Update on hypertrophic cardiomyopathy and a guide to the guidelines

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 individuals worldwide. Existing epidemiological studies might have underestimated the prevalence of HCM, however, owing to limited inclusion of individuals with early, incomplete phenotypic expression. Clinical manifestations of HCM include diastolic dysfunction, left ventricular outflow tract obstruction, ischaemia, atrial fibrillation, abnormal vascular responses and, in 5% of patients, progression to a 'burnt-out' phase characterized by systolic impairment. Disease-related mortality is most often attributable to sudden cardiac death, heart failure, and embolic stroke. The majority of individuals with HCM, however, have normal or near-normal life expectancy, owing in part to contemporary management strategies including family screening, risk stratification, thromboembolic prophylaxis, and implantation of cardioverter-defibrillators. The clinical guidelines for HCM issued by the ACC Foundation/AHA and the ESC facilitate evaluation and management of the disease. In this Review, we aim to assist clinicians in navigating the guidelines by highlighting important updates, current gaps in knowledge, differences in the recommendations, and challenges in implementing them, including aids and pitfalls in clinical and pathological evaluation. We also discuss the advances in genetics, imaging, and molecular research that will underpin future developments in diagnosis and therapy for HCM

Prediction of normal tissue damage induced by cancer chemotherapy

Cancer chemotherapeutic agents have a low therapeutic index and require a precise and safe prescription. Hematological toxicity is the most common dose limiting side effect of cancer drugs. Therefore, Hemopoietic Stem Cells (HSC) are the most relevant targets for dose determination.Studies of total body irradiation with or without autologous bone marrow transplantation showed that HSC concentrations differ between mouse, rat, rhesus monkey, dog and man. A highly significant correlation was found between bone marrow rescue dose and kg body weight and not between bone marrow rescue dose and BSA. Kg body weight appears to offer a better prescription unit for cancer chemotherapy than BSA, because it correlates better with dose limiting, normal tissue, target cells. This prediction is borne out by the results of chemotherapy in neonates. BSA has also been used as dose unit for drugs with non hematological side effects (e. g., cardiotoxicity of anthracyclines or neurotoxicity of methotrexate). The target for such drug side effects need to be determined before the proper dose unit can be selected. A review of available data shows that for at least some non hematological side effects BSA does not offer the proper prescription unit. The historical justifications for BSA as dose unit are re-examined (simplicity, correlation with blood volume, correlation with area under the curve) and considered invalid. The ultimate long term improvements from better prescription methods for cancer chemotherapeutic agents are less normal tissue side effects and better tumor control. The indiscriminate use of BSA as a universal dose unit for cancer chemotherapy would prevent such improvements and is discouraged. Instead, drug doses are to be expressed in units that correlate with dose limiting normal tissue cells