Watch the P Wave

eliminated.23,24 Similarly, antibiotics should not be prescribed for aspiration pneumonitis,25 or acute exacerbations of chronic bronchitis that do not fulfill the three criteria of Anthonisen et al.26 Public and patient education about appropriate antibiotic use likely decreases demand for antibiotics. Advertising, news stories, health fairs, educational handouts, and physician education have been associated with a 10% compounded yearly reduction in antibiotic use among Intermountain Health Care outpatients since 1999 (Eric Cannon, PharmD; personal communication; February 2003). Combating the pneumococcus has been termed a hundred years’ war.27 The dispatch of Waterer et al from the Memphis front suggests that we do not have to surrender. Nathan C. Dean, MD, FCCP Salt Lake City, UT Dr. Dean is Adjunct Professor of Medicine, University of Utah, and has received honoraria during the past 5 years from Pfizer, Abbott, Ortho-McNeil, Bristol Myers Squibb, Roche, Glaxo Smith Kline, Bayer, Elan, Chiron, and Merck. Dr. Dean has also served on advisory boards for Roche, Bayer, GlaxoSmithKline, and Bristol-Myers Squibb. Unrestricted grants for research have come to the Deseret Foundation, Salt Lake City, under Dr. Dean’s name from Roche, Pfizer, and Bristol-Myers Squibb. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Nathan C. Dean, MD, FCCP, Intermountain Health Care, 333 South Ninth East, Salt Lake City, UT 84102; e-mail: [email protected]

References 1 Ruiz-Gonzalez A, Falguera M, Noguies A, et al. Is Streptococcus pneumoniae the leading cause of pneumonia of unknown etiology? A microbiologic study of lung aspirates in consecutive patients with community-acquired pneumonia. Am J Med 1999; 106:385–390 2 Woodhead MA, Macfarlane JT, McCracken JS, et al. Prospective study of the aetiology and outcome of pneumonia in the community. Lancet 1987; 1:671– 674 3 Fine MJ, Smith MA, Carson C, et al. Prognosis and outcomes of patients with community-acquired pneumonia. JAMA 1995; 274:134 –141 4 Davidson R, Cavalcanti R, Brunton JL, et al. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med 2002; 346:747–750 5 Lonks JR, Garau J, Gomez L, et al. Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae. Clin Infect Dis 2002; 35:556 –564 6 Klugman KP. Bacteriologic evidence of antibiotic failure in pneumococcal lower respiratory tract infections. Eur Respir J Suppl 2002; 36:3s– 8s 7 Hoshino H, Watanabe H, Sugita R, et al. High rate of transmission of penicillin-resistant Streptococcus pneumoniae between parents and children. J Clin Microbiol 2002; 40:4357– 4359 8 Chen DK, McGeer A, de Azavedo JC, et al. Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. N Engl J Med 1999; 341:233–239 424

9 Feikin D, Schuchal A, Kolckac M, et al. Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995–1997. Am J Public Health 2000; 90:223–229 10 Ridley M, Lynn R, Barrie D, et al. Antibiotic resistant Staphylococcus aureus and hospital antibiotic policies. Lancet 1970; 1:230 –233 11 Seppala H, Klaukka T, Vuopio-Varkila J, et al. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. N Engl J Med 1997; 337:441– 446 12 Stephenson J. Icelandic researchers are showing the way to bring down rates of antibiotic-resistant bacteria. JAMA 1996; 275:175 13 Hyde TB, Gay K, Stephens DS, et al. Macrolide resistance among invasive Streptococcus pneumoniae isolates. JAMA 2001; 286:1857–1862 14 Pihlajamaki M, Kotilainen P, Kaurila T, et al. Macrolide resistant streptococcus pneumonia and use of antimicrobial agents. Clin Infect Dis 2001; 33:483– 488 15 de Neeling AJ, Overbeek BP, Horrevorts AM, et al. Antibiotic use and resistance of Streptococcus pneumoniae in the Netherlands during the period 1994 –1999. J Antimicrob Chemother 2001; 48:441– 444 16 Ho PL, Tse WS, Tsang KWT, et al. Risk factors for acquisition of levofloxacin resistant streptococcus pneumoniae: a case control study. Clin Infect Dis 2001; 32:701–707 17 Heffelfinger JD, Dowell SF, Jorgensen JH, et al. Management of community-acquired pneumonia in the era of pneumococcal resistance. Arch Intern Med 2000; 160:1399 –1408 18 Scheld WM. Maintaining fluoroquinolone class efficacy: review of influencing factors. Emerg Infect Dis 2003; 9:1–9 19 Garcia-Rey, Aguilar L, Baquero F. Importance of local variations in antibiotic consumption and geographical differences of erythromycin and penicillin resistance in Streptococcus pneumoniae. J Clin Microbiol 2002; 40:159 –164 20 Pallares R, Capdevila O, Linares J. The effect of cephalosporin resistance on mortality in adult patients with nonmeningeal infections. Am J Med 2002; 113:120 –126 21 Bent S, Saint S, Vittinghoff E, et al. Antibiotics in acute bronchitis: a meta-analysis. Am J Med 1999; 107:62– 67 22 Macfarlane JT, Holmes W, Gard P, et al. Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community. Thorax 2001; 56:109 –114 23 Hickner JUM, Bartlett JG, Besser RE, et al. Principles of appropriate antibiotic use for acute rhino-sinusitis in adults. Ann Intern Med 2001; 134:498 –505 24 Snow V, Mottur-Pilson C, Gonzalez R. Principles of appropriate antibiotic use for treatment of acute bronchitis in adults. Ann Intern Med 2001; 134:518 –520 25 Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med 2001; 344:665– 671 26 Anthonisen NR, Manfreda J, Warren CPW, et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987; 106:196 –204 27 Swartz MN. Attacking the pneumococcus: a hundred years’ war. N Engl J Med 2002; 346:722

Watch the P Wave It Can Change! is the fourth leading cause of mortality in C OPD the United States, accounting for 119,000 deaths

in the year 2000 alone.1 Acute exacerbations of Editorials

COPD are a common complication, resulting in significant morbidity2 and mortality.3 The ECG finding of P pulmonale refers to a pattern in which the P-wave amplitude in leads II, III, and/or aVF is augmented to ⬎ 2.5 mm.4 It is thought to reflect the overload of the right atrium (so-called right heart strain) and is accordingly a marker for disease processes that involve stress to the right heart circulation. Atrial enlargement and the P wave received attention in the first half of the 1900s, and a myriad of criteria were made for both right and left atrial enlargement. Despite the initial enthusiasm about its usefulness, P pulmonale fell out of favor over time due to concerns regarding its clinical validity. Indeed, studies5,6 seeking to correlate P pulmonale with echocardiographic findings were disappointing, demonstrating low sensitivity. Moreover, other ECG patterns, including right axis deviation, S1S2S3, S1Q3, and P-wave axis, have emerged as more sensitive indicators of right heart strain.7,8 However, there has been a renewed interest in the atrium, rekindled by the recent prominence of atrial fibrillation in clinical practice and the literature. With the availability of echocardiography, the ECG terms of enlargement was changed to right and left atrial abnormalities, because of the relative inadequacy of ECG in predicting atrial size.9 Not surprisingly, most of the literature relating to atrial abnormalities is dated. However, a PubMed search came up with some interesting citations. Perkiomaki et al10 studied the independent value of ECG variables in predicting cardiac events after acute myocardial infarction (AMI) in the era of modern therapy. Patients (1,034 patients) underwent standard electrocardiography from 5 to 7 days after experiencing an AMI. During 2 years of follow-up, 42 patients (4%) experienced cardiac death, and 259 patients (25%) experienced cardiac death, a nonfatal AMI, or unstable angina. After adjustment for all risk variables, ST-segment depression and atrial abnormality were the only ECG variables that independently predicted cardiac death. Mehta et al11 used echocardiography to conclude that left atrial abnormality was significantly diagnostic of left ventricular hypertrophy in the presence of left bundle-branch block. Bossone et al12 examined whether ECG features in patients with primary pulmonary hypertension were associated with a decrease in survival to determine the value of the ECG in risk stratification. They analyzed the ECGs of 51 untreated patients with primary pulmonary hypertension. Significant predictors of decreased survival by Cox regression analysis included pulmonary vascular resistance, cardiac inwww.chestjournal.org

dex, P-wave amplitude in lead II, p ⱖ 0.25 mV in lead II, QR wave in lead V1, and right ventricular hypertrophy. The authors suggested that an ECG might be useful for deciding therapeutic choices including the timing for lung transplantation listing. In the current issue of CHEST (see page 560), Asad and colleagues revisit the P wave and demonstrate the mechanistic underpinnings of this pattern. They contended that the low sensitivity of P pulmonale in prior studies was due to the inclusion of patients who, at the time of their ECG, were not experiencing acute right heart strain. Based on this reasoning, the authors sought to investigate a population consisting solely of patients whose conditions were of acute onset. In order to examine such a population, they identified 65 consecutive patients who had been admitted to the hospital from an emergency department setting with an acute COPD exacerbation. After the exclusion of 8 patients whose initial ECGs did not show a sinus rhythm, as well as 7 patients with P-wave amplitudes of ⬍ 1.5 mm, 50 patients were included for further analysis. To document tracings both before and after the initial phase of treatment, ECGs on each eligible patient were obtained at 0, 6, and 24 h after clinical presentation. Several findings deserve notice. First, although only 7 of the 50 patients demonstrated classic P pulmonale, each of them had a P-wave amplitude of ⬎ 1.5 mm in both leads II and aVF. Second, the P-wave axis, which is a more sensitive indicator of right heart strain, shifted slightly more than 5° to the left over the 24-h period. Finally, and most importantly, Asad and colleagues were able to demonstrate that the P-wave amplitude was significantly diminished at 24 h (presumably when most patients had improved clinically). In fact, all but 2 of the 50 patients (96%) were reported to have decreased P-wave amplitude at 24 h. While confirming that P pulmonale is an indicator of right heart strain, these results also provide indirect evidence that the P-wave amplitude correlates with the degree of right heart strain. Are these findings surprising? From a mechanistic standpoint, they should not be. Although P pulmonale has traditionally been characterized as an isolated hallmark of pulmonary disease, it should not be considered a static phenomenon. The P wave is dynamic and subject to change, like all other components of the ECG. Similar to the R wave and ST segment, which fluctuate as left ventricular myocytes are stretched in the setting of an acute insult to the left side of the heart, it would appear that the P wave also varies in size as right atrial cardiomyocytes are expanded in overload situations. Ultimately, it seems that P pulmonale merely represents an extreme at one end of a large continuum of P-wave amplitudes. CHEST / 124 / 2 / AUGUST, 2003

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The dynamic nature of the P wave is further documented by the known changes in P-wave amplitude and duration with exercise.13 Despite the well-conceived design of the study, several limitations also should be mentioned. The clinical characteristics and outcomes of the patients were not reported. It is thus not possible to precisely conclude that the observed decrease in P-wave amplitude correlated with clinical improvement or attenuation of right heart strain. That said, the alternative hypothesis that most of the 50 patients did not improve with in-hospital treatment does not seem credible. Additionally, due to technical concerns, the 7 patients with a P-wave amplitude of ⬍ 1.5 mm were not included in the analysis. However, the inclusion of these seven patients would not have significantly altered the results. Even if the seven patients had shown no change in P-wave amplitudes for ⬎ 24 h, the difference in amplitudes for leads II and aVF (0.78 and 0.80, respectively) would have been 0.69 and 0.70, respectively. Of course, COPD is not the only cause of acute right heart strain. Multiple other acute cardiopulmonary processes, including pneumonia, congestive heart failure, pulmonary embolism, and asthma, are associated with right atrial overload. In 1979, Gelb et al14 reported a similar finding in 129 patients with status asthmaticus. Interestingly, the likelihood of P pulmonale correlated significantly with the severity of disease, and a significant number of patients with P pulmonale lost this pattern with clinical improvement. As the authors suggest, after an appropriately designed clinical investigation, the P-wave amplitude could be considered as a convenient indicator of the efficacy of management of COPD exacerbation. A recent study15 has suggested that P-wave width could be used to monitor diuresis therapy in patients with congestive heart failure. Anticipating the day that appropriate clinical studies are accomplished, it is wise for clinicians to pay attention to dynamic changes in P-wave morphology. Patrick Yue, MD Stanford, CA J. Edwin Atwood, MD, Col USAMC Washington, DC Vic Froelicher, MD Palo Alto, CA Dr. Yue is a Cardiology Fellow, and Dr. Froelicher is Professor of Medicine, Stanford University. Dr. Atwood is affiliated with Walter Reed Army Medical Center. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). 426

Correspondence to: Vic F. Froelicher, MD, Palo Alto Veterans Affairs Medical Center, 3801 Miranda Ave, Bldg 100, Room E2-441, Palo Alto, CA 94304-1207; e-mail: [email protected]

References 1 Mannino DM, Homa DM, Akinbami LJ, et al. Chronic obstructive pulmonary disease surveillance: United States, 1971–2000. Respir Care 2002; 47:1184 –1199 2 Seemungal TA, Donaldson GC, Paul EA, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157:1418 –1422 3 Connors AF. Outcomes following acute exacerbation of severe chronic obstructive lung disease. Am J Respir Crit Care Med 1996; 154:959 –967 4 Goldberger AL. Clinical electrocardiography: a simplified approach. 6th ed. St. Louis, MO: Mosby, 1999 5 Reeves WC, Hallahan W, Schwiter EJ, et al. Two-dimensional echocardiographic assessment of electrocardiographic criteria for right atrial enlargement. Circulation 1981; 64:387–391 6 Kaplan JD, Evans GT Jr, Foster E, et al. Evaluation of electrocardiographic criteria for right atrial enlargement by quantitative two-dimensional echocardiography. J Am Coll Cardiol 1994; 23:747–752 7 Baljepally R, Spodick DH. Electrocardiographic screening for emphysema: the frontal plane P axis. Clin Cardiol 1999; 22:226 –228 8 Incalzi RA, Fuso L, De Rosa M, et al. Electrocardiographic signs of chronic cor pulmonale: a negative prognostic finding in chronic obstructive pulmonary disease. Circulation 1999; 99:1600 –1605 9 Chirife R, Feitosa GS, Frankl WS. Electrocardiographic detection of left atrial enlargement: correlation of P wave with left atrial dimension by echocardiography. Br Heart J 1975; 37:1281–1285 10 Perkiomaki JS, Zareba W, Greenberg HM, et al. Usefulness of standard electrocardiographic parameters for predicting cardiac events after acute myocardial infarction during modern treatment era. Am J Cardiol 2002; 90:205–209 11 Mehta A, Jain AC, Mehta MC, et al. Usefulness of left atrial abnormality for predicting left ventricular hypertrophy in the presence of left bundle branch block. Am J Cardiol 2000; 85:354 –359 12 Bossone E, Paciocco G, Iarussi D, et al. The prognostic role of the ECG in primary pulmonary. Chest 2002; 121:513–518 13 Sapin PM, Koch G, Blauwet MB, et al. Identification of false positive exercise tests with use of electrocardiographic criteria: a possible role for atrial repolarization waves. J Am Coll Cardiol 1991; 18:127–135 14 Gelb AF, Lyons HA, Fairshter RD, et al. P pulmonale in status asthmathicus. J Allergy Clin Immunol 1979; 64:18 –22 15 Song J, Kalus J, Caron M, et al. P-wave duration and dispersion in patients with decompensated heart failure. Pharmacotherapy 2002; 22:564 –568

Age and ARDS of 4,020 trauma patients, Johnston I net aal,study in this issue of CHEST (see page 653), have shown that the relationship of age to the risk of developing ARDS is much more complicated Editorials