Primecuts – This Week In The Journals

By Jacob J. Spinner, MD

Peer Reviewed

Last week Viola Davis made history as the first black woman to win an Emmy for Best Actress in a Drama. In accepting her award, she gave a moving speech on opportunity and bias against women of color [1]. At the same ceremony, Jeffrey Tambor won a supporting actor Emmy for his role as a transgender woman. Meanwhile, many mused at the continued sniping of Republican presidential candidates trying to unseat Donald Trump from the tops of the polls, while others marveled as one of New York’s finest, Pizza Rat, attempted to haul a slice bigger than his body back to his nest [2]. And on to the medical news.

Aspirin to Prevent Cancer

In a medical first, the United States Preventive Services Task Force (USPSTF) released draft recommendations for the use of daily low-dose aspirin therapy for primary prevention of cardiovascular disease and colorectal cancer in adults age 50-59 years with a 10% or higher 10-year CVD risk [3]. The guidelines stipulate that this recommendation applies only to individuals who are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take aspirin for at least 10 years. Data shows that aspirin can reduce the incidence of first heart attack by 22%, decrease CVD mortality by 6%, decrease colorectal cancer deaths by one third, and decrease colorectal cancer incidence by 40%. In adults age 60-69, the USPSTF recommends selectively offering daily aspirin therapy in individuals in whom the benefits might exceed the risks of treatment. While still open for public debate prior to finalization, these guidelines represent the first time a major American organization such as the USPSTF has recommended aspirin for cancer prevention. Critics were quick to point out the potential harms of such a sweeping recommendation, especially the increased risk of GI bleeding. However, considering that cardiovascular disease and cancer remain the two leading causes of death in the United States, these guidelines could have a significant impact on clinical practice for practitioners nationwide [4].

Approaching the Leadless Pacemaker

A multicenter group (LEADLESS II) reported in the New England Journal of Medicine about their advances with transvenous implantable leadless pacemakers [5]. Noting that the majority of adverse events associated with pacemakers relate to the leads, the pulse generator, or the surgical pocket, investigators have pursued a leadless pacemaker as a potential solution to many of the problems commonly encountered. These small devices, which are delivered to the right ventricle via the femoral vein, also potentially eliminate the effects of lead wires on tricuspid valve function. In this study, single chamber leadless pacemakers were implanted in over 500 patients with an indication for a single-chamber ventricular pacemaker, such as heart block or bradycardia. Patients were monitored for device efficacy and device-related complications over a six month follow-up period. The primary efficacy endpoint (therapeutically acceptable pacing capture threshold and sensing amplitude) was met by 90% of participants (p = 0.007), exceeding pre-specified goals. Similarly, over 93% of participants met the primary safety endpoint of freedom from device-related serious adverse events (p < 0.001). Complication rates were equivalent to or lower than those of traditional pacemakers. Device-related serious adverse events occurred in 6.7% of the first 300 patients to complete 6 months of follow-up. Adverse events included device dislodgement (in 1.7%), cardiac perforation (in 1.3%), and vascular complications (in 1.3%). A total of 19 deaths occurred within the first 6 months, though none of these was considered to be device-related. Overall the study was limited by its observational design and short follow-up period, as well as by the fact that only a single-chamber device model is available; no dual-chamber or bi-ventricular devices currently exist. Nonetheless, this ongoing study shows the potential for further advances in the world of minimally invasive devices.

Non-Invasive Ventilation for Central Sleep Apnea in Systolic Heart Failure

Sleep apnea is a common complication of systolic heart failure. Periods of central apnea and hypopnea are associated with increased sympathetic tone and decreased cardiac vagal tone, both of which are thought to contribute to the underlying pathophysiology of heart failure with a reduced ejection fraction and be associated with malignant arrhythmias [6]. Whereas nocturnal continuous positive airway pressure (CPAP) is a mainstay in the treatment of obstructive sleep apnea, previous studies have shown no benefit to using CPAP to treat central sleep apnea in heart failure patients.

A European trial published this week in the New England Journal of Medicine considered the effects of adaptive servo-ventilation, a form of non-invasive ventilation with separate inspiratory and expiratory pressure support, in patients with systolic heart failure (ejection fraction 45% or less) and predominantly central sleep apnea [6]. A total of 1325 subjects were randomized to either guideline-based medical treatment with adaptive servo-ventilation or to guideline-based medical treatment alone. The primary study endpoint was time to the first event of death from any cause, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening chronic heart failure. The average apnea-hypopnea index at 12 months in the servo-ventilation group was 6.6 events per hour, representing good control of sleep apnea. On analysis of the data, there was no significant difference in the incidence of the primary composite endpoint between the groups. There was also a statistically significant increase in all-cause mortality (34.8% vs. 29.3%, p=0.01) and cardiovascular mortality (29.9% vs. 24.0%, p=0.006) in the servo-ventilation group versus the control group. In addition, there was a more rapid decline in performance on a 6-minute walk test in the ventilation group compared to matched controls. The authors postulate that this increase in mortality may reflect that central sleep apnea is a beneficial compensatory mechanism in heart failure, allowing respiratory muscles to rest, limiting sympathetic nervous system activity, and limiting hypercapneic acidosis. It is also possible that positive airway pressure impairs cardiac function in patients with underlying systolic dysfunction, although this theory has been questioned previously. Further investigation is warranted to elucidate the underlying pathophysiology.

This study also illustrates the difficulty in drawing conclusions from surrogate markers in studies. Multiple small, prior studies had demonstrated improvements in brain natriuretic peptide, left ventricular ejection fraction, and quality-of-life scores with non-invasive ventilation. The data from this larger study demonstrate that improvements in surrogate markers (here the apnea-hypopnea index) do not necessarily correlate with symptomatic or mortality benefits [7].

Recess prevents myopia?

In an interesting study published in JAMA, researchers in China considered the effects of increasing outdoor activity time in populations of Chinese schoolchildren on the incidence of myopia [8]. Nearsightedness, they note, affects up to 80-90% of high school graduates in some areas of Asia, rapidly outpacing incidence rates in western populations. Observational studies seemed to imply increased time spent outdoors was associated with lower rates of myopia. In this study, nearly two thousand six-year olds were randomized to a standard school day or a schedule that included an extra forty-minute period spent outside. Parents in the experimental group were also instructed to encourage their children to increase time spent outside on weekends. The primary outcome was incidence of newly-diagnosed myopia based on quantitative refractive errors. After three years, the cumulative incidence of myopia was decreased by nearly 25% in the experimental group (30.4% vs. 39.5%, p<0.01). Limitations of the study include lack of blinding of the professionals performing the eye exams and questionable generalizability given the study population. Nonetheless, these results bolster the results of earlier small studies from Taiwan and China and raise an interesting argument in favor of increasing time outside the classroom for young students. 

Quick-Cuts

A review article summarizes the most current thinking regarding acute myeloid leukemia, its genetic underpinnings, and approaches to initial therapy [9].

A cross-sectional database study of American medical school faculty shows women are significantly less likely than their male counterparts to be full professors, even after accounting for numerous potential confounders [10].

Analysis of data from a prior Spanish study on the effects of the Mediterranean diet high in olive oil implies that the diet may have a beneficial effect in the prevention of breast cancer [11].

A few recent studies suggest even a single ankle sprain has the potential to limit how much a college student or a mouse runs and exercises for the rest of its life [12-14].

Dr.  Jacob J. Spinner is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Jennifer Mulliken, MD,  NYU Langone Medical Center

References

1. Park, Andrea. “Emmy Awards 2015: Viola Davis Wins Best Drama Series Actress.” CBS News, 20 Sept. 2015. Web. 21 Sept. 2015. http://www.cbsnews.com/news/emmy-awards-2015-viola-davis-wins-best-drama-series-actress/
2. Szulman, Jennifer. “‘Pizza Rat’ Makes His Inspirational Debut on the NYC Subway.” NY Daily News, 21 Sept. 2015. Web. 21 Sept. 2015.
3. “Draft Recommendation Statement.” Aspirin to Prevent Cardiovascular Disease and Cancer. United States Preventive Services Task Force, 15 Sept. 2015. Web. 21 Sept. 2015.  http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/aspirin-for-the-prevention-of-cardiovascular-disease-preventive-medication
4. Rabin, Roni Caryn. “In a First, Aspirin Is Recommended to Fight a Form of Cancer.” Well In a First Aspirin Is Recommended to Fight a Form of Cancer Comments. New York Times, 14 Sept. 2015. Web. 21 Sept. 2015.  http://well.blogs.nytimes.com/2015/09/14/in-a-first-aspirin-is-recommended-to-fight-a-form-of-cancer/?_r=0
5. Reddy VY, Exner DV, Cantillon CJ, et al. Percutaneous Implantation of an Entirely Intracardiac Leadless Pacemaker. NEJM. 2015; 373(12): 1125-1135. http://www.nejm.org/doi/full/10.1056/nejmoa1507192
6. Magaland UJ and AI Pack. Heart Failure and Sleep-Disordered Breathing – The Plot Thickens. NEJM, 2015; 373(12): 1166-1167.
7. Cowie MR, Woehrle H, Wegscheider K, et al. Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure. NEJM, 2015; 373(12): 1095-1105.
8. He M, Xiang F, Zeng Y, et al. Effect of Time Spent Outdoors at School on the Development of Myopia Among Children in China. JAMA, 2015; 314(11): 1142-1148.  http://jama.jamanetwork.com/article.aspx?articleid=2441261
9. Döhner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. NEJM. 2015; 373(12): 1136-1152.  http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61727-9/fulltext?rss=yes
10. Jena AB, Khullar D, Ho O, et al. Sex Differences in Academic Rank in US Medical Schools in 2014. JAMA, 2015; 314(11): 1149-1158.
11. Toledo E, Salas-Salvado, Donat-Vargas C, et al. Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial. JAMA Intern Med. Published online September 14, 2015. doi:10.1001/jamainternmed.2015.4838.       http://archinte.jamanetwork.com/article.aspx?articleid=2434738&resultClick=
12. Hubbard-Turner T, Turner MJ. Physical Activity Levels in College Students With Chronic Ankle Instability. J Athl Train. 2015 Jul;50(7):742-7.
13. Wikstrom EA, Hubbard Turner T, Woods S, et al. Developing a mouse model of chronic ankle instability. Med Sci Sports Exerc. 2015 Apr;47(4):866-72.  http://www.ncbi.nlm.nih.gov/pubmed/25083728
14. Hubbard-Turner T, Wikstrom EA, Guderian S, Turner MJ. An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan. J Sports Sci Med. 2015 Aug 11;14(3):556-61.

Share: Twitter | Facebook | Email