Use of apixaban in adults with congenital heart disease and atrial arrhythmias: The PROTECT-AR study.

BACKGROUND: Adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) face an increased risk of thromboembolic events. Limited data exist on the use of non-vitamin K oral anticoagulants for thromboprophylaxis in ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA. METHODS: PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia on routine apixaban treatment were included. The historical control group consisted of patients previously on vitamin K antagonist (VKA), who were analyzed prior to their transition to apixaban. The primary effectiveness endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. RESULTS: The study enrolled 218 ACHD patients with AA on apixaban, of which 73 were previous VKA users. The analysis covered 527 patient-years of prospective exposure to apixaban and 169 patient-years of retrospective exposure to VKA. The annualized rate of stroke or thromboembolism was 0.6% in the apixaban group and 1.8% in the VKA group (absolute difference - 1.2%; upper limit of one-sided 95% confidence interval [CI] 0.9%, lower than the predefined non-inferiority margin of +1.8%, Pnon-inferiority < 0.001). The annualized rate of major bleeding was 1.5% in the apixaban group and 2.4% in the VKA group (hazard ratio 0.64; 95% CI 0.19-2.10, P = 0.48). CONCLUSION: In ACHD patients with AA, routine apixaban use exhibited a non-inferior rate of stroke or thromboembolism compared to historical VKA use, alongside a similar rate of major bleeding.

Association of Health Status Metrics with Clinical Outcomes in Patients with Adult Congenital Heart Disease and Atrial Arrhythmias.

The prognostic value of health status metrics in patients with adult congenital heart disease (ACHD) and atrial arrhythmias is unclear. In this retrospective cohort study of an ongoing national, multicenter registry (PROTECT-AR, NCT03854149), ACHD patients with atrial arrhythmias on apixaban are included. At baseline, health metrics were assessed using the physical component summary (PCS), the mental component summary (MCS) of the Short-Form-36 (SF-36) Health Survey, and the modified European Heart Rhythm Association (mEHRA) score. Patients were divided into groups according to their SF-36 PCS and MCS scores, using the normalized population mean of 50 on the PCS and MCS as a threshold. The primary outcome was the composite of mortality from any cause, major thromboembolic events, major/clinically relevant non-major bleedings, or hospitalizations. Multivariable Cox-regression analyses using clinically relevant parameters (age greater than 60 years, anatomic complexity, ejection fraction of the systemic ventricle, and CHA2DS2-VASc and HAS-BLED scores) were performed to examine the association of health metrics with the composite outcome. Over a median follow-up period of 20 months, the composite outcome occurred in 50 of 158 (32%) patients. The risk of the outcome was significantly higher in patients with SF-36 PCS ≤ 50 compared with those with PCS > 50 (adjusted hazard ratio (aHR), 1.98; 95% confidence interval [CI], 1.02−3.84; p = 0.04) after adjusting for possible confounders. The SF-36 MCS ≤ 50 was not associated with the outcome. The mEHRA score was incrementally associated with a higher risk of the composite outcome (aHR = 1.44 per 1 unit increase in score; 95% CI, 1.03−2.00; p = 0.03) in multivariable analysis. In ACHD patients with atrial arrhythmias, the SF-36 PCS ≤ 50 and mEHRA scores predicted an increased risk of adverse events.

The Adult Congenital Heart Disease Anatomic and Physiological Classification: Associations with Clinical Outcomes in Patients with Atrial Arrhythmias.

The implications of the adult congenital heart disease anatomic and physiological classification (AP-ACHD) for risk assessment have not been adequately studied. A retrospective cohort study was conducted using data from an ongoing national, multicentre registry of patients with ACHD and atrial arrhythmias (AA) receiving apixaban (PROTECT-AR study, NCT03854149). At enrollment, patients were stratified according to Anatomic class (AnatC, range I to III) and physiological stage (PhyS, range B to D). A follow-up was conducted between May 2019 and September 2021. The primary outcome was a composite of death from any cause, any major thromboembolic event, major or clinically relevant non-major bleeding, or hospitalization. Cox proportional-hazards regression modeling was used to evaluate the risks for the outcome among AP-ACHD classes. Over a median 20-month follow-up period, 47 of 157 (29.9%) ACHD patients with AA experienced the composite outcome. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for the outcome in PhyS C and PhyS D were 1.79 (95% CI 0.69 to 4.67) and 8.15 (95% CI 1.52 to 43.59), respectively, as compared with PhyS B. The corresponding aHRs in AnatC II and AnatC III were 1.12 (95% CI 0.37 to 3.41) and 1.06 (95% CI 0.24 to 4.63), respectively, as compared with AnatC I. In conclusion, the PhyS component of the AP-ACHD classification was an independent predictor of net adverse clinical events among ACHD patients with AA.

Rationale and design of a prospective, observational, multicentre study on the safety and efficacy of apixaban for the prevention of thromboembolism in adults with congenital heart disease and atrial arrhythmias: the PROTECT-AR study.

INTRODUCTION: The risk for stroke in adults with congenital heart disease (ACHD) is increased, especially in the setting of commonly ensuing atrial arrhythmias (AA), namely atrial fibrillation, atrial flutter or intra-atrial re-entrant tachycardia. Data are limited regarding treatment with non-vitamin K oral anticoagulants in long-term studies involving patients with ACHD and AA. METHODS AND ANALYSIS: PReventiOn of ThromboEmbolism in Adults with Congenital HearΤ disease and Atrial aRrhythmias is a prospective, multicenter, single-arm, non-interventional cohort study designed to investigate the safety and efficacy of apixaban for the prevention of thromboembolism in ACHD with AA in a 'real-world' setting. Eligible patients will be evaluated by the means of available registries and clinical counter. The study aims to accumulate approximately 500 patient-years of exposure to apixaban as part of routine care. Enrolment will take place at four ACHD centres in Greece. The first patient was enrolled in July 2019. The primary efficacy endpoint is a composite of stroke, systemic or pulmonary embolism and intracardiac thrombosis. The primary safety endpoint is major bleeding, according to the International Society on Thrombosis and Haemostasis bleeding criteria. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board/independent ethics committee at each site prior to study commencement. All patients will provide written informed consent. Results will be disseminated at scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03854149; Pre-results.

Treatment practices and lipid profile of patients with acute coronary syndrome: results from a tertiary care hospital.

Background: Considering the increasing burden of cardiovascular risk factors and recent advances on the management of acute coronary syndromes (ACS), we studied the epidemiological characteristics and treatment strategies of patients presenting with ACS. We also evaluated the lipid profile and attainment of lipid goals in a 'real world' clinical setting.Methods: This was a substudy of IDEAL-LDL (Motivational interviewing to support low-density lipoprotein cholesterol (LDL-C) therapeutic goals and lipid-lowering therapy compliance in patients with acute coronary syndromes), a single-centre, prospective, randomised controlled trial. Baseline data from a total of 357 ACS patients were gathered using standardised methods.Results: Median age of patients was 60 years and 81.2% were males. Arterial hypertension and smoking were the most prevalent risk factors for coronary artery disease (CAD). Patients with ST-elevation myocardial infarction (STEMI) were heavier smokers, but were younger and exercised more compared to those with non-ST-elevation acute coronary syndrome (NSTE-ACS). Conversely, more NSTE-ACS patients had arterial hypertension, dyslipidaemia and diabetes mellitus. One-fifth of ACS patients was treated conservatively without a percutaneous coronary intervention (PCI). A combination of statin, dual antiplatelet therapy and beta-blockers were prescribed to 79.6% of patients upon discharge. A renin-angiotensin-aldosterone system inhibitor and a beta-blocker were prescribed to 67.3 and 91.8% of patients with LVEF ≤40%, respectively. Of patients with prior history of CAD, 63.1%, 71.4% and 58.3% received regularly statins, antiplatelets and beta-blocker treatment, respectively. Only 22.3% of these CAD patients had an optimal LDL-C of <70 mg/dl at admission.Conclusions: In hospitalised patients with ACS, management practices differed by ACS type and discharge medication was, mostly, in line with the latest guidelines. However, medication adherence and lipid lowering goals of secondary CAD prevention were largely unachieved.

Motivational interviewing to support LDL-C therapeutic goals and lipid-lowering therapy compliance in patients with acute coronary syndromes (IDEAL-LDL) study: rationale and design.

BACKGROUND: Achieving low-density lipoprotein cholesterol (LDL-C) target levels after an acute coronary syndrome (ACS) is of paramount importance, and is often burdened by undertreatment and medication or lifestyle non-adherence issues. OBJECTIVE: We examined the effect of a patient-centered, physician-led motivational intervention following ACS on relevant secondary prevention aspects. METHODS-DESIGN: The IDEAL-LDL is a single-center, randomized controlled clinical trial, conducted among patients hospitalized due to an ACS. Following discharge, all patients undergo a baseline assessment of lipid profile. Patients in the intervention group receive an in-person educational session and an informative leaflet, and also undergo two phone-based, motivational interviewing sessions at 1 and 6 months. These interventions emphasize on LDL-C goals, adherence to lipid-lowering medication, and healthy dietary-lifestyle habits, and are not provided to patients in the control group, who receive usual care. At 12 months after each patient's discharge, an in-person interview and lipid profile reassessment are performed. The primary outcomes are the assessment of LDL-C goal achievement (<70 mg/dL or >50% reduction from baseline levels) from baseline to 1 year and changes in medication adherence. Secondary outcomes relate to the incidence of the composite outcome of cardiovascular death, nonfatal myocardial infarction/stroke, need for myocardial revascularization, and recurrent hospitalization during the follow-up period. DISCUSSION: This paper describes the protocol, design, and rationale for key methodology for an ongoing clinical trial featuring a simple and feasible intervention. Similar adherence efficacy trials have not led to sufficient improvements, and there remains a gap regarding how adherence interventions should be implemented into clinical care.

Iatrogenic Lutembacher Syndrome after Percutaneous Mitral Commissurotomy.

Atrial septal defects (ASDs) are common immediately after percutaneous mitral commissurotomy (PMC). They are usually small, hemodynamically insignificant, and tend to decrease or disappear within 6 to 12 months. Herein, a case is described of persistent ASD in a patient with mitral valve stenosis who had undergone successful PMC three years previously. The patient had signs and symptoms of right heart failure and severe tricuspid regurgitation (TR) with borderline right ventricular systolic function on echocardiography, in addition to the ASD. Cardiac magnetic resonance (CMR) imaging played a significant role in decision-making by clarifying the anatomy of the ASD and severity of the shunt, measuring right ventricular systolic function, and providing absolute quantification for TR. The right ventricular systolic function was normal on CMR, rendering the patient suitable for surgical treatment. Persistent iatrogenic ASDs have become an increasingly common finding after invasive procedures requiring trans-septal puncture and the manipulation of catheters. Multimodality imaging can provide significant aid in the management of patients with valvular heart disease complicated by iatrogenic shunts.

Pregnancy in Patients With Congenital Heart Disease: A Contemporary Challenge.

The majority of female patients with congenital heart disease (CHD) survives into childbearing age and require evidence-based counseling regarding pregnancy options. Even though most of them will have an uneventful pregnancy, they may be at high risk of cardiac, obstetric, and fetal complications. Predictive factors for these complications have been previously identified in numerous studies and with the use of specific scores [CARdiac disease in PREGnancy, Zwangerschap bij Aangeboren HARtAfwijkingen, and World Health Organization (WHO) risk stratification.] Importantly, the subtype of CHD is of vital importance for the pregnancy outcome. Considering the above, the multidisciplinary management of these pregnant patients by experts in the field of CHD is imperative.

The role of catheter ablation in the management of patients with implantable cardioverter defibrillators presenting with electrical storm.

OBJECTIVE: Electrical storm (ES) is not uncommon among patients with an implantable cardioverter defibrillator (ICD) in situ. Catheter ablation (CA) may suppress the arrhythmia in the acute setting and prevent ES recurrence. METHODS: Nineteen consecutive patients with an ICD in situ presenting with ES underwent electrophysiologic studies followed by CA. CA outcome was classified as a complete success if both clinical and non-clinical tachycardia were successfully ablated, partial success if ≥1 non-clinical tachycardia episodes were still inducible post-CA, and failure if clinical tachycardia could not be abolished. Patients were followed for a median period (IQR) of 5.6 (1.8-13.7) months. The primary endpoint was event-free survival from ES recurrence. The secondary endpoint was event-free survival from a composite of ES and/or sustained ventricular tachycardia (VT) recurrence. RESULTS: Clinical arrhythmia was successfully ablated in 14 out of 19 (73.7%) cases after a single CA procedure. A completely successful CA outcome was associated with significantly increased ES-free survival compared with a partially successful or failed procedure (Log rank P=0.039). Nevertheless, patients with acute suppression of all tachycardia episodes (n=11), relative to those with a partially successful or a failed CA procedure (n=8), did not differ in incidence of the composite endpoint of sustained VT or ES (Log rank P=0.278). CONCLUSION: A single CA procedure can acutely suppress clinical arrhythmia in three-quarters of cases. A completely successful CA outcome can prolong ES-free survival; however, sporadic ICD therapies cannot be abrogated.

Initial Experience with Renal Denervation for the Treatment of Resistant Hypertension - The Utility of Novel Anesthetics and Metaiodobenzylguanidine Scintigraphy (MIBG).

BACKGROUND: The Symplicity-HTN 3 trial failed to show significant difference in blood pressure (BP) lowering between patients undergoing catheter-based renal denervation (RDN) and the sham-procedure arm of the study. However, there is still optimism about the role of RDN in the treatment of resistant hypertension, because identification of patients with increased sympathetic activity thus being good RDN responders, improvements in the RDN procedure and new technology RDN catheters are all expected to lead to better RDN results. We present our initial experience with RDN for the treatment of resistant hypertension, and the utility of novel anesthetics and cardiac (123)I-metaiodobenzylguanidine scintigraphy ((123)I-MIBG). METHODS AND RESULTS: Seven patients with resistant hypertension underwent RDN and were followed up for 6 months. MIBG was performed before RDN, in order to estimate sympathetic activity and predict the response to RDN. All patients were sedated with dexmedetomidine and remifentanil during RDN. All patients tolerated the procedure well, were hemodynamically stable and their peri-procedural pain was effectively controlled. A median of 7.6 ± 2.1 and 6 ± 1.4 ablations were delivered in the right and left renal artery respectively, making an average of 6.8 burns per artery. No peri-procedural or late complications - adverse events (local or systematic) occurred. At 6 months, mean reduction in office BP was -26.0/-16.3 mmHg (p=0.004/p=0.02), while mean reduction in ambulatory BP was -12.3/-9.2 mmHg (p=0.118/p=0.045). One patient (14.3%) was a non-responder. None of the cardiac (123)I-MIBG imaging indexes(early and late heart-to-mediastinum (H/M) count density ratio, washout rate (WR) of the tracer from the myocardium) were different between responders and non-responders. CONCLUSION: Patients with resistant hypertension who underwent RDN in our department had a significant reduction in BP 6 months after the intervention. (123)I-MIBG was not useful in predicting RDN response. Dexmedetomidine and remifentanil provided sufficient patient comfort during the procedure, allowing an adequate number of ablations per renal artery to be performed, and this could probably lead to improved RDN results.