Primecuts – This Week In The Journals

August 30, 2010

By Han Na Kim, MD

Faculty Peer Reviewed

In the national news, a ruling came from Washington DC that shocked NIH scientists and researchers across the nation’s universities. Chief Judge Royce Lamberth of Federal District Court for the District of Columbia ruled against President Obama’s stem cell policy and stopped federal funding of embryonic stem cell research that destroys embryos, claiming that this violates the Dickey-Wicker Amendment regarding federal spending bills. Lamberth commented, “The Dickey-Wicker Amendment unambiguously prohibits the use of federal funds for all research in which a human embryo is destroyed.” Current projects may continue, but the ruling, if upheld, would force many experiments in areas from diabetes to Parkinson’s disease to be suspended. The Obama administration will appeal.

Remember those Bellevue clinic patients who come in with total body pain and fatigue that you’ve brushed off as “somatization”? Perhaps we need to take them more seriously. The New York Times this week reported a study[1]published in the Proceedings of the National Academy of Sciences linking chronic fatigue syndrome to murine leukemia virus (MLV). The study found MLV-related virus gene sequences in the blood samples of 32 out of 37 chronic-fatigue patients but only 3 out of 44 healthy patients. Many experts remain skeptical, as there are several studies with conflicting results regarding the association, but in the meantime the American Association of Blood Banks recommended that people with chronic fatigue syndrome be discouraged from donating blood.

 Now for the headlines in the medical journals…

 This week in medical world, there were three interesting studies in cardiology:

 JAMA featured the Balloon Pump-Assisted Coronary Intervention Study (BCIS-1),[2] which showed that routine intra-aortic balloon pump (IABP) insertion before high-risk percutaneous coronary intervention does not reduce the incidence of major adverse cardiac and cardiovascular events (MACCE) in patients with severe left ventricular dysfunction and extensive coronary disease. There have been observational studies that reported improved outcomes with elective IABP insertion, but these have been retrospective, underpowered studies with selection bias. No randomized controlled trial investigating routine IABP use in high-risk procedures had been reported prior to BCIS-1. MACCE was defined as death, MI, stroke, or further revascularization at hospital discharge. Three hundred and one patients were enrolled in this prospective RCT conducted between December 2005 and January 2009 in 17 tertiary referral cardiac centers in the UK. Patients awaiting high-risk single-vessel or multi-vessel PCI to native coronary arteries or bypass grafts were included. Patients were randomized either to no IABP insertion or elective IABP insertion prior to PCI. The primary endpoint was MACCE at 28 days and secondary endpoints were 6-month all-cause mortality, major procedural complications, bleeding complications, TIA, and duration of hospital stay. The groups had similar baseline characteristics: mean age of 71, LVEF of 24%, and BCIS-1 Jeopardy Score of 10. Intention-to-treat analysis was applied and MACCE at hospital discharge occurred in 15.2% of the elective IABP and 16.0% of the no planned IABP groups (P =.85; OR 0.94 [95% CI, 0.51-1.76]). Of note, rescue IABP was inserted in 12% of the no-IABP group, mainly for prolonged hypotension. Patients who received rescue IABP placement had worse in-hospital outcomes than patients who received elective IABP. All-cause mortality at 6 months was 4.6% in the elective IABP group and 7.4% in the no-IABP group; the difference was not statistically significant. Major procedural complications occurred less with elective IABP insertion compared to no planned IABP (1.3% vs. 10.7%, P <0.001; OR, 0.11 [95% CI, 0.01-0.49]. Major or minor bleeding occurred in 19.2% in elective IABP group and 11.3% of no IABP group (P = .06; OR, 1.86 [95% CI, 0.93-3.79]). Overall, the study showed that elective IABP insertion did not reduce MACCE following PCI and therefore does not recommend routine elective IABP insertion before high-risk PCI. However, given that 12% of no IABP patients needed rescue IABP, standby IABP should be always available.

 Wanna know the secret to a long life? Keep reading.

 This week’s Circulation featured a study[3] showing exercise capacity as an independent predictor of all-cause mortality in older men. The study identified 5390 male veterans aged 65-92 who completed exercise tolerance tests (ETT) between 1986 and 2008. There were 2137 deaths during the median follow-up period of 8.1 years. Baseline exercise capacity among survivors was 6.3±2.4 metabolic equivalents (METs) compared to 5.3±2.0 METs in the group that died (P<.001), suggesting poor exercise capacity as a predictor of mortality. Patients were further categorized into fitness groups; compared with the least fit group (≤4 METs), hazard ratios of mortality were progressively lower with each 1-MET increase from a MET level of 5. Regardless of the age group, the mortality risk was 38% lower (hazard ratio=0.62; 95% CI, 0.54 to 0.71) in patients who achieved 5.1 to 6.0 METs compared to the least fit group, and further declined to 61% (hazard ratio=0.39; 95% CI, 0.32 to 0.49) in patients who achieved >9 METs. The data suggest that for any significant health benefit, exercise capacity of >5 METs may be necessary. The study further examined the association between change in fitness and mortality in 867 individuals by repeating the ETT at least 6 months after the initial test. Analysis showed that survival improved significantly when unfit patients became fit, with 35% lower mortality risk (hazard ratio=0.65; 95% CI, 0.46 to 0.93; P = 0.019) compared with subjects who were unfit during both ETTs. The relationship between exercise capacity and mortality may not demonstrate causality due to residual confounders, and interventional studies are needed to confirm. Nonetheless, the study strongly supports inverse and graded association between fitness and mortality risk.

 Another article in Circulation investigated the association between birth weight and incident atrial fibrillation (AF) among women, mainly white. This prospective study[4] followed 27 982 women aged >45 who were free of cardiovascular disease, cancer, and AF at baseline. Based on self-reported birth weights, patients were categorized into 5 birth weight groups: <2.5 kg, 2.5 to 3.2, 3.2 to 3.9, 3.9 to 4.5, and >4.5 kg. Median follow up period was 14.5 years.  The primary outcome was time to incident AF. During the follow-up period, 735 confirmed AF events occurred. Age-adjusted AF incidence rates increased with increasing birth weight: 1.45, 1.82, 1.88, 2.57, and 2.55 events per 1000 person-years. Relative risks of developing incident AF with increase in birth weight category were 1.27 (95% CI: 0.95-1.71), 1.31 (CI: 1.00-1.72), 1.75 (CI: 1.27-2.41) and 1.76 (CI: 1.16-2.67). Additionally, several statistical analyses with multivariable adjustments were performed. Adjusting for body-mass index, blood pressure, and history of diabetes did not affect the association between birth weight and incident AF, but when further adjusted for adult height, the association was substantially attenuated and became nonsignificant. Further adjustment for maximum body weight between 18 to 30 years of age attenuated the relationship between birth weight and AF even more: relative ratios 1.27 (CI: 0.94-1.71), 1.10 (CI: 0.83-1.46), 1.41 (CI: 1.01-1.96), 1.29 (CI: 0.84-1.98). The study concluded that increased birth weight is significantly associated with incident AF among women. Although early life determinants may play a role in incident AF, it seems that adult height and/or cumulative lifetime exposure to elevated body mass have greater impact on modifying the risk of AF.

 Do you have a pregnant patient with genital herpes or herpes zoster? Read on.

 JAMA published the largest study[5] to date investigating the risk of birth defects with the use of acyclovir, valacyclovir, and famciclovir (FDA pregnancy-risk category B drugs) in the first trimester of pregnancy. The study found that there was no increased risk of major birth defects with exposure to these antivirals. Prior to this study, there were no published data on valacyclovir, and famciclovir use was limited to 4 reported pregnancies. This was a population-based historical cohort study examining 837,795 live-born infants in Denmark between 1996 and 2008. Infants with chromosomal aberrations, genetic disorders, birth defect syndromes with known causes, or congenital viral infections were excluded. Nationwide registries were used to identify the cohort and gather data regarding dispensed antiviral drugs, major birth defects, and potential confounders. The primary objective of the study was to investigate the risk of any major birth defects diagnosed within the first year of life due to exposure to antiviral drugs during the first trimester. Among 1804 pregnancies with exposure to acyclovir, valacyclovir, or famciclovir in the first trimester, 40 infants (2.2%) were diagnosed with major birth defects compared to 19,920 (2.4%) infants in the unexposed group (adjusted prevalence odds ratios [POR], 0.89; 95% CI, 0.65-1.22). Despite the significance of the study, the result should be interpreted with several study limitations in mind: (1) defects diagnosed after one year of age would have been missed, (2) the study did not include abortions, (3) maternal comorbidity was incomplete, and (4) nonadherence to the dispensed medications would lead to underestimation of teratogenic effects. All in all, it seems that acyclovir, valacyclovir and famciclovir will still remain pregnancy category B drugs.

 Dr. Kim is a second year resident at NYU Langone Medical Center

Peer reviewed by Michael Tanner, MD, Section Editor – Class Act, Clinical Correlations

Image courtesy of Wikimedia Commons: President Obama speaks before signing the Stem Cell Research Executive Order on March 9, 2009.

References:

[1]  Lo S-C, Pripuzova N, Bingjie L, et al.  Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. www.pnas.org/cgi/doi/10.1073/pnas.1006901107.

 [2]  Perera D, Stables R, Thomas M, et al. Elective intra-aortic balloon counterpulsation during high-risk percutaneous coronary intervention: a randomized controlled trial. JAMA. 2010;304(8):867-874.

 [3]  Kokkinos P, Myers J, Faselis C, et al. Exercise capacity and mortality in older men: a 20-year follow-up study. Circulation. 2010;122(8):790-797.

 [4]  Conen D, Tedrow U, Cook NR, Buring JE, Albert CM. Birth weight is a significant risk factor for incident atrial fibrillation. Circulation. 2010;122(8):764-770.

 [5]  Pasternak B, Hviid A. Use of acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk of birth defects. JAMA. 2010;304(8):859-866.

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