the force with which the heart ejects blood, thus are not recommended in people with heart failure with a reduced ejection fraction. Supplements Certain alternative medicines carry a risk of exacerbating existing heart failure, and are not recommended. This includes aconite, ginseng, gossypol, gynura, licorice, lily of the valley, tetrandrine, and yohimbine. Aconite can cause abnormally slow heart rates and abnormal heart rhythms such as ventricular tachycardia. Ginseng can cause abnormally low or high blood pressure, and may interfere with the effects of diuretic medications. Gossypol can increase the effects of diuretics, leading to toxicity. Gynura can cause low blood pressure. Licorice can worsen heart failure by increasing blood pressure and promoting fluid retention. Lily of the valley can cause abnormally slow heart rates with mechanisms similar to those of digoxin. Tetrandrine can lead to low blood pressure through inhibition of L-type calcium channels. Yohimbine can exacerbate heart failure by increasing blood pressure through alpha-2 adrenergic receptor antagonism. Pathophysiology Heart failure is caused by any condition that reduces the efficiency of the heart muscle, through damage or overloading. Over time, these increases in workload, which are mediated by long-term activation of neurohormonal systems such as the renin–angiotensin system and the sympathoadrenal system, lead to fibrosis, dilation, and structural changes in the shape of the left ventricle from elliptical to spherical. The heart of a person with heart failure may have a reduced force of contraction due to overloading of the ventricle. In a normal heart, increased filling of the ventricle results in increased contraction force by the Frank–Starling law of the heart, and thus a rise in cardiac output. In heart failure, this mechanism fails, as the ventricle is loaded with blood to the point where heart muscle contraction becomes less efficient. This is due to reduced ability to cross-link actin and myosin myofilaments in over-stretched heart muscle. Diagnosis No diagnostic criteria have been agreed on as the gold standard for heart failure, especially heart failure with preserved ejection fraction (HFpEF). In the UK, the National Institute for Health and Care Excellence recommends measuring N-terminal pro-BNP (NT-proBNP) followed by an ultrasound of the heart if positive. In Europe, the European Society of Cardiology, and in USA, the AHA/ACC/HFSA, recommend measuring NT-proBNP or BNP followed by an ultrasound of the heart if positive. This is recommended in those with symptoms consistent with heart failure such as shortness of breath. The European