JACC: Heart Failure Vol. 2, No. 1, 2014� 2014 by the American College of Cardiology Foundation ISSN 2213-1779/$36.00Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jchf.2013.12.001

EDITORIAL COMMENT

Observation Is Never Obsolete*

Anju Nohria, MD, Lynne Warner Stevenson, MD

Boston, Massachusetts

The hallmark signs and symptoms of heart failure reflectcongestion, the manifestation of elevated ventricular fillingpressures. These are the symptoms that trigger heart failurehospitalizations, 80% to 95% of which are characterized bycongestion without hypoperfusion (the “warm and wet”profile) (1). Therapy during acute decompensated heartfailure focuses on relief of these symptoms and redesign ofa regimen to prevent their recurrence. Implantable hemo-dynamic monitoring has revealed that intracardiac fillingpressures usually increasing more than 2 weeks beforesymptoms lead to recurrent hospitalization, whether withreduced or preserved left ventricular ejection fraction (2,3).Treatment is not limited to symptom relief, because chroniccongestion also contributes to disease progression. Elevatedleft-sided filling pressures lead to chronic remodeling,worsened by mitral annular dilation with increased regur-gitant volume, pulmonary hypertension, and elevation ofright ventricular afterload (4). Backward congestion fromright-sided heart failure creates hepatic dysfunction (5),malnutrition, and inflammatory stimulation, and is impli-cated in the cardio-renal syndrome, which heralds furthercongestion and decline (6). Therefore, astute assessment andintervention to treat congestion are vital to relieving patientsymptoms, enhancing quality of life, and improving prog-nosis, leading to a class I recommendation for both acuteand chronic management of heart failure (7).

See pages 15 and 24

Clinical signs of elevated filling pressures can generally bedirectly attributed to elevated left- or right-sided heartpressures. Because the concordance between elevated right-and left-sided filling pressures is 75% to 80% in chronic heartfailure (8,9), the signs and symptoms from right and left areoften congruent. For instance, Drazner et al. (10) have shownpreviously that the most reliable sign of elevated left-sidedfilling pressures is the right-sided sign of elevated jugularvenous pressure (JVP). Conversely, the most useful symptom

*Editorials published in the Journal of the American College of Cardiology: Heart Failurereflect the views of the author and do not necessarily reflect the views of JACC: HeartFailure or the American College of Cardiology.

From the Cardiovascular Division, Brigham and Women’s Hospital, Boston,

Massachusetts. Dr. Nohria has served as a consultant for Vertex Pharmaceuticals; and

as an investigator for St. Jude Medical. Dr. Stevenson is supported for training clinical

investigators by the National Heart, Lung, and Blood Institute (U01 HL084877).

for elevated left-sided pressures is orthopnea, which ina patient with a history of heart failure should be considereddue to cardiac congestion unless otherwise explained.Accordingly, in the ESCAPE (Evaluation Study ofCongestive Heart Failure and Pulmonary Artery Catheteri-zation Effectiveness) trial, orthopnea predicted a pulmonarycapillary wedge pressure >22 mm Hg. Peripheral edemasuggests elevated right-sided heart pressures but is less spe-cific and less sensitive than JVP for elevated left-sided fillingpressures. Edema is generally absent in young patients withseverely elevated filling pressures, who may instead haveascites, whereas edema often occurs in elderly patients, inwhom it is related to peripheral factors in the absence ofelevated central venous pressures. Symptoms of abdominaldiscomfort, anorexia, and early satiety are associated morespecifically with elevated right-sided filling pressures (11).

A new symptom. Clinical assessment remains crucial forthe diagnosis and triage of heart failure. This assertion isparticularly true when evaluating for decompensation in apatient who has a history of heart failure, which accounts forapproximately 80% of heart failure–related hospitalizations.The study by Thibodeau et al. (12) in this issue of theJournal proposes a new item to the classic litany of heartfailure symptoms: “bendopnea,” which is shortness of breathor uncomfortable head fullness within 30 s of bending for-ward while sitting, such as to put on shoes or stockings. Thissymptom was also described recently as “flexo-dyspnea,”which was associated with an increase in echocardiographicindices of left-sided filling pressures (13). In the studyby Thibodeau et al., invasive hemodynamic monitoringdemonstrated that bending forward increased venous returnand filling pressures, provoking shortness of breath, usuallyin those patients who had baseline elevated filling pressuresand were thus more likely to reach the threshold pressuresneeded to elicit symptoms. Patients with bendopnea alsohad a higher body mass index, which may have aggravatedtheir discomfort when bending.

Each symptom we can elicit helps to complete the clinicalpicture, as there is marked heterogeneity between patientsregarding their perception of symptoms. We have allencountered patients who endorse 1 symptom but denyanother. It is particularly useful to know that bendopneacorrelates with elevated right-sided filling pressures. As fa-cility with the jugular venous examination regrettably de-clines, recognition of bendopnea may help alert clinicians tothe likely elevation of right-sided pressures.

A portfolio of symptoms is helpful for longitudinaltracking as well. Although there is marked variability be-tween patients in presentation, individual patients tend tohave typical early warning signs as congestion occurs. Forsome patients, difficulty putting on their shoes may alertthem to the need to re-evaluate their volume status anddiuretic regimen. It is also possible that a symptom such asbendopnea could be used as a simple provocative bedsidetest to identify patients with elevated filling pressures in theabsence of other signs or symptoms of congestion, much as

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careful observation during the supine physical examinationwill sometimes reveal increased respiratory rate in a patientunaware of orthopnea until asked.Validation of clinical signs for prognosis. The physicalexamination has been consistently shown to have prognosticvalue in heart failure assessments. A post-hoc analysis of theSOLVD (Studies Of Left Ventricular Dysfunction) treat-ment trial found that an elevated JVP and an audible thirdheart sound were each associated with an increased risk ofdeath and hospitalization for heart failure (14). Similarly,bedside hemodynamic profiles based on physical examina-tion findings of congestion and inadequate perfusionpredicted 1-year mortality and the need for urgent trans-plantation in patients with heart failure (1). These findingswere further supported by an analysis of the ESCAPE trial,in which patients discharged with a “wet” or “cold” profilehad a 50% increased risk of death or rehospitalizationcompared with those with a “dry” or “warm” profile (10).A reassessment of signs and symptoms of heart failure at1 month after hospital discharge provides further refinementof prognosis, particularly if orthopnea has recurred (15).

In this issue of the Journal, Caldentey et al. (16) con-ducted a post-hoc analysis of patients enrolled in the AF-CHF (Atrial Fibrillation and Congestive Heart Failure)trial to evaluate the prognostic value of baseline physicalexamination findings, including elevated JVP, third heartsound, rales, and peripheral edema, in patients with systolicheart failure. These authors confirmed that physical evidenceof congestion, defined by any of the 4 physical findings, isassociated with increased mortality and heart failure–relatedhospitalizations. Although a multivariate analysis was per-formed, the elevated right- and left-sided heart fillingpressures are so strongly aligned that the contribution ofrelated signs cannot be isolated. Furthermore, unlike diag-nostic or prognostic tests that require additional resources,there is no need for artificial restriction of the clinicalassessment. The components of the assessment are easilycollected and drawn into a composite picture that conveysmore than just the theoretical risk of death orhospitalization.Does the clinical picture still matter? In an era in whichchemical biomarkers and imaging characterization of theheart and hemodynamics are becoming increasingly focusedand refined, does the clinical picture still matter? As long asour assessment goals remain the diagnosis, prognosis, andtreatment of heart failure, the symptoms and signs willremain highly relevant.To diagnose heart failure. Although supermarket screeningcould increase the diagnosed prevalence of disease, we willcontinue to elicit the symptoms and physical signs of heartfailure to establish and prioritize diagnoses as patients pres-ent with their “chief complaints.” As the population accu-mulates comorbidities with age, such assessment is even morecrucial to determine the relative contribution of each comor-bidity to functional limitation. Biomarkers have been partic-ularly helpful in raising awareness about heart failure as

a possible newdiagnosis in the setting of dyspnea.However, inthe chronic management of patients with a known diagnosisof heart failure, most clinical assessments are performed todetermine instead the level of compensation/decompensationand the response to interventions.To predict outcomes in heart failure. Individual bio-markers such as the natriuretic peptides have been verystrong predictors of outcome. This is true ranging fromasymptomatic to end-stage disease. As a potential alert tomore serious disease, biomarkers can be used to define trialpopulations for newer therapies, patients in whom disease-exchanging therapies such as mechanical circulatory assistdevices may be considered, and those for whom a discussionof the goals of care should be initiated. However, the clinicalportrait of class IV heart failure, drawn from signs andsymptoms of congestion at rest or on minimal exertion,remains 1 of the most vivid and robust predictors of pooroutcome. The components of this assessment as refined inthe 2 accompanying studies (12,16) further enhance thisportrait.To guide therapy for heart failure. A target for treatmentmust be clinically relevant, must respond to the therapiesgiven, and must change quickly and consistently enough toguide serial intervention. The use of biomarkers to guidetherapy remains controversial. Using absolute levels ofnatriuretic peptides as targets has encouraged more vigorousup-titration of guideline-recommended therapies that donot, however, achieve the biomarker targets in most patients(17). Using individualized targets based on hospitaldischarge levels led to the same interventions as those guidedby using clinical assessment (18).

There is undeniable face validity in treatment based onsigns and symptoms of heart failure. It is these signs andsymptoms that make the patients feel and look sick to thosewho care for them. Even the patients’ preferences to tradesurvival for comfort can be closely linked to elevated JVP andthe overall burden of heart failure symptoms (19,20).Relieving the signs and symptoms of heart failure treats notonly the diagnosis but also the patient.Support for the arts. It is encouraging to see these 2studies sustain a focus on clinical assessment in heart failure,in contrasting settings. The value of physical signs has beennoted in large trials focused on the therapy of heart failure,but it is commendable that the physical examination wasperformed in 1,376 patients with such rigor to confirm itsimportance in the large AF-CHF trial focused on strategiesfor atrial fibrillation (16). The legendary caliber of the Ca-nadian cardiovascular training is upheld by the investigatorsin this trial.

At the other end of the spectrum, a detailed study of 102subjects in a dedicated advanced heart disease program il-lustrates how the care of each patient continues to providenew insight for the observant (12). The physiological studyof the phenomenon of bendopnea encourages perpetualcuriosity to discover what makes patients feel sick and whatmakes them feel better. Far beyond enumeration of

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components for billing codes, thoughtful elicitation of thesigns and symptoms of heart failure can be trusted tostrengthen the transcendent link between patient andphysician. Even when our patients cannot be cured, listeningmay help us render them able to put on their own shoesagain.

Reprint requests and correspondence: Dr. Anju Nohria,Cardiovascular Division, Brigham andWomen’sHospital, 75 FrancisStreet, Boston, Massachusetts 02115. E-mail: anohria@partners.org.

REFERENCES

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2. Zile MR, Bennett TD, St. John Sutton M, et al. Transition fromchronic compensated to acute decompensated heart failure: patho-physiological insights obtained from continuous monitoring of intra-cardiac pressures. Circulation 2008;118:1433–41.

3. Stevenson LW, Zile M, Bennett TD, et al. Chronic ambulatoryintracardiac pressures and future heart failure events. Circ Heart Fail2010;3:580–7.

4. Ramasubbu K, Deswal A, Chan W, Aguilar D, Bozkurt B. Echocar-diographic changes during treatment of acute decompensated heartfailure: insights from the ESCAPE trial. J Cardiac Fail 2012;18:792–8.

5. Battin DL, Ali S, Shahbaz AU, et al. Hypoalbuminemia and lym-phocytopenia in patients with decompensated biventricular failure. AmJ Med Sci 2010;339:31–5.

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10. Drazner MH, Hellkamp AS, Leier CV, et al. Value of clinicianassessment of hemodynamics in advanced heart failure: the ESCAPEtrial. Circ Heart Fail 2008;1:170–7.

11. Kato M, Stevenson LW, Palardy M, et al. The worst symptom asdefined by patients during heart failure hospitalization: implications forresponse to therapy. J Cardiac Fail 2012;18:524–33.

12. Thibodeau JA, Turer AT, Gualano SK, et al. Characterization of anovel symptom of advanced heart failure: bendopnea. J Am CollCardiol HF 2014;2:24–31.

13. Brandon N, Mehra MR. “Flexo-dyspnea”: a novel clinical observationin the heart failure syndrome. J Heart Lung Transplant 2013;32:844–5.

14. Drazner MH, Rame JE, Stevenson LW, Dries DL. Prognosticimportance of elevated jugular venous pressure and a third heart soundin patients with heart failure. N Engl J Med 2001;345:574–81.

15. Lucas C, Johnson W, Hamilton MA, et al. Freedom from congestionpredicts good survival despite previous class IV symptoms of heartfailure. Am Heart J 2000;140:840–7.

16. Caldentey G, Khairy P, Roy D, et al. Prognostic value of the physicalexamination in patients with heart failure and atrial fibrillation: insightsfrom the AF-CHF trial (Atrial Fibrillation and Chronic Heart Failure).J Am Coll Cardiol HF 2014;2:15–23.

17. Jourdain P, Jondeau G, Funck F, et al. Plasma brain natriureticpeptide-guided therapy to improve outcome in heart failure: theSTARS-BNP Multicenter Study. J Am Coll Cardiol 2007;49:1733–9.

18. Shah MR, Califf RM, Nohria A, et al. The STARBRITE trial:a randomized, pilot study of B-type natriuretic peptide-guidedtherapy in patients with advanced heart failure. J Card Fail 2011;17:613–21.

19. Lewis EF, Johnson PA, Johnson W, Collins C, Griffin L,Stevenson LW. Preferences for quality of life or survival expressed bypatients with heart failure. J Heart Lung Transplant 2001;20:1016–24.

20. Stevenson LW, Hellkamp AS, Leier CV, et al. Changing preferencesfor survival after hospitalization with advanced heart failure. J Am CollCardiol 2008;52:1702–8.

Key Words: atrial fibrillation - dyspnea - heart failure -

hemodynamics - outcomes - physical examination.