Criteria to predict carriers of a novel SCN5A mutation in a large Portuguese family affected by the Brugada syndrome.

AIMS: Brugada syndrome (BrS) is a life-threatening arrhythmia disorder associated with autosomal-dominant mutations in the SCN5A gene. We aimed to characterize the diagnostic challenges and clinical manifestations of a novel SCN5A mutation associated with BrS. METHODS AND RESULTS: From a novel SCN5A mutation (c.664C>T; p.Arg222X) identified in a proband with the characteristic electrocardiographic pattern and the history of sudden collapse, 122 family members were studied including 40 carriers of the mutation. The electrocardiographic diagnosis of BrS requires type 1 Brugada electrocardiogram (ECG) pattern in >1 right precordial lead (V1-V3), but recently an isolated lead with coved-type ECG was proposed to be enough for the diagnosis. In this family, these proposed criteria (PC) were more sensitive in detecting mutation carriers than the conventional criteria without repercussion on the specificity. Carriers had, on average, longer P-wave duration, PR, and QRS intervals and higher transmural dispersion of repolarization. The prevalence of late potentials was higher in carriers, and individual signal average ECG (SAECG) parameters (QRSf, LAS, and RMS40) also were related to SCN5A gene mutation. Three non-carriers were found to be affected by BrS, two with a spontaneous type 1 ECG with alternative placement of the precordial electrodes, and one only after the pharmacological provocative test, suggesting that other genes may play a role in the pathophysiology of this disease. CONCLUSION: The PC for BrS diagnosis should be implemented. Some parameters from the spontaneous ECG and the SAECG are more effective tools than the characteristic repolarization pattern to discriminate between carriers of SCN5A mutations.

[Diagnostic criteria for the Brugada syndrome: can they be improved?]. / Critérios de diagnóstico da síndrome de Brugada. Podemos melhorar?

INTRODUCTION: Diagnosis of Brugada syndrome (BS) currently requires documentation of a characteristic repolarization pattern (type 1 Brugada ECG). Mutations in the SCN5A gene, which codes for sodium channel Na(v) 1.5, are found in 38% of familial cases of BS. Sodium current dysfunction negatively affects the cardiac fast response action potential, particularly in atrial and ventricular myocytes and in the fast-conducting Purkinje system. OBJECTIVES: To detect carriers of SCN5A mutations without using the characteristic repolarization pattern (type 1 Brugada ECG). METHODS: Of a total of 141 members of three different families including 55 carriers of two nonsense SCN5A mutations causing BS, all those aged over 16 (113 individuals, 42 carriers) were studied. The PR interval (PR) and QT dispersion (QTd) between leads V1 and V3 were measured on conventional ECG. Using signal-averaged ECG the total duration of the filtered QRS complex (fQRS), the root-mean-square (RMS40) and the low-amplitude signal (LAS) were measured. The following procedures were developed to detect carriers/To detect carriers the following procedures were developed: (1) a screening test (ScreenTest) with PS (PR+fQRS) > or = 250 (250ms is 80% of the theoretical maximum in healthy individuals); and (2) a diagnostic test (DiagTest) for the simultaneous fulfillment of four conditions: PS > or = 250 and QTd > or = 10 and LAS > 26 and RMS40 < or = 29 (the latter two cut-offs are approximately 70% of the theoretical maximum in healthy carriers). RESULTS: Significant differences in PR, QTd, QRSf, RMS40 and LAS were found between carriers and non-carriers. The SCN5A gene was associated with all these variables, the strongest association being with PR. Both tests were applied to 63 family members (38 carriers). The ScreenTest was positive in 38 of 38 carriers, with eight false positives in 27 non-carriers (sensitivity [SE] = 100% and specificity [SP] = 66.67%). From ROC curve analysis a cut-off of PS = 252.5 shows SE = 100% and SP = 76% and a cut-off of PS = 260 shows SE=94.7% and SP = 84%. The DiagTest was positive in 36 of 38 carriers, with three false positives: SE = 94.74% and SP = 88.89%. From ROC curve analysis a multivariate logistic model identifies a cut-off with SE = 92% and SP = 92%. In the same group the SE and SP of the characteristic spontaneous repolarization pattern (type 1 Brugada ECG) to detect carriers were 52.4% and 97.2%, respectively, and the difference between the SE of the DiagTest and of the typical repolarization pattern is statistically significant. CONCLUSIONS: The ScreenTest and DiagTest are more effective tools than the characteristic repolarization pattern to discriminate between carriers and non-carriers of these two nonsense SCN5A mutations. We suggest their use in first-degree relatives of Brugada patients when the results of genetic testing are not available, in a score of disease probability in individuals with idiopathic Brugada ECG, and in patients with arrhythmias or other Brugada-related symptoms presenting type 2 or type 3 Brugada ECG.

[Pregnancy and acute pulmonary embolism: a case report]. / Tromboembolismo pulmonar agudo na gravidez. A propósito de um caso clínico.

We describe the case of a 37-year-old pregnant woman who presented at 29 weeks of gestation with syncope and shortness of breath caused by pulmonary embolism. Due to persistent hypotension thrombolytic therapy with tenecteplase was administered and the clinical and hemodynamic response was excellent, with no maternal or fetal hemorrhagic complications. The clinical presentation of pulmonary embolism is sometimes camouflaged by the physiological changes that occur in pregnancy and diagnosis is often delayed by reluctance to expose the fetus to ionizing radiation. Systemic thrombolysis is considered a high-risk treatment in pregnancy and very few women have received it. However the complication rates of thrombolytic therapy are acceptable in the light of the underlying disease.

Longitudinal left ventricular strain in hypertrophic cardiomyopathy: correlation with nonsustained ventricular tachycardia.

AIMS: Stratifying risk of sudden death is a major issue in the management of hypertrophic cardiomyopathy (HCM). Existing risk factors have low positive predictive value and new parameters are needed. Determination of myocardial deformation (strain) by 2D Speckle tracking is a new methodology for determining LV regional function and could correlate with myocite disarray and fibrosis. The aim of this study was to assess the relationship between strain analysis and nonsustained ventricular tachycardia (NSVT) in patients with HCM. METHODS: Thirty-two consecutive patients with HCM (mean age 55, 17-78) were studied. All underwent standard echocardiographic and two-dimensional strain examination. Twenty-four-hour Holter monitoring was performed and echocardiographic parameters were correlated with NSVT. RESULTS: Nine patients (28%) had one or more episodes of NSVT. Patients with NSVT had a higher value of maximal LV thickness (23.6 mm vs. 19.4 mm, P = 0.027). There were no significant associations between NSVT on Holter monitoring and LV outflow gradient left atrial diameter, E/Em or left ventricle ejection fraction. Patients with HCM and NSVT had significant reductions in mid septal, apical-septal, apical-lateral strain, and in mean longitudinal strain. Midseptal strain >-10.5% had a sensitivity of 89% and a specificity of 74% (area under the curve, 0.787; P < 0.0013) for predicting NSVT independently of age or maximum wall thickness. CONCLUSION: Lower end-systolic peak longitudinal strain obtained by 2D speckle tracking was a predictor of NSVT in HCM patients. This parameter could become a useful tool in stratifying SCD risk in this population.

[Severe left ventricular outflow tract obstruction as a complication of mitral valve repair: case report]. / Obstrução grave do tracto de saída do ventrículo esquerdo como complicação de valvuloplastia mitral: a propósito de um caso clínico.

Systolic anterior motion (SAM) is a postoperative complication of mitral valve repair, with an incidence of 5 to 10%. Early recognition of the signs and symptoms of SAM is essential for the management of these patients. This article focuses on the pathophysiology and dynamics of SAM and the treatment strategies described in the literature. The authors present a case study and echocardiographic images illustrating the clinical relevance of the mechanism involved, in order to clarify whether surgical reintervention is necessary.

Delayed lead perforation: a rare cause of pacemaker dysfunction.

A 65-year-old woman with a dual-chamber pacemaker implanted in 2006 for symptomatic carotid sinus hypersensitivity was incidentally found to have loss of ventricular capture on routine pacemaker interrogation. A chest X-ray raised the suspicion of perforation and migration of the right ventricular lead, confirmed by three-dimensional echocardiogram and CT scan. On the basis of this case, we review myocardial lead perforation, including predisposing factors, pathophysiological mechanisms, diagnostic approach and therapeutic options.

[Acute penetrating atherosclerotic ulcers in aortic arch: differential diagnosis of chest pain]. / Úlceras ateroscleróticas penetrantes agudas da crossa da aorta: diagnóstico diferencial de dor torácica.

Penetrating atherosclerotic ulcers (PAU) represent a pathological phenomenon in which ulceration of atheromatous lesions of the aorta penetrates the internal elastic lamina, reaching the middle muscular layer. These ulcers are more common in the descending thoracic aorta, being rare in the ascending aorta. The differential diagnosis between PAU and other entities of acute aortic syndromes (AAS) becomes difficult. The diagnosis of this disease is made through imaging studies: multidetector computed tomography (MDCT), magnetic resonance (MR) or transesophageal echocardiography (TEE). After diagnosis, the PAU of the ascending aorta should be treated surgically in an emergency context. In this paper the authors report a case of PAU in the aortic arch in a 84 years old patient admitted to the emergency room for chest pain. In this context a review of the natural evolution of this entity is made, with emphasis on diagnostic imaging modalities used for its characterization as well as their treatment options.

Spontaneous fluctuations between diagnostic and nondiagnostic ECGs in Brugada syndrome screening: Portuguese family with Brugada syndrome.

BACKGROUND: All family members of patients with Brugada syndrome (BS) should be screened. Fluctuations between diagnostic and nondiagnostic electrocardiogram (ECG) patterns in patients with BS are recognized, but systematic studies are lacking. The objective of this work was to prospectively evaluate the spontaneous changes between diagnostic and nondiagnostic ECG patterns in a family screened for BS. METHODS: One hundred twenty-nine family members were possibly affected plus the index case were screened with two ECGs with an interval of 6 months. Only coved-type ECG pattern was defined as diagnostic; type 2 and 3 ECGs were considered suggestive. RESULTS: The first ECG series made six diagnostics and the second 11, but only three patients maintained the diagnostic ECG. Patients with basal diagnostic ECG were older and more frequently symptomatic. Body mass index (BMI) was significantly lower in adults with diagnostic plus suggestive ECG when compared with the others. No significant gender difference was found among relatives with or without diagnostic ECG. CONCLUSION: Spontaneous phenotypic manifestation of BS was more frequent in older symptomatic patients, absent in children, and related with low BMI. ECG manifestations were intermittent in more than 3/4 of the affected patients. Fluctuations between diagnostic and nondiagnostic ECGs may have an implication on the correct phenotyping in family screening so several ECGs with drug challenging are mandatory.

A portuguese family with Brugada syndrome.

The authors present a family with Brugada syndrome, the largest ever described in Portugal. From a fortuitous electrocardiographic finding in a previously symptomatic young man with a family history of sudden death, 126 possibly affected family members were studied. This article describes the diagnostic approach, risk stratification for sudden death and therapeutic interventions offered to this family, and presents a brief review of Brugada syndrome.

Left ventricular noncompaction: diagnosis by three-dimensional echocardiography.

Left ventricular noncompaction (LVNC) is a rare congenital disease caused by an arrest in normal myocardial embryogenesis, leading to persistence of numerous prominent trabeculations that communicate with the left ventricle. It was first described as a congenital condition affecting children, but several cases have been reported of late presentation. The main clinical manifestations are congestive heart failure, arrhythmias (supraventricular or ventricular) and systemic embolism. We present the case of a 51-year-old patient brought to our emergency department after an episode of symptomatic ventricular flutter requiring electrical cardioversion. Two-dimensional echocardiography with color Doppler suggested the diagnosis and the three-dimensional echocardiogram revealed the deep trabeculations typical of LVNC.

Application of Risks Scores in Acute Coronary Syndromes. How Does ProACS Hold Up Against Other Risks Scores?

BACKGROUND: Multiple risk scores (RS) are approved in the prediction of worse prognosis in acute coronary syndromes (ACS). Recently, the Portuguese Journal of Cardiology has proposed the ProACS RS. OBJECTIVE: Application of several validated RS, as well as ProACS in patients, admitted for ACS. Evaluation of each RS's performance in predicting in-hospital mortality and the occurrence of all-cause mortality or non-fatal ACS at one-year follow-up and compare them to the ProACS RS. METHODS: A retrospective study of ACS was performed. The following RS were applied: GRACE, ACTION Registry-GWTG, PURSUIT, TIMI, EMMACE, SRI, CHA2DS2-VASc-HS, C-ACS and ProACS. ROC Curves were created to determine the predictive power for each RS and then were directly compared to ProACS. RESULTS: The ProACS, ACTION Registry-GWTG and GRACE showed a c-statistics of 0.908, 0.904 and 0.890 for predicting in-hospital mortality, respectively, performing better in ST-segment elevation myocardial infarction patients. The other RS performed satisfactorily, with c-statistics over 0.750, apart from the CHA2DS2-VASc-HS and C-ACS which underperformed. All RS underperformed in predicting worse long-term prognosis revealing c-statistics under 0.700. CONCLUSION: ProACS is an easily obtained risk score for early stratification of in-hospital mortality. When evaluating all RS, the ProACS, ACTION Registry-GWTG and GRACE RS showed the best performance, demonstrating high capability of predicting a worse prognosis. ProACS was able to demonstrate statistically significant superiority when compared to almost all RS. Thus, the ProACS has showed that it is able to combine simplicity in the calculation of the score with good performance in predicting a worse prognosis.

Acute myocardial infarction with angiographically normal coronary arteries.

The authors present the case of a 51-year-old woman, with no known cardiovascular risk factors, admitted with anterior acute myocardial infarction complicated by primary ventricular fibrillation, who underwent reperfusion therapy with tenecteplase. Left heart catheterization on the sixth day showed left ventricular anteroapical akinesia and normal coronary arteries. The causes of acute myocardial infarction with normal coronary arteries and its differential diagnosis are discussed.

Septic Shock of Unknown Origin: A Case Report of a Pseudoaneurysm of the Mitral-Aortic Intervalvular Fibrosa.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) is a rare complication of infective endocarditis and trauma, particularly of aortic valve surgery. Clinical symptoms are usually unspecific and generally due to complications. Transesophageal echocardiography (TEE) is the most commonly used exam to diagnose P-MAIVF. The main echocardiographic feature is the presence of a cavity communicating with the left ventricular outflow tract that expands during systole and collapses during diastole. Most frequent complications are formation of a fistulous tract and compression of adjacent structures. Surgical correction is usually the treatment of choice. The authors describe a case of a female patient with a septic shock of unclear origin. After antibiotic therapy and organ-supporting measures without apparent improvements, a TEE revealed infective endocarditis, complicated with P-MAIVF. Despite adequate treatment, the patient did not survive for long enough to be submitted to surgical repair.

Silent cardiac tumor with neurological manifestations.

Atrial myxoma is rare and can be completely asymptomatic. However, an untreated myxoma may result in catastrophic events. Diagnosis is usually suggested by echocardiography, and other imaging modalities can add important information. Myxoma can be cured surgically, and histological analysis usually gives the definite diagnosis. This article describes the case of a 61-year-old woman whose clinical presentation of an atrial myxoma was a stroke. Echocardiographic findings were highly suggestive of a cardiac myxoma. However, cardiac magnetic resonance showed unusual features for myxoma, since the mass was hyperintense in T1-weighted images and hypointense in T2-weighted sequences. Histology confirmed myxoma and the patient was surgically treated. This case enhances the importance of multimodality imaging in the differential diagnosis of cardiac masses. .

[Twiddler syndrome: rare cause of definitive pacemaker dysfunction]. / Síndrome de Twiddler: Causa Rara de Disfunção de Pacemaker Definitivo.

The authors present a case of Twiddler's syndrome, a rare complication after pacemaker implantation, first described in 1968. The article is complemented by an approach to the etiology and manifestations of this entity.

Os autores apresentam um caso de síndrome de Twiddler, uma complicação rara após implantação de pacemaker definitivo, primeiramente descrito em 1968, complementado com uma abordagem à etiologia e manifestações desta entidade.

Application of Risks Scores in Acute Coronary Syndromes. How Does ProACS Hold Up Against Other Risks Scores? / Aplicação de Escores de Risco em Síndromes Coronárias Agudas: Como o ProACS se Comporta Diante de Outros Escores de Risco?

Abstract Background: Multiple risk scores (RS) are approved in the prediction of worse prognosis in acute coronary syndromes (ACS). Recently, the Portuguese Journal of Cardiology has proposed the ProACS RS. Objective: Application of several validated RS, as well as ProACS in patients, admitted for ACS. Evaluation of each RS's performance in predicting in-hospital mortality and the occurrence of all-cause mortality or non-fatal ACS at one-year follow-up and compare them to the ProACS RS. Methods: A retrospective study of ACS was performed. The following RS were applied: GRACE, ACTION Registry-GWTG, PURSUIT, TIMI, EMMACE, SRI, CHA2DS2-VASc-HS, C-ACS and ProACS. ROC Curves were created to determine the predictive power for each RS and then were directly compared to ProACS. Results: The ProACS, ACTION Registry-GWTG and GRACE showed a c-statistics of 0.908, 0.904 and 0.890 for predicting in-hospital mortality, respectively, performing better in ST-segment elevation myocardial infarction patients. The other RS performed satisfactorily, with c-statistics over 0.750, apart from the CHA2DS2-VASc-HS and C-ACS which underperformed. All RS underperformed in predicting worse long-term prognosis revealing c-statistics under 0.700. Conclusion: ProACS is an easily obtained risk score for early stratification of in-hospital mortality. When evaluating all RS, the ProACS, ACTION Registry-GWTG and GRACE RS showed the best performance, demonstrating high capability of predicting a worse prognosis. ProACS was able to demonstrate statistically significant superiority when compared to almost all RS. Thus, the ProACS has showed that it is able to combine simplicity in the calculation of the score with good performance in predicting a worse prognosis.

Resumo Fundamento: Existem muitos escores de risco (ERs) aprovados na predição de um pior prognóstico em síndromes coronárias agudas (SCAs). Recentemente, a Revista Portuguesa de Cardiologia propôs o ER ProACS. Objetivo: Aplicar vários ERs validados, bem como o ProACS em pacientes internados por SCA. Avaliar o desempenho de cada ER em predizer mortalidade hospitalar e a ocorrência de mortalidade por todas as causas ou SCA não fatal em um ano de acompanhamento e compará-los com o ProACS. Métodos: Estudo retrospectivo de SCA. Os seguintes ERs foram aplicados: GRACE, ACTION Registry-GWTG, PURSUIT, TIMI, EMMACE, SRI, CHA2DS2-VASc-HS, C-ACS e ProACS. Curvas ROC foram criadas para determinar o poder preditivo de cada ER e diretamente comparadas com a do ProACS. Resultados: Os escores ProACS, ACTION Registry-GWTG e GRACE mostraram estatística-C de 0,908, 0,904 e 0,890, respectivamente, em predizer mortalidade hospitalar, mostrando melhor desempenho em pacientes com infarto do miocárdio com elevação do segmento ST. Os demais ERs mostraram desempenho satisfatório, com estatística-C acima de 0,750, com exceção de CHA2DS2-VASc-HS e C-ACS, que mostraram baixa performance. Todos os ERs apresentaram baixo desempenho em predizer um pior prognóstico em longo prazo, com estatística-C abaixo de 0,700. Conclusão: O ProACS é um escore de risco facilmente obtido para estratificação precoce de mortalidade intra-hospitalar. Ao avaliar todos os ERs, ProACS, ACTION Registry-GWTG e GRACE mostraram o melhor desempenho, com alta capacidade de predizer um pior prognóstico. O ProACS mostrou superioridade estatisticamente significativa em comparação aos outros ERs. Portanto, o ProACS mostrou-se capaz de combinar simplicidade no cálculo do escore com bom desempenho em predizer um pior prognóstico.

Noncompaction of the myocardium in a patient with acute myocardial infarction.

Left-ventricular non-compaction (LVNC) is a rare congenital cardiopathy, which results from the failure of the myocardial compaction process, leading to the persistence of numerous and deep trabeculations communicating with the ventricular cavity. Its main clinical manifestations are heart failure, arrhythmias (supraventricular or ventricular) and episodes of arterial embolism. The present case reports on a Brazilian patient living in Portugal, who was hospitalized due to acute myocardial infarction, which resulted in severe LV systolic dysfunction. During the patient's assessment, LVNC was diagnosed. The clinical presentation is described, as well as the echocardiographic evaluation (two-dimensional and three-dimensional), nuclear magnetic resonance (NMR) imaging and ventriculography results. The diagnostic criteria and therapeutic options are discussed.