António Leitão Marques

LR-PED rule: low risk pulmonary embolism decision rule - a new decision score for low risk pulmonary embolism.

INTRODUCTIONnWhen accurately diagnosed, non-massive Pulmonary embolism (PE) has a low mortality rate. However, some patients initially considered to be low risk show progressive deterioration. This research aims at developing a preliminary score that allows detection of low risk patients potentially eligible for outpatient treatment.nnnMATERIALS AND METHODSnRetrospective cohort study involving 142 asymptomatic/mildly symptomatic and hemodynamically stable patients with PE and no clinical/echocardiographic signs of right ventricular dysfunction. Collected data: risk factors, analytic/gasometric parameters, admission echocardiogram, thoracic CT angiography. Patients followed for 6months. Primary endpoint: 1-month all-cause mortality. Secondary endpoints: Intrahospital and 6-month all-cause mortality. A score designed for identification of very low risk patients eligible for outpatient treatment was developed and its prognostic accuracy compared to that of the Geneva and simplified PESI models.nnnRESULTSnA score for predicting 1-month mortality (Low Risk Pulmonary Embolism Decision [LR-PED] rule) was obtained using Binary Logistic Regression, including: age, atrial fibrillation at admission, previous heart failure, admission heart rate, creatinine, glycaemia, troponin I and C-reactive protein at admission. ROC curve analysis assessed its overall accuracy for predicting 1-month, intrahospital and 6-month mortality (AUC=0.756, 0.763 and 0.854, respectively). Compared to Geneva and simplified PESI, the LR-PED rule showed higher sensitivity and negative predictive value for the detection of the lowest risk patients. The net reclassification improvement index revealed significant successful upward risk reclassification by the LR-PED model of patients reaching primary or secondary outcomes.nnnCONCLUSIONSnLR-PED rule seems more attractive than Geneva or simplified PESI in its ability to identify patients at very low mortality risk who would be potentially eligible for outpatient treatment. Prospective validation of this score in larger cohorts is mandatory before its potential implementation.

Cardiovascular Risk Assessment of Pulmonary Embolism With the GRACE Risk Score

Despite the existence of several risk scores, the accurate prediction of the prognosis in pulmonary embolism (PE) remains a challenge. The Global Registry of Acute Coronary Events (GRACE) risk score has a high diagnostic performance for adverse outcomes in acute coronary syndrome. We aimed to assess the applicability and extend the use of the GRACE risk score to PE. A case-control study of 206 consecutive patients admitted with PE was performed. The GRACE, Geneva, Simplified Pulmonary Embolism Severity Index, Shock Index, and European Society of Cardiology risk scores were tested for the prediction of the primary end point: all-cause 30-day mortality. Comparisons between GRACE and the other risk scores were performed using receiver operating characteristic area under the curve and the integrated discrimination improvement index. All-cause 30-day mortality was observed in 18.9% of the patients. Unlike the other classifications, no adverse outcomes were observed in patients classified as low risk using the GRACE risk score (100% negative predictive value for GRACE risk score ≤113). The GRACE score showed greater discriminative performance than the Geneva score (area under the curve 0.623, 95% confidence interval [CI] 0.53 to 0.71), Shock Index (area under the curve 0.639, 95% CI 0.55 to 0.73), European Society of Cardiology (area under the curve 0.662, 95% CI 0.57 to 0.76), and Simplified Pulmonary Embolism Severity Index (area under the curve 0.705, 95% CI 0.61 to 0.80), although statistical significance was not reached. The integrated discrimination improvement index suggested a more appropriate risk classification with the GRACE score. In conclusion, our results have demonstrated that the GRACE risk score can accurately predict 30-day mortality in patients admitted for acute PE. Compared to previously proposed PE prediction rules, the GRACE risk score presented improved overall risk classification.

Atrial fibrillation in acute pulmonary embolism: prognostic considerations

Aims Although it is accepted that atrial fibrillation (AF) may be both the contributing factor and the consequence of pulmonary embolism (PE), data on the prognostic role of AF in patients with acute venous thromboembolism are scarce. Our aim was to study whether AF had a prognostic role in patients with acute PE. Methods Retrospective cohort study involving 270 patients admitted for acute PE. Collected data: past medical history, analytic/gasometric parameters, admission ECG and echocardiogram, thoracic CT angiography. Patients followed for 6u2005months. An analysis was performed in order to clarify whether history of AF, irrespective of its timing, helps predict intrahospital, 1-month and 6-month all-cause mortality. Results Patients with history of AF, irrespective of its timing (n=57, 21.4%), had higher intrahospital (22.8% vs 13.1%, p=0.052, OR 2.07, 95% CI 0.98 to 4.35), 1-month (35.1% vs 16.9%, p=0.001, OR 3.16, 95% CI 1.61 to 6.21) and 6-month (45.6% vs 17.4%, p<0.001, OR 4.67, 95% CI 2.37 to 9.21) death rates. The prognostic power of AF was independent of age, NT-proBNP values, renal function and admission blood pressure and heart rate and additive to mortality prediction ability of simplified PESI (AF: p=0.021, OR 2.31, CI 95% 1.13 to 4.69; simplified PESI: p=0.002, OR 1.47, CI 95% 1.15 to 1.89). The presence of AF at admission added prognostic value to previous history of AF in terms of 1-month and 6-month all-cause mortality prediction, although it did not increase risk for intrahospital mortality. Conclusions The presence of AF, irrespective of its timing, may independently predict mortality in patients with acute PE. These data should be tested and validated in prospective studies using larger cohorts.

A Review on State-of-the-Art Data Regarding Safe Early Discharge Following Admission for Pulmonary Embolism: What Do We Know?

Although most patients with acute pulmonary embolism (PE) remain hospitalized during initial therapy, some may be suitable for partial or complete outpatient management, which may have a significant impact on healthcare costs.

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

INTRODUCTIONnA 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.nnnAIMSnAdjusting 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).nnnMATERIALS AND METHODSnObservational 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.nnnRESULTSnR-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.nnnCONCLUSIONSnThe 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

AIMnTo derive and validate a score for the prediction of mid-term bleeding events following discharge for myocardial infarction (MI).nnnMETHODSnOne 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.nnnRESULTSnThe 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%.nnnCONCLUSIONnA 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 AIMnThe 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.nnnMETHODSnFrom 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.nnnRESULTSnPatients 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.nnnCONCLUSIONSnThe 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 OBJECTIVESnIntravenous 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.nnnMETHODSnOver 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.nnnRESULTSnPrevious 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.nnnCONCLUSIONSnContinuous 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.