Risk Of Adverse Cardiovascular Outcomes Research Articles

Atrial Fibrillation Detection and Management in Hypertension.

Hypertension is prevalent in >70% of atrial fibrillation patients. In turn, hypertensive patients have up to 73% greater likelihood of atrial fibrillation. Current guidelines recommend that a systematic atrial fibrillation screening may be justified in all patients aged ≥65 years with at least 1 cardiovascular disease, including hypertension. Although most blood pressure monitors include algorithms to detect atrial fibrillation with a high sensitivity of 96 [92-98]% and specificity of 94 [91-96]%, an electrocardiography confirmation is necessary to establish a diagnosis of atrial fibrillation. Early detection and diagnosis of atrial fibrillation is important to allow initiation of atrial fibrillation management. In the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4), hypertension was present in 88% of participants, and early rhythm control therapy lowered the risk of adverse cardiovascular outcomes in patients with early atrial fibrillation aged >75 or with CHA2DS2-VASc score ≥2 (Congestive heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65-74, Sex category [female]) and cardiovascular condition. Strategies for early atrial fibrillation detection should always be linked to a comprehensive atrial fibrillation work-up infrastructure organized within an integrated ABC pathway (Anticoagulation/Avoid stroke; Better symptom control; Cardiovascular and Comorbidity optimization). For secondary prophylaxis, blood pressure control should be embedded in a combined risk factor management program. In hypertensive patients where no atrial fibrillation is detected, intensive blood pressure lowering therapy for primary prophylaxis should be initiated to reduce the risk of developing atrial fibrillation and other cardiovascular complications in the future. The aim of the article is to review the current literature on atrial fibrillation detection and management in hypertensive patients.

Outcomes in diabetic patients treated with SGLT2-Inhibitors with acute myocardial infarction undergoing PCI: The SGLT2-I AMI PROTECT Registry

AimsTo investigate in-hospital and long-term prognosis in T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-I versus other oral anti-diabetic agents (non-SGLT2-I users). MethodsIn this multicenter international registry all consecutive diabetic AMI patients undergoing percutaneous coronary intervention between 2018 and 2021 were enrolled and, based on the admission anti-diabetic therapy, divided into SGLT-I users versus non-SGLT2-I users. The primary endpoint was defined as a composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE). Secondary outcomes included i) in-hospital cardiovascular death, recurrent AMI, occurrence of arrhythmias, and contrast-induced acute kidney injury (CI-AKI); ii) long-term cardiovascular mortality, recurrent AMI, heart failure (HF) hospitalization. ResultsThe study population consisted of 646 AMI patients (with or without ST-segment elevation): 111 SGLT2-I users and 535 non-SGLT-I users. The use of SGLT2-I was associated with a significantly lower in-hospital cardiovascular death, arrhythmic burden, and occurrence of CI-AKI (all p < 0.05). During a median follow-up of 24 ± 13 months, the primary composite endpoint, as well as cardiovascular mortality and HF hospitalization were lower for SGLT2-I users compared to non-SGLT2-I patients (p < 0.04 for all). After adjusting for confounding factors, the use of SGLT2-I was identified as independent predictor of reduced MACE occurrence (HR=0.57; 95%CI:0.33–0.99; p = 0.039) and HF hospitalization (HR=0.46; 95%CI:0.21–0.98; p = 0.041). ConclusionsIn T2DM AMI patients, the use of SGLT2-I was associated with a lower risk of adverse cardiovascular outcomes during index hospitalization and long-term follow-up. Our findings provide new insights into the cardioprotective effects of SGLT2-I in the setting of AMI. RegistrationData are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT05261867.

Cardiovascular Outcomes in Patients With Both Diabetes and Phenotypic Familial Hypercholesterolemia: A Nationwide Register-Based Cohort Study.

Patients with diabetes or familial hypercholesterolemia (FH) have an increased incidence of cardiovascular diseases compared with the population, but whether this risk is exacerbated in patients with combined traits is unknown. In this Swedish nationwide, register-based cohort study, patients with diabetes were included between 2002 and 2020. Adjusted Cox proportional hazards models were used to assess the risk of cardiovascular events in patients with or without phenotypic FH (≥6 points for phenotypic FH according to Dutch Lipid Clinic Network criteria) compared with general population control subjects without diabetes as reference. A total of 45,585 patients with type 1 diabetes (227,923 control subjects) and 655,250 patients with type 2 diabetes (655,250 control subjects) were followed for a median of 14.1 and 7.9 years, respectively. Of those, 153 and 7,197, respectively, had phenotypic FH. Compared with control subjects, patients with diabetes and phenotypic FH had higher risk of cardiovascular mortality (type 1: hazard ratio 21.3 [95% CI 14.6-31.0]; type 2: 2.40 [2.19-2.63]) and of a cardiovascular event (type 1: 15.1 [11.1-20.5]; type 2: 2.73 [2.58-2.89]). Further, patients with diabetes and phenotypic FH had higher LDL-cholesterol levels during observation (P < 0.05) and increased risk of all major cardiovascular outcomes (P < 0.0001) than patients with diabetes but without FH. The proportion receiving lipid-lowering treatment was higher in patients with phenotypic FH (P < 0.0001). Patients with both diabetes and phenotypic FH are more at risk for adverse cardiovascular outcomes and have higher LDL-cholesterol levels despite receiving intensified lipid-lowering therapy.

Evolving Role of Catheter Ablation for Atrial Fibrillation: Early and Effective Rhythm Control.

Catheter Ablation (CA) is an effective therapeutic option in treating atrial fibrillation (AF). Importantly, recent data show that CA as a rhythm control strategy not only significantly reduces AF burden, but also substantially improves clinical hard endpoints. Since AF is a progressive disease, the time of Diagnosis-to-Intervention appears crucial. Recent evidence shows that earlier rhythm control is associated with a lower risk of adverse cardiovascular outcomes in patients with early AF. Particularly, CA as an initial first line rhythm control strategy is associated with significant reduction of arrhythmia recurrence and rehospitalization in patients with paroxysmal AF. CA is shown to significantly lower the risk of progression from paroxysmal AF to persistent AF. When treating persistent AF, the overall clinical success after ablation remains unsatisfactory, however the ablation outcome in patients with "early" persistent AF appears better than those with "late" persistent AF. "Adjunctive" ablation on top of pulmonary vein isolation (PVI), e.g., ablation of atrial low voltage area, left atrial posterior wall, vein of Marshall, left atrial appendage, etc., may further reduce arrhythmia recurrence in selected patient group. New ablation concepts or new ablation technologies have been developing to optimize therapeutic effects or safety profile and may ultimately improve the clinical outcome.

Abstract 15919: Adverse Outcomes Related Amiodarone Toxicity in Early Rhythm Control of Patients With Atrial Fibrillation: A Nationwide Cohort Study

Background: Early rhythm control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients who had recently (within 1 year) been diagnosed with atrial fibrillation (AF). In real-world data, the most commonly selected initial rhythm control strategy was the Class III anti-arrhythmic drug (AAD) amiodarone, but adverse outcomes related amiodarone toxicity was not well reported in this population. This study sought to investigate the fatal and non-fatal adverse outcomes related amiodarone toxicity in early rhythm control of patients with AF. Methods: Using the database of Korean National Health Insurance Service, we analyzed the adverse outcomes related amiodarone toxicity in 140,908 (rhythm control: 57,148, rate control: 83,760) patients with AF undergoing rhythm control or rate control therapy, initiated within 1 year of AF diagnosis, between 2005 and 2015. Results: The most commonly used rhythm control strategy was the class III drug amiodarone (22,877 (40.0%) of 57,148 patients in early rhythm control), followed by class Ic drugs. Patients with amiodarone for initial rhythm control strategy showed higher rate of interstitial lung disease (1.43% vs. 0.75%, p&lt;0.001), sudden cardia arrest duet to Torsade de Pointes (0.31% vs. 0.17%, p=0.001), and hypothyroidism (16.5% vs. 8.12%, p&lt;0.001). But incidence rate of bradycardia needing a temporary pacemaker, bradycardia needing a permanent pacemaker, and toxic hepatitis were higher in early rhythm control patients with other AADs compared to patients with amiodarone. Conclusions: The most commonly used rhythm control strategy was amiodarone in AF patients undergoing early rhythm control. Using amiodarone for the initial rhythm control strategy showed a higher rate of interstitial lung disease, sudden cardia arrest duet to Torsade de Pointes, and hypothyroidism. Attention should be paid to amiodarone toxicity in selecting rhythm control strategy for these patients.

Heart rate surge at respiratory event termination in preterm and term born children with sleep disordered breathing

BackgroundRepetitive surges in heart rate (HR) at respiratory event termination underpin the altered autonomic HR control associated with sleep disordered breathing (SDB). As children born preterm are at greater risk of adverse cardiovascular outcomes, we aimed to determine whether the HR response to obstructive respiratory events was elevated compared to term-born children. MethodsFifty children (3–12 years) born preterm, were matched for SDB severity, age and gender with term born children. Multilevel modelling determined the effect of preterm birth and arousal on HR changes between a 10s baseline to the latter half of respiratory events and 15s post event during NREM and REM. Results1203 events were analysed (NREM: term 380; preterm 383; REM: term 207; preterm 233). During NREM fewer events terminated in arousal in the preterm compared with term group (preterm 68%; term 84%; χ2 = 27.2, p < 0.001). There were no differences in REM. During NREM, HR was lower in the preterm group at all event phases, with and without associated arousals (P < 0.01 for all). % change in HR from baseline to post event was higher in the preterm compared with term group (preterm: median 23% IQR (12%,34%); term: 18% (10%,29%); p < 0.01) and late event to post event (preterm: 30% (21%, 32%); term 28% (20%,39%); p < 0.01) in events associated with arousals. ConclusionThe greater magnitude of surges in HR following respiratory events terminating with arousal in preterm born children, although small, occur repeatedly throughout the night and may contribute to adverse cardiovascular outcomes, although further studies are required.

'Weekend warrior' and regularly active physical activity patterns confer similar cardiovascular and mortality benefits: a systematic meta-analysis.

It is well documented that physical activity (PA) is associated with a lower risk of non-communicable diseases including cardiovascular disease (CVD) as well as mortality.1–3 Previous PA guidelines as well as recent guidelines by the World Health Organization have recommended that all adults should aim for 150–300 min of moderate intensity PA per week or 75–150 min of vigorous intensity PA per week or an equivalent combination of moderate-intensity and vigorous-intensity PA per week.4 Evidence suggests these levels provide substantial health benefits in most people.2 Despite guideline recommendations and population-wide strategies to promote PA levels, most populations do not adhere to PA recommendations. A major reason for the low levels of adherence is the lack of time. The balance between frequency, duration, and intensity, which are components of PA, plays an important part in the protective effects of PA. To derive maximal benefits from PA, an appropriate intensity, frequency, and duration, which comprise the volume is essential. However, emerging evidence suggests that the intensity of PA may be more important than the quantity (frequency or duration).5 It is uncertain if the majority of PA concentrated into a few days confers similar cardiovascular benefits as that spread over more days. Following the seminal study by Lee et al.,6 a few recent reports have evaluated whether guideline recommended PA patterns concentrated in one or two sessions per week (commonly called the ‘weekend warrior’ pattern) or patterns spread over multiple sessions per week (i.e. regularly active pattern) may differ with respect to cardiovascular outcomes and mortality. Some studies have reported similar benefits,7 whereas other reports suggest that regularly active PA patterns confer more benefits than weekend warrior PA patterns.6,8 Given the sparseness and inconsistency of the data, there is a need to systematically synthesize the existing evidence. Furthermore, given the relatively low sample size of some of these previous studies, pooling the overall evidence will provide adequate power to reveal any true associations. In this context, we aimed to assess and compare the associations of weekend warrior and regularly active PA patterns vs. inactive PA patterns with the risk of adverse cardiovascular outcomes using a systematic review and meta-analysis of all published observational cohort studies conducted on the topic.

Predictors of increased risk of adverse cardiovascular outcomes among patients with myeloproliferative neoplasms and atrial fibrillation

BackgroundPatients with myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), have increased risk of cardiovascular (CV) disease. Atrial fibrillation (AF) is associated with adverse CV outcomes including arterial thrombosis, heart failure (HF), and CV death and coexists with MPN. Traditional risk scores (CHA2DS2-VASC and HAS-BLED) for estimating risks/benefits of anticoagulation to prevent thrombotic events in AF do not include MPN status. Therefore, we aimed to investigate CV outcomes in patients with MPN and AF and evaluate the predictive ability of traditional risk scores. MethodsWe conducted a single-center, retrospective cohort study of patients with MPN and AF. Primary outcome was composite of CV death and arterial thromboembolism; secondary outcomes were bleeding requiring emergency department visit or hospitalization, hospitalization for HF, and all-cause death. Multivariable competing-risk and Cox proportional hazards regression models were used to estimate risk of outcomes. Receiver operating characteristic (ROC) curve used to evaluate predictive ability of CHA2DS2-VASC and HAS-BLED of composite outcome and bleeding, respectively. ResultsA total 142 patients was included (62 ET, 54 PV, 26 MF). Composite outcome, bleeding, HF hospitalization and all-cause death occurred in 39 %, 30 %, 34 %, and 48 %, of patients respectively. After multivariable modeling, MF was associated with increased risk of composite outcome (SHR 2.70, 95 % CI 1.38–5.27) and all-cause mortality (HR 9.77, 95 % CI 4.88–19.54) but not bleeding (SHR 1.19, 95 % CI 0.51–2.80) or HF admissions (SHR 0.57, 95 % CI 0.19–1.72). CHA2DS2-VASC and HAS-BLED were poor predictors of composite outcome (C-statistic 0.52, 95 % CI 0.43–0.62) and bleeding (C-statistic 0.49, 95 % CI 0.40–0.58), respectively. ConclusionIn patients with MPN and AF, MF is associated with increased risk of CV death and arterial thrombosis and traditional risk scores do not accurately predict outcomes in this patient population. Further investigation is needed to refine risk scores in this patient population.

Sex-related short-term blood pressure variability differences in kidney transplant recipients.

Kidney transplant recipients (KTRs) display higher cardiovascular morbidity and mortality than the general population. Increased short-term blood pressure variability (BPV) is associated with a higher risk of adverse cardiovascular outcomes in chronic kidney disease (CKD). The aim of this study is to investigate sex differences in short-term BPV in KTRs. In total, 136 male and 69 female KTRs with valid 24 h ambulatory blood pressure monitoring were included in this analysis. Systolic and diastolic BPV indices [SD, weighted SD (wSD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM)] were calculated with validated formulas for the 24 h, daytime and nighttime periods. Age, time from transplantation surgery and history of major comorbidities did not differ between men and women. During the 24-h period, systolic BPV indices did not differ between men and women (SBP-ARV: 9.4 ± 2.2 vs. 9.9 ± 2.5; P = 0.212). During the daytime period, SBP-CV and SBP-VIM were significantly higher in females compared with male participants (SBP-CV: 9.9 ± 2.4 vs. 11 ± 3.1%; P = 0.022 and SBP-VIM: 12.6 ± 3.0 vs 14.2 ± 3.9; P = 0.008); daytime SBP-SD and SBP-ARV, and all studied indexes during nighttime did not differ between groups. No significant between-group differences in 24 h and daytime diastolic BPV indices were detected. Nighttime DBP-CV was marginally higher in men (12.0 ± 3.6 vs. 11.4 ± 4.0; P = 0.053); the rest nighttime diastolic BPV indices measured were also nonsignificantly higher in men. In conclusion, 24-h systolic and diastolic BPV parameters did not differ between male and female KTRs, but short-term BPV over the respective day- and nighttime periods showed different trends in men and women. Further studies are needed to examine possible differences in long-term BPV in KTRs.

Risk of Adverse Cardiovascular Outcomes in Differentiated Thyroid Cancer Survivors: A Systematic Review and Meta-Analysis.

Introduction: Long-term cardiovascular (CV) risk is a concern for differentiated thyroid cancer (DTC) survivors. Methods: We performed a systematic review and meta-analysis evaluating the risks of CV mortality and morbidity in DTC survivors compared with the general population. Respective meta-analyses were conducted for data that were adjusted for relevant confounders and crude data. We searched five electronic databases from inception to October 2021, supplemented with a hand search. Two reviewers independently screened citations, reviewed full text articles, extracted data, and critically appraised the studies, with discrepancies resolved by a third reviewer. The primary outcome was CV mortality. Secondary outcomes included atrial fibrillation, ischemic heart disease, stroke, and heart failure. We estimated the relative risk (RR) and confidence intervals [CI] of outcomes using random-effects models (adjusted for age and gender), compared with the general population. Results: We reviewed 3409 unique citations, 65 full text articles, and included 7 studies. CV mortality risk was significantly increased in DTC survivors in one study adjusted for confounders-adjusted RR (aRR) 3.35 ([CI 1.66-6.67]; 524 DTC, 1572 controls). The risk of CV morbidity in DTC survivors, adjusted for risk factors, was estimated as follows: atrial fibrillation-aRR 1.66 [CI 1.22-2.27] (3 studies, 4428 DTC, I2 = 75%), ischemic heart disease-aRR 0.97 [CI 0.84-1.13] (2 studies, 3910 DTC, I2 = 0%), stroke-aRR 1.14 [CI 0.84-1.55] (2 studies, 3910 DTC, I2 = 69%), and heart failure-aRR 0.98 [CI 0.60-1.59] (2 studies, 3910 DTC, I2 = 79%). In meta-analyses of unadjusted data, the risks of CV mortality were not significantly increased but the CV morbidity risks were similar to adjusted data. Conclusions: There is limited evidence suggesting that DTC survivors may be at an increased risk of CV death and atrial fibrillation (after adjustment for confounders). We did not observe a significantly increased risk of ischemic heart disease, stroke, or heart failure. Most analyses were subject to significant heterogeneity and further research, with careful attention to CV risk factors, is needed to clarify CV risk in DTC survivors. Registration: PROSPERO CRD42021244743.

Antiplatelet therapy and risk of adverse cardiovascular events in peripheral artery disease

Abstract Background Antiplatelet therapy has been shown to reduce adverse cardiovascular (CV) events in patients with PAD, but despite the well-established medication benefit, large-scale epidemiological data evaluating antiplatelet agent of choice with low bleeding risk and high antithrombotic effect is sparse. Purpose We explored Danish healthcare registers to examine guideline-recommended antiplatelet therapy and associated risk of adverse CV outcomes in patients with PAD. Methods All patients with a first-time diagnosis of PAD between January 1, 1997 and December 31, 2016 were identified. Patients alive six months after diagnosis were divided into four treatment groups: aspirin, clopidogrel, dual therapy (DAPT), and no antiplatelet therapy. Logistic regression models were used to estimate 1-year risk of myocardial infarction (MI), stroke, CV death, all-cause mortality, and gastrointestinal (GI) bleeding. Results We identified a total of 85,771 PAD patients [median age 70.6 (IQR 63–77 years), 52% male]. The results suggest that compared to no antiplatelet therapy, use of clopidogrel alone significantly decreased 1-year risk of incident MI, stroke, CV death and all-cause mortality with odds ratios 0.56 (CI 0.46–0.68), 0.69 (CI 0.59–0.81), 0.72 (CI 0.56–0.94), and 0.79 (CI 0.65–0.97) respectively. Likewise, aspirin monotherapy was associated with only a marginal reduction in 1-year risk of stroke by 11% and all-cause mortality by 7%. Odds ratios for GI bleeding were estimated to be 1.18 (CI 1.04–1.34), 1.34 (CI 0.94–1.91), and 1.54 (CI 1.05–2.26) for aspirin, clopidogrel, and DAPT groups, respectively. Conclusion In this nationwide study, clopidogrel is associated with significantly reduced risk of MI, stroke, CV death and all-cause mortality with low risk of bleeding and appears to support clopidogrel as antiplatelet agent of choice for CV risk reduction in patients with PAD. Funding Acknowledgement Type of funding sources: None.

Baseline cardiovascular risk in subjects with type 2 diabetes and chronic kidney disease from the FLOW trial

Abstract Background Patients with chronic kidney disease and type 2 diabetes (T2D) have a high risk of progression to kidney failure as well as cardiovascular (CV) events. It is established that glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and reduce body weight. Some CV outcomes trials have shown that GLP-1RAs reduce CV risk in people with T2D at high CV risk; for example, the SUSTAIN 6 trial demonstrated that the GLP-1RA semaglutide significantly lowered the rate of major CV events (CV death, non-fatal myocardial infarction and non-fatal stroke) versus placebo. Some trials have also indicated that GLP-1RAs reduce albuminuria and estimated glomerular filtration rate (eGFR) decline. Based on these previous results indicating potential kidney-protective effects, the FLOW trial (NCT03819153) is evaluating once-weekly, subcutaneous semaglutide 1.0 mg versus placebo on kidney- and CV-related outcomes in participants with T2D. We describe the baseline characteristics and the calculated CV risk of this patient population using the atherosclerotic CV disease (ASCVD) and second manifestations of arterial disease (SMART) risk calculators. Methods FLOW is an ongoing, multicentre, randomised, double-blind, parallel-group, event-driven, phase 3b trial, with participants randomised 1:1 to semaglutide or placebo, each in addition to standard of care. Recruitment is complete and 3,535 participants with T2D, an eGFR ≥25–≤75 mL/min/1.73 m2, and urine albumin-to-creatinine ratio ≥100–≤5,000 mg/g have been enrolled. The primary endpoint is time to first occurrence of a kidney composite that includes ≥50% persistent eGFR reduction, kidney failure (persistent eGFR &amp;lt;15 mL/min/1.73 m2 or initiation of chronic dialysis or kidney transplantation), and kidney-related death, or CV death. Key secondary outcomes include time to first occurrence of CV death, myocardial infarction or stroke. Results The baseline clinical characteristics and demographics are shown (Table 1). Median age was 68 years, 30% were female, mean diabetes duration was 17 years, and 98% had a history of hypertension. Overall, 52% of participants had a previous CV event. The calculated 10-year risk for ASCVD events in those without prior ASCVD was 31% in males and 18% in females, and in those with previous CV events was 37–56% in males and 35–53% in females depending on the type of CV disease reported in the calculator (Table 2). Conclusions The FLOW trial has completed enrolment. Based on the ASCVD and SMART risk calculators, the enrolled population has a substantial risk for adverse CV outcomes. Event ascertainment is ongoing, and the FLOW trial will provide evidence for the potential of semaglutide to improve kidney and CV outcomes in the T2D population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novo Nordisk

Completeness of revascularization by FFRCT and prognosis in stable chest pain

Abstract Introduction Major randomized trials of patients with stable chest pain (CP) demonstrated no prognostic benefits of coronary revascularization over optimal medical treatment (OMT). However, in a recent large-scale study, completeness of revascularization was associated with a reduced risk of all-cause death and non-fatal myocardial infarction (MI). Purpose To evaluate the association between completeness of revascularization relative to the result of coronary CT angiography (CTA) derived fractional flow reserve (FFRCT) and 3-year prognosis in patients with new onset stable CP and coronary stenosis. Methods Multicenter cohort 3-year follow-up sub-study of 900 patients from the Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care (ADVANCE) registry at three Danish sites, the “ADVANCE-DK Registry”. All patients had at least one ≥30% coronary stenosis by CTA and underwent subsequent core laboratory FFRCT analysis by HeartFlow. The FFRCT result was abnormal when ≤0.80 (2 cm distal to stenosis). Patients were classified according to completeness of revascularization by FFRCT: 1) completely revascularized (CR-FFRCT), all coronary arteries with an abnormal FFRCT test result revascularized; 2) incompletely revascularized (IR-FFRCT), ≥1 coronary artery with an abnormal FFRCT test result not revascularized. The primary endpoint (PE) was a composite of all-cause death and spontaneous MI. The secondary endpoint (SE) was a composite of cardiovascular (CV) death and spontaneous MI. Results Patient characteristics are given in Table 1. In total 36 (4.0%) patients suffered a PE (all-cause death, n=24; MI, n=12) and 22 (2.4%) an SE (CV death, n=10; MI, n=12). Overall, an abnormal vs a normal FFRCT test result was associated with an increased risk of both the PE, 6.6% vs 2.1%, relative risk (RR): 3.1; 95% CI: 1.6–6.3, p&amp;lt;0.001 and of the SE, 5.0% vs 0.6%, RR: 8.7; 95% CI: non assessable, p&amp;lt;0.001. In patients with abnormal FFRCT, revascularization vs no revascularization did not reduce the risk of the PE or the SE (data not shown). Patients with IR-FFRCT vs CR-FFRCT had a numerical, but not statistical significantly, increased risk of the PE, 8.6% vs 4.2%, RR: 2.14; 95% CI: 0.87–5.26, p=0.10), and an increased risk of the SE, 7.1% vs 2.4%, RR: 3.13; 95% CI: 1.02–9.63, p=0.04, Figure 1. In CR-FFRCT versus normal FFRCT no difference in the risk of the PE or the SE was observed, Figure 1. Univariate sensitivity analyses performed in the IR-FFRCT group did not reveal any differences in the risk of the PE or the SE after adjustment for neither statin therapy at follow-up (−/+), baseline risk variables (&amp;lt; / ≥3), amount of CAC (&amp;lt; / ≥400), degree of stenosis by CTA (&amp;lt; / ≥50%) nor referral to ICA (−/+). Conclusion In symptomatic patients with coronary stenosis by CTA, incomplete revascularization determined by FFRCT is associated with an increased risk of adverse cardiovascular outcomes compared to complete revascularization. Funding Acknowledgement Type of funding sources: None.

Single pill treatment in daily practice is associated with improved clinical outcomes and all-cause mortality in cardiovascular diseases: results from the START project

Abstract Objective Current guidelines for the management of arterial hypertension, dyslipidemia, or secondary cardiovascular (CV) prevention recommend combination drug treatments with single pill combinations (SPC). This concept is expected to improve adherence to treatment and, as a consequence, to reduce the risk of adverse CV outcomes associated with these clinical conditions. Aim of our study was to assess whether SPC are clinically superior to multi pill combination (MPC) with identical drugs in reducing CV events and al-cause mortality in a huge population under real world conditions in daily practice. Methods We analyzed an anonymized claims dataset (AOK PLUS, a statutory German sickness fund) including patients with hypertension and other CV diseases in the years 2012–2017; minimum follow-up was 1 year or until date of death, After 1:1-Propensity Score Matching (PSM), selected CV outcomes (myocardial infarction, stroke, transitory ischemic attack, coronary artery disease, heart failure, acute renal failure, cardiovascular hospitalization, all cause hospitalization) as well as all-cause mortality were compared using Incidence Rate Ratios (IRRs) and non-parametric tests. Results 50,622 patients (25,311 patients in SPC versus MPC group) aged ≥18 years treated with SPC or identical MPC were followed up for at least 1 year or until death. No significant differences in baseline characteristics were observed after PSM. Nine different clinical outcomes were compared for each group. In all comparisons, significantly lower incidence rate ratios (IRR) were identified for SPC, confirmed by comparison of Kaplan-Meier estimates: stroke (IRR=0.77; 95% CI 0.67–0.88; p&amp;lt;0.001), transitory ischemic attack (IRR=0.61; 95% CI 0.48–0.78; p&amp;lt;0.001), myocardial infarction (IRR=0.76; 95% CI 0.63–0.90; p=0.0016), coronary artery disease (IRR=0.66; 95% CI 0.57–0.77; p&amp;lt;0.001), heart failure (IRR=0.59; 95% CI 0.54–0.64; p&amp;lt;0.001), acute renal failure (IRR=0.54; 95% CI 0.56–0.64; p&amp;lt;0.001) all cause hospitalization (IRR=0.72; 95% CI 0.71–0.74; p&amp;lt;0.001), cardiovascular hospitalization (IRR=0.63; 95% CI 0.57–0.69; p&amp;lt;0.001), and all-cause mortality (IRR=0.62; 95% CI 0.57–0.68; p&amp;lt;0.001). The mean time to first events and time to death were also in favor to SPC (any event: SPC 966.052 days/median 873; MPC 846.936 days/median 647; death: SPC 1,719.424 days; MPC 1,657.248 days; log rank for both comparisons: p&amp;lt;0.001). Conclusion In clinical practice, the SPC regimen is associated with a lower incidence of CV events and lower all-cause mortality. Time to the event is also significantly longer in the SPC group compared to MPC. These results strongly support the concept of SPC and the implementation into daily practice to improve patient's prognosis. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): APONTIS PHARMA GmbH &amp; Co. KG

Long-term effects of coronavirus disease 2019 on the cardiovascular system: the CV COVID-19 registry

Abstract Background Patients with COVID-19 have an increased risk of cardiovascular adverse events during the acute phase. However, the long-term cardiovascular outcomes are unknown. Objective We aimed to determine the long-term effects of COVID-19 in the cardiovascular system. Methods This is a multicenter, observational, retrospective registry conducted at 17 centers in Spain and Italy. Consecutive patients older than 18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions were included. Patients were classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome was cardiovascular (CV) death at 1-year. The secondary outcomes included acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias at 1-year. Outcomes were compared between the two groups. An independent clinical event committee adjudicated events. Results A total of 4427 patients were included, 3578 (80.8%) patients with COVID-19 and 849 (19.2%) without COVID-19. COVID-19 patients were older, had a higher rate of classical cardiovascular risk factors, except for active smoking, and had fewer comorbidities. At a median time of 13.5 (IQR 11.8–15.8) months, after an adjustment by baseline characteristics, there was no difference in CV death (1.4% vs. 1.1%; HR 1.03 [0.49–2.18]; p=0.941) between patients with COVID-19 and without. However, COVID-19 patients experienced higher rate of venous thromboembolism (VTE) (3.9% vs. 0.6%, HR 6.11 [2.46–15.16]; p=0.001), major bleeding (2.9% vs. 0.5%, HR 5.38 [1.95–14.84]; p=0.001), and serious cardiac arrhythmias (2.6% vs. 0.9%, HR 2.25 [1.07–4.73]; p=0.033). During follow-up, between discharge and end of follow-up, COVID-19 patients did not experience a higher risk of adverse cardiovascular outcomes (composite of CV death, any MI, ischemic stroke, systemic arterial thrombosis, VTE, heart failure hospitalization, or any serious arrhythmia) compared to patients without (HR 0.80; [0.53–1.21]; p=0.298). Conclusions At 1-year follow-up, COVID-19 was not associated with an increased risk of cardiovascular death but with a higher risk of VTE events, major bleeding, and serious cardiac arrhythmias. COVID-19 was not associated with a higher risk of adverse cardiovascular events during follow-up. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Carlos III Institute, Madrid, Spain

Impact of obstructive sleep apnoea on long-term atrial fibrillation-free survival after catheter ablation

Abstract Introduction Early rhythm-control therapy of atrial fibrillation (AF) (including catheter ablation) has been established as significantly lowering risk of adverse cardiovascular outcomes and improving overall survival and quality of life. Obstructive sleep apnoea (OSA) is a common but often overlooked comorbidity in patients with AF that may lead to difficulties in maintaining sinus rhythm. Data on the impacts of its treatment on recurrence remain conflicting. Objective To determine the prevalence of OSA in a population of AF patients submitted to catheter ablation and its impact on recurrence after a successful procedure. Methods Retrospective study of patients with AF consecutively submitted to catheter ablation in a tertiary centre between January 2017 and December 2020. The main outcome was AF recurrence after ablation. Sociodemographic variables and clinical data were retrieved for each patient, including type of AF, comorbidities, screening and diagnosis of OSA, treatment of OSA prior to ablation, time from ablation to recurrence of AF, method of ablation (radiofrequency or cryo). Statistical comparison between patients with and without OSA was made, including survival curves and Cox regression to determine time to recurrence and adjust for confounding variables. Results A total of 189 patients were included with a mean age of 63.49±11.09 years. Mean follow-up time after ablation was 2.76±1.56 years. Patients who recurred after ablation had undergone more electrical cardioversions prior to the procedure (1.640±1.583 vs 0.800±0.966, p 0.002), had more persistent AF (p 0.036) and had more OSA (32.7% vs 15.7%, p=0.011). There were no differences regarding age, gender, body-mass index, history of hypertension, diabetes, chronic kidney disease or heart failure, method of ablation and diagnosis of OSA prior to ablation. Forty-nine patients (18.7%) had OSA, with only 16 (32.7%) having been diagnosed before ablation. OSA was screened in only 60 cases (31.7%), mostly due to symptoms (76.1%) and not per protocol. Patients with OSA had earlier recurrence of AF after ablation (p Log-rank 0.012) with a hazard two times greater of recurrence, even after adjusting for confounding (p 0.026; hazard-ratio 2.025; confidence interval 95% 1.086–3.775). One year recurrence rate was 31% in patients with OSA (vs 15%). Regarding patients under treatment for OSA prior to ablation, there was no difference in survival (p Log-rank 0.859). Conclusion In real-world practice, OSA is still a largely underinvestigated condition that significantly impairs AF control and contributes to worse cardiovascular outcomes. Recurrence was 2 times higher in patients with OSA. No impact of treatment in time to recurrence was found. Efforts must be made to increase screening of this condition in order to improve outcomes. Further studies are needed to clarify the benefits of OSA treatment in AF recurrence. Funding Acknowledgement Type of funding sources: None.

S837 Risk of Adverse Cardiovascular Outcomes in Postmenopausal Women With Inflammatory Bowel Disease

S837 Risk of Adverse Cardiovascular Outcomes in Postmenopausal Women With Inflammatory Bowel Disease

Development and Internal Validation of a Risk Prediction Model for Acute Cardiovascular Morbidity in Preeclampsia.

Women with preeclampsia are at increased short-term risk of adverse cardiovascular outcomes during pregnancy and the early postpartum period. We aimed to develop and internally validate a risk assessment tool to predict acute cardiovascular morbidity in preeclampsia. The study was conducted at an academic obstetrics hospital. Participants with preeclampsia at delivery from 2007 to 2017 were included. A model to predict acute cardiovascular morbidity at delivery and within 6 weeks after delivery was developed and evaluated. The primary composite outcome included pulmonary edema/acute heart failure, myocardial infarction, aneurysm, cardiac arrest/ventricular fibrillation, heart failure/arrest during surgery or procedure, cerebrovascular disorders, cardiogenic shock, conversion of cardiac rhythm, and difficult-to-control severe hypertension. We assessed model discrimination and calibration. We used bootstrapping for internal validation. A total of 4171 participants with preeclampsia were included. The final model comprised 8 variables. Predictors positively associated with acute cardiovascular morbidity (presented as odds ratio with 95% confidence interval) were: gestational age at delivery (20-36 weeks: 5.36 [3.67-7.82]; 37-38 weeks: 1.75 [1.16-2.64]), maternal age (≥ 40 years: 1.65 [1.00-2.72]; 35-39 years: 1.49 [1.07-2.09]), and previous caesarean delivery (1.47 [1.01-2.13]). The model had an area under the receiver operating characteristic curve of 0.72 (95% CI 0.69-0.74). Moreover, it was adequately calibrated and performed well on internal validation. This risk prediction tool identified women with preeclampsia at highest risk of acute cardiovascular morbidity. If externally validated, this tool may facilitate early interventions aimed at preventing adverse cardiovascular outcomes in pregnancy and postpartum.

Non-High-Density Lipoprotein Cholesterol and Cardiovascular Outcomes in Chronic Kidney Disease: Results from KNOW-CKD Study.

As non-high-density lipoprotein cholesterol (non-HDL-C) levels account for all atherogenic lipoproteins, serum non-HDL-C level has been suggested to be a marker for cardiovascular (CV) risk stratification. Therefore, to unveil the association of serum non-HDL-C levels with CV outcomes in patients with non-dialysis chronic kidney disease (ND-CKD), the patients at stages 1 to 5 (n = 2152) from the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD) were prospectively analyzed. The subjects were divided into quintiles by serum non-HDL-C level. The primary outcome was a composite of all-cause death or non-fatal CV events. The median duration of follow-up was 6.940 years. The analysis using the Cox proportional hazard model unveiled that the composite CV event was significantly increased in the 5th quintile (adjusted hazard ratio 2.162, 95% confidence interval 1.174 to 3.981), compared to that of the 3rd quintile. A fully adjusted cubic spline model depicted a non-linear, J-shaped association between non-HDL-C and the risk of a composite CV event. The association remained robust in a series of sensitivity analyses, including the analysis of a cause-specific hazard model. Subgroup analyses reveled that the association is not significantly altered by clinical conditions, including age, gender, body mass index, estimated glomerular filtration rate, and albuminuria. In conclusion, high serum non-HDL-C level increased the risk of adverse CV outcomes among the patients with ND-CKD. Further studies are warranted to define the optimal target range of non-HDL-C levels in this population.

Erectile dysfunction, phosphodiesterase-5 inhibitor use and risk of cardiovascular disease and mortality in people with diabetes: A systematic review and meta-analysis

BackgroundPhosphodiesterase-5 inhibitors (PDE5-Is), used in the management of erectile dysfunction (ED), have potential cardioprotective benefits. The impact of PDE5-Is on reducing adverse cardiovascular outcomes in patients with diabetes mellitus (DM) and ED is uncertain. Using a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs), we evaluated if (i) the association of PDE5-Is in people with ED and DM and their risk of cardiovascular disease (CVD) and mortality and (ii) ED confers an excess risk of CVD and mortality in patients with DM compared with no DM. MethodsStudies were identified from MEDLINE, Embase, the Cochrane Library, Web of Science citation search and search of bibliographies to April 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. ResultsEighteen unique studies reported on the cardiovascular impact of ED in patients with and without DM. In the general population, the RRs (95% CIs) of ED for composite CVD/MACE, all-cause mortality, CHD and stroke were 1.43 (1.31–1.55), 1.47 (1.31–1.65), 1.59 (1.39–1.82), and 1.34 (1.15–1.56), respectively. The respective estimates were 1.68 (1.15–2.45), 1.40 (0.90–2.18), 1.41 (1.24–1.61) and 1.32 (1.09–1.60) in the diabetes population. Interaction analyses suggested similar risk in both populations. Six studies reported the cardiovascular effects of PDE5-Is in people with ED and DM. Limited RCT data showed no significant differences in the risk of major adverse cardiac event (MACE), coronary heart disease (CHD) and all-cause mortality comparing PDE5-I use with non-use: RRs (95% CIs) of 3.47 (0.17–69.19), 1.31 (0.10–16.54) and 0.35 (0.12–1.05), respectively. ConclusionsED confers no excess risk of CVD and mortality in patients with DM compared with no DM. Limited and inadequately powered data shows no significant differences in the risk of adverse cardiovascular outcomes comparing use of PDE5-Is with non-use in patients with ED and DM.PROSPERO Registration: CRD42022324537