Publications

BACKGROUND

Although chronic obstructive pulmonary disease (COPD) is a major cause of disability worldwide, its determinants remain poorly defined.

OBJECTIVE

We hypothesized that both pulmonary and extra-pulmonary factors would predict prospective disablement across a hierarchy of activities in persons with COPD.

METHODS

Six hundred and nine participants were studied at baseline (T0) and 2.5 years later (T1). The Valued Life Activities (VLA) scale quantified disability (10-point scale: 0 = no difficulty and 10 = unable to perform), defining disability as any activity newly rated 'unable to perform' at T1. Predictors included pulmonary (lung function, 6-minute walk distance and COPD severity score) and extra-pulmonary (quadriceps strength and lower extremity function) factors. Prospective disability risk was tested by separate logistic regression models for each predictor (baseline value and its change, T0-T1; odds ratios were scaled at 1 standard deviation per factor. Incident disability across a hierarchy of obligatory, committed and discretionary VLA subscales was compared.

RESULTS

Subjects manifested a 40% or greater increased odds of developing disability for each predictor (baseline and change over time). Disability in discretionary activities developed at a rate 2.2-times higher than observed in committed activities, which was in turn 2.5-times higher than the rate observed in obligatory activities (p < 0.05 for each level).

CONCLUSIONS

Disability is common in COPD. Both pulmonary and extra-pulmonary factors are important in predicting its development.

As a result of advances in cancer diagnosis and treatment, young women within the reproductive-aged group are now more likely to survive cancer. Reproductive-aged women with cancer may be interested in deferring pregnancy either temporarily or permanently at cancer diagnosis, during therapy or after treatment. Currently, there are limited guidelines to aide clinicians in managing the contraceptive needs in this special population. After reviewing the evidence regarding the safety and efficacy of available methods of contraception for women who have been diagnosed with cancer, the Society of Family Planning recommends that women of childbearing age who are being treated for cancer avoid combined hormonal contraceptive methods (containing estrogen and progestin) when possible because they may further increase the risk of venous thromboembolism (VTE) (Level A). The copper T380A intrauterine device, a highly effective, reversible, long-acting, hormone-free method, should be considered the first-line contraceptive option for women with a history of breast cancer (Level A), although for women being treated with tamoxifen, the levonorgestrel-containing intrauterine system (IUS) which decreases endometrial proliferation may be preferable (Level B). Women who develop anemia may benefit from use of a progestin-containing contraceptive (Level A). Women who develop osteopenia or osteoporosis following chemotherapy should avoid the progestin-only contraceptive injection (Level B). More information is needed in many areas. There are insufficient data to evaluate the risk of VTE when progestin-only contraceptives are used by women at high risk of VTE. Information is also needed on whether the levonorgestrel-containing IUS affects the risk of breast cancer recurrence and whether hormonal contraceptives affect the risk of breast cancer among women who have received chest wall, or "mantle field," radiation. Finally, studies of the safety and effectiveness of IUS use by women who are immunosuppressed and studies of whether progestin-only contraceptives affect the risk of fracture among cancer survivors or, more generally, women with osteopenia would be useful.

BACKGROUND

In 2005, the American College of Cardiology/American Heart Association published performance measures to provide a standard of care for hospitalized patients with heart failure (HF). Despite increasing compliance with these measures, hospital mortality and readmission rates remain stagnant. Whether compliance with HF performance measures improves patient outcomes at the hospital level is unclear.

METHODS

We evaluated compliance with HF performance measures at 3,655 US hospitals. Patients admitted with a diagnosis of HF in 2008 were identified using the US Department of Health and Human Services Hospital Compare database. Compliance with 4 specific performance measures was examined: evaluation of left ventricular systolic function, administration of angiotensin-converting enzyme inhibitor I or angiotensin-receptor blocker for left ventricular systolic dysfunction, offering smoking cessation advice and counseling, and providing discharge instructions. Thirty-day mortality and readmission rate were recorded.

RESULTS

Hospitals reporting greater compliance with the 4 performance measures had significantly lower 30-day mortality rates. However, these hospitals were also located in areas of higher socioeconomic status and treated higher volumes of patients with HF. After adjusting for socioeconomic and hospital factors, only evaluation of left ventricular systolic function was associated with lower 30-day mortality, and evaluation of left ventricular systolic function and smoking cessation counseling were associated with lower readmission rates.

CONCLUSIONS

We found that socioeconomic factors and hospital volume were stronger predictors of mortality than compliance with HF performance measures. After adjusting for socioeconomic factors and hospital volume, only 1 of the 4 performance measures was associated with lower 30-day mortality and 2 were associated with lower readmissions.

Mixed cohorts of patients with ischemic and nonischemic end-stage heart failure (HF) with a QRS duration of ≥120 ms and requiring intravenous inotropes do not appear to benefit from cardiac resynchronization therapy (CRT). However, CRT does provide greater benefit to patients with nonischemic cardiomyopathy and might, therefore, be able to reverse the HF syndrome in such patients who are inotrope dependent. To address this question, 226 patients with nonischemic cardiomyopathy who received a CRT-defibrillator and who had a left ventricular ejection fraction of ≤35% and QRS of ≥120 ms were followed up for the outcomes of death, transplantation, and ventricular assist device placement. Follow-up echocardiograms were performed in patients with ≥6 months of transplant- and ventricular assist device-free survival after CRT. The patients were divided into 3 groups: (1) never took inotropes (n = 180), (2) weaned from inotropes before CRT (n = 30), and (3) dependent on inotropes at CRT implantation (n = 16). At 47 ± 30 months of follow-up, the patients who had never taken inotropes had had the longest transplant- and ventricular assist device-free survival. The inotrope-dependent patients had the worst outcomes, and the patients weaned from inotropes experienced intermediate outcomes (p <0.0001). Reverse remodeling and left ventricular ejection fraction improvement followed a similar pattern. Among the patients weaned from and dependent on inotropes, a central venous pressure <10 mm Hg on right heart catheterization before CRT was predictive of greater left ventricular functional improvement, more profound reverse remodeling, and longer survival free of transplantation or ventricular assist device placement. In conclusion, inotrope therapy before CRT is an important marker of adverse outcomes after implantation in patients with nonischemic cardiomyopathy, with inotrope dependence denoting irreversible end-stage HF unresponsive to CRT.

Multiple published studies have established erectile dysfunction (ED) as an independent risk marker for cardiovascular disease (CVD). In fact, incident ED has a similar or greater predictive value for cardiovascular events than traditional risk factors including smoking, hyperlipidemia, and family history of myocardial infarction. Here, we review evidence that supports ED as a particularly significant harbinger of CVD in 2 populations: men <60 years of age and those with diabetes. Although addition of ED to the Framingham Risk Score only modestly improved the 10-year predictive capacity of the Framingham Risk Score for myocardial infarction or coronary death data in men enrolled in the Massachusetts Male Aging Study, other epidemiologic studies suggest that the predictive value of ED is quite strong in younger men. Indeed, in the Olmstead County Study, men 40 to 49 years of age with ED had a 50-fold higher incidence of new-incident coronary artery disease than those without ED. However, ED had less predictive value (5-fold increased risk) for coronary artery disease in men 70 years and older. Several studies, including a large analysis of more than 6300 men enrolled in the ADVANCE study, suggest that ED is a particularly powerful predictor of CVD in diabetic men as well. Based on the literature reviewed here, we encourage physicians to inquire about ED symptoms in all men more than 30 years of age with cardiovascular risk factors. Identification of ED, particularly in men <60 years old and those with diabetes, represents an important first step toward CVD risk detection and reduction.

RATIONALE

The impact of modern treatments of pulmonary arterial hypertension (PAH) on pulmonary vascular pathology remains unknown.

OBJECTIVES

To assess the spectrum of pulmonary vascular remodeling in the modern era of PAH medication.

METHODS

Assessment of pulmonary vascular remodeling and inflammation in 62 PAH and 28 control explanted lungs systematically sampled.

MEASUREMENTS AND MAIN RESULTS

Intima and intima plus media fractional thicknesses of pulmonary arteries were increased in the PAH group versus the control lungs and correlated with pulmonary hemodynamic measurements. Despite a high variability of morphological measurements within a given PAH lung and among all PAH lungs, distinct pathological subphenotypes were detected in cohorts of PAH lungs. These included a subset of lungs lacking intima or, most prominently, media remodeling, which had similar numbers of profiles of plexiform lesions as those in lungs with more pronounced remodeling. Marked perivascular inflammation was present in a high number of PAH lungs and correlated with intima plus media remodeling. The number of profiles of plexiform lesions was significantly lower in lungs of male patients and those never treated with prostacyclin or its analogs.

CONCLUSIONS

Our results indicate that multiple features of pulmonary vascular remodeling are present in patients treated with modern PAH therapies. Perivascular inflammation may have an important role in the processes of vascular remodeling, all of which may ultimately lead to increased pulmonary artery pressure. Moreover, our study provides a framework to interpret and design translational studies in PAH.