Challenges and Controversies in Hypertrophic Cardiomyopathy: Clinical, Genomic and Basic Science Perspectives

Abstract

Figure 1

A: Deep left ventricular (LVP) and aortic root (AOP) pressures in hypertrophic cardiomyopathy at rest and during supine bicycle exercise, which elicits an abnormal LVP diastolic decay, suggesting impaired ventricular relaxation; LVP decays throughout diastole, in sharp contrast to the normal pattern shown in panel C. B: Pressure-flow relation with large early and enormous mid- and late-systolic dynamic gradients in hypertrophic cardiomyopathy. From top downward: aortic velocity signal, and deep left ventricular (LV), left ventricular outflow tract (LVOT), and aortic root (AO) micromanometric signals, measured by retrograde triple-tip pressure plus velocity multisensor left-heart catheter. Left atrial (LA) micromanometric signal was measured simultaneously by trans-septal catheter. The vertical straight line identifies the onset of SAM-septal contact, determined from a simultaneous M-mode mitral valve echocardiogram (not shown); the majority of aortic ejection flow is already completed by this time. The huge mid- and late- systolic gradient (hatched area) is maintained in the face of minuscule remaining forward or even negative aortic velocities. SAM, systolic anterior motion of the mitral valve. Adapted from Pasipoularides, with permission of PMPH-USA.

Figure 2

Diagram showing all single nucleotide polymorphism-trait associations with P-value ≤ 5.0 × 10⁻⁸, mapped onto the human genome by chromosomal locations and displayed on the human karyotype. The Genome-wide Association Studies (GWAS) Catalog is supplied jointly by the National Human Genome Research Institute (NHGRI) and the European Bioinformatics Institute (EMBL-EBI). The diagram is released nightly and the latest version is made available on the NHGRI-EBI Catalog website.

Figure 3

The genome integrates intrinsic and environmental signals. The Bernardian environment and epigenetic regulatory factors influence through (bidirectional) information flow and signaling pathways variable human gene transcription and expression, while protein levels and function are affected by various post-translational adjustments. Since epigenetic states are reversible, they can be modified by environmental factors, which may contribute to modifiable changes between normal and abnormal phenotypes. Interfering with the activity of factors that modify the chromatin state can possibly affect the expression of unwanted gene-variants. The human organism is effectively a “supraorganism,” a blend of human and microbiome genes and traits, including the metabolome. The relationship between different “-ome/-omics” components, protein levels, post-translational modification, protein localization and activity affecting phenotypic traits, is shown schematically in this general overview. mRNA, messenger RNA; miRNA, microRNA. Reproduced from Pasipoularides, with permission of Int J Cardiol and Elsevier.