Paulo Dinis

Stroke prediction with an adjusted R-CHA2DS2VASc score in a cohort of patients with a Myocardial Infarction

INTRODUCTION A new risk stratification scheme incorporating the original CHADS2 score and renal function, entitled R(2)CHADS(2), was validated in the ROCKET-AF and ATRIA study cohorts. AIMS Adjusting and validating a modified R-CHA2DS2VASc score as a predictor of ischaemic stroke and all-cause mortality in patients discharged following admission for a Myocardial Infarction (MI). MATERIALS AND METHODS Observational retrospective single-centre cohort study including 1711 patients admitted with MI and discharged alive. We tested the prognostic performance of R-CHA2DS2VASc, based on the original CHA2DS2VASc score with few modifications (addition of renal function parameters [glomerular filtration rate and urea], performance of a revascularization procedure and history of atrial fibrillation). R-CHA2DS2VASc was evaluated for its discriminative performance and calibration in the prediction of ischaemic stroke (primary endpoint), all-cause mortality and a composite endpoint of ischemic stroke plus all-cause mortality (secondary outcomes) during follow-up. RESULTS R-CHA2DS2VASc scores areas under the curve (AUC) for the occurrence of primary and secondary outcomes were: Ischaemic stroke: AUC 0.717 ± 0.031, p<0.001 (vs. 0.681 ± 0.043 for CHA2DS2VASc, p=0.290); all-cause mortality during follow-up: AUC 0.811 ± 0.014, p<0.001 (vs. 0.782 ± 0.019 for GRACE, p=0.245); composite endpoint: AUC 0.803 ± 0.014, p<0.001. The integrated discrimination improvement index (IDI) and relative IDI for the primary endpoint were 0.015 and 28.2%, respectively, while the IDI and relative IDI for all-cause mortality were 0.13 and 72.1%, suggesting a large improvement in risk stratification. An R-CHA2DS2VASc score below 3 had a negative predictive value of 98.6% for the occurrence of ischaemic stroke. CONCLUSIONS The modified R-CHA2DS2VASc score has shown good calibration and high discriminative performance in the prediction of post-discharge ischaemic stroke and all-cause mortality. The inclusion of renal function in thromboembolic risk predicting schemes seems warranted.

BLEED-Myocardial Infarction Score: Predicting mid-term post-discharge bleeding events

AIM To derive and validate a score for the prediction of mid-term bleeding events following discharge for myocardial infarction (MI). METHODS One thousand and fifty patients admitted for MI and followed for 19.9 ± 6.7 mo were assigned to a derivation cohort. A new risk model, called BLEED-MI, was developed for predicting clinically significant bleeding events during follow-up (primary endpoint) and a composite endpoint of significant hemorrhage plus all-cause mortality (secondary endpoint), incorporating the following variables: age, diabetes mellitus, arterial hypertension, smoking habits, blood urea nitrogen, glomerular filtration rate and hemoglobin at admission, history of stroke, bleeding during hospitalization or previous major bleeding, heart failure during hospitalization and anti-thrombotic therapies prescribed at discharge. The BLEED-MI model was tested for calibration, accuracy and discrimination in the derivation sample and in a new, independent, validation cohort comprising 852 patients admitted at a later date. RESULTS The BLEED-MI score showed good calibration in both derivation and validation samples (Hosmer-Lemeshow test P value 0.371 and 0.444, respectively) and high accuracy within each individual patient (Brier score 0.061 and 0.067, respectively). Its discriminative performance in predicting the primary outcome was relatively high (c-statistic of 0.753 ± 0.032 in the derivation cohort and 0.718 ± 0.033 in the validation sample). Incidence of primary/secondary endpoints increased progressively with increasing BLEED-MI scores. In the validation sample, a BLEED-MI score below 2 had a negative predictive value of 98.7% (152/154) for the occurrence of a clinically significant hemorrhagic episode during follow-up and for the composite endpoint of post-discharge hemorrhage plus all-cause mortality. An accurate prediction of bleeding events was shown independently of mortality, as BLEED-MI predicted bleeding with similar efficacy in patients who did not die during follow-up: Area Under the Curve 0.703, Hosmer-Lemeshow test P value 0.547, Brier score 0.060; low-risk (BLEED-MI score 0-3) event rate: 1.2%; intermediate risk (score 4-6) event rate: 5.6%; high risk (score ≥ 7) event rate: 12.5%. CONCLUSION A new bedside prediction-scoring model for post-discharge mid-term bleeding has been derived and preliminarily validated. This is the first score designed to predict mid- term hemorrhagic risk in patients discharged following admission for acute MI. This model should be externally validated in larger cohorts of patients before its potential implementation.

Improving risk stratification in non-ST-segment elevation myocardial infarction with combined assessment of GRACE and CRUSADE risk scores

BACKGROUND Risk assessment is fundamental in the management of acute coronary syndromes (ACS), enabling estimation of prognosis. AIMS To evaluate whether the combined use of GRACE and CRUSADE risk stratification schemes in patients with myocardial infarction outperforms each of the scores individually in terms of mortality and haemorrhagic risk prediction. METHODS Observational retrospective single-centre cohort study including 566 consecutive patients admitted for non-ST-segment elevation myocardial infarction. The CRUSADE model increased GRACE discriminatory performance in predicting all-cause mortality, ascertained by Cox regression, demonstrating CRUSADE independent and additive predictive value, which was sustained throughout follow-up. The cohort was divided into four different subgroups: G1 (GRACE<141; CRUSADE<41); G2 (GRACE<141; CRUSADE≥41); G3 (GRACE≥141; CRUSADE<41); G4 (GRACE≥141; CRUSADE≥41). RESULTS Outcomes and variables estimating clinical severity, such as admission Killip-Kimbal class and left ventricular systolic dysfunction, deteriorated progressively throughout the subgroups (G1 to G4). Survival analysis differentiated three risk strata (G1, lowest risk; G2 and G3, intermediate risk; G4, highest risk). The GRACE+CRUSADE model revealed higher prognostic performance (area under the curve [AUC] 0.76) than GRACE alone (AUC 0.70) for mortality prediction, further confirmed by the integrated discrimination improvement index. Moreover, GRACE+CRUSADE combined risk assessment seemed to be valuable in delineating bleeding risk in this setting, identifying G4 as a very high-risk subgroup (hazard ratio 3.5; P<0.001). CONCLUSIONS Combined risk stratification with GRACE and CRUSADE scores can improve the individual discriminatory power of GRACE and CRUSADE models in the prediction of all-cause mortality and bleeding. This combined assessment is a practical approach that is potentially advantageous in treatment decision-making.

Encerramento percutâneo de foramen ovale patente – registo da prevenção da embolia cerebral paradoxal

INTRODUCTION The natural history and therapeutic interventions for secondary prevention after a cerebrovascular event in patients with patent foramen ovale (PFO) are not yet established. This study aims to assess the safety and efficacy of percutaneous PFO closure in a population of patients with ischemic cerebrovascular disease of unknown etiology. METHODS This prospective observational study included patients with a history of cryptogenic transient ischemic attack (TIA) or stroke who underwent percutaneous PFO closure. The effectiveness of the device for the secondary prevention of TIA or stroke was assessed by comparing observed events in the sample with expected events for this clinical setting. RESULTS The sample included 193 cases of percutaneous PFO closure (age 46.4 ± 13.1 years, 62.2% female) with a mean follow-up of 4.3 ± 2.2 years, corresponding to a total exposure to ischemic events of 542 patient-years. The high-risk characteristics of the PFO were assessed prior to device implantation. There were seven primary endpoint events during follow-up (1.3 per 100 patient-years), corresponding to a relative risk reduction of 68.2% in recurrent TIA or stroke compared to medical therapy alone. The procedure was associated with a low rate of device- or intervention-related complications (1.5%). CONCLUSIONS In this long-term registry, percutaneous PFO closure was shown to be a safe and effective therapy for the secondary prevention of cryptogenic stroke or TIA.

Remodelagem cardíaca induzida pelo exercício físico em atletas de nível competitivo e militares de forças especiais

INTRODUCTION Exercise-induced cardiac remodeling is frequent in athletes. This adaptation is structurally manifested by an increase in cardiac dimensions and mass. Soldiers are also subject to intense physical exercise, although with different characteristics. OBJECTIVE To compare exercise-induced cardiac remodeling in competitive athletes and in soldiers on a special forces training course. METHODS We studied 17 soldiers (all male and Caucasian, mean age 21±3 years) who completed a special forces course and 17 basketball players (47.3% male, 64.7% Caucasian, mean age 21±3 years). Assessment included a transthoracic echocardiogram and analysis of myocardial mechanics. This assessment was performed at the beginning and end of the military course and the sports season, respectively. RESULTS Cardiac remodeling was observed in both groups. The soldiers presented a predominantly eccentric pattern, with increased left ventricular (LV) size (49.7±3.2 vs. 52.8±3.4 mm; p<0.01), increased LV mass (93.1±7.7 vs. 100.2±11.4 g/m2; p<0.01) and decreased relative wall thickness (0.40±0.1 vs. 0.36±0.1; p=0.05). The basketball players showed a concentric pattern, with decreased LV size (52.0±4.7 vs. 50.4±4.7 mm; p=0.05), and increased relative wall thickness (0.33±0.1 vs. 0.36±0.1; p=0.05). Although there was no significant difference in LV myocardial strain in the groups separately, when compared there was a significant decrease (-20.2±1.6% vs. -19.4±2.1%; p=0.03). CONCLUSION Cardiac remodeling was frequent, with an eccentric pattern in soldiers and a concentric pattern in basketball players. Myocardial deformation may represent a physiological adaptation to physical exercise.

Device entrapped in subvalvular apparatus: A surprising result

( u ( S E t l m S d p 58 days after admission (one month after the procedure). This case illustrates a rare and dramatic complication of percutaneous leak closure, but without significant hemodynamic impact on mitral valve and LV function. A 72-year old woman with a history of mechanical aortic prosthesis since 2010 and early infective prosthetic endocarditis (medical treatment) was hospitalized for acute heart failure in February 2015. Transesophageal echocardiography showed a severe paravalvular leak in the posterior portion of the aortic prosthesis (Figure 1A, arrow) and a pseudoaneurysm with fistulization to the left ventricle (LV) and aorta (Figure 1B, arrow), moderate mitral regurgitation and mild LV systolic dysfunction. Surgery was considered high risk and percutaneous closure of the paravalvular leak was attempted. The procedure was guided by fluoroscopy and transesophageal echocardiography. After confirming the stability of the device (Amplatzer ® Vascular Plug II 12 mm/9 mm) and reduction of the paravalvular leak without functional compromise of the mechanical prosthesis

Additional Cardiac Remodeling Induced by Intense Military Training in Competitive Athletes

Since the 19th century, cardiac adaptations induced by physical exercise have been known. Henschen, in 1899, recognized cardiomegaly in long distance skiers through percussion of heart borders, concluding that this increase was related to cavity dilatation and wall hypertrophy of the left ventricle (LV), and that these changes resulted in physical benefits for the athletes.1,2 With the evolution of complementary diagnostic means, mainly echocardiography, Morganroth et al.,3 in 1975, developed the hypothesis that cardiac morphological changes depended on hemodynamic overload associated with physical exercise: dynamic exercise associated with eccentric hypertrophy due to volume overload, resulting in increased cardiac cavities by serial sarcomere addition; and static exercise associated with concentric hypertrophy due to pressure overload, with LV wall hypertrophy and parallel sarcomere addition.3-5 209

Does percutaneous left atrial appendage closure affect left atrial performance

Mailing Address:: Marta Madeira Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra Quinta dos Vales, S. Martinho do Bispo. Postal Code: 3045-043, Coimbra Portugal E-mail: marta.jesus.madeira@gmail.com Does Percutaneous Left Atrial Appendage Closure Affect Left Atrial Performance? Marta Madeira,*1,2 Rogério Teixeira,*1,2 Liliana Reis,1 Paulo Dinis,1 Luís Paiva,1,2 Ana Botelho,1 Marco Costa,1 Lino Gonçalves1,2 Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra Hospital Geral,1 Coimbra Portugal Faculdade de Medicina da Universidade de Coimbra,2 Coimbra Portugal * Both authors contributed equally to the paper

Myocardial deformation and volume of exercise: a new overlap between pathology and athlete’s heart?

Regular physical exercise induces cardiac adaptations that can overlap pathological conditions. Controversy still persists about the variability of myocardial deformation in different types and intensity of exercise. The aim of this study was to assess myocardial longitudinal deformation in athletes with different level of exercise. Two groups of young athletes involved in endurance sports characterized by high intensity dynamic component were enrolled. According to the level and the number of exercise training hours/week, two groups were defined: Group 1—high level (national/international and ≥ 20 training-hours/week; N = 60); Group 2—low level (recreational/regional and < 10 training-hours/week; N = 48). A comprehensive transthoracic echocardiogram including evaluation of global longitudinal strain (GLS) assessed by 2D speckle-tracking was performed. Athletes in Group 1 showed more pronounced cardiac remodeling and enhanced diastolic function. No significant differences were evident in left ventricle ejection fraction (LVEF) between groups. Overall, GLS (absolute values) was 18.0 ± 2.5%, but significantly lower in Group 1 compared to Group 2 (17.3 ± 2.6% vs. 18.9 ± 2.1%; p = 0.001). Thirty-three (31%) athletes had GLS below 17%, more frequently in Group 1 (79% vs. 45%; p = 0.001), with higher LV and left atrium volumes, lower E wave and A wave peak velocities and E/e′ ratio. In a multivariate analysis to belong to Group 1 was the only independent variable associated with GLS < 17% (OR 6.5; 95% CI 2.4–17.4; p < 0.001). The athletes with a GLS < 17% were all men, more frequently involved in high level exercise, with higher chamber volumes and lower E/e′ ratio. Left ventricular global myocardial longitudinal deformation evaluated by GLS was significantly lower in athletes with higher level of exercise. Although GLS in athletes overlap several pathological conditions, these lower values are associated with an enhanced diastolic performance that allows discrimination between physiologic adaptations and pathology.

Eosinophilic Myocarditis: Clinical Case and Literature Review

Eosinophilic myocarditis is a rare and potentially lethal disease characterized by eosinophil infiltration of the myocardium.1 The association between eosinophilia and myocardial injury is well established and may present several etiologies, from hypersensitivity and autoimmune diseases to neoplasias and infections.1,2 In some cases the etiology remains unknown, and it is denominated idiopathic hypereosinophilic syndrome. Clinical manifestations present a wide spectrum, ranging from mild symptomatology to severe symptoms such as retrosternal pain, rhythm disturbances, and sudden death.2,3 The definitive diagnosis is made through endomyocardial biopsy.1 Cardiac magnetic resonance imaging is a valid alternative, identifying the main structural changes caused by myocarditis.4 Treatment includes neurohumoral therapy, management of cardiac complications, and in cases selected, systemic corticosteroid therapy.5 Next, we present the case of a patient with symptomatology suggestive of myocardial infarction, but who in the course of the investigation had the diagnosis of eosinophilic myocarditis.