Older patients with isolated DHF have reduced cardiac cycle-dependent changes in proximal thoracic aortic area and distensibility (beyond that which occurs with normal aging), and this correlates with and may contribute to their severe exercise intolerance.

Objective To determine if low to moderate doses of anthracycline-based chemotherapy (Anth-bC) are associated with subclinical cardiovascular (CV) injury. Background Cancer survivors that receive Anth-bC experience premature CV events. It is unknown whether low to moderate doses of anthracyclines a) promote early subclinical CV disease manifested by deteriorations in left ventricular ejection fraction (LVEF) or increases in aortic stiffness, or b) are associated with change in quality of life (QOL). Methods In 53 men and women with breast cancer, leukemia, or lymphoma, we assessed left ventricular volumes, LVEF, circumferential strain, aortic pulse wave velocity (PWV), late gadolinium enhancement, serum B-type natriuretic peptide (BNP), troponin I (TnI), and the impact of treatment on QOL before, and 1, 3, and 6 months after receipt of Anth-bC. Results Participants averaged 50±2 (range 19–80) years in age, 58% were women, 17% were black, and they each received a range of 50 to 375 mg/m2 of doxorubicin equivalent chemotherapy. Left ventricular end systolic volume (LVESV; 48±3 to 54±3 ml; p=0.02), left ventricular strain (−17.7±0.4 to −15.1±0.4; p=0.0003), PWV (6.7±0.5 to 10.1±1 m/sec; p=0.0006), and QOL deterioration (15.4±3.3 to 28.5±3.9; p=0.008) increased, while LVEF (58±1 to 53±1%; p=0.0002) decreased within 6 months after low to moderate doses of Anth-bC. All findings persisted after accounting for age, gender, race (white/black), doxorubicin equivalent dose, doxorubicin administration technique, comorbidities associated with CV events, and cancer diagnosis (p=0.02 to 0.0001 for all). There were no new late gadolinium enhancement findings after 6 months. Conclusions Low to moderate doses of Anth-bC are associated with the early development of subclinical abnormalities of cardiac and vascular function that in other populations are associated with the future occurrence of CV events.

Fast cine cardiac MRI provides a mechanism to assess left ventricular contraction and diagnose inducible myocardial ischemia in patients not well suited for stress echocardiography.

Background-Regional assessments of left ventricular (LV) wall motion obtained during MRI cardiac stress tests can be used to identify myocardial injury and ischemia, but the utility of MRI stress test results for the assessment of cardiac prognosis is not known. Methods and Results-Two hundred seventy-nine patients referred (because of poor LV endocardial visualization with echocardiography) for dobutamine/atropine MRI for the detection of inducible ischemia were followed for an average of 20 months. After MRI stress testing, the occurrence of myocardial infarction, cardiac death, death attributable to any cause, coronary arterial revascularization, and unstable angina or congestive heart failure requiring hospitalization was determined. In a multivariate analysis, the presence of inducible ischemia (hazard ratio 3.3, CI 1.1 to 9.7) or an LV ejection fraction Ͻ40% (hazard ratio 4.2, CI 1.3 to 13.9) was associated with future MI or cardiac death independent of the presence of risk factors for coronary arteriosclerosis. Conclusions-In patients with poor echocardiograms, the results of cardiac MRI stress tests can be used to forecast myocardial infarction or cardiac death.

A B S T R A C T PurposeCancer survivors exposed to anthracyclines experience an increased risk of cardiovascular (CV) events. We hypothesized that anthracycline use may increase aortic stiffness, a known predictor of CV events. Patients and MethodsWe performed a prospective, case-control study involving 53 patients: 40 individuals who received an anthracycline for the treatment of breast cancer, lymphoma, or leukemia (cases), and 13 ageand sex-matched controls. Each participant underwent phase-contrast cardiovascular magnetic resonance measures of pulse wave velocity (PWV) and aortic distensibility (AoD) in the thoracic aorta at baseline, and 4 months after initiation of chemotherapy. Four one-way analyses of covariance models were fit in which factors known to influence thoracic aortic stiffness were included as covariates in the models. ResultsAt the 4-month follow-up visit, aortic stiffness remained similar to baseline in the control participants. However, in the participants receiving anthracyclines, aortic stiffness increased markedly (relative to baseline), as evidenced by a decrease in AoD (P Ͻ .0001) and an increase in PWV (P Ͻ .0001). These changes in aortic stiffness persisted after accounting for age, sex, cardiac output, administered cardioactive medications, and underlying clinical conditions known to influence aortic stiffness, such as hypertension or diabetes (P Ͻ .0001). ConclusionA significant increase in aortic stiffness occurs within 4 months of exposure to an anthracycline which was not seen in an untreated control group. These results indicate that previously regarded cardiotoxic cancer therapy adversely increases thoracic aortic stiffness, a known independent predictor of adverse cardiovascular events.

Fat in the renal sinus (RS), a region of the kidney in which low pressure venous and lymphatic vessels are present, may indirectly influence blood pressure (BP). The purpose of this study was to assess the association between RS fat and control of BP upon receipt of antihypertensive medications. Two hundred-five (205) participants aged 55 to 85 years at risk for cardiovascular (CV) events underwent magnetic resonance imaging assessments of abdominal and RS fat, measurement of blood pressure, and determination of the number of prescribed antihypertensive medications. Multivariable linear regression was used to determine associations between RS fat, blood pressure, and the number of prescribed antihypertensive medications. Abdominal fat averaged (416 ± 160 cm3, median and interquartile range (IQR) of 396 cm3 and 308 to 518 cm3); intraperitoneal (IP) fat averaged (141 ± 73 cm3, median and IQR of 129 cm3 and 86 to 194 cm3); and RS fat averaged (4.6 ± 3.2 cm3, median and IQR of 4.2 cm3 and 2.2 to 6.6 cm3). After accounting for age, gender, height, body mass index (BMI), and IP fat, RS fat correlated with the number of prescribed antihypertensive medications (p=0.010), stage II hypertension (p=0.02), and renal size (p=<0.001). In conclusion, after accounting for other body fat depots and risk factors for hypertension, renal sinus fat volume is associated with the number of prescribed antihypertensive medications and stage II hypertension. These results indicate that further studies are warranted to determine if fat accumulation in the renal sinus promotes hypertension.

Background Cardiovascular magnetic resonance (CMR) T1 mapping characteristics are elevated in adult cancer survivors; however, it remains unknown whether these elevations are related to age or presence of coincident cardiovascular comorbidities. Methods and Results We performed blinded CMR analyses of left ventricular (LV) T1 and extracellular volume fraction (ECV) in 327 individuals (65% women, aged 64±12 years). Thirty-seven (37) individuals had breast cancer or a hematologic malignancy but had not yet initiated their treatment, and 54 cancer survivors that received either anthracycline-based (n=37) or non-anthracycline-based (n=17) chemotherapy 2.8±1.3 years earlier were compared to 236 cancer-free participants. Multivariable analyses were performed to determine the association between T1/ECV measures and variables associated with myocardial fibrosis. Age-adjusted native T1 was elevated pre- (1058±7 ms) and post- (1040±7 ms) receipt of anthracycline chemotherapy versus comparators (965±3 ms, p<0.0001 for both). Age-adjusted ECV, a marker of myocardial fibrosis, was elevated in anthracycline-treated cancer participants (30.4±0.7%) compared with either pre-treatment cancer (27.8±0.7%, p<0.01) or cancer-free comparators (26.9±0.2%, p<0.0001). T1 and ECV of non-anthracycline survivors was no different than pre-treatment survivors (p=0.17 and p=0.16, respectively). Native T1 and ECV remained elevated in cancer survivors after accounting for demographics (including age), myocardial fibrosis risk factors, and LV ejection fraction or myocardial mass index (p<0.0001 for all). Conclusions Three years after anthracycline-based chemotherapy, elevations in myocardial T1 and ECV occur independent of underlying cancer or cardiovascular comorbidities suggesting that imaging biomarkers of interstitial fibrosis in cancer survivors are related to prior receipt of a potentially cardiotoxic cancer treatment regimen.

elderly patients with HFNEF do not exhibit marked reduction in leg FMAD. These data suggest that mechanisms other than impaired femoral arterial endothelial function contribute to the severe exercise intolerance experienced by these individuals.