Determining pathogenicity in cardiac genetic testing: Filling in the blank spaces
Major advances have been made in our understanding of the genetic basis of inherited heart diseases. The clinical benefits of genetic testing are unequivocal, with the greatest clinical utility being cascade (predictive) testing of relatives after the identification of the pathogenic (disease-causing) mutation in the family proband [1]. Since over 90% of genetic heart diseases are inherited as an autosomal dominant trait, offspring of clinically or genetically affected individuals have a 50% chance of carrying the same mutation and therefore at risk of developing disease. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - March 6, 2015 Category: Cardiology Authors: Christopher Semsarian, Jodie Ingles Tags: Editorial Commentary Source Type: research

Recent findings of long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFAs) on atherosclerosis and coronary heart disease (CHD) contrasting studies in Western countries to Japan
Recent long-term randomized clinical trials (RCTs) of long chain n-3 polyunsaturated fatty acids (LCn-3 PUFAs) on coronary heart disease (CHD) among high risk patients conducted in Western countries all failed to show their clinical benefits. In striking contrast, an RCT of LCn-3 PUFAs on CHD conducted in Japan, which is a combination of secondary and primary prevention, showed a significant 19% reduction. Potential reasons for this discrepancy are large differences in doses of LCn-3 PUFAs administered (300-900 mg/day in Western countries vs. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - March 6, 2015 Category: Cardiology Authors: Akira Sekikawa, Margaret F. Doyle, Lewis H. Kuller Source Type: research

Biological Pacemakers: Ready for the clinic?
Biological pacemakers (BioP) have been created by both gene and cell therapy in animal models of human disease. Cell-based BioP have been developed by delivery of spontaneously-beating embryoid bodies derived from embryonic stem cells (ESCs) into the myocardium, or human mesenchymal stem cells (hMSCs) “loaded” with pacemaker channel genes (HCN2)[1]. The translational potential of these two approaches has been limited for reasons described below. Somatic gene transfer with a single or combination of different ion channels, and more recently a human transcription factor (TBX18), have all been shown to create BioP...
Source: Trends in Cardiovascular Medicine - March 6, 2015 Category: Cardiology Authors: Eugenio Cingolani Source Type: research

Determining Pathogenicty in cardiac genetic testing: Filling in the blank Spaces
Major advances have been made in our understanding of the genetic basis of inherited heart diseases. The clinical benefits of genetic testing are unequivocal, with the greatest clinical utility being cascade (predictive) testing of relatives after the identification of the pathogenic (disease-causing) mutation in the family proband.1 Since over 90% of genetic heart diseases are inherited as an autosomal dominant trait, offspring of clinically or genetically affected individuals have a 50% chance of carrying the same mutation and therefore at-risk of developing disease. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - March 6, 2015 Category: Cardiology Authors: Christopher Semsarian, Jodie Ingles Source Type: research

Are SK Channels a Logical Target for Treating Ventricular Arrhythmias? First, do no harm
Advances in the use of selective ion channel blockers in the pharmacologic treatment of cardiac arrhythmias in the past half century have been slow, incremental and bumpy. The CAST trial made evident the danger of suppressing ventricular ectopy using selective sodium channel blockers in the setting of ischemic heart disease [1]. While selective hERG channel blockers are used for the treatment of atrial fibrillation, the risk of Torsade de Pointes associated with these drugs is well recognized, and all new drugs are now screened for interaction with this channel and risk of ventricular proarrhythmia. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - March 6, 2015 Category: Cardiology Authors: David R. Van Wagoner Source Type: research

New Approaches to Establish Genetic Causality
Cardiovascular medicine has evolved rapidly in the era of genomics with many diseases having primary genetic origins becoming the subject of intense investigation. The resulting avalanche of information on the molecular causes of these disorders has prompted a revolution in our understanding of disease mechanisms and provided new avenues for diagnoses. At the heart of this revolution is the need to correctly classify genetic variants discovered during the course of research or reported from clinical genetic testing. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - March 4, 2015 Category: Cardiology Authors: Elizabeth M. McNally, Alfred L. George Source Type: research

Cardiac magnetic resonance for prediction of arrhythmogenic areas
Catheter ablation has been widely used to manage recurrent atrial and ventricular arrhythmias. It has been established that contrast-enhanced magnetic resonance can accurately characterize the myocardium. In this review, we summarize the role of cardiac magnetic resonance in identification of arrhythmogenic substrates, and the potential utility of cardiac magnetic resonance for catheter ablation of complex atrial and ventricular arrhythmias. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - March 2, 2015 Category: Cardiology Authors: Esra Gucuk Ipek, Saman Nazarian Source Type: research

Cardiac Memory: The Slippery Slope Twixt Normalcy and Pathology
‘Cardiac memory’ is an altered repolarization phenotype resulting from prior rate, rhythm and/or activation changes. The various types of memory depend on biophysical properties of cardiac ion channels, and/or trafficking of those channels, and/or epigenetic changes in the genes determining the channels. The processes that engage the memory function presage changes in function that ultimately can lead to pathological remodeling: hence – rather than completely benign - memory may be a warning of disease to come. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 24, 2015 Category: Cardiology Authors: Michael R. Rosen, Lennart Bergfeldt Source Type: research

Enhancer-associated long noncoding RNAs: A novel frontier with new perception in cardiac regeneration
Heart is the first organ to form and function during embryogenesis; nonetheless, its patho- physiological complications still remain eminent. Heart failure (HF) is not only a major health concern of the present population but also an emerging threat for future generations [1]. Its global mortality and morbidity has pressed scientists to attain better understanding about the molecular basis of this disease. Postnatal heart shows lower rate of cardiomyocyte proliferation. Moreover, following cardiac injury, the poor regenerative potential combined with progressive loss of cardiomyocytes leads to heart failure. (Source: Trend...
Source: Trends in Cardiovascular Medicine - February 23, 2015 Category: Cardiology Authors: Prince Jeyabal, Rajarajan Amirthalingam Thandavarayan, Sahana Suresh Babu, Prasanna Krishnamurthy Source Type: research

Minimal invasive mitral valve surgery does make a difference: Should it be the gold standard for mitral valve repair?
Mitral valve regurgitation is associated with significant long-term morbidities including the development of atrial fibrillation, heart failure, and shortened life expectancy. Mitral valve repair improves long-term outcome in patients with mitral regurgitation [1]. Open chest procedures remain the gold standard for mitral repair and remain the context from which to compare durability and outcomes. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 20, 2015 Category: Cardiology Authors: Danny Ramzy, Alfredo Trento Tags: Editorial Commentary Source Type: research

RNA-stabilizing proteins as molecular targets in cardiovascular pathologies
The stability of mRNA has emerged as a key step in the regulation of eukaryotic gene expression and function. RNA stabilizing proteins (RSPs) contain several RNA recognition motifs, and selectively bind to adenylate-uridylate-rich elements in the 3′ untranslated region of several mRNAs leading to altered processing, stability, and translation. These post-transcriptional gene regulations play a critical role in cellular homeostasis; therefore act as molecular switch between ‘normal cell’ and ‘disease state.’ Many mRNA binding proteins have been discovered to date, which either stabilize (HuR/Hu...
Source: Trends in Cardiovascular Medicine - February 20, 2015 Category: Cardiology Authors: Sahana Suresh Babu, Darukeshwara Joladarashi, Prince Jeyabal, Rajarajan A. Thandavarayan, Prasanna Krishnamurthy Source Type: research

Minimal invasive mitral valve surgery does make a different: Should it be the gold standard for mitral valve repair?
Mitral valve regurgitation is associated with significant long term morbidities including the development of atrial fibrillation, heart failure and shortened life expectancy. Mitral valve repair improves long-term outcome in patients with mitral regurgitation [1]. Open chest procedures remain the gold standard for mitral repair and remain the context from which to compare durability and outcomes. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 20, 2015 Category: Cardiology Authors: Danny Ramzy, Alfredo Trento Source Type: research

Progress in Implantable Cardioverter-Defibrillator Therapy: Advancement Beyond Technology Alone
Over 50 years ago, an American president ambitiously challenged his country to land a man on the moon. When it comes to the progress in implantable cardioverter-defibrillator (ICD) technology, no such challenge has ever been issued nor required. Nevertheless, its history is actually quite remarkable, from its original conception to a commonly utilized approach to anti-arrhythmia therapy in high-risk cardiovascular patients. Beginning with relatively large, thoracotomy-based systems with limited diagnostic and therapeutic capabilities, the ICD has evolved into a powerhouse of technology, offering an ever-growing spectrum of...
Source: Trends in Cardiovascular Medicine - February 20, 2015 Category: Cardiology Authors: Deepak Bhakta, Lynne D. Foreman Source Type: research

Optimal Approaches to Diabetic Patients with Multivessel Disease
Diabetes has become a global pandemic in the twenty-first century, with a significant rise in prevalence in developed and developing countries. The number of individuals affected continues to increase as detrimental lifestyle choices become more common, including decreased physical activity and increased intake of saturated fats. A recent survey of worldwide prevalence of diabetes demonstrated a rate of 6.4% in 2010, affecting 285 million adults, and an expected rise to 7.7% in 2030 (439 million adults) [1]. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 20, 2015 Category: Cardiology Authors: Louai Razzouk, Michael Farkouh Source Type: research

The past, present, and future of pacemaker therapies
Since its introduction into clinical practice, electronic pacing has saved many lives. Despite continuous improvements, electronic pacemakers have important shortcomings, which stimulated the development of biological alternatives. Biological pacemakers generate the cardiac impulse using genes or cells to treat bradycardias. Over the past decade, significant improvements have been made in biological pacemakers, but issues remain in relation to long-term outcomes and safety. Concurrently, efforts to improve electronic pacemakers have also intensified. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 20, 2015 Category: Cardiology Authors: Gerard J.J. Boink, Vincent M. Christoffels, Richard B. Robinson, Hanno L. Tan Source Type: research

RNA stabilizing proteins as molecular targets in cardiovascular pathologies
The stability of mRNA has emerged as a key step in the regulation of eukaryotic gene expression and function. RNA stabilizing proteins (RSPs) contain several RNA recognition motifs, and selectively bind to Adenylate- and uridylate- Rich Elements in the 3’ untranslated region of several mRNAs leading to altered processing, stability and translation. These post-transcriptional gene regulations play a critical role in cellular homeostasis; therefore act as molecular switch between ‘normal cell’ and ‘disease state’. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 20, 2015 Category: Cardiology Authors: Sahana Suresh Babu, Darukeshwara Joladarashi, Rajarajan Prince Jeyabal, Amirthalingam Thandavarayan, Prasanna Krishnamurthy Source Type: research

Depression in Cardiovascular Disease: From Awareness to Action
In this issue of Trends in Cardiovascular Medicine, Drs. Bradley and Rumsfeld [1] provide a clear, contemporary review of the phenomenology, assessment, and treatment of depression in patients with heart disease. Their article adds to a large volume of such reviews written over the last 15 years. It should be clear at this point that depression in cardiac patients is common, underrecognized, persistent, and deadly. Furthermore, it is also increasingly clear that psychotherapy and antidepressant medications are well-tolerated and generally effective in treating depression in this population. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 20, 2015 Category: Cardiology Authors: Jeff C. Huffman, Christopher M. Celano Source Type: research

Outflow tract ventricular Arrhythmias: When and how to treat?
In the 1970s, many studies demonstrated that premature ventricular contractions (PVCs) were associated with up to a 3-fold increase in mortality in patients with prior myocardial infarction.[1-2] In subsequent decades, several large series also demonstrated that even in apparently healthy people, this association is still present.[3] When more detailed analysis focuses on specific characteristics of PVCs, the association becomes more nuanced. A study of exercise-induced PVCs demonstrated that patients with RBBB or multiple morphology PVCs had increased mortality, but patients with a LBBB morphology alone had unchanged mort...
Source: Trends in Cardiovascular Medicine - February 19, 2015 Category: Cardiology Authors: Gregory E. Supple Source Type: research

Treating cocaine cardiotoxicity: Does receptor subtype matter?
Cardiovascular complications of cocaine use may be life-threatening, as reviewed in this issue by Stankowski et al. [1]. Cocaine blocks presynaptic reuptake of catecholamines and increases catecholamine release from central and peripheral stores. Heart rate and blood pressure are therefore increased through stimulation of α- and β-adrenergic receptors. Patients presenting with cocaine-related chest pain in emergency departments have an increased risk of acute myocardial infarction, typically occurring within a few hours of drug use [2]. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 12, 2015 Category: Cardiology Authors: Victor P. Long, Cynthia A. Carnes Tags: Editorial Commentary Source Type: research

Depression and Cardiovascular Disease
There is a wealth of evidence linking depression to increased risk for cardiovascular disease (CVD) and worse outcomes among patients with known CVD. In addition, there are safe and effective treatments for depression. Despite this, depression remains under-recognized and undertreated in patients at risk for or living with CVD. In this review, we first summarize the evidence linking depression to increased risk of CVD and worse patient outcomes. We then review the mechanisms by which depression may contribute to cardiovascular risk and poor cardiovascular outcomes. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 12, 2015 Category: Cardiology Authors: Steven M. Bradley, John S. Rumsfeld Source Type: research

Hormone therapy in menopause: An update on cardiovascular disease considerations
Cardiovascular disease (CVD) remains the number one cause of death and morbidity worldwide, and while overall CVD incidence rates declined in both genders between 1999 and 2007, age-specific data suggest that coronary risk factors in women are on the rise. While early observational data favored MHT's role in primary CVD prevention, the initial interventional study data from the WHI did not. Further detailed analyses of both observational and interventional data have pointed to the possibility that MHT may play a role in primary CVD prevention if initiated within 10 years of menopause and less than 60 years of age (the timi...
Source: Trends in Cardiovascular Medicine - February 11, 2015 Category: Cardiology Authors: Georgina E. Hale, Chrisandra L. Shufelt Tags: Trends In Cardiovascular Medicine Source Type: research

PCSK9 inhibition in patients with hypercholesterolemia
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that plays an important role in modulating low-density lipoprotein cholesterol (LDL-C) levels by targeting LDL-C receptors for lysosomal degradation. Genetic association studies have demonstrated that loss-of-function mutations in PCSK9 are associated with low plasma LDL-C levels and a reduction in the incidence of adverse cardiovascular events. Monoclonal antibodies directed against PCSK9 have been developed and have been shown in phase 1, 2, and 3 trials to dramatically reduce LDL-C regardless of background lipid-lowering therapy, including in cli...
Source: Trends in Cardiovascular Medicine - February 10, 2015 Category: Cardiology Authors: Nihar R. Desai, Marc S. Sabatine Source Type: research

PCSK9 Inhibition for Patients with Hypercholesterolemia
Proprotein convertase subtilisin kexin type 9 (PCSK9) is a serine protease that plays an important role in modulating low density lipoprotein cholesterol (LDL-C) levels by targeting LDL-C receptors for lysosomal degradation. Genetic association studies have demonstrated that loss-of-function mutations in PCSK9 are associated with low plasma LDL-C levels and a reduction in the incidence of adverse cardiovascular events. Monoclonal antibodies directed against PCSK9 have been developed and have been shown in phase 1, 2, and 3 trials to dramatically reduce LDL-C regardless of background lipid lowering therapy, including in cli...
Source: Trends in Cardiovascular Medicine - February 10, 2015 Category: Cardiology Authors: Nihar R. Desai, Marc S. Sabatine Source Type: research

Protein trafficking in cardiovascular disease: How the science has evolved and where it must go
The current issue of TCM features a review by Xiao and Shaw [1] on protein trafficking in cardiac myocytes. The fact that the subject of protein trafficking has found its way into a journal devoted to reviews of advances in cardiovascular medicine is a clear indication of how far our scientific understanding of heart disease has come. It also portends where it must go in the future and exemplifies why a complete understanding of human disease is crucial to the development of truly effective (both in terms of cost and absence of unwanted side effects), truly mechanism-based therapies to prevent disease. (Source: Trends in C...
Source: Trends in Cardiovascular Medicine - February 6, 2015 Category: Cardiology Authors: Jeffrey E. Saffitz Tags: Editorial Commentary Source Type: research

My Approach to the Long QT Syndrome (LQTS)
Long QT syndrome (LQTS) is a potentially lethal cardiac disorder and thus must be dealt with respectfully. A nonchalant approach could lead to disaster. LQTS is a genetic disorder, with a prevalence of 1 in 2000 live births, characterized by a prolongation of the QT interval and by a propensity for life-threatening arrhythmias, especially, but not only, under conditions of physical or emotional stress. Mutations on at least 16 genes can cause LQTS but just three are in genetic subgroups important for clinical management because the conditions triggering the arrhythmic events (syncope, cardiac arrest, or sudden death) are l...
Source: Trends in Cardiovascular Medicine - February 6, 2015 Category: Cardiology Authors: Peter J. Schwartz Source Type: research

The implantable cardioverter–defibrillator: An update
The implantable cardioverter–defibrillator (ICD) provides life-saving therapy to prevent sudden cardiac death. ICDs have been implanted in millions of patients worldwide since the first human implant in 1980. Clinical trials have helped establish guidelines for ICD implantation in primary and secondary prevention of sudden cardiac death. Recent trials have also tested and compared various programing strategies to avoid unnecessary shocks and improve survival among ICD recipients. ICDs may also assist with monitoring for heart failure management. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 5, 2015 Category: Cardiology Authors: Jared D. Miller, Omair Yousuf, Ronald D. Berger Source Type: research

Circulating endothelial Cells in coronary artery disease and acute coronary syndrome
Circulating endothelial cells (CEC) have been put forward as a promising biomarker for diagnosis and prognosis of coronary artery disease and acute coronary syndromes. This review entails current insights into the physiology and pathobiology of CEC, including their relationship with circulating endothelial progenitor cells and endothelial microparticles. Additionally, we present a comprehensive overview of the diagnostic and prognostic value of CEC quantification, as well as possibilities for improvement, for example by inclusion of CEC morphology, transcriptomics, and proteomics. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 5, 2015 Category: Cardiology Authors: David E. Schmidt, Marco Manca, Imo E. Hoefer Source Type: research

The Promise of Enhancer-Associated Long Noncoding Rnas in Cardiac Regeneration
Heart failure is a worldwide epidemic, and represents a major cause of morbidity and mortality. Current clinical therapies for heart disease prolong survival by protecting the viable muscle but are unable to replenish lost cardiomyocytes to restore function. Over the last decade, the notion of promoting cardiac regeneration has engendered considerable research interest. New strategies envisage the transfer of stem cells into the damaged myocardium, the mobilization of cardiac precursor cells or the promotion of cardiomyocyte proliferation in situ and direct reprogramming of non-cardiac cells into electromechanically couple...
Source: Trends in Cardiovascular Medicine - February 5, 2015 Category: Cardiology Authors: Samir Ounzain, Thierry Pedrazzini Source Type: research

The Implantable Cardioverter-Defibrillator: An Update
The implantable cardioverter-defibrillator (ICD) provides life-saving therapy to prevent sudden cardiac death. ICDs have been implanted in millions of patients worldwide since the first human implant in 1980. Clinical trials have helped establish guidelines for ICD implantation in primary and secondary prevention of sudden cardiac death. Recent trials have also tested and compared various programming strategies to avoid unnecessary shocks and improve survival among ICD recipients. ICDs may also assist with monitoring for heart failure management. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 5, 2015 Category: Cardiology Authors: Jared D. Miller, Omair Yousuf, Ronald D. Berger Source Type: research

Calm down when the heart is stressed: Inhibiting calmodulin-dependent protein kinase II for antiarrhythmias
Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a pivotal role in many regulatory processes of cellular functions ranging from membrane potentials and electric–contraction (E-C) coupling to mitochondrial integrity and survival of cardiomyocytes. The review article by Hund and Mohler in this issue of Trends in Cardiovascular Medicine highlights the importance of the elevated CaMKII signaling pathways under stressed conditions such as myocardial hypertrophy and ischemia in the detrimental remodeling of ion channels and in the genesis of cardiac arrhythmias. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 4, 2015 Category: Cardiology Authors: Dayue Darrel Duan Tags: Editorial Commentary Source Type: research

Universal therapeutic targeting of age-related protein quality control system dysfunction in chronic diseases?
Aging is inevitable. Aging constitutes a principal risk factor for most, if not all chronic disorders including heart disease. Although the rate and degree to which a person ages is a reflection of their genetics, family history, environment and life style, ultimately the age-related underlying proteomic changes occur that widely affect all aspects of cell physiology. There still lacks a complete mechanistic understanding of how aging alters the proteome. Even so, numerous pathways and processes involved in aging have been implicated including age-related dysfunction of the protein quality control (PQC) processes. (Source:...
Source: Trends in Cardiovascular Medicine - February 4, 2015 Category: Cardiology Authors: Jennifer E. Van Eyk Source Type: research

Calm Down When the Heart Is Stressed– inhibiting calmodulin-dependent protein kinase II for antiarrhythmias
Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a pivotal role in many regulatory processes of cellular functions ranging from membrane potentials and electric-contraction (E-C) coupling to mitochondrial integrity and survival of cardiomyocytes. The review article by Hund and Mohler in this issue of Trends in Cardiovascular Medicine highlights the importance of the elevated CaMKII signaling pathways under stressed conditions such as myocardial hypertrophy and ischemia in the detrimental remodeling of ion channels and in the genesis of cardiac arrhythmias. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 4, 2015 Category: Cardiology Authors: Dayue Darrel Duan Source Type: research

Ed Board
(Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 1, 2015 Category: Cardiology Source Type: research

Table of Contents
(Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - February 1, 2015 Category: Cardiology Source Type: research

SK Channels and Ventricular Arrhythmias in Heart Failure
Small-conductance Ca2+-activated K+ (SK) currents are important in the repolarization of normal atrial (but not ventricular) cardiomyocytes. However, recent studies showed that the SK currents are upregulated in failing ventricular cardiomyocytes, along with increased SK channel protein expression and enhanced sensitivity to intracellular Ca2+. The SK channel activation may be either antiarrhythmic or proarrhythmic, depending on the underlying clinical situations. While the SK channel is a new target of antiarrhythmic therapy, drug safety is still one of the major concerns. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - January 28, 2015 Category: Cardiology Authors: Po-Cheng Chang, Peng-Sheng Chen Source Type: research

Outflow Tract Ventricular Arrhythmias: An Update
During the last 20 years, the molecular etiology for many ventricular tachyarrhythmias once referred to as “idiopathic”, has been elucidated. These arrhythmias are due to mutations in ion channels or structural proteins, and include ventricular tachyarrhythmias due to long and short QT syndromes, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia (VT). However, the basis for the most common form of idiopathic ventricular arrhythmia, that which originates from right or left ventricular outflow tracts, has remained elusive. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - January 28, 2015 Category: Cardiology Authors: Bruce B. Lerman Source Type: research

MY APPROACH to the Patient With Pulmonary Embolism
Acute pulmonary embolism (PE) is a potentially life-threatening condition that kills thousands of patients every year. If untreated, the estimated mortality rate of “all-comers” with a PE is approximately 30%. However, with prompt diagnosis and early institution of appropriate therapy, the expected percent mortality can be reduced to single digits. Because acute PE can occur in all “shapes and sizes,” the treatment approach should be predicated on the perceived severity of the PE and risk of death. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - January 23, 2015 Category: Cardiology Authors: Jonathan David Rich Source Type: research

MY APPROACH to Low-Level Troponin Elevations
Cardiac troponin (cTn) I and T complement clinical assessment and the ECG in the early diagnosis of acute myocardial infarction (AMI). cTns are structural proteins unique to the heart. cTn levels in peripheral blood are quantitative markers of cardiomyocyte damage. Thereby, cTns are organ-specific, but not disease-specific, markers. Although AMI is a very important cause of cardiomyocyte damage, and clearly the dominant one in patients presenting with acute chest pain and substantial cTn elevations (eg, 50 times the 99th percentile), multiple other acute and chronic disorders seem to lead to cardiomyocyte damage that can b...
Source: Trends in Cardiovascular Medicine - January 23, 2015 Category: Cardiology Authors: Christian E. Mueller Source Type: research

Emerging Concepts of heart failure in tetralogy of Fallot
As our understanding of tetralogy of Fallot (TOF) evolves, so too does our approach to treating those born with ‘la maladie bleu’. Prior to the birth of cardiac surgery, the outlook for children with unrepaired TOF was bleak, with a median age of death of 9 years (1). Advances in diagnosis, cardiac surgery, and cardiopulmonary bypass led to dramatic improvements in survival, starting with the Blalock-Taussig-Thomas shunt in 1945 (2) and culminating in primary neonatal repair in 1973 (3). Early mortality after corrective surgery has dropped from 25% to less than 2% in recent decades (4), leading to a growing pop...
Source: Trends in Cardiovascular Medicine - January 22, 2015 Category: Cardiology Authors: Luke Burchill, Gary Webb Source Type: research

Mechanisms Underlying the Cardiac Benefits of Exercise: Still Running in the Dark
Disclosures: The author reports research support for work related to exercise physiology and cardiovascular health from the American Heart Association (FTF2220328), the National Institutes of Health (RO1-DA-029141, RO1- HL-117037), and the National Football League Players’ Association. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - January 21, 2015 Category: Cardiology Authors: Aaron L. Baggish Source Type: research

Molecular mechanisms of peripartum cardiomyopathy: A vascular/hormonal hypothesis
Peripartum cardiomyopathy (PPCM) is characterized by the development of systolic heart failure in the last month of pregnancy or within the first 5 months postpartum. The disease affects between 1:300 and 1:3000 births worldwide. Heart failure can resolve spontaneously but often does not. Mortality rates, like incidence, vary widely based on location, ranging from 0% to 25%. The consequences of PPCM are thus often devastating for an otherwise healthy young woman and her newborn. The cause of PPCM remains elusive. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - January 16, 2015 Category: Cardiology Authors: Natalie A. Bello, Zoltan Arany Source Type: research

Ionic Mechanisms of Arrhythmogenesis
The understanding of ionic mechanisms underlying cardiac rhythm disturbances (arrhythmias) is an issue of significance in the medical science community. Several advances in molecular, cellular and optical techniques in the past few decades have substantially increased our knowledge of ionic mechanisms that are thought to underlie the arrhythmias. The application of these techniques in the study of ion channel biophysics and regulatory properties has provided a wealth of information, with some important therapeutic implications for dealing with the disease. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - January 16, 2015 Category: Cardiology Authors: Justus M. Anumonwo, Sandeep V. Pandit Source Type: research

Molecular Mechanisms of Peripartum Cardiomyopathy: A vascular/Hormonal Hypothesis.
Peripartum cardiomyopathy (PPCM) is characterized by the development of systolic heart failure in the last month of pregnancy or within the first five months postpartum. The disease affects between 1:300 and 1:3000 births worldwide. Heart failure can resolve spontaneously, but often does not. Mortality rates, like incidence, vary widely based on location, ranging from 0-25%. The consequences of PPCM are thus often devastating for an otherwise healthy young woman and her newborn. The cause of PPCM remains elusive. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - January 16, 2015 Category: Cardiology Authors: Natalie A. Bello, Zoltan Arany Source Type: research

Pathophysiology and progression of atrial fibrillation: Do we have a comprehensive model?
Atrial fibrillation is defined as any episode of high frequency, irregular electrical atrial activity according to ECG criteria lasting>30s [1]. The electrophysiological side of the rhythm disturbance seems clarified: AF is initiated when an ectopic beat encounters a vulnerable substrate, and AF is maintained by high frequency of the trigger, by multiple circuit reentry or by one or more rotors with fibrillatory conduction [2,3]. Whilst the radiofrequency ablation technique provided proof that ectopic beats from the pulmonary veins are important triggers [4], the nature of the vulnerable substrate is less clear and may ...
Source: Trends in Cardiovascular Medicine - January 14, 2015 Category: Cardiology Authors: Ursula Ravens Source Type: research

MY APPROACH to patients intolerant to statins*
The appropriate use of statins to reduce atherosclerotic cardiovascular disease has become a contentious topic lately, and perceived intolerance to statins is a common clinical problem. It is my impression that the term statin intolerance is used loosely in clinical practice. My first step is to carefully assess the history that led to this label. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - January 6, 2015 Category: Cardiology Authors: Seth S. Martin Tags: MY APPROACH Source Type: research

MY APPROACH to Patients Intolerant to Statins
The appropriate use of statins to reduce atherosclerotic cardiovascular disease has become a contentious topic lately, and perceived intolerance to statins is a common clinical problem. It is my impression that the term statin intolerance is used loosely in clinical practice. My first step is to carefully assess the history that led to this label. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - January 6, 2015 Category: Cardiology Authors: Seth S. Martin Source Type: research

The Bicuspid Aortic Valve Aortopathy Mystery Continues: Are we that Mediocre?
Although the bicuspid aortic valve (BAV) was described over five-hundred years ago by Leonardo da Vinci[1], its association with a clinical aortopathy was not recognized until 1928 when Canadian physician Maude Abbott reported on 200 patients with untreated aortic coarctation[2]. In that seminal work, Dr Abbott found the BAV associated to aortopathy in 2 ways: As a risk for infective endocarditis in these patients, and as a common congenital feature in patients with coarctation and ascending aorta rupture, which led her to argue “for a congenital weakness of the [aortic]wall just above the cusps, as the probable caus...
Source: Trends in Cardiovascular Medicine - January 2, 2015 Category: Cardiology Authors: Hector I. Michelena Source Type: research

Atrial remodeling, fibrosis, and atrial fibrillation
The fundamental mechanisms governing the perpetuation of atrial fibrillation (AF), the most common arrhythmia seen in clinical practice, are poorly understood, which explains in part why AF prevention and treatment remain suboptimal. Although some clinical parameters have been identified as predicting a transition from paroxysmal to persistent AF in some patients, the molecular, electrophysiological, and inflammation changes leading to such a progression have not been described in detail. Oxidative stress, atrial dilatation, calcium overload, inflammation, microRNAs, and myofibroblast activation are all thought to be invol...
Source: Trends in Cardiovascular Medicine - December 30, 2014 Category: Cardiology Authors: José Jalife, Kuljeet Kaur Source Type: research

What do we know about the cardiac benefits of exercise?
Exercise has long been considered an essential element for sustaining cardiovascular health. A vast literature of clinical studies suggests that exercise serves as an effective intervention for the primary and secondary prevention of cardiovascular disease, although the optimal nature, intensity, and duration of exercise for maximizing these cardiovascular benefits remain unclear. On a molecular level, exercise induces physiologic growth of the heart primarily by driving cardiomyocyte hypertrophy, notably through the interconnected IGF-1-PI3K-AKT1 and C/EBPβ-CITED4 pathways. (Source: Trends in Cardiovascular Medicine)
Source: Trends in Cardiovascular Medicine - December 30, 2014 Category: Cardiology Authors: Xin Wei, Xiaojun Liu, Anthony Rosenzweig Source Type: research

Atrial Remodeling, Fibrosis and Atrial Fibrillation
Fundamental mechanisms governing the perpetuation of atrial fibrillation (AF), the most common arrhythmia seen in clinical practice, are poorly understood, which explains in part why AF prevention and treatment remain suboptimal. Although some clinical parameters have been identified as predicting a transition from paroxysmal to persistent AF in some patients, the molecular, electrophysiological and structural changes leading to such a progression have not been described in detail. Oxidative stress, atrial dilatation, calcium overload, inflammation, microRNAs and myofibroblast activation are all thought to be involved in A...
Source: Trends in Cardiovascular Medicine - December 30, 2014 Category: Cardiology Authors: José Jalife, Kuljeet Kaur Source Type: research