Francisca Caetano

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.

Estimating glomerular filtration rate in acute coronary syndromes: Different equations, different mortality risk prediction

Aims: Renal dysfunction is a powerful predictor of adverse outcomes in patients hospitalized for acute coronary syndrome. Three new glomerular filtration rate (GFR) estimating equations recently emerged, based on serum creatinine (CKD-EPIcreat), serum cystatin C (CKD-EPIcyst) or a combination of both (CKD-EPIcreat/cyst), and they are currently recommended to confirm the presence of renal dysfunction. Our aim was to analyse the predictive value of these new estimated GFR (eGFR) equations regarding mid-term mortality in patients with acute coronary syndrome, and compare them with the traditional Modification of Diet in Renal Disease (MDRD-4) formula. Methods and results: 801 patients admitted for acute coronary syndrome (age 67.3±13.3 years, 68.5% male) and followed for 23.6±9.8 months were included. For each equation, patient risk stratification was performed based on eGFR values: high-risk group (eGFR<60ml/min per 1.73m2) and low-risk group (eGFR⩾60ml/min per 1.73m2). The predictive performances of these equations were compared using area under each receiver operating characteristic curves (AUCs). Overall risk stratification improvement was assessed by the net reclassification improvement index. The incidence of the primary endpoint was 18.1%. The CKD-EPIcyst equation had the highest overall discriminate performance regarding mid-term mortality (AUC 0.782±0.20) and outperformed all other equations (ρ<0.001 in all comparisons). When compared with the MDRD-4 formula, the CKD-EPIcyst equation accurately reclassified a significant percentage of patients into more appropriate risk categories (net reclassification improvement index of 11.9% (p=0.003)). The CKD-EPIcyst equation added prognostic power to the Global Registry of Acute Coronary Events (GRACE) score in the prediction of mid-term mortality. Conclusion: The CKD-EPIcyst equation provides a novel and improved method for assessing the mid-term mortality risk in patients admitted for acute coronary syndrome, outperforming the most widely used formula (MDRD-4), and improving the predictive value of the GRACE score. These results reinforce the added value of cystatin C as a risk marker in these patients.

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.

ACHTUNG-Rule: a new and improved model for prognostic assessment in myocardial infarction

Background: Thrombolysis In Myocardial Infarction (TIMI), Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (PURSUIT) and Global Registry of Acute Coronary Events (GRACE) scores have been developed for risk stratification in myocardial infarction (MI). The latter is the most validated score, yet active research is ongoing for improving prognostication in MI. Aim: Derivation and validation of a new model for intrahospital, post-discharge and combined/total all-cause mortality prediction – ACHTUNG-Rule – and comparison with the GRACE algorithm. Methods: 1091 patients admitted for MI (age 68.4 ± 13.5, 63.2% males, 41.8% acute MI with ST-segment elevation (STEMI)) and followed for 19.7 ± 6.4 months were assigned to a derivation sample. 400 patients admitted at a later date at our institution (age 68.3 ± 13.4, 62.7% males, 38.8% STEMI) and followed for a period of 7.2 ± 4.0 months were assigned to a validation sample. Three versions of the ACHTUNG-Rule were developed for the prediction of intrahospital, post-discharge and combined (intrahospital plus post-discharge) all-cause mortality prediction. All models were evaluated for their predictive performance using the area under the receiver operating characteristic (ROC) curve, calibration through the Hosmer–Lemeshow test and predictive utility within each individual patient through the Brier score. Comparison through ROC curve analysis and measures of risk reclassification – net reclassification improvement index (NRI) or Integrated Discrimination Improvement (IDI) – was performed between the ACHTUNG versions for intrahospital, post-discharge and combined mortality prediction and the equivalent GRACE score versions for intrahospital (GRACE-IH), post-discharge (GRACE-6PD) and post-admission 6-month mortality (GRACE-6). Results: Assessment of calibration and overall performance of the ACHTUNG-Rule demonstrated a good fit (p value for the Hosmer–Lemeshow goodness-of-fit test of 0.258, 0.101 and 0.550 for ACHTUNG-IH, ACHTUNG-T and ACHTUNG-R, respectively) and high discriminatory power in the validation cohort for all the primary endpoints (intrahospital mortality: AUC ACHTUNG-IH 0.886 ± 0.035 vs. AUC GRACE-IH 0.906 ± 0.026; post-discharge mortality: AUC ACHTUNG-R 0.827 ± 0.036 vs. AUC GRACE-6PD 0.811 ± 0.034; combined/total mortality: AUC ACHTUNG-T 0.831 ± 0.028 vs. AUC GRACE-6 0.815 ± 0.033). Furthermore, all versions of the ACHTUNG-Rule accurately reclassified a significant number of patients in different, more appropriate, risk categories (NRI ACHTUNG-IH 17.1%, p (2-sided) = 0.0021; NRI ACHTUNG-R 22.0%, p = 0.0002; NRI ACHTUNG-T 18.6%, p = 0.0012). The prognostic performance of the ACHTUNG-Rule was similar in both derivation and validation samples. Conclusions: All versions of the ACHTUNG-Rule have shown excellent discriminative power and good calibration for predicting intrahospital, post-discharge and combined in-hospital plus post-discharge mortality. The ACHTUNG version for intrahospital mortality prediction was not inferior to its equivalent GRACE model, and ACHTUNG versions for post-discharge and combined/total mortality demonstrated apparent superiority. External validation in wider, independent, preferably multicentre, registries is warranted before its potential clinical implementation.

Expressão fenotípica da miocardiopatia hipertrófica e realce tardio na ressonância magnética cardíaca

INTRODUCTION AND AIM The prognostic value of late gadolinium enhancement (LGE) for risk stratification of hypertrophic cardiomyopathy (HCM) patients is the subject of disagreement. We set out to examine the association between clinical and morphological variables, risk factors for sudden cardiac death and LGE in HCM patients. METHODS From a population of 78 patients with HCM, we studied 53 who underwent cardiac magnetic resonance. They were divided into two groups according to the presence or absence of LGE. Ventricular arrhythmias and morbidity and mortality during follow-up were analyzed. RESULTS Patients with LGE were younger at the time of diagnosis (p=0.046) and more often had a family history of sudden death (p=0.008) and known coronary artery disease (p=0.086). On echocardiography they had greater maximum wall thickness (p=0.007) and left atrial area (p=0.037) and volume (p=0.035), and more often presented a restrictive pattern of diastolic dysfunction (p=0.011) with a higher E/É ratio (p=0.003) and left ventricular systolic dysfunction (p=0.038). Cardiac magnetic resonance supported the association between LGE and previous echocardiographic findings: greater left atrial area (p=0.029) and maximum wall thickness (p<0.001) and lower left ventricular ejection fraction (p=0.056). Patients with LGE more often had an implantable cardioverter-defibrillator (ICD) (p=0.015). At follow-up, no differences were found in the frequency of ventricular arrhythmias, appropriate ICD therapies or mortality. CONCLUSIONS The presence of LGE emerges as a risk marker, associated with the classical predictors of sudden cardiac death in this population. However, larger studies are required to confirm its independent association with clinical events.

Fabry disease presenting as apical left ventricular hypertrophy in a patient carrying the missense mutation R118C

Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by abnormalities of the GLA gene, which encodes the enzyme α-galactosidase A. A deficiency of this enzyme leads to the lysosomal accumulation of glycosphingolipids, which may cause left ventricular hypertrophy that is typically concentric and symmetric. We present the case of a 60-year-old woman with symptoms of dyspnea, atypical chest pain and palpitations, in whom a transthoracic echocardiogram revealed an apical variant of hypertrophic cardiomyopathy. Analysis of specific sarcomeric genetic mutations was negative. The patient underwent a screening protocol for Anderson-Fabry disease, using a dried blood spot test, which was standard at our institution for patients with left ventricular hypertrophy. The enzymatic activity assay revealed reduced α-galactosidase A enzymatic activity. Molecular analysis identified a missense point mutation in the GLA gene (p.R118C). This case report shows that Anderson-Fabry disease may cause an apical form of left ventricular hypertrophy. The diagnosis was only achieved because of systematic screening, which highlights the importance of screening for Anderson-Fabry disease in patients with unexplained left ventricular hypertrophy, including those presenting with more unusual patterns, such as apical variants of left ventricular hypertrophy. This case also supports the idea that the missense mutation R118C is indeed a true pathogenic mutation of Anderson-Fabry disease.

Continuous infusion or bolus injection of loop diuretics for patients admitted for severe acute heart failure: Is one strategy better than the other?

INTRODUCTION AND OBJECTIVES Intravenous loop diuretics are an essential part of acute heart failure management; however, data to guide their use is sparse. Our aim was to compare continuous intravenous infusion of loop diuretics with intravenous bolus administration in terms of efficacy and adverse events in patients admitted with severe acute heart failure. METHODS Over a period of three years, 110 patients were admitted to our cardiac intensive care unit with acute heart failure. Clinical, laboratory and prognostic parameters were compared according to the diuretic strategy used and mortality and readmission for acute heart failure during follow-up were analyzed. RESULTS Previous medical history was similar in the two groups. At admission, the continuous infusion group met criteria for worse prognosis: lower systolic blood pressure (p=0.011), more severe renal injury (p=0.008), lower left ventricular ejection fraction (p=0.016) and higher incidence of restrictive pattern of diastolic dysfunction (p=0.032). They were more often treated with vasopressors (p=0.003), inotropes (p=0.010), renal support therapy (p=0.003) and non-invasive ventilation (p<0.001). They had longer hospitalizations (p=0.014) and a higher incidence of cardiorenal syndrome (p=0.009); however, at discharge, there were no differences in renal function between the groups. In-hospital mortality was similar, and during follow-up there were no differences in mortality or readmission for acute heart failure. CONCLUSIONS Continuous infusion was preferred in patients presenting with worse clinical status, in whom renal dysfunction was transiently worse. However, in-hospital mortality and creatinine at discharge were similar. Continuous infusion thus appears to counteract the initial dire prognosis of more unstable patients.

Síndrome cardiorrenal na insuficiência cardíaca aguda: um círculo vicioso?

INTRODUCTION AND OBJECTIVE Worsening renal function has an unquestionably negative impact on prognosis in patients with acute heart failure (HF). In Portugal there is little information about the importance of this entity in HF patients admitted to hospital. The objective of this work was to assess the prevalence of cardiorenal syndrome and to identify its key predictors and consequences in patients admitted for acute HF. METHODS This was a retrospective study of 155 patients admitted for acute HF. Cardiorenal syndrome was defined as an increase in serum creatinine of ≥26.5 μmol/l. Clinical, laboratory and echocardiographic parameters were analyzed and compared. Mortality was assessed at 30 and 90 days. RESULTS Cardiorenal syndrome occurred in 46 patients (29.7%), 5.4 ± 4.4 days after admission; 66.7% (n=24) did not recover baseline creatinine levels. The factors associated with cardiorenal syndrome were older age, chronic renal failure, moderate to severe mitral regurgitation, higher admission blood urea nitrogen, creatinine and troponin I, and lower glomerular filtration rate. Patients who developed cardiorenal syndrome had longer hospital stay, were treated with higher daily doses of intravenous furosemide, and more often required inotropic support and renal replacement therapy. They had higher in-hospital and 30-day mortality, and multivariate analysis identified cardiorenal syndrome as an independent predictor of in-hospital mortality. CONCLUSIONS Renal dysfunction is common in acute HF patients, with a negative impact on prognosis, which highlights the importance of preventing kidney damage through the use of new therapeutic strategies and identification of novel biomarkers.

Gradiente elevado no trato de saída do ventrículo esquerdo: estenose aórtica, miocardiopatia hipertrófica obstrutiva ou ambas?

The authors report the case of a patient diagnosed with both hypertrophic cardiomyopathy and aortic stenosis. Due to clinical deterioration, additional investigation was performed, and a high left ventricular outflow tract gradient was identified. Correct identification of the condition causing the symptoms was challenging, and involved several imaging techniques, the contribution of transesophageal echocardiography being crucial. The final diagnosis of severe aortic stenosis led to successful valve replacement surgery. The presence of these two conditions in the same patient has been documented, although it is uncommon. This association poses particular diagnostic and therapeutic challenges, which are discussed in this paper.

Padrão de Brugada tipo 1 induzido pela febre

Brugada syndrome, first described over 20 years ago, is characterized by a typical electrocardiographic pattern with coved-type ST-segment elevation in the right precordial leads and a high risk of sudden death in otherwise healthy young adults. The electrocardiographic pattern is sometimes intermittent, and fever is a possible trigger. The authors present the case of a 68-year-old woman who came to the emergency department with fever and syncope. A diagnosis of community-acquired pneumonia was made. The electrocardiogram performed when the patient had fever revealed a type 1 Brugada pattern, which disappeared after the fever subsided. After other causes of Brugada-like pattern were excluded, Brugada syndrome was diagnosed and a cardioverter-defibrillator was implanted. This case demonstrates that this entity can be diagnosed at more advanced ages and highlights the usefulness of electrocardiography in a febrile state.