Dilated cardiomyopathy (DCM) is a common heart muscle disorder of nonischemic etiology associated with heart failure development and the risk of malignant ventricular arrhythmias and sudden cardiac death. A tailored approach to risk stratification and prevention of sudden cardiac death is required in genetic DCM given its variable presentation and phenotypic severity. Currently, advances in cardiogenetics have shed light on disease mechanisms, the complex genetic architecture of DCM, polygenic contributors to disease susceptibility and the role of environmental triggers. Parallel advances in imaging have also enhanced disease recognition and the identification of the wide spectrum of phenotypes falling under the DCM umbrella. Genotype-phenotype associations have been also established for specific subtypes of DCM, such as DSP (desmoplakin) or FLNC (filamin-C) cardiomyopathy but overall, they remain elusive and not readily identifiable. Also, despite the accumulated knowledge on disease mechanisms, certain aspects remain still unclear, such as which patients with DCM are at risk for disease progression or remission after treatment. Imagenetics, that is, the combination of imaging and genetics, is expected to further advance research in the field and contribute to precision medicine in DCM management and treatment. In the present article, we review the existing literature in the field, summarize the established knowledge and emerging data on the value of genetics and imaging in establishing genotype-phenotype associations in DCM and in clinical decision making for DCM patients.

Background: Endothelial dysfunction and inflammation are associated with the progression of coronary artery disease (CAD) and the pathophysiology of acute coronary syndrome (ACS). We examined the prognostic role of endothelial function and pro-inflammatory cytokines in patients admitted with ACS. Methods: The study population consisted of 864 subjects. From 663 subjects who presented with chest pain, ACS was diagnosed in 460. We additionally recruited 201 consecutive patients with stable CAD. Endothelial function was assessed using flow-mediated dilatation (FMD). Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels were measured via ELISA. Subjects with ACS were followed up for major adverse cardiovascular events (MACE), defined as cardiovascular death, cardiac arrest, myocardial infarction, stroke, nonfatal stroke, other arterial thrombotic events, and hospitalization due to cardiovascular conditions. Results: There was a stepwise impairment in FMD, logTNF-α, and logIL-6 in patients with chest pain of non-epicardial CAD etiology compared to patients with stable CAD and those with ACS (p < 0.001 for all). Moreover, patients who presented with chest pain had increased odds of ACS in accordance with the increasing levels of TNF-α, IL-6, and impaired FMD (p < 0.05 for all). Interestingly, from all these markers, in patients with ACS, we found that only TNF-α levels above 5.19 pg/mL had a 2.5-times-increased risk of MACE compared to patients with TNF-α levels below 5.19 pg/mL, independently of other confounders. Conclusions: In the current study, we found that patients who presented with ACS had impaired endothelial function and increased levels of IL-6 and TNF-α.

Danon disease (DD) is a rare, X-linked genetic disorder caused by LAMP2 deficiency. Clinical phenotype involves early cardiomyopathy development along with pre-excitation, skeletal myopathy, retinopathy, and cognitive impairment. We highlight how a noninvasive diagnostic approach based on clinical and imaging red flags for DD can be employed to raise high clinical suspicion for DD, which was confirmed by genetic testing results. (Level of Difficulty: Intermediate.)