Jennifer E. Liu

The discipline of Cardio-Oncology has seen tremendous growth over the past decade. It is devoted to the cardiovascular (CV) care of the cancer patient, especially to the mitigation and management of CV complications or toxicities of cancer therapies, which can have profound implications on prognosis. To that effect, many studies have assessed CV toxicities in patients undergoing various types of cancer therapies; however, direct comparisons have proven difficult due to lack of uniformity in CV toxicity endpoints. Similarly, in clinical practice, there can be substantial differences in the understanding of what constitutes CV toxicity, which can lead to significant variation in patient management and outcomes. This document addresses these issues and provides consensus definitions for the most commonly reported CV toxicities, including cardiomyopathy/heart failure and myocarditis, vascular toxicity, and hypertension, as well as arrhythmias and QTc prolongation. The current document reflects a harmonizing review of the current landscape in CV toxicities and the definitions used to define these. This consensus effort aims to provide a structure for definitions of CV toxicity in the clinic and for future research. It will be important to link the definitions outlined herein to outcomes in clinical practice and CV endpoints in clinical trials. It should facilitate communication across various disciplines to improve clinical outcomes for cancer patients with CV diseases.

BACKGROUND: With aging, left ventricular filling tends to decrease in early diastole, reducing the mitral ratio of peak early to late diastolic filling velocity (E/A). However, the prognostic significance of low or high E/A in older adults remains to be elucidated in population-based samples. METHODS AND RESULTS: Doppler echocardiograms were analyzed in 3008 American Indian participants in the second Strong Heart Study examination who had no more than mild mitral or aortic regurgitation. Participants were followed for a mean of 3 years after Doppler echocardiography to assess risks of all-cause and cardiac death associated with E/A <0.6 or >1.5; 2429 (81%) participants had normal E/A ratio, 490 (16%) had E/A <0.6, and 89 (3%) had E/A >1.5. All-cause mortality was higher with E/A <0.6 or E/A >1.5 (12% and 13% versus 6%), as was cardiac mortality (4.5% and 6.5% versus 1.6%; both P<0.001). Adjusting for age, sex, body mass index, systolic blood pressure, HDL and LDL cholesterol, smoking, hypertension, diabetes, coronary heart disease, left ventricular hypertrophy, and low ejection fraction (<40%), the relative risk of all-cause death with E/A >1.5 was 1.73 (95% CI, 0.99 to 3.03; P=0.05); the relative risk of cardiac death was 2.8 (95% CI, 1.19 to 6.75; P<0.05). E/A <0.6 was not independently associated with increased all-cause or cardiac mortality (P=0.19 and 0.31, respectively) after adjusting for covariates. CONCLUSIONS: In a population-based sample of middle-aged and elderly adults, mitral E/A >1.5 at baseline Doppler echocardiography is associated with 2-fold increased all-cause and 3-fold increased cardiac mortality independent of covariates; mitral E/A <0.6 was also associated with 2-fold increased all-cause and cardiac mortality but not independent of covariates.

BACKGROUND: Ambulatory blood pressure may be higher or lower than clinic blood pressure. Attention has focused on "white coat hypertension" (normal ambulatory blood pressure elevated in the clinic). The converse phenomenon of high ambulatory blood pressure but normal office blood pressure-"white coat normotension"-has not been studied. OBJECTIVE: To assess whether white coat normotension (awake ambulatory blood pressure > 134/90 mm Hg and clinic blood pressure < 140/90 mm Hg) is associated with target organ damage. DESIGN: Cross-sectional observational study. SETTING: University hospital hypertension center and participant work sites. PATIENTS: 295 clinically normotensive adults and 64 patients with sustained hypertension (elevated clinic and ambulatory blood pressure). MEASUREMENTS: Target organ abnormalities were measured by echocardiography and arterial ultrasonography in 61 patients with white coat normotension, 234 with sustained normotension (normal clinic and ambulatory blood pressure), and 64 with sustained hypertension. RESULTS: Patients with white coat normotension were older; had higher body mass indices, serum creatinine concentrations, and glucose levels; and a higher prevalence of current smokers. Left ventricular mass index and relative wall thickness were higher by 13 g/m2 (CI, 8 to 18 g/m2) and by 0.03 (CI, 0.01 to 0.04), respectively, in patients with white coat normotension compared with those who had sustained normotension. Patients with white coat normotension and those with sustained hypertension did not differ significantly for left ventricular mass index (4 g/m2 [CI, - 3 to 10 g/m2) or relative wall thickness (0.01 [CI, -0.01 to 0.03]). The prevalence of discrete atherosclerotic plaques was similar in patients with white coat normotension (17 of 61, or 28% [CI, 17% to 39%]) and those with sustained hypertension (17 of 64, or 27% [CI, 16% to 38%]), but the difference lost significance after adjustment for age. CONCLUSIONS: White coat normotension is associated with left ventricular mass and carotid wall thickness similar to those in sustained hypertension. The association of white coat normotension with prognostically important target organ damage may partly explain the ability of high normal left ventricular mass and high normal clinic blood pressure to predict subsequent hypertension and cardiovascular events in patients with clinical normotension.