Hugo Martinez

By Evan M. Harvey, Murad Almasri and Hugo R. Martinez

Cardiomyopathies (CMs) encompass a heterogeneous group of structural and functional (systolic and diastolic) abnormalities of the myocardium and are either confined to the cardiovascular system or are part of a systemic disorder. CMs represent a leading cause of morbidity and mortality and account for a significant percentage of death and cardiac transplantation. The 2006 American Heart Association (AHA) classification grouped CMs into primary (genetic, mixed, or acquired) or secondary (i.e., infiltrative or autoimmune). In 2008, the European Society of Cardiology classification proposed subgrouping CM into familial or genetic and nonfamilial or nongenetic forms. In 2013, the World Heart Federation recommended the MOGES nosology system, which incorporates a morpho-functional phenotype (M), organ(s) involved (O), the genetic inheritance pattern (G), an etiological annotation (E) including genetic defects or underlying disease/substrates, and the functional status (S) of a particular patient based on heart failure symptoms. Rapid advancements in the biology of cardio-genetics have revealed substantial genetic and phenotypic heterogeneity in myocardial disease. Given the variety of disciplines in the scientific and clinical fields, any desired classification may face challenges to obtaining consensus. Nonetheless, the heritable phenotype-based CM classification offers the possibility of a simple, clinically useful diagnostic scheme. In this chapter, we will describe the genetic basis of dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic cardiomyopathy (ACM), LV noncompaction cardiomyopathy (LVNC), and restrictive cardiomyopathy (RCM). Although the descriptive morphologies of these types of CM differ, an overlapping phenotype is frequently encountered within the CM types and arrhythmogenic pathology in clinical practice. CMs appear to originate secondary to disruption of “final common pathways.” These disruptions may have purely genetic causes. For example, single gene mutations result in dysfunctional protein synthesis causing downstream dysfunctional protein interactions at the level of the sarcomere and a CM phenotype. The sarcomere is a complex with multiple protein interactions, including thick myofilament proteins, thin myofilament proteins, and myosin-binding proteins. In addition, other proteins are involved in the surrounding architecture of the sarcomere such as the Z-disk and muscle LIM proteins. One or multiple genes can exhibit tissue-specific function, development, and physiologically regulated patterns of expression for each protein. Alternatively, multiple mutations in the same gene (compound heterozygosity) or in different genes (digenic heterozygosity) may lead to a phenotype that may be classic, more severe, or even overlapping with other disease forms.

Part of the book: Cardiomyopathy

By Hugo Martinez, Neely R. Alberson, Jarot J. Guerra and Ismael A. Salas De Armas

Meaningful and contemporary data regarding the clinical use of mechanical circulatory support (MCS) is founded on the work conducted in the 1950s when a “heart-lung” machine was incorporated to provide support during surgical interventions. Following this milestone, the need to support artificial circulation in patients with heart failure initiated an investigational and legislative collaboration to implement the mission-oriented Artificial Heart Program in the United States during the 1960s. In the subsequent decades, technological discoveries have integrated a series of mechanical systems employed as therapeutic options for short- and long-term artificial circulation in children and adults with advanced heart failure. Since their clinical application, MCS devices have been employed as a bridge to transplantation in over 4000 patients globally. In recent years, the adverse effects and economic burden of MCS have been counterbalanced by the harmonization of therapeutic protocols, the inclusion of multidisciplinary insight, and the allowance of families and patients to participate in shared decision making to address candidacy. In this chapter, we provide a review of the historical aspects of MCS, a therapeutic option for overcoming complexities encountered in reestablishing adequate hemodynamic states and providing a reasonable quality of life.

Part of the book: Ventricular Assist Devices