence of angina) at 5 years. Patients whose angina had resolved at 1 year with conservative management were not at higher risk of cardiovascular death or myocardial infarction than those who never experienced angina (adjusted hazard ratio, 0.97 [95% CI, 0.82-1.15]). Angina affects almost one-quarter of patients with stable coronary artery disease but resolves without events or coronary revascularization in most patients. Resolution of angina within 1 year with conservative management predicted outcomes similar to lack of angina, whereas persistence or occurrence was associated with worse outcomes. Because most patients with angina are likely to experience resolution of symptoms, and because there is no demonstrated outcome benefit to routine revascularization, this study emphasizes the value of conservative management of stable coronary artery disease. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN43070564.

Impact of COVID-19 pandemic and infection on in hospital survival for patients presenting with acute coronary syndromes: A multicenter registry

IntroductionThe impact of Covid-19 on the survival of patients presenting with acute coronary syndrome (ACS) remains to be defined. MethodsConsecutive patients presenting with ACS at 18 Centers in Northern-Italy during the Covid-19 outbreak were included. In-hospital all-cause death was the primary outcome. In-hospital cardiovascular death along with mechanical and electrical complications were the secondary ones. A case period (February 20, 2020-May 3, 2020) was compared vs. same-year (January 1–February 19, 2020) and previous-year control periods (February 20–May 3, 2019). ACS patients with Covid-19 were further compared with those without. ResultsAmong 779 ACS patients admitted during the case period, 67 (8.6%) tested positive for Covid-19. In-hospital all-cause mortality was significantly higher during the case period compared to the control periods (6.4% vs. 3.5% vs. 4.4% respectively; p 0.026), but similar after excluding patients with COVID-19 (4.5% vs. 3.5% vs. 4.4%; p 0.73). Cardiovascular mortality was similar between the study groups. After multivariable adjustment, admission for ACS during the COVID-19 outbreak had no impact on in-hospital mortality. In the case period, patients with concomitant ACS and Covid-19 experienced significantly higher in-hospital mortality (25% vs. 5%, p < 0.001) compared to patients without. Moreover, higher rates of cardiovascular death, cardiogenic shock and sustained ventricular tachycardia were found in Covid-19 patients. ConclusionACS patients presenting during the Covid-19 pandemic experienced increased all-cause mortality, driven by Covid-19 positive status due to higher rates of cardiogenic shock and sustained ventricular tachycardia. No differences in cardiovascular mortality compared to non-pandemic scenarios were reported.

Patients with recurrent syncope and implantable loop recorder exhibit better survival than the control group without implantable loop recorder

Abstract Introduction In 30% of patients with syncope, the underlying cause remains unexplained after clinical investigations. Unexplained syncope tends to recur, significantly impacting patients' quality of life of patients and mortality. Thus, there is a need for timely and more accurate diagnosis to initiate treatment. Dedicated care pathways are recommended by ESC guidelines. Purpose Patients with recurrent syncope were followed over time and patient outcomes with ILR were compared to patients with the same syncope burden, age, gender and mortality risk score who did not receive an ILR. Method A representative database of 4.9 million patients insured by German company statuary health insurances (BKK) was analysed over a time period of 10 years, 2007–17. Patients with recurrent syncope (two times ICD-10 GM diagnosis codes R55), age between 45–84 and no diagnosis code for the syncope were included in the analysis and followed for at least 2 years. Patients with ILR were matched to patients without ILR based on age, gender and Charlson Comorbidity index (CCI) using mahalanobis distances. The index event was the device implant in the ILR group and the second syncope event in the control group. Life expectancy, syncope hospitalisations, fall related injuries, health care costs, diagnoses and treatment rates were compared between the groups. Results A total of 412 patients with ILR for recurrent unexplained syncope were matched to the control group. Overall mean age was 68, mean was CCI 2.7, 42% were females. The risk of death was 2.35 times higher in the control group during follow up as shown in Figure 1 (p-value logrank test &amp;lt;0.0001). Cardiovascular related diagnosis and treatment rates were higher in the ILR group with 69% of patients having a cardiology diagnosis compared to 41% in the control group. Over a quarter (27%) of ILR patients received an implantable cardiac device compared to 5% in the control group. Ablation rates were 7% in the ILR group compared to 0% in the control group. Median health care costs were € 3,847 higher in the ILR group including the costs of the ILR implant, follow up and higher rates of cardiac treatments. These extra costs appear moderate given the substantially higher mortality risk in the control group. Conclusion This study of patients with recurrent unexplained syncope shows a remarkable difference in life expectancy in patients with ILR compared to a matched control group. Two large claim data analysis have recently shown higher rates of cardiovascular death as well as all-cause mortality in patients with unexplained syncope. A more vigilant cardiac workup might be needed to identify a possible underlying cardiac condition. Higher rates of cardiac device therapy in the ILR group were likely to play an important role for their better life expectancy. Cardiac therapies such as pacemakers, defibrillators and ablation have also been shown to significantly improve patients' quality of life. Life Expectancy Comparison Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The data analysis was funded by Medtronic

1679 E/e predicts exercise capacity and adverse cardiovascular outcomes in patients with chronic kidney disease

Abstract Funding Acknowledgements Nil OnBehalf NA Background Patients with chronic kidney disease(CKD) have reduced physical fitness that contributes to the disproportionately elevated risk of cardiovascular disease in this population. Our aim was to assess the association between E/e’ and exercise capacity in CKD patients and the prognostic role of E/e’. Methods Patients with Stage 3/4 CKD, without previous cardiac disease were prospectively recruited. Recruited patients underwent transthoracic echocardiogram and exercise stress echocardiogram with assessment of exercise E/e’. Patients were compared, one to one, to age, gender and risk factor matched controls and were followed annually for 5 years for cardiovascular death and major adverse cardiovascular events (MACE). Exercise capacity was assessed as metabolic equivalents (METs) with reduced exercise capacity defined as METS of ≤7. Raised exercise E/e’ was defined as exercise E/average e’ of &amp;gt;13. Results 156 CKD patients (62.8 ± 10.6 yrs, male 62%) were compared to 156 matched controls. CKD patients had higher rates of anemia (p &amp;lt; 0.01), larger left ventricular indexed mass (p &amp;lt; 0.01), larger LAVI (p &amp;lt; 0.01) and higher resting (p &amp;lt; 0.01) and exercise E/e’ (p &amp;lt; 0.01). Overall, CKD patients achieved lower METs (p &amp;lt; 0.01) with exercise and a greater proportion of CKD patients had METs ≤7 (p &amp;lt; 0.01). Receiver operating curves (Figure1) showed exercise E/e’ (AUC 0.89, CI 0.84-0.95, p &amp;lt; 0.01) to be the strongest predictor of reduced exercise capacity in CKD patients. Exercise E/e’ of &amp;gt;13 was also associated with higher rates of cardiovascular death and MACE amongst CKD patients. Conclusion Exercise E/e’ is a strong predictor of exercise capacity amongst CKD patients, who commonly have reduced exercise capacity presumably consequent to diastolic dysfunction. Raised exercise E/e’ in CKD patients is predictor of cardiovascular death and MACE. Abstract 1679 Figure.

P4455The controversial role of genetics behind premature CAD: a plausible excuse for the young?

Abstract Introduction The complex interaction between genes and environmental factors contribute to individual-level risk of coronary artery disease (CAD), often resulting in premature CAD. The role for genetic risk scores in premature CAD is still controversial. Objective To evaluate the importance of conventional risk factors and of a genetic risk score in younger and older patients with coronary artery disease Methods From a group of 1619 pts with angiographic documented CAD from the GENEMACOR study, we selected 1276 pts admitted for ACS and analysed them in 2 groups (group A: ≤50 years, n=491 pts, 87.2% male, mean age 44±4.9 and group B: &gt;50 years, n=785 pts, 75.2% male, mean age 57±4.2). Univariate analysis was used to characterize the traits of each group and we used ROC curves and respective AUCs to evaluate the power of genetics in the prediction of CAD, through a Genetic Risk Score (GRS). Results 99.3% of the young patients had at least one modifiable risk factor, 18.4% had 2 modifiable risk factors and 75.2% had 3 or more modifiable risk factors. The pattern of risk factors contributing to CAD were different among groups: family history (A: 27.5%, B: 21.4%, p=0.015) and smoking habits (A: 64.8%, B: 42.9%, p&lt;0.001) were more frequent among patients under 50, and traditional age-linked factors like hypertension (A: 58%, B: 75.7%, p&lt;0.001), diabetes (A: 21.6%, B: 38.6%, p&lt;0.001) were more common in the older group. Acute ST-elevation myocardial infarction was more frequent among the young (A: 55.4%, B: 47.4%, p=0.006), as non-ST clinical presentation was higher among elder patients. Regarding angiographic presentation, single vessel CAD was higher in group A (A: 50.3%, B: 40.9%, p&lt;0.001), while multivessel diasease was higher in group B (A: 33.3%, B: 53.9%, p&lt;0.001). At a mean follow-up of 5 years, older patients had a worst prognosis, registering a higher rate of cardiovascular death (A: 4.1%, B: 8.6%, p=0.002) and higher MACE (A: 26.8%, B: 31%, p=0.128),. Adding the genetic risk score (GRS), we achieved only a slight improvement in the AUC for predicting CAD (0.796-&gt;0.805, p=0.0178 and 0.748-&gt;0.761, p=0.0007 in patients under and over 50, respectively). Conclusion Coronary artery disease is not all the same, as premature CAD shares a unique and specific pattern of risk factors, clinical presentation, angiographic severity and prognosis. Genetics should not be used as an excuse to justify premature CAD, as there is frequently more than one potentially reversible risk factor present even in young patients and the additive predictive value of GRS is modest.

Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry.

Aims To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs).Methods and resultsPatients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25–110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18–0.92; P = 0.03].Conclusion Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences.

Chronic kidney disease and risk for cardiovascular and limb outcomes in patients with symptomatic peripheral artery disease: The EUCLID trial.

In patients with symptomatic peripheral artery disease (PAD), the impact of chronic kidney disease (CKD) on major adverse cardiovascular events has not been fully evaluated. The Examining Use of Ticagrelor In PAD (EUCLID) trial randomized 13,885 patients with PAD to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. This post hoc analysis compared the incidence of the primary composite endpoint (cardiovascular death, myocardial infarction (MI), or ischemic stroke) in patients with CKD (eGFR < 60 mL/min/1.73 m2) with those without CKD (eGFR ⩾ 60 mL/min/1.73 m2). The primary safety endpoint was thrombolysis in MI (TIMI) major bleeding. A total of 13,483 patients were included; 3332 (25%) had CKD, of whom 237 had stage 4/5 disease. Median follow-up was approximately 30 months. After statistical adjustment, patients with CKD had a higher rate of the primary endpoint compared with those without CKD (6.75 vs 3.72 events/100 patient-years; adjusted hazard ratio (HR) 1.45, 95% CI 1.30-1.63). CKD was not associated with increased risk of hospitalization for acute limb ischemia (ALI) (adjusted HR 0.96, 95% CI 0.69-1.34) or major amputation (adjusted HR 0.92, 95% CI 0.66-1.28). CKD was not associated with a significantly increased risk of major bleeding (adjusted HR 1.21, 95% CI 0.89-1.64), but minor bleeding was significantly increased (adjusted HR 1.51, 95% CI 1.07-2.15). In conclusion, patients with PAD and CKD had higher rates of cardiovascular death, MI, and ischemic stroke, but similar rates of ALI, major amputation, and TIMI major bleeding when compared with patients without CKD. ClinicalTrials.gov Identifier: NCT01732822.

Idiopathic Ventricular Fibrillation and Otherwise Normal Electrocardiograms

Background: Idiopathic ventricular fibrillation (IVF) in patients with normal baseline electrocardiograms (ECGs) is a rare disease. Little information is available on the clinical features and long-term follow-up of out-of-hospital cardiac arrest (OHCA) survivors presenting with true IVF and 12-lead ECGs that remain normal over time. Objective: To define the clinical and ECG characteristics, as well as long-term clinical outcomes of a large cohort of survivors of OHCA due to true IVF. Methods: OHCA survivors with VF as the presenting rhythm, normal baseline and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular (AV) conduction abnormalities, and without structural heart disease were included in a registry. Results: A total of 245 OHCA survivors with IVF (median age: 38 years; males 59%) were recruited from 25 centres. All had normal baseline and follow-up ECGs, and no evidence of structural heart disease. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in 4 of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs (AADs) only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, p=0.001). The ECG and echocardiogram of all patients remained unchanged over time. Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤ 16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis (HR 0.41, 95% CI 0.18-0.92, p=0.03). Discussion: OHCA survivors of true IVF with normal baseline and follow-up ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences. Funding: The study was supported by a grant of the Swiss Heart Foundation. Declaration of Interest: G.C. has received a research grant from the Swiss National Foundation. P.L. has received speaker fees and research grants from Boston Scientific, Abbott and Medtronic Research support from UCLH Biomedicine NIHR. F.L. is consultant and has received research support from Medtronic Plc, Abbott, Boston Scientific and Microport. S.B. has received speaker’s bureau from Medtronic and Microport. C.P. has received research grant from Biotronik and Biosense Webster. P.B. is consultant for Biotronik. A.A. is consultant to Abbott, Biosense Webster, Daiichi-Sankyo, Boston Scientific, Medtronic, Microport-CRM; and has received speaker fee from Daiichi-Sankyo, Boston Scientific, Medtronic, Microport-CRM Ethics Approval Statement: Data were collected in accordance with regulations set by the local Institutional Ethics Committee and/or Institutional Review Board.