Distal Upper Extremity Arterial Calcification as a Predictor for Subclinical Coronary Artery Disease by Coronary Artery Calcium Scoring.

Several studies have linked calcification of the thoracic and lower extremity arterial trunks to an increased risk of developing coronary artery disease (CAD). Calcifications of the radial and/or ulnar artery are regularly identified in hand/wrist x-rays; however, the clinical relevance of these findings as related to identifying subclinical CAD is not well understood. Associations between CAD and upper extremity calcifications have been reported, but the timeline is unclear. The purpose of this study was to evaluate the association between upper extremity arterial calcifications on hand radiographs with CAD by coronary artery calcification (CAC) scoring in patients with no known history of CAD. This is a pilot single-center, prospective, matched cohort study. We included patients with no known history of CAD, related symptoms, or major risk factors. We recruited five patients with calcifications (cal+) and five patients matched by age, race, sex, and medical history but without calcifications (cal-). CAC scores were determined from computed tomography scanning, and lipid profile was evaluated. In the cal+ group, the mean CAC total score was 244.1; in the control (cal-) group, it was 85.2. The mean total cholesterol levels were 220.8 mg per dL and 167 mg per dL in the cal+ and cal- groups, respectively. Two cal+ patients with CAC scores of 937 and 669 died shortly after being enrolled in our study. Preliminary findings suggest that calcifications in the radial or ulnar artery in otherwise asymptomatic patients with no history of CAD may be an independent sign of CAD.

Cardiovascular risk among ultra-endurance runners.

BACKGROUND: Our objective was to determine the prevalence and clinical correlates of conventional cardiovascular risk factors among ultra-endurance marathon runners. METHODS: An electronic internet survey to characterize modifiable cardiovascular risk factors including diabetes, hypertension, dyslipidemia, tobacco exposure and obesity (BMI>30) among competitive ultra-endurance runners. RESULTS: Among 290 respondents (mean±SD, 42±11 years, 31.4% female), 106 (36.6%) had at least one established cardiovascular risk factor. Female sex, younger age and participation in competitive high school or collegiate sports were associated with freedom from cardiovascular risk factors. There were no significant associations between risk factor status and either hours per week of running training (risk factor negative: 10±7 vs. risk factor positive: 11±8 hours, P=0.42) or years of ultra-endurance competition (6±8 vs. 7±9 years, P=0.38). Runners with at least one cardiovascular risk factor were more likely to have had personal or peer concerns about excessive alcohol use. CONCLUSIONS: Conventional cardiovascular risk factors are common among ultra-endurance runners. Early-life participation in competitive sports, rather than adult exercise habits, is associated with freedom from the development of cardiovascular risk factors during middle age. Determining mechanistic explanations for the legacy effect of early life exercise as a means to reduce cardiovascular risk among aging athletes represents an important area of future work.

The ELISA Detectability and Potency of Pegfilgrastim Decrease in Physiological Conditions: Key Roles for Aggregation and Individual Variability.

PEGylated recombinant human granulocyte colony stimulating factor (pegfilgrastim) is used clinically to accelerate immune reconstitution following chemotherapy and is being pursued for biosimilar development. One challenge to overcome in pegfilgrastim biosimilar development is establishing pharmacokinetic (PK) similarity, which is partly due to the degree of PK variability. We herein report that commercially available G-CSF and PEG ELISA detection kits have different capacities to detect pegfilgrastim aggregates that rapidly form in vitro in physiological conditions. These aggregates can be observed using SDS-PAGE, size-exclusion chromatography, dynamic light scattering, and real-time NMR analysis and are associated with decreased bioactivity as reflected by reduced drug-induced cellular proliferation and STAT3 phosphorylation. Furthermore, individual variability in the stability and detectability of pegfilgrastim in human sera is also observed. Pegfilgrastim levels display marked subject variability in sera from healthy donors incubated at 37 °C. The stability patterns of pegfilgrastim closely match the stability patterns of filgrastim, consistent with a key role for pegfilgrastim's G-CSF moiety in driving formation of inactive aggregates. Taken together, our results indicate that individual variability and ELISA specificity for inactive aggregates are key factors to consider when designing and interpreting studies involving the measurement of serum pegfilgrastim concentrations.

Catecholamine response to exercise in patients with non-obstructive hypertrophic cardiomyopathy.

KEY POINTS: Intense physical activity, a potent stimulus for sympathetic nervous system activation, is thought to increase the risk of malignant ventricular arrhythmias among patients with hypertrophic cardiomyopathy (HCM). As a result, the majority of patients with HCM deliberately reduce their habitual physical activity after diagnosis and this lifestyle change puts them at risk for sequelae of a sedentary lifestyle: weight gain, hypertension, hyperlipidaemia, insulin resistance, coronary artery disease, and increased morbidity and mortality. We show that plasma catecholamine levels remain stably low at exercise intensities below the ventilatory threshold, a parameter that can be defined during cardiopulmonary exercise testing, but rise rapidly at higher intensities of exercise. These findings suggest that cardiopulmonary exercise testing may be a useful tool to provide an individualized moderate-intensity exercise prescription for patients with HCM. ABSTRACT: Intense physical activity, a potent stimulus for sympathetic nervous system activation, is thought to increase the risk of malignant ventricular arrhythmias among patients with hypertrophic cardiomyopathy (HCM). However, the impact of exercise intensity on plasma catecholamine levels among HCM patients has not been rigorously defined. We conducted a prospective observational case-control study of men with non-obstructive HCM and age-matched controls. Laboratory-based cardiopulmonary exercise testing coupled with serial phlebotomy was used to define the relationship between exercise intensity and plasma catecholamine levels. Compared to controls (C, n = 5), HCM participants (H, n = 9) demonstrated higher left ventricular mass index (115 ± 20 vs. 90 ± 16 g/m2 , P = 0.03) and maximal left ventricular wall thickness (16 ± 1 vs. 8 ± 1 mm, P < 0.001) but similar body mass index, resting heart rate, peak oxygen consumption (H = 40 ± 13 vs. C = 42 ± 7 ml/kg/min, P = 0.81) and heart rate at the ventilatory threshold (H = 78 ± 6 vs. C = 78 ± 4% peak heart rate, P = 0.92). During incremental effort exercise in both groups, concentrations of adrenaline and noradrenaline were unchanged through low- and moderate-exercise intensity until reaching a catecholamine threshold (H = 82 ± 4 vs. C = 85 ± 3% peak heart rate, P = 0.86) after which levels of both molecules rose rapidly. In patients with mild non-obstructive HCM, plasma catecholamine levels remain stably low at exercise intensities below the ventilatory threshold but rise rapidly at higher intensities of exercise. Routine cardiopulmonary exercise testing may be a useful tool to provide an individualized moderate-intensity exercise prescription for patients with HCM.

Congenital Abnormalities of the Pericardium.

Congenital abnormalities of the pericardium are a rare group of disorders that include congenital absence of the pericardium, pericardial cysts, and diverticula. These congenital defects result from alterations in the embryologic formation and structure of the pericardium. Although many cases are incidentally found, they can present as symptomatic, life-threatening disease. Owing to their rarity, many cases are inappropriately diagnosed. Alterations in the embryologic formation and structure may result in the formation of these congenital abnormalities. We review the presentation, diagnosis, and management of congenital absence of the pericardium, pericardial cysts, and diverticula. A summary of multimodality imaging features is provided.

Failing the failing heart: a review of palliative care in heart failure.

Heart failure (HF) is the most common reason for hospital admission for patients older than 65 years. With an aging population and improving survival in heart failure patients, the number of people living with HF continues to grow. As this population increases, the importance of treating symptoms of fatigue, dyspnea, pain, and depression that diminish the quality of life in HF patients becomes increasingly important. Palliative care has been shown to help alleviate these symptoms and improve patients' satisfaction with the care they receive. Despite this growing body of evidence, palliative care consultation remains underutilized and is not standard practice in the management of HF. With an emphasis on communication, symptom management, and coordinated care, palliative care provides an integrated approach to support patients and families with chronic illnesses. Early communication with patients and families regarding the unpredictable nature of HF and the increased risk of sudden cardiac death enables discussions around advanced care directives, health care proxies, and deactivation of permanent pacemakers or implantable cardioverter defibrillators. Cardiologists and primary care physicians who are comfortable initiating these discussions are encouraged to do so; however, many fear destroying hope and are uncertain how to discuss end-of-life issues. Thus, in order to facilitate these discussions and establish an appropriate relationship, we recommend that patients and families be introduced to a palliative care team at the earliest appropriate time after diagnosis.

An evaluation of the prevalence and severity of pain and other symptoms in acute decompensated heart failure.

BACKGROUND: Heart failure is characterized by recurrent decompensations and persistent symptoms that decrease quality of life. Shortness of breath and fatigue are commonly identified symptoms but there is limited data on pain in heart failure patients. The Edmonton Symptom Assessment System (ESAS) was used to identify the prevalence and severity of pain and other symptoms experienced by patients with acute decompensated heart failure. METHODS: This is a cross-sectional study that evaluated patients with a history of chronic heart failure admitted to the hospital with acute decompensated heart failure. A standardized questionnaire (ESAS) was administered to patients within 24 hours of hospital admission. Exclusion criteria included patients <18 years of age, admission for a noncardiac reason, active malignancy, history of chronic pain, outpatient chronic pain medication use, and those actively followed by the palliative care service. RESULTS: One hundred patients, 67 males, with a mean age of 58 ± 17 years were recruited. The mean ejection fraction (EF) was 37%± 18%. Sixty patients (60%) reported pain of any degree. Patients with lower EF (≤ 40%, n=61) reported significantly higher pain scores (4.1 ± 3.6) compared to patients with higher EF (>40%, n=36, 2.7 ± 3.4, p<0.05). Tiredness, shortness of breath, and decreased well-being were the most severe symptoms with mean scores of 6.3 ± 2.8, 6.1 ± 3.1, and 5.7 ± 2.6, respectively. CONCLUSION: Pain is a common, underrecognized symptom in patients with chronic but acute decompensated heart failure. Decreased well-being, shortness of breath, and tiredness are the most common and severe symptoms in patients with chronic heart failure, regardless of ejection fraction.

Trends in colorectal cancer incidence rates in New Zealand, 1981-2004.

BACKGROUND: Incidence rates of colorectal cancer (CRC) in New Zealand rank among the highest worldwide. Internationally, there has been evidence of a shift in colon cancer from left- to right-sided. The objective of this study was to determine trends in left- and right-sided colon and rectal cancers incidence by sex, age and ethnicity. METHODS: Using datasets created by linking data from the New Zealand Cancer Registry to the census data, we analysed a total of 47,694 CRCs from 1981 to 2004. Cancers were divided into right-sided colon (cecum to the splenic flexure); left-sided colon (descending and sigmoid colon); and rectal (rectosigmoid junction and rectum). RESULTS: Left- and right-sided colon, and rectal cancer incidence rates increased by 13-20% among men. In women, colon cancer rates increased by 25% for right-sided cancers, decreased by 8% for left-sided cancers and remained unchanged for rectal cancers. This corresponds with an increase in right-sided cancers from 57% to 65% of total colon cancers in women. The incidence of all CRCs increased at a faster rate among Maori than non-Maori. CONCLUSION: We identified a left- to right-sided shift in colon cancer limited to women over the age of 65. While Maori trends in site distribution parallel those of their non-Maori counterparts, the rapid increase in Maori incidence rates is noteworthy. It is unclear why such shifts in CRC site distribution are occurring.

Pilot study of palliative care consultation in patients with advanced heart failure referred for cardiac transplantation.

BACKGROUND: Heart failure (HF) in its chronic form is an irreversible and progressive disease. Palliative care (PC) interventions have traditionally been focused on patients with advanced cancer. We performed a pilot study to assess the feasibility of implementing the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for early PC intervention in patients with advanced HF who were seeking or received potentially curative therapies. METHODS: Twenty consecutive patients with advanced HF referred to PC from the heart transplant service with stage D, New York Heart Association (NYHA) class III-IV symptoms were analyzed retrospectively in a tertiary care setting. Data were reviewed to assess the clinical impact of PC intervention. Feedback was obtained to assess satisfaction of the patients, their families, and the health care professionals. An independent assessment of the impact of the PC service in the care of each patient was performed by a cardiologist and PC physician by use of a scoring system. RESULTS: Twenty consecutive patients with HF were analyzed. PC consult was obtained for a variety of reasons. All patients complained of a high symptom burden. PC consultation resulted in a decrease in the use of opioids and increased patient satisfaction. Patients and their family members generally reported improved holistic care, continuity of care, more focused goals of care, and improved planning of treatment courses. The nonstandardized scoring system used to determine the impact of the PC service showed an average of moderate to significant impact when assessed by both a cardiologist and a PC physician. CONCLUSION: PC consultation appears to be beneficial in the treatment and quality of life of advanced HF patients, independent of their prognosis. This pilot study demonstrated feasibility and sufficient evidence of clinical benefit to warrant a larger randomized clinical trial assessing the benefit of standard involvement by PC in patients with advanced HF, independent of the patient's prognosis or treatment goals.