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Q wreincacom 1Ds6409 Review Paper The Physical Examination in Heart Failure—Part I s we have moved into the et T.5 major components and mers of Ihe physical examination of patients with crn nc na Leena as Rel ets Pay oratory testing and technology, the most heart failure specialists is proposed based on the information needed at the undeminning procedure of all medi- fine ofthe encounter. The challenges o our subspecially regarding this diagnostic cine, the physical examination, is at foo! are the prevention of is exincion during an era of seemingly limitless com rik of extinction. The death knell prehensive laboratory testing, the promotion of is widespread vse, and, over the ‘may well be the retirement of the ast years, the subjection ofits components fo the rigors of blinded controlled studies. generation of physicians proficient in Pat addresses the staging ofthe physical examination in heart failure, general the bedside examination; for these observation ofthe patient, vtl signs, and assessment of arterial pulse and neck physicians during their evrly to mid eins. (CHF. 2007;13:41-47) °2007 le Jacq careers, diagnoses emanated from the patient's history and a well-performed physical examination, pethaps supple mented by the high-tech modalities of the day—a chest xray and electrocar- UN*"SIY ot diogram (ECG). ‘Address for correspondence: In this regatd, the medical profes- Cor V,Leiex, MD, Division of Cardiology, The Ohio State Universi, Davis Heart sion, with is educational system, is Lng Research iste, 473 Wes! 12th Avenve, Columbus, OH 4310 its own culprit—another example of E-mail: carlleier@osumc.edu “We have met the enemy and he is Manuscript received November 6, 2006; accepted December 21, 2006 us!” The cours in history and physical ‘examination typically offered during or capable of teaching the course, mentioning the $2000 to $4000 price the second year of medical school is The course director frequently has ag, which would provide a more com- generally assigned few or no course to scramble t0 serape together vol- prehensive response). credits by most medical schools It is unteer instructors, and those who Students can fill some of the void often regarded as an orphan course, are volunteered per quota from each during the clinical elerkships of the last joining medical ethics, statistics, and clinical department, cognizant of the 2 years of medical school, when they ‘others trying to wedge themselves in fact that the system does not value are exposed to the bedside skills of good among the factladen, higher-credit this teaching activity, At the end of clinicians. Instead of posing questions courses. Despite this meager status, the course, a thank-you note cov- like "What did the echocardiogram most students are still atracted to the ers the time and instructorship of show?” the good clinician will ask the training sessions because the course the volunteers—instead of any finan- student, “Do you relly need an echo offers them their first contact with real cial reward or academic recognition. here?" ox if already performed, “Did patientsand tangible disease statesand Thus the instructors, often includ- the echo confirm your physical findings thus, i offers a sense of coming closer ing residents from the departments of in this patient?" Following the advice to being a real doctor. Somehow most radiology, pathology, and dermatology, ofthe clinician, a significant disparity students also sense that the physical go through che motion of delivering between a physical fining and labora examination is probably important in what they possibly absorbed from the tory result will be taken back to the their future roles as physicians. At this course text or syllabus the night before bedside by the student for clarification point, their idealism is often stymied the teaching session. The stusents’ and instruetion—an educational model by the realities of our medical educa- questions may not be addressed with for augmenting physical examination tion and training systems. answers of understanding (much less, skills throughout one’s careet. Formal ‘Unfortunately, the instructors for any depth) or tragically, by a response courses or rraining in more advanced this important course may be those suggesting that “If you're not sure, levels of the physical examination who are the least trained, experienced, you'll we aT sean anyway” (without are rarely available for senior medical Carl V-leier, MD;! Kanu Chatterjee, MD? From the Division of Cardiovascular Medicine, The Ohio State University College ‘of Medicine and Public Health, Columbus, OH: and the Division of Cardiology, University of Califomia, San Francisco, San Francisco, CA? physical examination—port | jenvary -febriary 2007 41 ihe Essential or Basic Components of the Hoon Fale Exar [General appearance Vito signs laload pressure and heart ste) in recumbent ond upright postions Respivaioty cate and patlern and body tomperaure a: needed or cbserved Jugular venous pressure and hepatojuguer refx ‘Auscutation of ches, pereusion os needed Precordial palpotion and auscultation Liver span (cephalocoudl dimension ot midelovicular line) ond tenderness | Examination for peripheral edema end perfusion As needed or observed | ‘kin appearance and temperature jo lovch) of honds and feet Pulte character, contour, and duration (cartid and/a Femaral sites) scudents, residents, or subspecialty fel- Level I. The Quick Look or lows. Many cardiology fellows are more Augenblick likely to correctly select the proper Heart failure is one of the medical stent type and size for an obstructive conditions that can, when appropriate, coronary lesion than correctly recog- render itself for clinical assessment at nize a systolic murmur as tricuspid a glance. A brief look at the patient rezungitation at the bedside. at bedside or even from the doorway “The reasons to attain and maintain following therapy for acute heart fail- the skill of performing a good diagnos ure/pulmonary edema will give you @ tic physical examination are several, rapid smpression of the effectiveness presented at the end of Part Il of this of your treatment: whether the patient seties, Meanwhile, we will begin with is improving ot whether you need to a brief definition. stay or return shortly thereafter for reevaluation and possible modification The Physical Examination of the treatment plan. The same quick in Heart Failure lance may also be appropriate in the For the purpose of this paper the physi- physician assessment of the outpatient cal examination is defined asall bedside who. stops by the office for a more examination method that are nonin- detailed visit with the nurse practitio- vasive and nonelectroni. This deini- ner or simply for renewal of prescrip- tion brings the stethoscope, sphyzmo- tions. As is true forall aspects of the ‘manometer, percussion hammer, and physical examination, the amount of similar portable mechanical tools into information garnered from the augen- the realm of the physical examination, lick is directly proportional to the ‘As is true for most medical dis- clinical experience of the inguiting ciplines and Inboratory scudies, the physician or nurse. (From a pragmat- physical examination for heart failure ic perspective, che usual augenblic, ‘can be viewed as a staged procedure: although quite informative, does not a diagnostic modality with varying take billing beyond level L) depths or levels of interrogation of Occasionally, one adds palpation investigation. (This is not to be con- of che pulse, a quick look ae the neck fused or matched with levels of billing veins, or brief listen to the chest as for reimbursement.) There is no physt- part ofthe augenblick assessment. 50% of sysol): increased left ventricular mass Lavorlly dsploced let ventricular impuso: ventricular chamber enlargement Reduced inensiy ofS, wih unchanged PR interval elevation of le venticlar end dlastolc pressure Increased inlensty of P: pulmonary arterial hypertension [see Figue 2 Pst Il 5, dollop: increased venticulrslfiness in diastole (educed venrcuar compliance) 5, golop in adults (without severe arioventcular vale regulation or pregnancy}: increased vonticlar diastolic pressure and filing Syselie murmur eloog lower lef sternal border, which increases on insptaion: cuspid regurgitation Coo), most hands and fee: low cardiac oulpu, increased sympathetic fone, and elvated systemic vascular resistance failure over time has taken its oll ‘metabolically and systemically. B. Height, Weight, and Body Mass Index. The day-to-day change in boxy ‘weight is one of the most useful param- «ters for following and managing fluid ‘volume status in heart failure. Body weight is a physical parameter that a patient can understand and readily employ in his/her self-care. (Obesity, as it evokes the metabolic syndrome, is a risk factor forthe devel- ‘opment of cardiac disease and heart failure. Its prognostic impact on the patient once heart failure has devel- oped, however, remains somewhat controversial, with evidence support- ing obesity as a predictor of a more favorable outcome. Obesity certainly does not improve dyspnea on exertion and is often the inertia or excuse used by the patient to keep from initiating an effective exercise and conditioning pro- gram, Obesity remains a risk factor for a less favorable outcome after cardiac physical exemination—perh janvary -febroary 2007 Figure 1, Sketches of some of the more common carotid pulke contours encountered vanced stages of heart failure. (A) A normal pulse contour is provided for comparison. (B) Reduced pulse amplitude and duration in heart failure gencrally implica Pulee is followed by the n Of the markedly reduced 2 reduced stroke volume. (C) The rahi rly large refleted wave, rendering the dicot oke volume and cardiac output and elevated systemic and duration ofthis i pulse damp vascular resistance of severe heart failure. (D) A sketch (top) and an. actual pulse recording with clectrocardiogram of ‘weaker pulse alternating with a strony Carotid arteries in patiente with severe nsplantation, causing m: to prefer a body mass index of no mor than 30 ka/m? for listing the heart fal ure patient for the procedure programs . Vital Signs. Pulse. The pulse rate provides information on the level of cardiac compensation and the ade quacy of B-blocker therapy. The pulse sus alternans (bottom) Pulbus alterans, lee, cat be palpated over the femoral or regularity provides information about the patient's underlying rhythm, For the patient in atrial fibrillation, suibtraccing the peripheral pulse rate fiom the central or cardiac heart rate (determined from precordial auscul- tation) provides the pulse deficit; a arge pulse deficit generally represents a rapid cardiac rare with a reduced stroke volume for many of the ventric ular contractions and usually reflects 1 compromised hemodynamic status During attial fbvillation, che centr heart rate (precordial auscultation) at ring exercise (eg, walking about the room or hallway) serves as Useful index of the degree of atsioven tricular nodal blockade. Inadequate contro! of ventricular rate during atrial fibillation can by itself evoke heart fail lure, cause short- and long-term dete heart failure, and account for much of a patient’s dyspnea on exertion The character and contour of d pulse are important (Figure 1). C pulse amplitude and duration are largely indicative of left ventricular (LV) stroke volume. Loss of vascular compliance (stiffening of aorta and arteties) as in aging or vascular disease can accentuate systolic blood pressure and pulse amplituxle, and thus amplify and mask the reduced stroke volume The reduct ever, representing a shortened LV ejec in pulse duration, how tion time, may still be indicative of a reduced stroke volume in this serting. (Asis tue forall aspects of the physi cal examination, appreciation of pulse enerally de rience, but can be greatly facilitated duration ops from expe- and reinforced by concomitant non- invasive measurement of LV ejection time from the carotid pulse.) A dicrotie pulse contour can be palpable in severe low-output heart failure (Figure 1 In the absence of carotid occlusive disease, a miniscule or absent carotid pulse by palpation during sinus rhythm or rate-controlled atrial fibrillation is ked reduction of his finding can aortic. valvular indicative of a ma stroke volume, but also teptesent sever stenosis (occasionally in the absence outflow murmur). Thi lesion can be the cause of a patient's of a syst underlying cardiomyopathic ventricle and heart failure or certainly be a major condition complicating his/her heart failure. The carotid and femoral arteries tare generally the preferred sites to palpate pulsus paradoxus and palsus alternans (Figure 1). Both paradoxus and akterans in heart failure are a consequence of marked ventricular enlargement and systolic dysfune- tion with a reduced stroke volume and cardiac output, and these puls- es often occur together in the same patient. Pulsus paradoxus is commonly encountered in patients with large, dilated, cardiomyopathic ventricles. Tn adult human heart failure, a tead- ily palpable pulsus alternans is almost always indicative of LV enlargement with a markedly reduced ejection frac: tion and stroke volume. Nonsustained ventricular tachycardia or even a pre- mature ventricular beat can bring out ppulsus alternans over the ensuing 4 tw 10 sinus beats in the patient who is approaching the advanced stages of cardiomyopathic systolic heart failure. Pulse character and contour can provide diagnostic clues for underlying causes of or conditions contributing to a patient's heart failure; examples include hyperthyroidism and hypothy- roidism and aortic valvular stenosis and insufficiency. Marked diminution for absence of peripheral pulses can be indicative of a markedly depressed stroke volume and/or the presence of severe occlusive vascular disease as a comorbid condition. Signs of chronic limb hypoperfusion and ischemia sup- port the latter consideration and tend to shift one's impression of the under- Iying cardiac diagnosis for heart failure from nonischemic considerations to the conditions caused by atheroscle- rotic coronary arteries, such as postin- farction remodeling, hibernating myo- cardium, and related cor Blood Pressure. As heart failure moves through its course of gradual dete- rioration, systemic systolic. pressure falls while diastolic pressure remains unchanged or increases somewhat. ‘Thus, pulse pressure (systolic minus diastolic pressure) decreases during this course. A pulse pressurelsystolic pressure ratio of less than 0.25 implic cates a cardiac index of less than 2.2 Limin/m’ and a less favorable clinical outcome." Loss of vascular compliance increases pulse pressure, limiting the application of this ratio in the elderly and in patients with vaseu- Jar disease and related conditions. Tn acute heart failure, blood pres- sure is often used as a guide ro choos- ing interventions such as vasodilators, positive inotropic agents, vasopres- sors, of mechanical-assist devices. In chronic heart failure, blood pressure is a major parameter used to deter- mine the adequacy of therapy, with a therapeutic target of systolic pressure less than 120 mm Hg, Blood pressure, along with symproms, also indicates the possibilty of excessive dosing, To more precisely assess the level and adequacy of vasodilator therapy or neurchormonal inhibition, particu- larly in the setting of certain comorbid conditions (eg, diabetic neuropathy, aging), blood pressure and heart rate are recorded in the supine (or semire cumbent) and upright positions after at least 60 seconds of stabilization in each position. Respiration. For adult humans, arespic ratory rate of 18 or more breaths per minute is regarded as tachypnea. An incremental rise in respiratory rate occurs in concert with increasing respiratory insufficiency and distres. AAs the patient's course advances into severe stages of chronic low-output heart failure, the regular respiratory pattern gradually changes toa breath: ing periodicity of hyperpnea (lasting 5— 15 seconds) alternating with apnea or hhypopnea (lasting 5-20 seconds); this finding is referred to as Cheyne-Stokes respiration or respiratory pattern. The bedside recognition of this pattern is obviously more diffcule when hypop- nea, rather than apnea, alternate with hyperpnea. The importance of recognizing Cheyne-Stokes breathing petiodicity relates to an appreciation of the patient's hear failure status as persistent decompensation, matkedly depressed cardiac output, and poor clinical outcome. The Cheyne-Stokes respiratory pattern is accentuated during sleep, particularly when a sleep disorder, a common feature of heart failure, is superimposed on the disturbed respi- ratory pattern. Patients frequently awaken with an alarming sense of choking or inability to breathe; at times, these events can be dificult 10 distinguish from paroxysmal nocturnal dyspnea. Spouses are often terrified in this setting because “Sometimes he just stops breathing! “Temperature. As heatt failure moves toward its advanced stages, limb and cutaneous vasoconstriction reduces the body's surface temperature, as recorded by surface (eg, forehead or eat) thermometers. Recordings taken via sublingual, rectal and voiding urine thermometers offer more precise determinations of core body tempera- ture in this seting. Hypothermia in patients hospital fred with heart failure is an unfa- vorable prognosticator. On the other hand, a forehead or ear temperature recording of 99°F or more should raise concem of a comorbidity (eg, infection or phlebitis) exacerbating the patient's heart failure. D. Neck Veins. The light beam of a penlight directed along the neck region overlying the internal jugular vein ora well lit room greatly enhance the evaluation of the blood column in this vessel. It is often necessary to examine both sides of the neck to detect and properly assess jugular venous pulsation, pressure, and other characteristics. The methods used to ‘measure jugular venous pressure by physical examination are numerous. ‘Ten cardiologists will likely determine the level of jugular venous disten- tion and pressure 10 different ways. Nevertheless, the unifying theme and the essential measurement is simply the vertical distance between the mid right atrium to the top of the observ- able column of blood in the internal jugular vein, The position of the mid right atrium is estimated to be near the intersection of the 4th or 5th intercostal space and the midaxillary line; the vertical line to the top of january february 2007 45 46 Figure 2. Sketches of sme of the sbmoctial waveforms of the internal jugular vein in heart failure. Panel (A) show's the normal patern when made visible dure Ing supie prong or ay reorder a neni un cate, The stave larger than the wave, provides physical evidence thatthe patient si sinus ‘hythn. (B) The waveform of tricuspid reyurptation. The v wave can be of varying st vara lar than the wan The wane i not alae apparent with large v wave and can be absorbed by the upstroke ofthe v wave during tachy- ‘contmon pattern of the jugular venous pulse in impaired right ventricular filing of restrictive cardiomyopathy, ight ventricular iypertophy or constrictive percandal disease. the observable blood column in the approach. Ifthe examiner is not inter internal jugular vein, irrespective of ested in taking the time needed co body angulation, is perpendicular to measure from the mid right atrium, the floor. The external jugular vein, recording the specific method (and alhough more readily seen in most then, che measurement using i) is patients, can give a misleading impres- helpful tothe subsequent examiners in sion and measurement of central following the degree of venous disten- venous pressure, particularly in the tion and jugular venous pressure; for ‘elderly with less elastic veins. example, “The patients jugular vein Ifa patient is followed by the same was noted 3 em above the clavicle physician or nurse, the specific meth- with the patient in a 45° semirecum- ‘xl employed is less important than the _bent position.” Simply adding the ver consistency of using the same method. tical column height above the angle In situations where the patients likely of Louis to the “presumed” distance to be examined by different providers from the angle of Louis to the mid ‘ver time, the most important aspect right atrium (typically estimated as is to record the height of the column 5, 6, or 8 cm) still depends on noting above the mid right atrium in centi- body angulation and is fraughe with ‘meters (of blood as the actual content considerable variability depending on of the column, although centimeters body and chest size and habitus of water is typically used as the pres- Some heart failure specialists sim- sure parameter; their relative fluid ply examine the internal jugular veins densities [specific gravities} are close while the patient is standing or sitting ‘enough to use either term). In other upright 0") with legs dependent.' words, simply recording the observed Venous distention above the clavicles, vertical height of the column above which are located about 12 0 16 em the mid right atrium cuts through all above the right atrium in these post- ‘methods and is generally the preferred tions for mose patients, is then simply viewed as elevated jugular venous pressure. For patients whose jugular ‘venous activity is not noted above the clavicles, howeves, these body posi tions do not readily lend themselves to the addition of manual pressure 10 the abdominal region co determine the presence of epacojugular reflux, indicative of latent or manginal vole ume overload in 30° or more semire- ‘curmbent positions A patient's jugular venous pres- sure can be so markedly clevated that venous pulsations along the neck are diminished or masked to the point ‘of being difficult to detect, and thus render the false impression of nondis- tention and normal venous pressure Examining the upper jugular region near the angle of the jaw and looking for prominent descents (generally, ¥ descents) while the patient is inhal- ing (ie, inspiratory phase) or placing the patient in a standing or 90° siting (with legs dependent) position will usually reveal jugular venous move- ‘ment to uncover the elusive, marked elevation of jugular venous pressure, ‘The character and contour of jugu- Jar venous pulsation (a and v waves andl descents); its movement with respira tion (generally a drop with inspiration); ascending distention of the jugular vein with firm abdominal pressure (to elicit venous filing via hepatojugular [abdominojugular] reflux of blood); loss of its waveforms and descents dur- ing venous occlusion (finger compres: sion) at the base of the neck, which cblierates the transmission of waves and descents ffom the right atrium; palpation ofthe carotid pulse (rypically deeper and slightly medial to the inter nal jugular vein); and other maneuvers allow rapid and amesuivocal identifica- tion of the internal jugular vein and its clear distinction from the carotid pulse ‘Venous v-wave pulsation from tricuspid requitation can be strikingly promi- nent, and is frequently misinterpreted as a carotid pulse by less-experienced ‘examiners, Respiratory shifts in the level of the jugular venous column (usually lower on inspiration) reflect comparable changes in intrathoracic pressure physical examination —par | Tenwory «Febuary | | | Learning to palpate the intemal jugular vein can be very helpful in esti- ‘mating jugular venous pressure or sim- ply locating the vein in patients whose neck and internal jugular veins are dif ficult to examine (eg obese, eritical- care, of ventilatorasssted patients) Locating the internal jugular vein by palpation can also guide a proficient and safe insertion of central venous and right heart catheters at this ste The determination of central venous pressure via examination of the inter- ral jugular vein is extremely important in the evaluation ofthe cardiac patient {in general and is absolutely essential in the management of the heart failure patient.“* This determination provides close estimations fright atrial pressures and right ventricular diastolic pressures and in the absence of substantial pul- ‘monary pathology, a general approx: tation (low or normal vs elevated) of LY filling pressures. In the absence of conditions that intervene between the right and left sides of the heart (cz lung disorders, pulmonary emboli), Stevenson and Perlof? found that jugu- Jar venous pressures above or below 10 cm correspond to respective pulmonary capillary wedge pressures of above ot below 22 mm Hg with an accuracy of about 80% Thus he determination of jugular venous pressure represents the best bedside means of assessing the status of intravascular fluid volume, which is a critical determination for the optimal administration and adjust- ment of heart failure therapies The authors agree with our colleague, Dr Lynne Wamet Stevenson, who empha- sized this point by stating, “If you are ‘not willing to take the time to acquire and retain facility at reading jugular venous pulations, you need to find a different population (other than heart failure) to serve." Prominent veins over the hands can be used to garner an estimation of mean right atrial pressure. The hand is elevated over the head, and the surface veins of the hands or lower forearm are lightly massaged to move blood centrally and thus, flatten. che veins. The arm is then slowly lowered and dlosely observed for the return of venous fillingdistention; the vertical height of this level to the mid right atrium approximates mean right atrial pressure, This method is rarely need: ed, but can be useful in patients whose internal jugular veins are difficult to evaluate or are occluded. The finding of prominent systolic ‘or v waves (larger than a waves) in the internal jugular vein generally suggests the presence of significant tricuspid regurgitation, even in the absence of a systolic murmur, and. supports the diagnosis of this valvular lesion when a tricuspid murmur is difficult to distinguish by auscultation from concomitant mitral or aortic systolic ‘murmurs (Figure 2). Tricuspid regurgi- tation is an important finding in heart failure with respect to management and. prognosis.’ Prompt y descents implicate restricted filling of the right ventriele as seen with right ventricular hypertrophy, restrictive cardiomyopa- thy, or constrictive pericarditis. And of coursey a century ago, Sir Thomas Lewis and others used neck vein pat- terns to identify, describe, and cat- cegorize cardiac rhythms, dyschythmias, and heart block—a skill since largely replaced by the electrocardiogram. Rerenences (ited peepee treats ‘hme feo lore cna pot db Pryneal exomnatan Congest Her? Fal 50017297308, 2 Srey Wal the nd Gynonss"in chon’ heat fare aa 1969r261-654-808 3 hale", Wonka 0. Manns oneloion in chane egos bear a nc coring sel my ead nape (he care Am Mad, 1991 90:383-190 44 Birpon’ Si. Evy GA, Sladen IR, of a Enaride cordon xominoson m patie ee eee ‘estor nile gus venous ition. An Ci Corded 1998:22508-974 5 Drazner Mi, Rome I. Severson IW, eo Progrsseinpovance of late. gular ‘ener preite and 6 thd Fert sound in Peters with neo fore A Engh) Ma 2001248 574-581 (6 Drezner MH, Rome J, res DL Tid hart sound. ond elevated ugar venovs pres eel See ateaternte anter aerate peaek se fGnate Ich wertclar Fale. Am | Mad 203 4h at Chet fetch hig ‘Stop in chon hoor fave on inscaon tthe tinal phot, Heer Inertial 00558 ‘examination—par | ienuary - febwary 2007 a R wwwilejacq.com 1D:5622 Review Paper B-Type Natriuretic Peptide: A Critical Review there have been more than 5000 publications over the past decade regarding the biology and clinical application of natriuretic peptide test- ing. The availability of commercial assays for B-type natriuretic peptide (or brain natriuretic peptide [BNP]) and amino-terminal proBNP_ (NI proBNP) have greatly facilitated thei ‘broad clinical adoption in the diagno- sis and risk stratification of congestive heart felure and cardiac dysfunction, Biology of BNP and NT-proBNP Contrary to popular belief, BNP is not a recent discovery: There has been evidence of a circulatory substance that regulates diuresis and natriuresis in the body for almost half a century: Nevertheless, the discovery of citcue lating natriuretic peptides was offi- cially credited to Professor de Bold and colleagues' in 1981, and BNP was idencified and characterized from porcine brain in 1988 BNP belongs to a family of short peptides with a similar cysteine-rich ring structure linked by a disulfide bond. The 2 pro- Aovype natriuretic peptides, arial (or A.type) natriuretic peptide (ANP) and BNP facilitated natriuresis und diuresis fn animal experiments. From animal models, we have learned that ANP js produced primarily in the atria and is stored in secretory vesicles under normal conditions. Its expression is increased in response to stretch in both. atrial and ventricular tissues in heart failure.’ BNP is coexpressed in secie- tory vesicles with ANB and its expres- sion is likewise augmented in response to pressure and volume overload in both the atria and the ventricles In Biype natriuretic peptide Notrivrelic peptides have been used as tools for diagnosis ond risk stories tion in patients with heart failere, myocardial inforction, and unstable coronary syndromes, as well asin the general population. The biology of inroassoy and intraindividual voriations of plasma notivrelic peptide levels is sill not clearly understood despite their broad adoption in clinical practice. Interpretation of plesma nativretc peptide levels therefore requires avalabiliy ofthe clinical con tex as well as considerations of various confounders. I is clear that high plasma raivurefic peptide levels can be highly suggestive of underlying myocardial dis ‘ease, although a specific underlying cause canno! be identified based on the 1s! results, The potential use of natriuretic peptide levels to monitor and guide patient ‘management or detect subclinical disease states is curently under investigation [CHF 2007; 13:48-52) ©2007 te Jocq W.H. Wilson Tang, MO From the Deparment of Cardiovasculor Medicine, The Clovelond Clinic Foundation, Cleveland, OH ‘Address for correspondence: W. H. Wilson Tang, MD, Section of Heart Failure and Cardiac Transplantation Medicine, Department of Cardiovascular Medicine, The Cleveland Clinic, 9500 Euclid Avenue, Desk F25, Cleveland, OH 44195 Emoil: tongw@cct org ‘Manuscript received Seplember 4, 2006; revised November 6, 2006; ceccepted December 7, 2006 ‘contrast, the endothelial C-type natri- peptides on their receptors, natriuretic uretic peptide (CNP) possesses only peptides receptors (NPR)-A (primarily vasodilatory effects and has a short for ANP and BNP) and NFR-B (for halflife. Overall, CNP does not exert CNP), which are both mediated via any natriuretic or diuretic effects cyclic guanosine monophosphate. The Several different physioloyic effects active moieties of natriuretic peptides ‘of natriuretic peptides have been sub- are cleared by renal excretion, active sequently identified, including inhi- metabolism of neutral endopeprides bition of neurohormonal overactiva- es, and binding to membrane-bound tion, vascular and pulmonary smooth NPR-C (or “clearance") receptors. In muscle relaxation (which gave their contrast, the inactive moieties (i, therapeutic vasodilatory effects), and the aminoterminal fragments that inhibition of cardiac hypertrophy and are cleaved from the propeptides) are ‘ventricular fibrosis.’ In contrast, natri- cleared primarily by the kidneys. uretic peptides also have the pro- Increased transcripeion of ANP and pensity to cause lipolysis, increase BNP messenger RNA has been dem- ‘endothelial vascular permeability, and onstrated in both atria and ventricles, reduce intravascular volumes.* All correlating with both plasma levels and these physiologic effects are a result of with increasing severity of heat failure the actions of circulating natriuretic in pacing-induced animal models This january february 2007 q f | | | é f | j

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