Genetic Factors Involved in Cardiomyopathies and in Cancer

Figures

• 

  Figure 1. Schematic representation of the interplay of environmental and genetic factors participating in the development of dilated cardiomyopathy (DCM).RV: right ventricle; LV: leftventricle; RA: right atrial; LA: left atrial.

• 

  Figure 2. Late gadolinium enhancement patters seen in cardiomyopathies. (A) Typical left and right ventricular junction pattern, characteristic of hypertrophic cardiomyopathy (HCM), (B) midmyocardial lineal pattern characteristic of idiopathic/genetic dilated cardiomyopathy (DCM), (C) subendocardial left ventricle pattern characteristic of myocarditis and left form of arrhythmogenic cardiomyopathy (ACM), which can also be seen in low proportion of cases with cancer therapy-induced cardiomyopathy (CCM).

• 

  Figure 3. A 56-year-old female with cancer therapy-induced cardiomyopathy (CCM) (primary breast large B-cell lymphoma 10 years before treated with cyclophosphamide, hydroxy-daunorubicin, vincristine sulfate, prednisone, and radiotherapy). After familial evaluation was diagnosed with arrhythmogenic cardiomyopathy (ACM) caused by a DSP p.Q447*. (A) Cardiac magnetic resonance: four-chamber (up) and short-axis (down) views showing a mildly dilated left ventricle (LV)(end-diastolic volume 185 mL, 104 mL/m2), with LV hypertrabeculation from base to apex and severely impaired systolic function (left ventricle ejection fraction 29%). (B) LV global subepicardial late gadolinium enhancement (it is seen like a white ring). (C) Electrocardiogram showing a rS-type complex from V1 to V6, mild ST segment depression and negative T waves in V6, I, and aVL.

• 

  Figure 4. Schematic representation of the interaction between different cardiomyopathies (CMY) and cancer. HCM:Hypertrophic cardiomyopathy; ACM: Arrhythmogenic cardiomyopathy; DCM: dilated cardiomyopathy; RCM: Restrictive cardiomyopathy; LMNA: lamin A/C mutation; RAS/MAPK: RAS/mitogen activated protein kinasevariants.

• 

  Figure 5. Chord diagram clustered by colors. Colors in the chords correspond to KEGG (Kyoto Encyclopedia of Genes and Genomes terms) pathways, containing the genes involved with the main cardiomyopathies (33 genes listed in Table 3), and were crossed with the KEGG database [108]. The results of 57 KEGG pathways were analyzed, filtered by oncology/cancer/tumor terms, and the connections were plotted. KEGG database covers information at different molecular levels. The KEGG Pathways database is a collection of manually curated pathways including information on molecular interactions, reactions, and network relationships. The KEGG database contains more than 24 million annotated genes and 530 pathways with more than six million pathway-linked genes [109].

• 

  Figure 6. Proposal of a diagnostic algorithm in the evaluation of Cancer therapy-induced cardiomyopathy (CCM) with suspicious inherited cardiomyopathy. LV: left ventricle; HF: heart failure; CV: cardiovascular; CMY: Cardiomyopathies; LGE: late gadolinium enhancement, ECG: Electrocardiogram; CMR: cardiac magnetic resonance; LVEF: left ventricle ejection fraction; RAS/MAPK: RAS/mitogen activated protein kinasepathway; RV: right ventricle; AV: atrioventricular.