The current role and future prospects of D-dimer biomarker.

D-dimers have been discovered as by-products of fibrinolysis. In situations where the fundamental pathology is associated with increased thrombolytic activity, D-dimer assays could serve an integral role in the clinical workup, and have an already established role in the diagnosis of clinical disorders of venous thromboembolism, and disseminated intravascular coagulation. However, there is growing literature suggesting that this is not the only clinical scenario where D-dimers may be of significance.

Analysis of biomarkers for risk of acute kidney injury after primary angioplasty for acute ST-segment elevation myocardial infarction: results of the HORIZONS-AMI trial.

Objectives: Contrast-induced acute kidney injury (CI-AKI) may occur after percutaneous coronary intervention (PCI).

Methods: We evaluated patients with ST-elevation myocardial infarction (STEMI) undergoing emergency PCI with serial biomarkers.

Results: Of the 390 patients enrolled in the HORIZONS-AMI biomarker substudy, 56 (14.

Impact of pre-procedural cardiopulmonary instability in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial).

Rapid reperfusion with primary percutaneous coronary intervention improves survival in patients with ST-segment elevation myocardial infarction. Preprocedural cardiopulmonary instability and adverse events (IAE) may delay reperfusion time and worsen prognosis. The aim of this study was to evaluate the relation between preprocedural cardiopulmonary IAE, door-to-balloon time (DBT), and outcomes in the Harmonizing Outcomes With Revascularization and Stents in AMI (HORIZONS-AMI) trial.

Impact of delay to reperfusion on reperfusion success, infarct size, and clinical outcomes in patients with ST-segment elevation myocardial infarction: the INFUSE-AMI Trial (INFUSE-Anterior Myocardial Infarction).

Objectives: Our aim was to study the impact of delay from symptom onset to first coronary device on infarct size and clinical outcomes at 30 days and 1 year in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention.

Background: Longer delay from symptom onset to reperfusion has been linked to increased mortality and worse clinical outcome. The mechanisms underpinning this association are not entirely clear.

Complementary prognostic utility of myocardial blush grade and ST-segment resolution after primary percutaneous coronary intervention: analysis from the HORIZONS-AMI trial.

Background: Both ST-segment resolution (STR) and myocardial blush grade (MBG) have prognostic utility after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction. We sought to clarify how frequently MBG and STR provide discordant measures of reperfusion success and to determine the independent prognostic significance of each on long-term outcomes.

Methods: In HORIZONS-AMI, core laboratory measures of both MBG and STR were assessed in 2,367 patients undergoing primary PCI.

Impact of scheduled angiographic follow-up in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

Routine scheduled angiographic follow-up (SAF) after percutaneous coronary intervention (PCI) has been associated with a higher rate of target vessel revascularization (TVR). Its benefits are not known. SAF at 13 months after ST-segment elevation myocardial infarction (STEMI) was planned in the first 1,800 successfully stented patients enrolled in the Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial.

Torsades de pointes following acute myocardial infarction: evidence for a deadly link with a common genetic variant.

Background: Although QT prolongation following myocardial infarction (MI) is generally moderate, cases with marked QT prolongation leading to life-threatening torsades de pointes (TdP) have been described.

Objective: To investigate the genetic substrate of this phenomenon.

Methods: We studied 13 patients who developed TdP in the subacute phase of MI (2-11 days) and a group of 133 ethnically matched controls with uncomplicated MI.

Susceptibility genes for coronary heart disease and myocardial infarction.

Coronary heart disease and its main complication, myocardial infarction is leading cause of death worldwide. Over the past years, much progress has been made in the pharmacotherapy of major risk factors like dyslipidemias, diabetes mellitus and hypertension. The targeting of coronary risk factors coupled with advances in the management of coronary artery disease has improved patient survival.

Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death.

Background: L-type calcium channel (LTCC) mutations have been associated with Brugada syndrome (BrS), short QT (SQT) syndrome, and Timothy syndrome (LQT8). Little is known about the extent to which LTCC mutations contribute to the J-wave syndromes associated with sudden cardiac death.

Objective: The purpose of this study was to identify mutations in the α1, β2, and α2δ subunits of LTCC (Ca(v)1.

An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

Background: Brugada syndrome (BrS) is a common heritable channelopathy. Mutations in the SCN5A-encoded sodium channel (BrS1) culminate in the most common genotype.

Objective: This study sought to perform a retrospective analysis of BrS databases from 9 centers that have each genotyped >100 unrelated cases of suspected BrS.

A mutation in the beta 3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype.

Background: Brugada syndrome, characterized by ST-segment elevation in the right precordial ECG leads and the development of life-threatening ventricular arrhythmias, has been associated with mutations in 6 different genes. We identify and characterize a mutation in a new gene.

Methods And Results: A 64-year-old white male displayed a type 1 ST-segment elevation in V1 and V2 during procainamide challenge.

Dual variation in SCN5A and CACNB2b underlies the development of cardiac conduction disease without Brugada syndrome.

Background: Inherited loss of function mutations in SCN5A have been linked to overlapping syndromes including cardiac conduction disease and Brugada syndrome (BrS). The mechanisms responsible for the development of one without the other are poorly understood.

Methods: Direct sequencing was performed in a family with cardiac conduction disease.

Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome.

Introduction: The Brugada Syndrome (BrS), an inherited syndrome associated with a high incidence of sudden cardiac arrest, has been linked to mutations in four different genes leading to a loss of function in sodium and calcium channel activity. Although the transient outward current (I(to)) is thought to play a prominent role in the expression of the syndrome, mutations in I(to)-related genes have not been identified as yet.

Methods And Results: One hundred and five probands with BrS were screened for ion channel gene mutations using single strand conformation polymorphism (SSCP) electrophoresis and direct sequencing.

Gain of function in IKs secondary to a mutation in KCNE5 associated with atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common clinical arrhythmia and a major cause of cardiovascular morbidity and mortality. Among the gene defects previously associated with AF is a gain of function of the slowly activating delayed rectifier potassium current IKs, secondary to mutations in KCNQ1. Coexpression of KCNE5, the gene encoding the MiRP4 beta-subunit, has been shown to reduce IKs.

Genetic predisposition and cellular basis for ischemia-induced ST-segment changes and arrhythmias.

Recent reports have highlighted the importance of a family history of sudden death as a risk for ventricular fibrillation (VF) in patients experiencing acute myocardial infarction (AMI), pointing to the possibility of a genetic predisposition. This report briefly reviews 2 recent studies designed to examine the hypothesis that there is a genetic predisposition to the development of arrhythmias associated with AMI. Ventricular tachycardia and VF (VT/VF) complicating AMI as well as arrhythmias associated with Brugada syndrome, a genetic disorder linked to SCN5A mutations, have both been linked to phase 2 reentry.

Novel mutation in the SCN5A gene associated with arrhythmic storm development during acute myocardial infarction.

Background: Ventricular tachycardia (VT) and ventricular fibrillation (VF) complicating Brugada syndrome, a genetic disorder linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) both have been linked to phase 2 reentry.

Objective: Given the mechanistic similarities in arrhythmogenesis, the purpose of this study was to examine the contribution of SCN5A mutations to VT/VF complicating AMI.

Methods: Nineteen consecutive patients developing VF during AMI were enrolled in the study.

A novel mutation in KCNQ1 associated with a potent dominant negative effect as the basis for the LQT1 form of the long QT syndrome.

Introduction: Long QT Syndrome (LQTS) is an inherited disorder characterized by prolonged QT intervals and life-threatening polymorphic ventricular tachyarrhythmias. LQT1 caused by KCNQ1 mutations is the most common form of LQTS.

Methods And Results: Patients diagnosed with LQTS were screened for disease-associated mutations in KCNQ1, KCNH2, KCNE1, KCNE2, KCNJ2, and SCN5A.

Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death.

Background: Cardiac ion channelopathies are responsible for an ever-increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST-segment elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death.

Methods And Results: Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing.

Functional expression of "cardiac-type" Nav1.5 sodium channel in canine intracardiac ganglia.

Background: The autonomic nervous system has been implicated in several arrhythmogenic diseases, including long QT syndrome type 3 (LQT3) and Brugada syndrome. Scarce information on the cellular components of the intrinsic cardiac ganglia from higher mammals has limited our understanding of the role of the autonomic nervous system in such diseases.

Objectives: The purpose of this study was to isolate and characterize the electrophysiologic properties of canine intracardiac neurons.

The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient.

Rhythmic cardiac contractions depend on the organized propagation of depolarizing and repolarizing wavefronts. Repolarization is spatially heterogeneous and depends largely on gradients of potassium currents. Gradient disruption in heart disease may underlie susceptibility to fatal arrhythmias, but it is not known how this gradient is established.

Cryptic 5' splice site activation in SCN5A associated with Brugada syndrome.

The Brugada syndrome (BS) is characterized by ST segment elevation in the right precordial leads and sudden cardiac death. The disease is linked to mutations in SCN5A in approximately 20% of cases. We collected a large family with BS and have identified a novel intronic mutation.

Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations.

Background: The Brugada syndrome is an arrhythmogenic disease caused in part by mutations in the cardiac sodium channel gene, SCN5A. The electrocardiographic pattern characteristic of the syndrome is dynamic and is often absent in affected individuals. Sodium channel blockers are effective in unmasking carriers of the disease.

Sudden death associated with short-QT syndrome linked to mutations in HERG.

Background: Sudden cardiac death takes the lives of more than 300 000 Americans annually. Malignant ventricular arrhythmias occurring in individuals with structurally normal hearts account for a subgroup of these sudden deaths. The present study describes the genetic basis for a new clinical entity characterized by sudden death and short-QT intervals in the ECG.

Characterization of Cyt2Bc toxin from Bacillus thuringiensis subsp. medellin.

We cloned and sequenced a new cytolysin gene from Bacillus thuringiensis subsp. medellin. Three IS240-like insertion sequence elements and the previously cloned cyt1Ab and p21 genes were found in the vicinity of the cytolysin gene.