Primecuts – This Week In The Journals

May 2, 2016

Mars_HubbleBy Nydia Ekasumara, MD

Peer Reviewed

Fighting resumes in Syria as an air strike hit the Al Quds hospital in the divided city of Aleppo, killing 27 people including children and staff members. This is just one in a disconcerting chain of attacks by government forces against health services in Syria, as two hospitals in Maarat al-Noaman were hit earlier this year [1]. Meanwhile, in the United States, the Defense Department announced “administrative” punishment, but no criminal charges, for the 16 American military personnel involved in an attack against a Doctors Without Borders hospital in Kunduz, Afghanistan that resulted in 42 deaths. This ruling stems from the conclusion that the American military team responsible for carrying out the attack had no deliberate intent to strike a medical facility, and instead acted on incorrect intelligence. Human rights groups are unsatisfied with the ruling, classifying the attack as a war crime. [2] As war zones continue to jeopardize the lives of thousands on Earth, a collaborative effort of the private company SpaceX and NASA announced plans to investigate whether Mars could one day be inhabitable by humans using an un-manned scientific expedition by 2018 [3]. In similarly impressive medical news this week, new studies showed a benefit from using invasive interventions to control two common heart diseases, a new diagnostic tool was proposed to prognosticate ICU admission in patients presenting with community acquired pneumonia, and a potential new strategy to reduce post-operative acute kidney injury in patients admitted for coronary artery bypass grafting (CABG) was highlighted.

There were multiple studies published this week in interventional cardiology. The first article addresses the very common clinical problem of atrial fibrillation (AF). It is estimated that 42% patients with AF have concomitant heart failure (HF) [3]. When patients’ symptoms are not controlled by medical therapy alone, catheter ablation (CA) is a treatment option. The Ablation vs Amiodarone for Treatment of Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted ICD/CRTD (AATAC) multicenter randomized trial [4] looked at the effect of CA versus amiodarone in over 200 patients with persistent AF and HF (defined by New York Heart Association (NYHA) functional class II to III and reduced LVEF <40%). Patients with AF with reversible etiology or previous valvular or coronary heart disease requiring surgical intervention were excluded. At the end of 24 months, more patients in the CA group were free from AF (70% in the CA group versus 34% in the amiodarone group; P<0.001) and there was a significantly lower rate of both the composite outcome of AF and HF- related unplanned hospitalization and all-cause mortality, with a number needed to treat of 3.8 and 10 respectively. The CA group also showed a statistically significant improvement in LV ejection fraction (LVEF), functional status as measured by the 6 minute walk distance, and patient reported quality of life measured by the Minnesota Living With Heart Failure Questionnaire (MLHFQ) score. Taken altogether, CA appears to be superior to amiodarone in reducing the recurrence of AF among patients with HF. For patients with AF and HF who do not tolerate rate control drugs, CA is a good treatment option to maintain sinus rhythm.

The second study of emerging invasive techniques in cardiology evaluated the treatment of aortic stenosis with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement in intermediate risk patients. TAVR is a minimally invasive procedure that uses a catheter to insert a bioprosthetic aortic valve which is typically reserved for patients with aortic stenosis (AS) who are at high- risk for surgical complications. The Placement of Aortic Transcatheter Valves (PARTNER) 2 trial [10] compares TAVR with surgical aortic valve replacement among intermediate-risk patients. In this study, 2032 patients with severe AS were randomly assigned to TAVR or surgical repair. Among the cohort assigned to TAVR, some were assigned to transthoracic or transfemoral access. Both the TAVR and surgical groups saw a significant reduction in symptoms as measured by NYHA class and improvement of echocardiographic findings (increase of aortic valve area and LVEF, and decrease of aortic-valve gradients), without a significant difference in the incidence of disabling stroke or death at 2 years. Within the TAVR group, the transfemoral-access TAVR group had a lower death and stroke rate compared to surgery (hazard ratio 0.79; P=0.05). The TAVR group also had significantly shorter ICU and total length of stay compared to the surgery group (2 vs 4 days, P<0.001 and 6 vs 9 days P<0.001, respectively). A higher rate of major vascular complications (i.e. vascular dissection, vessel perforation, and access site hematoma) was seen in the TAVR group compared to the surgery group (7.9% vs 5%, P=0.008). The authors did not stratify whether transthoracic or transfemoral access causes more complications in patients undergoing TAVR. The surgical repair group suffered higher rates of life-threatening bleeding (10.4% vs 3.4%, P<0.001), AKI (1.3% vs 3.1%, P=0.006), and new onset AF (9.1% vs 25.4%, P<0.001) as compared to the TAVR group. Taken together, this study shows that among intermediate risk patients, TAVR is non-inferior to surgical aortic valve replacement in mortality and stroke outcomes. The benefit of TAVR includes shorter hospital and ICU stay, and lower risk of surgical complications. The findings of this study suggest that TAVR is a viable choice for intermediate-risk patients with severe AS, expanding the population of patients for whom TAVR may be considered in the future.

Patient selection and risk stratification is not only critical in studies of invasive interventions like the one above, but is also important of clinical triage in patients presenting to the hospital for care. This week in a study published in Chest, the paradigm for risk stratification in patients presenting with community acquired pneumonia was revisited. The Etiology of Pneumonia in the Community (EPIC) study [7] is a prospective cohort study that assessed whether procalcitonin (PCT) can be used as a biomarker in determining whether patients with community acquired pneumonia (CAP) will require invasive respiratory or vasopressor support (IRVS). Out of the 1770 adults with CAP, 115 (6.5%) subjects required IRVS within 72 hours. Initial serum PCT concentrations were higher in those who required IRVS compared to those who did not (median 1.43 ng/ml in the IRVS group vs 0.14 ng/ml in the usual care group; p<0.01). A logistic regression model showed a linear correlation between PCT level and IRVS risk between 0.05 ng/ml to 10 ng/ml. An undetectable PCT level (<0.05 ng/ml) corresponded to a 4.0% IRVS risk while a level of 10 ng/ml corresponded to a 22.4% risk. Adding PCT to existing pneumonia severity score (American Thoracic Society (ATS) Minor Criteria for severe CAP, Pneumonia Severity Index (PSI), and SMART-COP) [8,9,10] improves the discriminatory ability of the test to predict which patients may require a higher level of care. For example, adding PCT > 0.83 ng/ml to the high risk criteria reduces the number of misclassified patients (patients who are considered low risk from ATS criteria but ended up requiring IRVS) from 77 to 44 out of 1770 patients. The strong association between PCT concentration and the risk of IRVS augments existing pneumonia severity scoring systems and may aid in earlier identification of patients presenting with CAP who will require an ICU admission.

Finally, risk for post-operative acute kidney injury (AKI) was addressed in an article published in the New England Journal of Medicine. AKI is often seen after coronary artery bypass surgery (CABG) due to intraoperative hypoperfusion and the systemic inflammatory response. Albumin maintains oncotic pressure and intravascular volume. A low pre-operative serum albumin is associated with post-operative AKI in patients undergoing CABG. This study [11] looks at whether preoperative albumin repletion decreases the risk of developing AKI among patients undergoing CABG. In this study, 220 pre-CABG patients with serum albumin < 4.0 g/dl were randomly selected to receive albumin or normal saline (NaCl) prior to surgery. During the intra-operative period, there was higher urine output in the albumin group compared to the control group (P=0.006); however no significant difference in hemodynamics, vasopressor requirements, or additional volume of infusion (NaCl or albumin). There was a statistically significant reduction in the incidence of postoperative AKI in the albumin versus control group (13.7% in the albumin group vs 25.7% in the control group). There was no significant difference between the two groups in the incidence of severe AKI, need for renal replacement treatment (RRT), hospital or ICU stay, and in 30-day mortality. Based on the results of this study, preoperative albumin infusion appears to have some renal protective benefit without a significant change in mortality or hospitalization. This study corroborates previous literature that showed that the addition of albumin in patients with severe sepsis improves hemodynamics without conferring a survival benefit [12]. The mechanism behind this reno-protective effect remains unclear. Additional study is warranted prior to incorporating this intervention into standard clinical practice.

Mini cuts

A 24-year prospective cohort study of 189,158 female nurses (Nurses’ Health Studies) showed that longer duration of rotating night shift work is associated with a statistically significant increase in coronary artery disease (CAD) [13].

The VitamIN D treatIng patients with Chronic heArT failurE (VINDICATE) study [14] showed that high-dose vitamin D supplementation for 1 year is associated with significant improvement in LVEF and reversal of LV remodeling in patients with left ventricular systolic dysfunction (LVSD) on echocardiography. There was no significant effect on functional status as measured by the 6-minute walk test.

There is an association between lower lung function as measured by FVC with increased exposure to ambient pollution, as measured by proximity to major roadway, estimated exposure to particulate matter with diameter smaller than 2.5 μm (PM2.5), and black carbon exposure. This study again suggests pollution adversely affects children’s lung health [15].

Dr. Nydia Ekasumara, internal medicine resident,  NYU Langone Medical Center

Peer reviewed by Kerrilynn Carney, 3rd year internal medicine resident at NYU Langone Medical Center

Image courtesy of Wikimedia Commons





4. Maisel WH, Stevenson LW. Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy. Am J Cardiol. 2003;91():2D–8D. 

5. Di Biase L, Mohanty P, Mohanty S, Santangeli P, et al. Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: Results From the AATAC Multicenter Randomized Trial. Circulation. 2016;133:1637-1644, published online before print March 30 2016, doi:10.1161/CIRCULATIONAHA.115.019406  

6. Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med 2016;374:1609-20.  

7. Self WH, Grijalva CG, Williams DJ, et al.Procalcitonin As An Early Marker Of The Need For Invasive Respiratory Or Vasopressor Support In Adults With Community-Acquired Pneumonia Chest. 2016. doi:10.1016/j.chest.2016.04.010

8. Brown, SM, Jones BE, Jepson AR, et al. Validation of the Infectious Disease Society of America/American Thoracic Society 2007 guidelines for severe community-acquired pneumonia. Crit Care Med. 2009 Dec;37(12):3010-6. doi: 10.1097/CCM.0b013e3181b030d9.

9. Flanders DW, Tucker G, Krishnadasan A, et al. Validation of the Pneumonia Severity Index. J Gen Intern Med. 1999 Jun; 14(6): 333–340. doi: 10.1046/j 1525-1497.1999.00351.x 

10. Charles PG, Wolfe R, Whitby M, et al. SMART-COP: A Tool for Predicting the Need for Intensive Respiratory or Vasopressor Support in Community-Acquired Pneumonia. Clinical Infectious Diseases 2008; 47:375–84. DOI: 10.1086/589754

11. Lee EH, Kim WJ, Kim JY, et al. Effect of Exogenous Albumin on the Incidence of Postoperative Acute Kidney Injury in Patients Undergoing Off-pump Coronary Artery Bypass Surgery with a Preoperative Albumin Level of Less Than 4.0 g/dl. Anesthesiology 5 2016, Vol.124, 1001-1011. doi:10.1097/ALN.0000000000001051  

12. Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, Fanizza C, Caspani L, Faenza S, Grasselli G, Iapichino G, Antonelli M, Parrini V, Fiore G, Latini R, Gattinoni L; ALBIOS Study Investigators: Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med 2014; 370:1412–21

13. Vetter C, Devore EE, Wegrzyn LR, et al. Association Between Rotating Night Shift Work and Risk of Coronary Heart Disease Among Women. JAMA. 2016;315(16):1726-1734. doi:10.1001/jama.2016.4454.  

14. Witte KK, Byrom R, Gierula J, et al. Effects of Vitamin D on Cardiac Function in Patients With Chronic HF: The VINDICATE Study. J Am Coll Cardiol. 2016;():. doi:10.1016/j.jacc.2016.03.508.

15. Rice MB, Rifas-Shiman SL, Litonjua AA, et al. Lifetime Exposure to Ambient Pollution and Lung Function in Children, American Journal of Respiratory and Critical Care Medicine, Vol. 193, No. 8 (2016), pp. 881-888. doi: 10.1164/rccm.201506-1058OC