It is of importance to better understand the pathophysiological mechanisms leading to heart maladaptation and the timely identification and management of patients at risk for developing symptomatic heart failure (HF). High blood pressure is the major modifiable risk factor for overt HF. In patients with hypertension the process of myocardial remodeling/dysfunction starts long before the onset of HF symptoms. The long-term increased afterload (high pressure) and, consequently, the chronically increased cardiac performance lead to left ventricular (LV) concentric remodeling, decreased longitudinal systolic deformation (strain), diastolic dysfunction and increased LV oxygen requirements. Atherosclerosis is another key pathological process leading to symptomatic HF. The buildup of plaque in the coronary arteries and therefore their narrowing lead to reduced oxygen supply to the heart muscle. The burdening of the heart resulting from the atherosclerotic process then accelerates the progression of cardiac remodeling and dysfunction. Recent studies revealed a high prevalence of asymptomatic LV systolic and diastolic dysfunction/remodeling in the community and their association with subclinical atherosclerotic lesions of coronary arteries. In this chapter we discussed the different aspects of cardiac maladaptive responses to a chronically increased hemodynamic load and atherosclerosis.