2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients With Advanced Heart Failure and Cardiac Transplant)

Since the 1995 publication of its Core Cardiovascular Training Statement (COCATS),1 the American College of Cardiology (ACC) has played a central role in defining the knowledge, experiences, skills, and behaviors expected of all clinical cardiologists upon completion of training. Subsequent updates have incorporated major advances and revisions—both in content and structure—including, most recently,

Recent advances in heart transplantation [version 1; referees: 2 approved]

Despite advances in medical and electrical therapies for heart failure, morbidity and mortality remain high and patients often progress to end-stage heart failure. Over the last five decades, heart transplantation is considered a standard therapy for select patients with end-stage heart failure. However, while heart transplantation has become a treatment of choice for end-stage heart failure, challenges still exist for improvement in the short- and long-term outcomes. While there is an increase in the number of patients with end-stage heart failure, the number of donor organs remains a major limiting factor. Heart transplantation candidates in the current era are also more complex: older, antigen-sensitized, and on mechanical circulatory support at the time of listing and transplant. Such potential heart transplant recipients have an increased chance of problems, including antibody-mediated rejection and primary graft dysfunction. Recent advances could address the current challenges and include: 1) attempts to expand the pool of donor hearts; 2) changes in heart transplantation allocation policy allowing for more equitable organ distribution; and 3) advances in the management of antibody sensitization. Developments in these areas could result in improved survival and quality of life for heart transplantation recipients

Molecular signature analysis: the potential of gene-expression analysis in cardiomyopathy

Despite the expanding knowledge base of the molecular and cellular pathophysiology and management of cardiomyopathy, it still remains difficult to accurately distinguish between patients who will someday develop circulatory collapse and require cardiac transplantation from those with excellent long-term prognosis. Of equal importance, current medical practice does not include strategies to tailor therapies to patients most likely to benefit, while at the same time seeking predictors of poor or adverse responsiveness. Gene-expression analysis using microarray technology, by providing a phenotypic resolution not possible with standard clinical criteria, has enormous potential to provide better information regarding prognosis and response to therapy in heart-failure patients. Emerging data demonstrate that a molecular signature can accurately identify etiology in cardiomyopathy, supporting ongoing efforts to identify expression profiling-based biomarkers, although microarray research in cardiomyopathy is still in its earliest stages. The ultimate potential application of transcriptome-based molecular signature analysis is individualization of the management of heart-failure patients, whereby a patient with a newly diagnosed cardiomyopathy could, through molecular signature analysis, be offered an accurate assessment of prognosis, and how individualized medical therapy could affect his or her outcome

Molecular signature analysis: using the myocardial transcriptome as a biomarker in cardiovascular disease

With the emergence of microarray technology, it is now possible to simultaneously assess the expression of tens of thousands of gene transcripts, providing a resolution and precision of phenotypic characterization not previously possible. In the field of cardiomyopathy, microarray studies have largely focused on gene discovery, identifying differentially expressed genes characteristic of diverse disease states, through which novel genetic pathways and potential therapeutic targets may be elucidated. However, gene expression profiling may also be used to identify a pattern of genes (a molecular signature) that serves as a biomarker for clinically relevant parameters. One study thus far does demonstrate that a molecular signature can accurately identify etiology in cardiovascular disease, supporting ongoing efforts to incorporate expression-profiling-based biomarkers in determining prognosis and response to therapy in heart failure. Microarray research in cardiomyopathy is still in its earliest stages. Nevertheless, the ultimate potential application of transcriptome-based molecular signature analysis is individualization of the management of patients with heart failure, whereby a patient with a newly diagnosed cardiomyopathy could, through molecular signature analysis, be offered an accurate assessment of prognosis and how individualized medical therapy could affect his or her outcome

Novel Pathogenetic Mechanisms in Myocarditis: Nitric Oxide Signaling

The nitric oxide (NO) signaling pathway plays important roles in the regulation of most organ systems, participating in physiologic regulation and pathophysiologic organ dysfunction. Physiologic NO signaling is mediated by the precise subcellular localization of NO synthases (NOS) in proximity to target effector molecules. Organ dysfunction can occur by NOS downregulation, loss of spatial localization, or the induction of high-output NOS isoforms, such as calcium-independent NOS, leading to nitrosative stress. Myocarditis represents a prototypic clinical scenario for the dysregulation of NOS isoforms within the heart. This article reviews the physiologic roles for neuronal and endothelial NOS in cardiac function and the various consequences of spatial regulation of NOS informs and calcium-independent NOS induction, which influences organ function, antiviral immunity, and apoptosis