The current clinical practice for management of post-infarction ventricular septal rupture: a European survey.

Aims: Many historical and recent reports showed that post-infarction ventricular septal rupture (VSR) represents a life-threatening condition and the strategy to optimally manage it remains undefined. Therefore, disparate treatment policies among different centres with variable results are often described. We analysed data from European centres to capture the current clinical practice in VSR management. Methods and results: Thirty-nine centres belonging to eight European countries participated in a survey, filling a digital form of 38 questions from April to October 2022, to collect information about all the aspects of VSR treatment. Most centres encounter 1-5 VSR cases/year. Surgery remains the treatment of choice over percutaneous closure (71.8% vs. 28.2%). A delayed repair represents the preferred approach (87.2%). Haemodynamic conditions influence the management in almost all centres, although some try to achieve patients stabilization and delayed surgery even in cardiogenic shock. Although 33.3% of centres do not perform coronarography in unstable patients, revascularization approaches are widely variable. Most centres adopt mechanical circulatory support (MCS), mostly extracorporeal membrane oxygenation, especially pre-operatively to stabilize patients and achieve delayed repair. Post-operatively, such MCS are more often adopted in patients with ventricular dysfunction. Conclusion: In real-life, delayed surgery, regardless of the haemodynamic conditions, is the preferred strategy for VSR management in Europe. Extracorporeal membrane oxygenation is becoming the most frequently adopted MCS as bridge-to-operation. This survey provides a useful background to develop dedicated, prospective studies to strengthen the current evidence on VSR treatment and to help improving its currently unsatisfactory outcomes.

Adverse Clinical Outcomes and Associated Predictors in Rivaroxaban-Treated Atrial Fibrillation Patients With Renal Impairment.

Renal impairment confers worse prognosis in patients with atrial fibrillation (AF) but there is scarce evidence about the influence of direct-acting oral anticoagulants in routine clinical practice. Herein, we compared clinical outcomes between patients with AF with and without renal impairment on rivaroxaban and investigated predictors for clinical outcomes in patients with AF with renal impairment. This was a multicenter study including patients with AF on rivaroxaban for at least 6 months. During 2.5 years follow-up, ischemic strokes (IS)/transient ischemic attacks (TIA)/systemic embolisms (SE)/myocardial infarctions (MI), major bleeding, and major adverse cardiovascular events (MACE) were recorded. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault equation, renal impairment was defined as a CrCl <60 ml/min, and 1,433 patients (34.8% with CrCl <60 ml/min) were included. Patients with CrCl <60 ml/min showed higher event rates for major bleeding (1.87%/year vs 0.62%/year; p = 0.003) and MACE (1.97%/year vs 0.62%/year; p = 0.002) but similar event rates for IS/TIA/SE/MI (0.66%/year vs 0.67%/year; p = 0.955). In patients with renal impairment, CHA2DS2-VASc was associated with higher risk of IS/TIA/SE/MI; HAS-BLED and any dependency level were associated with higher risk of major bleeding; and male gender and heart failure were associated with higher risk of MACE. Antiplatelets were independently associated with increased risk of IS/TIA/SE/MI and MACE. In conclusion, in patients with AF on rivaroxaban, the incidence of IS/TIA/SE/MI did not increase in those with renal impairment, suggesting that rivaroxaban may be an effective option in this subgroup. In patients with AF, male gender, heart failure, dependency, antiplatelets, CHA2DS2-VASc, and HAS-BLED were associated with increased risk of adverse outcomes.

Outcomes and drivers of inappropriate dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVE: There has been limited systematic evaluation of outcomes and drivers of inappropriate non-vitamin K antagonist oral anticoagulants (NOACs) dosing among patients with atrial fibrillation (AF). This review identified and systematically evaluated literature on clinical and economic outcomes of inappropriate NOAC dosing and associated patient characteristics. METHODS: MEDLINE, Embase, Cochrane Library, International Pharmaceutical Abstracts, Econlit, PubMed and NHS EEDs databases were searched for English language observational studies from all geographies published between 2008 and 2020, examining outcomes of, or factors associated with, inappropriate NOAC dosing in adult patients with AF. RESULTS: One hundred and six studies were included in the analysis. Meta-analysis showed that compared with recommended NOAC dosing, off-label underdosing was associated with a null effect on stroke outcomes (ischaemic stroke and stroke/transient ischaemic attack (TIA), stroke/systemic embolism (SE) and stroke/SE/TIA). Meta-analysis of 15 studies examining clinical outcomes of inappropriate NOAC dosing found a null effect of underdosing on bleeding outcomes (major bleeding HR=1.04, 95% CI 0.90 to 1.19; p=0.625) but an increased risk of all-cause mortality (HR=1.28, 95% CI 1.10 to 1.49; p=0.006). Overdosing was associated with an increased risk of major bleeding (HR=1.41, 95% CI 1.07 to 1.85; p=0.013). No studies were found examining economic outcomes of inappropriate NOAC dosing. Narrative synthesis of 12 studies examining drivers of inappropriate NOAC dosing found that increased age, history of minor bleeds, hypertension, congestive heart failure and low creatine clearance (CrCl) were associated with an increased risk of underdosing. There was insufficient evidence to assess drivers of overdosing. CONCLUSIONS: Our analysis suggests that off-label underdosing of NOACs does not reduce bleeding outcomes. Patients prescribed off-label NOAC doses are at an increased risk of all-cause mortality. These data underscore the importance of prescriber adherence to NOAC dosing guidelines to achieve optimal clinical outcomes for patients with AF. PROSPERO REGISTRATION NUMBER: CRD42020219844.

Predicting performance of the HAS-BLED and ORBIT bleeding risk scores in patients with atrial fibrillation treated with Rivaroxaban: Observations from the prospective EMIR Registry.

BACKGROUND: Assessing bleeding risk during the decision-making process of starting oral anticoagulation (OAC) therapy in atrial fibrillation (AF) patients is essential. Several bleeding risk scores have been proposed for vitamin K antagonist users but, few studies have focused on validation of these bleeding risk scores in patients taking direct oral anticoagulants (DOACs). The aim was to compare the predictive ability of HAS-BLED and ORBIT bleeding risk scores in AF patients taking rivaroxaban in the EMIR ('Estudio observacional para la identificación de los factores de riesgo asociados a eventos cardiovasculares mayores en pacientes con fibrilación auricular no valvular tratados con un anticoagulante oral directo [Rivaroxaban]) Study. METHODS AND RESULTS: EMIR Study was an observational, multicenter, post-authorization, and prospective study that involved AF patients under OAC with rivaroxaban at least 6 months before enrolment. We analysed baseline clinical characteristics and adverse events after 2.5 years of follow-up and validated the predictive ability of HAS-BLED and ORBIT scores for major bleeding (MB) events.We analysed 1433 patients with mean age of 74.2 ± 9.7 (44.5% female). Mean HAS-BLED score was 1.6 ± 1.0 and ORBIT score was 1.1 ± 1.2. The ORBIT score categorised a higher proportion of patients as 'low-risk' (87.1%) compared with 53.5% using the HAS-BLED score. There were 33 MB events (1.04%/year) and 87 patients died (2.73%/year). Both HAS-BLED and ORBIT had a good predictive ability for MB{Area under the curve (AUC) 0.770, [95% confidence interval (CI) 0.693-0.847; P <0.001] and AUC 0.765 (95% CI 0.672-0.858; P <0.001), respectively}. There was a non-significant difference for discriminative ability of the two tested scores (P = 0.930) and risk reclassification in terms of net reclassification improvement (NRI) -5.7 (95% CI -42.4-31.1; P = 0.762). HAS-BLED score showed the best calibration and ORBIT score showed the largest mismatch in calibration, particularly in higher predicted risk patients. CONCLUSION: In a prospective real-world AF population under rivaroxaban from EMIR registry, the HAS-BLED score had good predictive performance and calibration compared with ORBIT score for MB events. ORBIT score presented worse calibration than HAS-BLED in this DOAC treated population.

Impact of heart failure on the clinical profile and outcomes in patients with atrial fibrillation treated with rivaroxaban. Data from the EMIR study.

BACKGROUND: The aim of this study was to analyze the impact of the presence of heart failure (HF) on the clinical profile and outcomes in patients with atrial fibrillation (AF) anticoagulated with rivaroxaban. METHODS: Observational and non-interventional study that included AF adults recruited from 79 Spanish centers, anticoagulated with rivaroxaban ≥ 6 months before inclusion. Data were analyzed according to baseline HF status. RESULTS: Out of 1,433 patients, 326 (22.7%) had HF at baseline. Compared to patients without HF, HF patients were older (75.3 ± 9.9 vs. 73.8 ± 9.6 years; p = 0.01), had more diabetes (36.5% vs. 24.3%; p < 0.01), coronary artery disease (28.2% vs. 12.9%; p < 0.01), renal insufficiency (31.7% vs. 22.6%; p = 0.01), higher CHA2DS2-VASc (4.5 ± 1.6 vs. 3.2 ± 1.4; p < 0.01) and HAS-BLED (1.8 ± 1.1 vs. 1.5 ± 1.0; p < 0.01). After a median follow-up of 2.5 years, among HF patients, annual rates of stroke/systemic embolism/transient ischemic attack, major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, revascularization and cardiovascular death), cardiovascular death, and major bleeding were 1.2%, 3.0%, 2.0%, and 1.4%, respectively. Compared to those patients without HF, HF patients had greater annual rates of MACE (3.0% vs. 0.5%; p < 0.01) and cardiovascular death (2.0% vs. 0.2%; p < 0.01), without significant differences regarding other outcomes, including thromboembolic or bleeding events. Previous HF was an independent predictor of MACE (odds ratio 3.4; 95% confidence interval 1.6-7.3; p = 0.002) but not for thromboembolic events or major bleeding. CONCLUSIONS: Among AF patients anticoagulated with rivaroxaban, HF patients had a worse clinical profile and a higher MACE risk and cardiovascular mortality. HF was independently associated with the development of MACE, but not with thromboembolic events or major bleeding.

Effect of Duration of Anticoagulation in the Incidence of Stroke in Patients With Left-Ventricular Thrombus.

The optimal duration of anticoagulation in patients with left-ventricular thrombus (LVT) is unclear. In the present study, we aimed to analyze the effect of treatment duration (≤12 months [short-term anticoagulation, (STA)] versus >12 months [long-term anticoagulation, (LTA)]) in the incidence of stroke and other secondary outcomes (acute myocardial infarction, bleeding, and mortality). Multivariate Cox regression was used to determine the association between treatment duration and stroke, adjusted for baseline embolic risk. A total of 98 cases of LVT (age 64.3 ± 12.8 years, female 18 [18%]) were identified. Sixty-one patients (62%) received LTA. Patients receiving LTA were older than those receiving STA (66.5 ± 11.6 vs 60.7 ± 13.9 years, p = 0.029), more often had atrial fibrillation (31% vs 0%, p <0.001), and had a higher CHA2DS2-VASc score (4.3 ± 1.6 vs 3.6 ± 1.6, p = 0.046). Stroke occurred in 2 and 10 patients (3% vs 27%, p <0.001), acute myocardial infarction in 2 and 3 patients (3% vs 8%, p = 0.292), bleeding in 4 and 3 patients (7% vs 8%, p = 0.773), and mortality in 12 and 7 patients (20% vs 19%, p = 0.927) in the LTA and STA groups, respectively. In multivariate analysis, after adjusting for embolic risk, LTA was associated with decreased risk of stroke at 5 years (adjusted hazard ratio 0.16; 95% confidence interval 0.03 to 0.72, p = 0.017). In conclusion, our data suggest that prolonged anticoagulation in patients with LVT may be associated with significantly lower risk of stroke.

Outcomes and predictive value of the 2MACE score in patients with atrial fibrillation treated with rivaroxaban in a prospective, multicenter observational study: The EMIR study.

BACKGROUND: The aim of the study was to evaluate the performance of the 2MACE in patients with atrial fibrillation (AF) treated with rivaroxaban and to improve the accuracy of 2MACE. METHODS: This was a post-authorization and observational study of AF adults treated with rivaroxaban for ≥ 6 months. The primary endpoint was any of the major adverse cardiac events (MACE), namely, cardiovascular death, non-fatal myocardial infarction, and myocardial revascularization. The area under the curve (AUC) was calculated to evaluate the performance of 2MACE, and a new score, 2MACER to predict MACE. RESULTS: A total of 1433 patients were included (74.2 ± 9.7 years, CHA2DS2-VASc 3.5 ± 1.5, 26.9% 2MACE ≥ 3). The annual event rates (follow-up 2.5 years) were 1.07% for MACE, 0.66% for thromboembolic events and 1.04% for major bleeding. Patients with 2MACE ≥ 3 (vs. < 3) had higher risk of stroke/systemic embolism/transient ischemic attack (odds ratio [OR] 5.270; 95% CI 2.216-12.532), major bleeding (OR 4.624; 95% CI 2.163-9.882), MACE (OR 3.202; 95% CI 1.548-6.626) and cardiovascular death (OR 3.395; 95% CI 1.396-8.259). 2MACE was recalculated giving 1 more point to patients with baseline a glomerular filtration rate < 50 mL/min/1.73 m² (2MACER); 2MACER vs. 2MACE: IDI 0.1%, p = 0.126; NRI 23.9%, p = 0.125; AUC: 0.651 (95% CI 0.547-0.755) vs. 0.638 (95% CI 0.534-0.742), respectively; p = 0.361. CONCLUSIONS: In clinical practice, AF patients anticoagulated with rivaroxaban exhibit a low risk of events. 2MACE score acts as a modest predictor of a higher risk of adverse outcomes in this population. 2MACER did not significantly increase the ability of 2MACE to predict MACE.

Optimal surgical timing after post-infarction ventricular septal rupture.

BACKGROUND: Ventricular septal rupture (VSR) following acute myocardial infarction (AMI) is a dangerous condition. Surgical VSR closure is the definitive therapy, but there is controversy regarding the surgical timing and the bridging therapy between diagnosis and intervention. The objective of this study is to analyze the ideal time of surgical repair and to establish the contribution of mechanical circulatory support (MCS) devices on the prognosis. METHODS: We designed an observational, retrospective, multicenter study, selecting all consecutive patients with post-AMI VSR between January 1, 2008 and December 31, 2018, with non-exclusion criteria. The main objective of this study was to analyze the optimal timing for surgical repair of post-AMI VSR. Secondary endpoints were to determine which factors could influence mortality in the patients of the surgical group. RESULTS: A total of 141 patients were included. We identified lower mortality rates with an odds ratio of 0.3 (0.1-0.9) in patients operated on from day 4 compared with the surgical mortality in the first 24 hours after VSR diagnosis. The use of MCS was more frequent in patients treated with surgery, particularly for intra-aortic balloon pump (IABP; 79.6% vs. 37.8%, p < 0.001), but also for veno-arterial extracorporeal membrane oxygenation (VA-ECMO; 18.2% vs. 6.4%, p = 0.134). Total mortality was 91.5% for conservative management and 52.3% with surgical repair (p < 0.001). CONCLUSIONS: In our study, we observed that the lowest mortality rates in patients with surgical repair of post-AMI VSR were observed in patients operated on from day 4 after diagnosis of VSR, compared to earlier interventions.

Use of rivaroxaban attenuates renal function impairment in patients with atrial fibrillation: insights of the EMIR study.

BACKGROUND: In atrial fibrillation (AF) patients on vitamin K antagonists, a progressive deterioration of renal function is common but there is limited evidence with long-term use of rivaroxaban. Herein, we investigated the change in renal function in AF patients after 2 years of rivaroxaban treatment. METHODS: The EMIR registry is an observational and multicentre study including AF patients treated with rivaroxaban for at least 6 months prior to inclusion. Changes in analytical parameters were recorded during 2 years of follow-up. Renal function was estimated using the Cockroft-Gault equation. RESULTS: 1433 patients (638, 44.5% women, mean age of 74.2 ± 9.7 years) were included. Creatinine clearance (CrCl) was available at baseline and at 2 years in 1085 patients. At inclusion, 33.2% of patients had impaired renal function (CrCl <60 ml/min). At 2 years, we were not able to find changes in the proportion of patients with impaired renal function, which increased to 34.6% (p = 0.290). However, the baseline mean CrCl was 76.0 ± 30.5 ml/min and slightly improved at 2 years (77.0 ± 31.8 ml/min; p = 0.014). Overall, the proportion of patients with CrCl <60 ml/min at baseline that had CrCl ≥60 ml/min at 2 years was significantly higher compared to that of patients with CrCl ≥60 ml/min at baseline and CrCl <60 ml/min after (22.2% vs. 13.1%; p < 0.001) CONCLUSIONS: In AF patients on long-term rivaroxaban therapy, a decrease in renal function was not observed. We even observed a slight improvement in the patients with renal impairment. These results reinforce the idea that rivaroxaban may be a safe option even in patients with renal impairment.

In-hospital outcomes of mechanical complications in acute myocardial infarction: Analysis from a nationwide Spanish database.

BACKGROUND: Mechanical complications represent an important cause of mortality in myocardial infarction (MI) patients. This is a nationwide study performed to evaluate possible changes in epidemiology or prognosis of these complications with current available strategies. METHODS: Information was obtained from the minimum basis data set of the Spanish National Health System, including all hospitalizations for acute myocardial infarction (AMI) from 2010 to 2015. Risk-standardized in-hospital mortality ratio was calculated using multilevel risk adjustment models. RESULTS: A total of 241,760 AMI episodes were analyzed, MI mechanical complications were observed in 842 patients: cardiac tamponade in 587, ventricular septal rupture in 126, and mitral regurgitation due to papillary muscle or chordae tendineae rupture in 155 (there was more than one complication in 21 patients). In-hospital mortality was 59.5%. On multivariate adjustment, variables with significant impact on in-hospital mortality were: age (OR 1.06; 95% CI 1.04-1.07; p < 0.001), ST-segment elevation AMI (OR 2.91; 95% CI 1.88-4.5; p < 0.001), cardiogenic shock (OR 2.35; 95% CI 1.66-3.32; p < 0.001), cardio-respiratory failure (OR 3.48; 95% CI 2.37-5.09; p < 0.001), and chronic obstructive pulmonary disease (OR 1.85; 95% CI 1.07-3.20; p < 0.001). No significant trends in risk-adjusted in-hospital mortality were detected (IRR 0.997; p = 0.109). Cardiac intensive care unit availability and more experience with mechanical complications management were associated with lower adjusted mortality rates (56.7 ± 5.8 vs. 60.1 ± 4.5; and 57 ± 6.1 vs. 59.9 ± 5.6, respectively; p < 0.001). CONCLUSIONS: Mechanical complications occur in 3.5 per thousand AMI, with no significant trends to better survival over the past few years. Advanced age, cardiogenic shock and cardio-respiratory failure are the most important risk factors for in-hospital mortality. Higher experience and specialized cardiac intensive care units are associated with better outcomes.

Temporal trends in postinfarction ventricular septal rupture: the CIVIAM Registry.

INTRODUCTION AND OBJECTIVES: Postinfarction ventricular septal rupture is a rare but severe complication of myocardial infarction with high mortality rates. Our goal was to analyze which factors could have an impact on mortality due to this entity over the past decade, including those related to mechanical circulatory support. METHODS: The CIVIAM registry is an observational, retrospective, multicenter study carried out in Spain. We designed a comparative analysis, focused on description of in-hospital management and in-hospital and 1-year total mortality as the primary endpoints, dividing the total observation time into 2 equal temporal periods (January 2008 to June2013 and July 2013 to December 2018). RESULTS: We included 120 consecutive patients. Total mortality during this period was 61.7% at 1-year follow-up. Patients in the second period were younger. One-year mortality was significantly reduced in the second period (75.6% vs 52.7%, P=.01), and this result was confirmed after adjustment by confounding factors (OR, 0.40; 95%CI, 0.17-0.98). Surgical repair was attempted in 58.7% vs 70.3%, (P=.194), and percutaneous closure in 8.7% and 6.8%, respectively (P=.476). Heart transplant was performed in 1 vs 5 patients (2.2% vs 6.8%, P=.405). The main difference in the clinical management between the 2 periods was the greater use of venoarterial extracorporeal membrane oxygenatiom in the second half of the study period (4.4% vs 27%; P=.001). CONCLUSIONS: Postinfarction ventricular septal rupture still carries a very high mortality risk. There has been a progressive trend to increased support with venoarterial extracorporeal membrane oxygenatiom and greater access to available corrective treatments, with higher survival rates.

Prevención secundaria antitrombótica intensiva tardía luego de un infarto del miocardio ¿Cuándo, en quiénes y cómo? / Late intensive antithrombotic secondary prevention after myocardial infarction. When, in whom and how?

La probabilidad de nuevos eventos cardiovasculares mayores (ECVM) en pacientes luego de un infarto agudo del miocardio depende de diferentes variables, como el tiempo que haya pasado después del primer evento, el escenario de presentación (síndrome coronario agudo con/sin elevación del ST) y los factores de riesgo asociados. Dichos eventos se han relacionado con la respuesta proinflamatoria persistente1, la actividad plaquetaria y la actividad de la trombina2. La llegada de medicamentos con actividad antitrombótica más potente y específica en puntos clave del proceso trombótico ha permitido evaluar su efecto en el escenario de la prevención secundaria antitrombótica intensiva luego del primer año de un infarto del miocardio3. En este tipo de prevención se han propuesto diferentes estrategias terapéuticas, entre ellas se ha extendiendo la doble terapia antiplaquetaria (DTA) (4, iniciando terapias antiplaquetarias adicionales5, o usando dosis bajas de anticoagulantes directos más aspirina6. Sin embargo, las características similares y, a su vez, heterogéneas en esta población, generan dudas de cuándo, en quiénes y cómo usar este tipo de terapia.

Contemporary differences between men and women with acute coronary syndromes: CIAM multicenter registry.

AIM: Differences exist in the diagnosis and treatment of acute coronary syndrome (ACS) between men and women. However, recent advancements in the management of ACSs might have attenuated this sex gap. We evaluated the status of ACS management in a multicenter registry in 10 tertiary Spanish hospitals. METHODS: We enrolled 1056 patients in our study, including only those with type 1 myocardial infarctions or unstable angina presumably not related to a secondary cause in an 'all-comers' design. RESULTS: The women enrolled (29%) were older than men (71.0 ±â€Š12.8 vs. 64.0 ±â€Š12.3, P = 0.001), with a higher prevalence of hypertension (71.0 vs. 56.5%, P < 0.001), insulin-treated diabetes (13.7 vs. 7.9%, P = 0.003), dyslipidemia (62.2 vs. 55.3%, P = 0.038), and chronic kidney disease (16.9 vs. 9.1%, P = 0.001). Women presented more frequently with back or arm pain radiation (57.3 vs. 49.7%, P = 0.025), palpitations (5.9 vs. 2.0%, P = 0.001), or dyspnea (33.0 vs. 19.4%, P = 0.001). ACS without significant coronary stenosis was more prevalent in women (16.8 vs. 8.1%, P = 0.001). There were no differences in percutaneous revascularization rates, but drug-eluting stents were less frequently employed in women (75.4 vs. 67.8%, P = 0.024); women were less often referred to a cardiac rehabilitation program (19.9 vs. 33.9%, P = 0.001). There were no significant differences in in-hospital complications such as thrombosis or bleeding. CONCLUSION: ACS presenting with atypical symptoms and without significant coronary artery stenosis is more frequent in women. Selection of either an invasive procedure or conservative management is not influenced by sex. Cardiac rehabilitation referral on discharge is underused, especially in women.