The final step (F2), etiological investigation, incorporating advanced imaging techniques as well as genetic testing, biopsies, and specialized laboratory tests, such as serum electrophoresis, serum free light chains, serum angiotensin-converting enzyme, plasma metanephrines, has to be applied to identify the underlying cause [45] in patients who are obese when a specific etiology of heart failure is suspected, despite the difficulties described and the possibility that obesity itself may be the underlying etiology. This evidence concerns the gene ACE and heart failure.