Premature acute coronary syndrome: understanding the early onset.

INTRODUCTION: Acute coronary syndrome (ACS) is less frequent in young adults, but it has become a significant health problem, associated with the increasing prevalence of modifiable risk factors. OBJECTIVES: To characterize patients admitted with premature ACS, comparing with those with nonpremature ACS. METHODS: We performed a retrospective study encompassing patients of the Portuguese Registry (ProACS), comparing two groups: one composed of men less than 55 and women less than 65 years old; and other with men ≥55 and women ≥65 years old at the ACS admission. The primary endpoint was the composite of in-hospital mortality, stroke and myocardial reinfarction (re-MI). RESULTS: A total of 29 870 patients were enrolled and 25% had premature ACS, with a mean age of 50 ± 7 years old. They had a larger prevalence of smoking habits, obesity and dyslipidemia. ST-segment elevation MI (STEMI) was the main admission diagnosis in young patients and coronary angiogram mainly revealed one vessel disease in this subgroup. They had a lower Killip-Kimball (KK) class and mostly preserved left ventricular ejection fraction (LVEF). Composite endpoint was more frequent in nonpremature ACS patients. Nonpremature age, presentation with syncope or cardiac arrest, KK class >1, multivessel disease and LVEF <40% were independent predictors of the primary endpoint ( P < 0.001). Younger patients had lower rates of in-hospital all-cause mortality, re-MI and stroke. One-year all-cause mortality and 1-year cardiovascular and non-cardiovascular readmissions were also lower. CONCLUSIONS: Premature ACS affects 25% of the ACS population, mostly presenting with STEMI, but generally associated with better clinical evolution. Nevertheless, prevention measures are essential to correct modifiable cardiovascular risk factors and reduce coronary events.

Giant Left Ventricular (Pseudo?) Aneurysm Complicating Anterior Myocardial Infarction.

The differential diagnosis of true aneurysms and pseudoaneurysms is challenging, and multimodality cardiac imaging is often necessary. We report a case in which the limitations of these techniques are exposed, showing that post-operative evaluation of tissue layers remains the gold standard in establishing this diagnosis. (Level of Difficulty: Beginner.).

Functional analysis of two novel TBX5 variants present in individuals with Holt-Oram syndrome with different clinical manifestations.

Holt-Oram syndrome (HOS) is a rare disorder characterized by cardiac and upper-limb defects. Pathogenic variants in TBX5-a gene encoding a transcription factor important for heart and skeletal development-are the only known cause of HOS. Here, we present the identification and functional analysis of two novel TBX5 pathogenic variants found in two individuals with HOS presenting distinct phenotypes. The individual with the c.905delA variant has a severe cardiac phenotype but mild skeletal defects, unlike the individual with the c.246_249delGATG variant who has no cardiac problems but severe upper limbs malformations, including phocomelia. Both frameshift variants, c.246_249delGATG and c.905delA, generate mRNAs harbouring premature stop codons which, if not degraded by nonsense mediated decay, will lead to the production of shorter TBX5 proteins, p.Gln302Argfs*92 and p.Met83Phefs*6, respectively. Immunocytochemistry results suggest that both mutated proteins are produced and furthermore, like the wild-type protein, p.Gln302Argfs*92 mutant appears to be mainly localized in the nucleus, in contrast with p.Met83Phefs*6 mutant that displays a higher level of cytoplasmic localization. In addition, luciferase activity analysis revealed that none of the TBX5 mutants are capable of transactivating the NPPA promoter. In conclusion, our results provide evidence that both pathogenic variants cause a severe TBX5 loss-of-function, dramatically reducing its biological activity. The absence of cardiac problems in the individual with the p.Met83Phefs*6 variant supports the existence of other mechanisms/genes underlying the pathogenesis of HOS and/or the existence of an age-related delay in the development of a more serious cardiac phenotype. Further studies are required to understand the differential effects observed in the phenotypes of both individuals.

P2Y12 inhibitor loading dose before catheterization in ST-segment elevation myocardial infarction: Is this the best strategy? / Dose de carga do inibidor P2Y12 antes do laboratório de hemodinâmica no enfarte agudo do miocárdio com supradesnivelamento do segmento ST ­ Será mesmo a melhor estratégia?

INTRODUCTION AND OBJECTIVES: In ST-segment elevation myocardial infarction (STEMI) the benefit of dual antiplatelet therapy is unequivocal, but the optimal time to administer the loading dose (LD) of a P2Y12 inhibitor is the subject of debate and disagreement. The main aim of this study was characterize current practice in Portugal and to assess the prognostic impact of P2Y12 inhibitor LD administration strategy, before versus during or after primary percutaneous coronary intervention (PCI). METHODS: This multicenter retrospective study based on the Portuguese National Registry on Acute Coronary Syndromes included patients with STEMI and PCI performed between October 1, 2010 and September 19, 2017. Two groups were established: LD before PCI (LD-PRE) and LD during or after PCI (LD-CATH). RESULTS: A total of 4123 patients were included, 66.3% in the LD-PRE group and 32.4% in the LD-CATH group. Prehospital use of a P2Y12 inhibitor was a predictor of the composite bleeding endpoint (major bleeding, need for transfusion or hemoglobin [Hb] drop >2g/dl), Hb drop >2g/dl and reinfarction. There were no differences between groups in major adverse events (MAE) (in-hospital mortality, reinfarction and stroke) or in-hospital mortality. CONCLUSIONS: Prehospital use of a P2Y12 inhibitor was associated with an increased risk of bleeding, predicting the composite bleeding outcome and Hb drop >2g/dl, with no differences in mortality or MAE, calling into question the benefit of this strategy.

p.G360R Is a Pathogenic GLA Gene Mutation Responsible for a Classic Phenotype of Fabry Disease.

The authors report the case of a classic phenotype of Fabry disease in a 60-year-old male patient presenting with left ventricular hypertrophy and stroke. Genetic analysis revealed 2 GLA-gene variants, i.e., p.R356Q and p.G360R. This clinical case highlights that the finding of 2 or more GLA gene variants in a Fabry patient should lead to a careful evaluation in order to determine their exact role in the condition. This case also provides the first clinical evidence that the p.G360R mutation is pathogenic and responsible for a classic phenotype of Fabry disease. The clinical improvement following the initiation of enzyme replacement therapy reinforces the importance of Fabry disease awareness and diagnosis in patients exhibiting red flags, such as left ventricular hypertrophy and stroke.

Mechanical Prosthetic Heart Valve Thrombosis in a Patient Receiving Rivaroxaban.

Direct oral anticoagulants are not approved for use in patients with mechanical valves. When used to replace vitamin K antagonists, they may cause catastrophic consequences. The authors describe the case of a patient who, after discontinuation of warfarin and introduction of rivaroxaban, developed thrombosis of his mechanical mitral prosthesis.

One aneurysm and two pseudoaneurysms, same patient.

Ventricular pseudoaneurysms are rare pathological entities that mainly arise in the context of myocardial infarction or post-cardiac surgery. The clinical presentation is usually non-specific, and at times patients are asymptomatic. Mortality is high even with timely surgical intervention.The authors present a case of postoperative recurrence of a left ventricular pseudoaneurysm superimposed on an ischaemic true aneurysm.

Cardiogenic shock: Inotropes and vasopressors. / Choque cardiogénico ­ fármacos inotrópicos e vasopressores.

Cardiogenic shock is characterized by a decrease in myocardial contractility, and presents a high mortality rate. Inotropic and vasopressor agents have been recommended and used for several years in the treatment of patients in shock, but they remain controversial. Despite its beneficial effect on myocardial contractility, the side effects of inotropic therapy (arrhythmias and increased myocardial oxygen consumption) may be associated with increased mortality. The pharmacodynamics of different inotropic agents suggest benefits in specific situations, but these differences have not been reflected in reduced mortality in most studies, making it difficult to formulate recommendations. This review integrates data from different studies on the use of inotropes and vasopressors in patients with cardiogenic shock, proposing a therapeutic scheme for the pharmacological treatment of patients in cardiogenic shock according to the patient's hemodynamic profile.

Congenital left ventricular apical aneurysm presenting as ventricular tachycardia.

The authors present the case of a 34-year-old male patient seen in our department due to palpitations. On the electrocardiogram monomorphic ventricular tachycardia (VT) was documented, treated successfully with amiodarone. The subsequent study revealed a normal echocardiogram and an apical aneurysm of the left ventricle on magnetic resonance imaging, confirmed by computed tomography coronary angiography that also excluded coronary disease. He underwent an electrophysiological study to determine the origin of the VT and to perform catheter ablation using electroanatomical mapping. VT was induced and radiofrequency applications were performed in the left ventricular aneurysm area. VT was no longer inducible, with acute success. Despite this it was decided to implant a subcutaneous implantable cardioverter-defibrillator (ICD). Eight months after the ablation the patient was admitted again due to VT, treated by the ICD.

Changes in referral protocols for cardiac surgery: do financial considerations come at a cost?

INTRODUCTION AND OBJECTIVES: The aim of this study was to determine whether changes to referral protocols for cardiac surgery have had an impact on waiting times, hospitalizations and mortality during the waiting period and during the first year of follow-up after surgery. METHODS: In this retrospective study of patients referred for cardiac surgery between January 1, 2008 and September 30, 2014, the study population was divided into two groups: those referred before (group A, January 1, 2008 to August 31, 2011) and after (group B, September 1, 2011 to September 30, 2014) the change in referral protocols. A telephone follow-up was conducted. RESULTS: There were 864 patients referred for cardiac surgery, 557 in group A and 307 in group B. Patient characteristics were similar between groups. The mean waiting time for surgery was 10.6±18.5 days and 55.7±79.9 days in groups A and B, respectively (p=0.00). During the waiting period two patients (0.4%) were hospitalized in group A and 28 (9.1%) in group B (p=0:00); mortality was, respectively, 0% and 2.3% (p=0.00). During one-year follow-up 12.8% of group A patients and 16% of group B patients were hospitalized. Cardiovascular mortality in this period was around 5% in both groups (p>0.05). CONCLUSION: Changes to referral protocols for cardiac surgery had an impact on waiting times, on the number of hospitalizations and on mortality in this period.

Holt-Oram syndrome: a case report.

Holt-Oram syndrome is clinically characterized by morphological abnormalities of the upper limbs and congenital cardiac defects. Although the disease is congenital, the diagnosis may only be made later in life. It is a rare autosomal dominant disorder, caused by a mutation in the TBX5 gene located on chromosome 12, but sporadic cases have also been reported. We describe the case of a 75-year-old man with known morphological alterations of the upper limbs since birth and congenital cardiac defect (atrial septal defect), who later in life also manifested with advanced atrioventricular block.

Role of cardiac multidetector computed tomography in the exclusion of ischemic etiology in heart failure patients.

INTRODUCTION AND AIMS: Differentiation of ischemic from non-ischemic etiology in heart failure (HF) patients has both therapeutic and prognostic implications. One possible approach to this differentiation is direct visualization of the coronary tree. Multidetector computed tomography (MDCT) has emerged as an alternative to invasive coronary angiography (ICA), but its performance and additional clinical value are still not well validated in patients with left ventricular (LV) dysfunction. We aimed to assess the value of coronary MDCT angiography (CTA) in the exclusion of ischemic etiology in HF patients and to determine whether the Agatston calcium score could be used as a gatekeeper for CTA in this context. METHODS: We retrospectively selected symptomatic HF patients with LV ejection fraction (LVEF) <50%, as assessed by echocardiography, referred for CTA between April 2006 and May 2013. Patients with previously known CAD or valvular disease were excluded. The performance of MDCT in the detection of coronary artery disease (CAD) and/or exclusion of an ischemic etiology for HF was studied. Obstructive CAD was defined as the presence of ≥50% luminal stenosis in at least one epicardial coronary artery as assessed by CTA and was assumed in patients with an Agatston coronary artery calcium (CAC) score >400. In patients referred for ICA, an ischemic etiology was assumed in the presence of ≥75% stenosis in two or more epicardial vessels or ≥75% stenosis in the left main or proximal left anterior descending artery. RESULTS: During this period 100 patients (mean age 57.3±10.5 years, 64% men) with HF and systolic dysfunction were referred for MDCT to exclude CAD. Median effective radiation dose was 4.8 mSv (interquartile range 5.8 mSv). Mean LVEF was 35±7.7% (range 20-48%) and median CAC score was 13 (interquartile range 212). Seven patients were in atrial fibrillation. Almost half of the patients (40%) had no CAC and none of these had significant stenosis on CTA. In an additional group of 33 patients CTA was able to confidently exclude obstructive CAD. Twenty-seven patients were classified as positive for CAD (16 due to CAC >400 and 11 with ≥50% stenosis) and were associated with lower LVEF (p=0.004). Of these, 21 patients subsequently underwent ICA: obstructive CAD was confirmed in nine and only six had criteria for ischemic cardiomyopathy. CONCLUSION: In our HF population, MDCT was able to exclude an ischemic etiology in 73% of cases in a single test. According to our results the Agatston calcium score may serve as a gatekeeper for CTA in patients with HF, with a calcium score of zero confidently excluding an ischemic etiology.

The value of electrocardiography for differential diagnosis in wide QRS complex tachycardia.

Correct diagnosis in wide QRS complex tachycardia remains a challenge. Differential diagnosis between ventricular and supraventricular tachycardia has important therapeutic and prognostic implications, and although data from clinical history and physical examination may suggest a particular origin, it is the 12-lead surface electrocardiogram that usually enables this differentiation. Since 1978, various electrocardiographic criteria have been proposed for the differential diagnosis of wide complex tachycardias, particularly the presence of atrioventricular dissociation, and the axis, duration and morphology of QRS complexes. Despite the wide variety of criteria, diagnosis is still often difficult, and errors can have serious consequences. To reduce such errors, several differential diagnosis algorithms have been proposed since 1991. However, in a small percentage of wide QRS tachycardias the diagnosis remains uncertain and in these the wisest decision is to treat them as ventricular tachycardias. The authors' objective was to review the main electrocardiographic criteria and differential diagnosis algorithms of wide QRS tachycardia.

[Syncope unit: experience of a center using diagnostic flowcharts for syncope of uncertain etiology after initial assessment]. / Unidade de Síncope - Experiência de um centro com base em organigramas de decisão para síncope de etiologia incerta após a avaliação inicial.

INTRODUCTION AND OBJECTIVES: Syncope is a common symptom that leads to 1% of admissions to hospital emergency departments, and is associated with high costs to the health system. The cardiology department of Faro Hospital has had a syncope unit since July 2007. The aim of this study is to analyze its results in terms of etiological diagnosis and treatment of syncope, using diagnostic flowcharts based on European Society of Cardiology (ESC) guidelines. METHODS: We conducted a retrospective study of all patients referred to the syncope unit of Faro Hospital between July 2007 and August 2011. We analyzed demographic data, characteristics of syncopal episodes, diagnostic methods, etiology of syncope and treatment. The percentages of syncope of cardiac and uncertain etiology were compared with data from other international syncope units. Statistical analysis was performed using SPSS version 13.0. RESULTS: Of the 304 patients referred to the syncope unit for loss of consciousness, 245 (80.7%) had syncope. Most had reflex syncope (52.2%), 20% had cardiac syncope, 15.6% had orthostatic hypotension, and in 12% of cases etiology remained undetermined. The percentages of cardiac and uncertain etiology were similar to data published by other syncope units. CONCLUSIONS: The Faro Hospital syncope unit obtained similar results to those published by other international syncope units through application of diagnostic flowcharts for etiological diagnosis of syncope. The flowcharts presented can be of value for the proper application of ESC guidelines on syncope.

[Fulminant myocarditis]. / Miocardite fulminante - a propósito de um caso clínico.

A 46-year-old woman was admitted due to diplopia because of ophthalmoplegia, which improved with corticosteroid therapy. Eight days later, she was admitted with fulminant myocarditis in cardiogenic shock, with severe left ventricular dysfunction and frequent episodes of nonsustained ventricular tachycardia. As there was no clinical improvement, an endomyocardial biopsy was performed that revealed inflammatory infiltrate, vasculitis, and PCR positive for cytomegalovirus, Epstein-Barr virus, parvovirus B19 and enterovirus. Left ventricular function recovered with heart failure treatment and corticosteroids. Three months later, after progressive withdrawal of prednisolone, there was recurrence of myocarditis and left ventricular dysfunction, which was successfully treated by restarting corticosteroid therapy. One month later she was readmitted with fulminant myocarditis which again responded to steroids. She intermittently presented cutaneous purpura lesions. At this time the provisional diagnosis was vasculitis and she started monthly cycles of cyclophosphamide. Before the second cycle she was admitted with pneumonia and ventricular dysfunction and died.

Implementation of a pre-hospital network favoring primary angioplasty in STEMI to reduce mortality: the Algarve Project.

OBJECTIVE: To analyze the impact of reperfusion by either primary percutaneous coronary intervention (PPCI) or fibrinolysis, and mortality rates of a pre-hospital fast-track network for treating patients with ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: A pre-hospital network for STEMI patients, designated the Green Lane for Acute Myocardial Infarction (GL-AMI), has been implemented in the southern region of Portugal --the Algarve Project. We performed an observational study based on a prospective registry of 1338 patients admitted to Faro Hospital between 2004 and 2009, classified in two groups according to the method of admission: emergency department group (EDG) and GL-AMI group (GLG). More patients from GLG were reperfused (p < 0.0001). PPCI was the preferred method of reperfusion, 73.1% in GLG and 45.3% in EDG. Time delays were significantly shorter in GLG, except for pre-hospital delay: pre-hospital delay (p = 0.11); door-to-needle (p < 0.0001); door-to-balloon (p < 0.0001); and delay between symptoms and reperfusion (p < 0.0001). In-hospital mortality (4.3% vs 9.2%, p = 0.0007) and 6-month mortality (6.3% vs 13.8%, p < 0.0001) were significantly lower in GLG. CONCLUSIONS: The Algarve Project significantly reduced the time delay between onset of symptoms and reperfusion, significantly increased the rate of reperfusion, and significantly reduced in-hospital and six-month mortality.

Female gender: an independent factor in ST-elevation myocardial infarction.

INTRODUCTION: Cardiovascular disease is the leading cause of death in women. In ST-elevation myocardial infarction (STEMI) in particular, the question has been raised whether specific characteristics of women confer a worse prognosis. OBJECTIVE: To evaluate the differences in STEMI patients between the genders in cardiovascular risk profile, clinical presentation, therapeutic approach and in-hospital and 6-month mortality rates. METHODS: We analyzed 1578 patients admitted consecutively with STEMI during a 7-year period (from January 13, 2002 to December 31, 2008). The patients were divided into two groups according to gender, and compared in terms of baseline clinical and demographic characteristics, pre-hospital and in-hospital delay, clinical presentation on admission, reperfusion therapy, severity of coronary disease and in-hospital and 6-month mortality. RESULTS: Of the 1578 patients, 26% were female. Women were older (by 8 years), and had a higher cardiovascular risk profile. On admission, their clinical presentation was more severe, with a higher frequency of anterior myocardial infarction and acute heart failure symptoms. Women had longer ischemic times and lower rates of reperfusion therapy. Mortality in women was significantly higher than in men, both in-hospital (17.5 vs. 5.3%) and at 6 months (23.5% vs. 8.2%). After adjustment in multivariate analysis, mortality in women remained higher. CONCLUSIONS: The adverse demographic and clinical profile could partially explain the worse prognosis of STEMI in women. This, together with longer pre-hospital delays, led to underuse of reperfusion therapy. Even so, female gender by itself had a negative and independent influence on mortality in STEMI patients.