The Key to Unraveling the Mystery of Mortality in Heart Failure
2003; Lippincott Williams & Wilkins; Volume: 107; Issue: 13 Linguagem: Inglês
10.1161/01.cir.0000014688.12415.c0
ISSN1524-4539
Autores Tópico(s)Cardiovascular Function and Risk Factors
ResumoHomeCirculationVol. 107, No. 13The Key to Unraveling the Mystery of Mortality in Heart Failure Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBThe Key to Unraveling the Mystery of Mortality in Heart FailureAn Integrated Approach Prakash C. Deedwania, MD Prakash C. DeedwaniaPrakash C. Deedwania From the Division of Cardiology, Department of Medicine, VA Central California Health Care System and University of California San Francisco Medical Education Program, Fresno, Calif, and University of California San Francisco School of Medicine, San Francisco, Calif. Originally published8 Apr 2003https://doi.org/10.1161/01.CIR.0000014688.12415.C0Circulation. 2003;107:1719–1721Heart failure (HF) is a growing public health problem in the United States. Nearly 5 million Americans suffer from HF, and an estimated 550 000 new cases of HF are diagnosed each year.1 HF is the No. 1 discharge diagnosis in patients ≥65 years of age and results in a substantial burden on healthcare expenditures. It is estimated that in 2001, more than $24 billion was spent as direct cost for the care of patients with HF.1 Furthermore, HF is associated with a significant increase in morbidity and mortality.See p 1764Although considerable progress has been made in our approach to the pharmacological management of patients with HF, most patients remain at increased risk of cardiac death. To further improve outcomes in patients with HF, newer therapeutic modalities, including devices such as biventricular pacemaker, automatic internal cardioverter-defibrillators (AICDs), and left ventricular assist devices, have been increasingly utilized. Several recent randomized controlled trials have shown that such devices can indeed further improve the outcome in patients with HF.2–4 However, these devices are expensive, and their widespread or injudicious application in unselected patients with HF is likely to have a substantial impact on healthcare expenditures. On the other hand, appropriate use of device therapy in properly selected patients (who are at high risk of mortality) is essential to improve clinical outcome. Thus, there is a need to develop a strategy to accurately identify those patients with HF who are at increased risk of mortality. The paper by Vrtovec and associates5 in the present issue of Circulation provides such a strategy by showing that routinely available diagnostic tests, such as measurement of QT interval on 12-lead ECG and measurement of B-type natriuretic peptide (BNP), can indeed identify the HF patients who are at increased risk of overall mortality, sudden cardiac death, and death due to pump failure.Prognostic Predictors of Mortality in HFHF is associated with a significant increase in overall mortality. It has been stated that mortality in HF is comparable to that observed in many cancers. The total number of deaths attributable to HF is also on the rise in the United States, increasing by 148% between 1979 and 2000.1 This increase is likely to continue as the overall number of patients with HF increases as a result of the aging of the US population, as well as improved survival of patients with myocardial infarction. Despite significant advances in therapy for HF, many patients with HF remain at increased risk of death.6 Because the clinical diagnosis of HF includes a whole host of patients with a wide spectrum of clinical presentations and functional status, there is considerable variation in their prognosis. Recent data indicate that, on the basis of the degree of severity of HF, the mortality rate for patients with HF can range between 10% and 50% per year.6 Clearly, the patients with advanced HF are at the highest risk of death. The mode of death can also vary according to the severity of HF. For example, patients with New York Heart Association (NYHA) class II/III HF are at increased risk of sudden cardiac death, whereas patients with NYHA class IV HF are at greater risk of dying from pump failure.Mortality in patients with HF also varies according to the degree of hemodynamic and biochemical abnormalities, the extent of ventricular dilation and dysfunction, electrophysiological changes, and the use of various drugs. The Table shows a variety of different parameters that have been frequently described as predictors of mortality in HF. In total, more than 60 parameters have been related to mortality in HF. Whereas all of the listed parameters have been shown to have significant predictive value in the univariate model, many of them do not retain their predictive value in the multivariate regression analyses.6 It is obvious that the clinician cannot effectively utilize all of these predictors in clinical practice to stratify HF patients into high- and low-risk categories. Furthermore, because many of these predictors do not have significant independent predictive value when combined with other parameters, it might not be clinically meaningful or necessary to evaluate them for risk prediction. It is, therefore, necessary to use an integrated approach to find the most cost-effective strategy for risk stratification of patients with HF. A variety of different models have been utilized and described previously for risk stratification of patients with HF.7–8 For example, in 1989 we had described that, in a multivariate regression model in patients with mild to moderate HF, left ventricular ejection fraction was the best predictor of total mortality, whereas the presence of nonsustained ventricular tachycardia was a better predictor for the risk of sudden cardiac death.7 Subsequently, the predictive value of nonsustained ventricular tachycardia for sudden death was also shown in patients with severe HF.8 More recently, studies have utilized the newer biochemical markers such as BNP and revealed that measurement of BNP can also identify HF patients at increased risk of sudden cardiac death.9Predictors of Mortality in Heart FailureDemographic ParametersBiochemical Markers Advanced age Serum electrolytes Etiology Blood urea nitrogen/creatinine Gender/race Plasma norepinephrine Symptom deviation Plasma aldosterone Diabetes Plasma endothelin Obesity Angiotensin II Prior myocardial infarction B-type natriuretic peptide Impaired renal functionElectrophysiological ParametersFunctional Parameters Increased heart rate NYHA class Decreased heart rate variability Six-minute walk test Prolonged QRS duration Exercise duration Conduction delays (bundle branch blocks) Peak oxygen consumption Abnormal signal-averaged ECG Anaerobic threshold T-wave alternansVentricular Function Cardiac arrhythmias Ejection fraction Atrial fibrillation Cardiothoracic ratio Nonsustained ventricular tachycardia Ventricular volumes Sustained ventricular tachycardia Sphericity indexPharmacological Agents Ventricular mass/stress ACE inhibitor/AII receptor blockers Mitral regurgitation β-Blocking agentsHemodynamic Parameters Spironolactone Intracardiac pressures Vasodilating drugs Cardiac output/index Antiarrhythmic agents Systemic/pulmonary vascular resistance Restrictive ventricular filling A-V oxygen differenceAn Integrated ApproachAlthough many of the previous studies utilized a number of established parameters that are predictive of mortality, the available results are of limited value because some studies have failed to utilize all of the commonly available predictors of outcome. The study by Vrtovec et al5 published in this issue of Circulation has attempted to overcome some of those deficiencies by including most of the commonly utilized parameters that have been shown to have predictive value for risk of mortality in patients with advanced HF. They have utilized an interesting strategy by first identifying patients with advanced HF by measuring plasma BNP levels and selecting only the patients who have BNP levels >400 pg/mL. Then, they compared the predictive value of QTc interval obtained from leads II and V4 on a standard 12-lead ECG against many of the previously established and commonly available parameters for determining the risk of all-cause mortality, cardiac mortality, sudden cardiac death, and death due to pump failure. By using such an integrated approach, Vrtovec et al5 have been able to demonstrate that such simple parameters as QTc interval and plasma BNP levels can indeed accurately identify subgroups of patients with HF who are at increased risk of overall mortality, sudden cardiac death, and death due to pump failure. The results from this study should be of considerable clinical interest because the most powerful and independent predictors in their study were prolonged QTc (>440 ms) and increasing levels of BNP. It is interesting to note that not only did patients with prolonged QTc have a 5- and 9-fold increased risk of all-cause mortality and death due to pump failure, respectively, but also the risk of sudden death was increased 6-fold in those with QTc >440 ms.5 Furthermore, their results indicate that the progressive increase in BNP levels was also an independent predictor of all-cause, cardiac, and pump failure deaths but not of sudden cardiac death.5 These data demonstrate the advantage of such an integrated approach because a recent study that did not utilize QTc interval had shown that levels of BNP were predictive of increased risk of sudden cardiac death.10 The discrepancy in the results of these two studies suggests that, unless one utilizes an integrated approach using most of the commonly available parameters, the studies can provide data that might have limited clinical utility.The study by Vrtovec et al5 has some limitations. For example, they have not utilized the cardiothoracic ratio available from chest x-rays in their multivariate regression model. It would have been important to utilize such information because of the fact that a previous study had failed to show independent predictive value of QT or JT intervals when the cardiothoracic ratio was used in patients with mild to moderate HF.11 Also, the investigation by Vrtovec et al5 did not give any information about ventricular arrhythmias and heart rate variability measured on 24-hour Holter monitoring, both of which have been shown to provide independent predictive information about the risk of sudden cardiac death. Regardless of these limitations, the present study by Vrtovec and associates has important clinical value.Clinical Implications and Future DirectionDespite significant advances in medical therapy, patients with HF remain at increased risk of overall mortality and sudden cardiac death. The results of several recent trials indicate that AICD implantation can reduce the risk of sudden cardiac death. Also, devices such as biventricular pacing for resynchronization therapy and left ventricular assist devices can improve the clinical outcome in patients with HF. However, because of the significant cost, these devices cannot be utilized for all patients with HF. An integrated approach such as the one utilized by Vrtovec et al5 in this issue of Circulation can help identify those patients who are at increased risk of overall mortality, sudden cardiac death, and pump failure death. By using such a risk stratification strategy to identify high-risk individuals, the clinician should be able to more effectively utilize the limited healthcare resources while providing the necessary and proven therapy to those who need it the most. Such a strategy is essential to provide proven therapies to patients who are most likely to benefit. Future studies should be conducted to prospectively examine the clinical usefulness and merit of such an integrated approach to prescribe treatment with expensive devices such as resynchronization with biventricular pacing and/or AICDs. Unless we utilize such a strategy, the cost of health care for HF patients could break the bank without necessarily providing the optimal care for those who really need it.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.FootnotesCorrespondence to Prakash C. Deedwania, MD, Division of Cardiology, Department of Medicine, VA Central California Health Care System, UCSF Medical Education Program, 2615 East Clinton Ave (111), Fresno, CA 93703. E-mail [email protected] References 1 American Heart Association. Heart Disease and Stroke Statistics—2003 Update. Dallas, Tex: American Heart Association; 2002.Google Scholar2 Connolly SJ, Hallstrom AP, Cappato R, et al. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials: AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator studies. Cardiac Arrest Study Hamburg Canadian Implantable Defibrillator Study. Eur Heart J. 2000; 21: 2071–2078.CrossrefMedlineGoogle Scholar3 Gold MR, Nisam S. Multicenter Automatic Defibrillator Implantation Trial. Multicenter Unsustained Tachycardia Trial. Primary prevention of sudden cardiac death with implantable cardioverter defibrillators: lessons learned from MADIT and MUSTT. Pacing Clin Electrophysiol. 2000; 23: 1981–1985.CrossrefMedlineGoogle Scholar4 Louis AA, Manousos IR, Coletta AP, et al. Clinical trials update: the Heart Protection Study, IONA, CARISA, ENRICHD, ACUTE, ALIVE, MEDIT II and REMATCH. Eur J Heart Fail. 2002; 4: 111–116.CrossrefMedlineGoogle Scholar5 Vrtovec B, Reynolds D, Zewail A, et al. Prolonged QTc interval and high B-type natriuretic peptide levels together predict mortality in patients with advanced heart failure. Circulation. 2003; 107: 1764–1769.LinkGoogle Scholar6 Eichhorn EJ. Prognosis determination in heart failure. Am J Med. 2001; 110 (7A): 14S–36S.CrossrefMedlineGoogle Scholar7 Gradman A, Deedwania P, Cody R, et al. Predictors of total mortality and sudden death in mild to moderate heart failure: Captopril-Digoxin Study Group. J Am Coll Cardiol. 1989; 14: 564–570.CrossrefMedlineGoogle Scholar8 Doval HC, Nul DR, Grancelli HO, for the GESICA-GEMA investigators. Nonsustained ventricular tachycardia in severe heart failure: independent marker of increased mortality due to sudden death. Circulation. 1996; 94: 3198–3203.CrossrefMedlineGoogle Scholar9 Maisel A, B-type natriuretic peptide levels: diagnostic and prognostic in congestive heart failure. What's next? Circulation. 2002; 105: 2328–2331.LinkGoogle Scholar10 Berger R, Huelsman M, Strecker K, et al. B-type natriuretic peptide predicts sudden death in patients with chronic heart failure. Circulation. 2002; 105: 2392–2397.LinkGoogle Scholar11 Brooksby P, Batin PD, Nolan J, et al. The relationship between QT intervals and mortality in ambulant patients with chronic heart failure: the United Kingdom Heart Failure Evaluation and Assessment of Risk Trial (UK-HEART). Eur Heart J. 1999; 20: 1335–1341.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Vallebona A, Gigli G, Orlandi S, Orlandi D, Gigli L and Reggiardo G (2012) The Etiology-Filling Pattern-Pulmonary Artery Pressure Score: A Simple Tool for Risk Stratification of Patients with Systolic Heart Failure, Congestive Heart Failure, 10.1111/j.1751-7133.2012.00294.x, 19:1, (39-43), Online publication date: 1-Jan-2013. Wu X, Cao Y, Nie J, Liu H, Lu S, Hu X, Zhu J, Zhao X, Chen J, Chen X, Yang Z and Li X (2013) Genetic and Pharmacological Inhibition of Rheb1-mTORC1 Signaling Exerts Cardioprotection against Adverse Cardiac Remodeling in Mice, The American Journal of Pathology, 10.1016/j.ajpath.2013.02.012, 182:6, (2005-2014), Online publication date: 1-Jun-2013. Mandour Ali M, Lotfy S, Koura I, Derbala M and Allam A (2013) The dilemma of ischemic heart failure; how FDG-PET can guide therapy and improve outcomes? Case report, The Egyptian Heart Journal, 10.1016/j.ehj.2012.12.001, 65:2, (117-122), Online publication date: 1-Jun-2013. Nienaber C and Powell J (2011) Management of acute aortic syndromes, European Heart Journal, 10.1093/eurheartj/ehr186, 33:1, (26-35), Online publication date: 1-Jan-2012. Buss S, Riffel J, Malekar P, Hagenmueller M, Asel C, Zhang M, Weiss C, Katus H and Hardt S (2012) Chronic Akt blockade aggravates pathological hypertrophy and inhibits physiological hypertrophy, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00211.2011, 302:2, (H420-H430), Online publication date: 1-Jan-2012. de Jong S (2011) Hartfalen: laboratoriumonderzoek Handboek hartfalen, 10.1007/978-90-313-8543-0_5, (39-51), . Okuda K, Watanabe E, Sano K, Arakawa T, Yamamoto M, Sobue Y, Uchiyama T and Ozaki Y (2011) Prognostic Significance of T-Wave Amplitude in Lead aVR in Heart Failure Patients with Narrow QRS Complexes, Annals of Noninvasive Electrocardiology, 10.1111/j.1542-474X.2011.00439.x, 16:3, (250-257), Online publication date: 1-Jul-2011. Javed F, Benjo A, Reddy K, Shoaib Akram M, Khan S, Sabharwal M, Nadkarni G, Aziz E and Herzog E (2011) Dexmedetomidine Use in the Setting of Cocaine-Induced Hypertensive Emergency and Aortic Dissection: A Novel Indication, Case Reports in Medicine, 10.1155/2011/174132, 2011, (1-4), . Vigliano C, Cabeza Meckert P, Diez M, Favaloro L, Cortés C, Fazzi L, Favaloro R and Laguens R (2011) Cardiomyocyte Hypertrophy, Oncosis, and Autophagic Vacuolization Predict Mortality in Idiopathic Dilated Cardiomyopathy With Advanced Heart Failure, Journal of the American College of Cardiology, 10.1016/j.jacc.2010.09.080, 57:14, (1523-1531), Online publication date: 1-Apr-2011. Tigen K, Karaahmet T, Gurel E, Mutlu B, Basaran Y and Cevik C (2009) Prognostic Utility of Anemia and Pro-B-Type Natriuretic Peptide in Patients With Nonischemic Dilated Cardiomyopathy and Normal Renal Function, The American Journal of the Medical Sciences, 10.1097/MAJ.0b013e31818128b5, 337:2, (109-115), Online publication date: 1-Feb-2009. Buss S, Muenz S, Riffel J, Malekar P, Hagenmueller M, Weiss C, Bea F, Bekeredjian R, Schinke-Braun M, Izumo S, Katus H and Hardt S (2009) Beneficial Effects of Mammalian Target of Rapamycin Inhibition on Left Ventricular Remodeling After Myocardial Infarction, Journal of the American College of Cardiology, 10.1016/j.jacc.2009.08.031, 54:25, (2435-2446), Online publication date: 1-Dec-2009. Hombach V, Merkle N, Torzewski J, Kraus J, Kunze M, Zimmermann O, Kestler H and Wohrle J (2009) Electrocardiographic and cardiac magnetic resonance imaging parameters as predictors of a worse outcome in patients with idiopathic dilated cardiomyopathy, European Heart Journal, 10.1093/eurheartj/ehp293, 30:16, (2011-2018), Online publication date: 2-Aug-2009. Godkar D, Bachu K, Dave B, Niranjan S and Khanna A (2008) B-Type Natriuretic Peptide (BNP) and ProBNP: Role of Emerging Markers to Guide Therapy and Determine Prognosis in Cardiovascular Disorders, American Journal of Therapeutics, 10.1097/MJT.0b013e31815af96f, 15:2, (150-156), Online publication date: 1-Mar-2008. Palpant N, Day S, Herron T, Converso K and Metzger J (2008) Single histidine-substituted cardiac troponin I confers protection from age-related systolic and diastolic dysfunction, Cardiovascular Research, 10.1093/cvr/cvn198, 80:2, (209-218), Online publication date: 1-Nov-2008., Online publication date: 1-Nov-2008. Hoes A and Mosterd A (2007) Epidemiologie: prevalentie, incidentie en prognose Leerboek hartfalen, 10.1007/978-90-313-6347-6_2, (29-45), . Tigen K, Karaahmet T, Kahveci G, Tanalp A, Bitigen A, Fotbolcu H, Bayrak F, Mutlu B and Basaran Y (2007) N-Terminal Pro Brain Natriuretic Peptide to Predict Prognosis in Dilated Cardiomyopathy with Sinus Rhythm, Heart, Lung and Circulation, 10.1016/j.hlc.2007.02.083, 16:4, (290-294), Online publication date: 1-Aug-2007. Kestler H, Kraus J, Hoher M, Hombach V and Wohrle J (2007) Prognostic significance of electrocardiogram and cine magnetic resonance imaging parameters in patients with idopathic dilated cardiomyopathy 2007 34th Annual Computers in Cardiology Conference, 10.1109/CIC.2007.4745425, 978-1-4244-2533-4, (77-80) Day S, Westfall M, Fomicheva E, Hoyer K, Yasuda S, Cross N, D'Alecy L, Ingwall J and Metzger J (2006) Histidine button engineered into cardiac troponin I protects the ischemic and failing heart, Nature Medicine, 10.1038/nm1346, 12:2, (181-189), Online publication date: 1-Feb-2006. Travin M and Bergmann S (2005) Assessment of myocardial viability, Seminars in Nuclear Medicine, 10.1053/j.semnuclmed.2004.09.001, 35:1, (2-16), Online publication date: 1-Jan-2005. Cho G, Song J, Park W, Han S, Choi S, Doo Y, Oh D and Lee Y (2005) Mechanical Dyssynchrony Assessed by Tissue Doppler Imaging Is a Powerful Predictor of Mortality in Congestive Heart Failure With Normal QRS Duration, Journal of the American College of Cardiology, 10.1016/j.jacc.2004.11.074, 46:12, (2237-2243), Online publication date: 1-Dec-2005. Sunkomat J and Gaballa M (2006) Stem cell therapy in ischemic heart disease, Cardiovascular Drug Reviews, 10.1111/j.1527-3466.2003.tb00125.x, 21:4, (327-342) Huang P, Fu J, Chen L, Ju C, Wu K, Liu H, Liu Y, Qi B, Qi B and Liu L (2019) Redd1 protects against post‑infarction cardiac dysfunction by targeting apoptosis and autophagy, International Journal of Molecular Medicine, 10.3892/ijmm.2019.4366 April 8, 2003Vol 107, Issue 13 Advertisement Article InformationMetrics https://doi.org/10.1161/01.CIR.0000014688.12415.C0PMID: 12682028 Originally publishedApril 8, 2003 Keywordsheart failureEditorialsdeath, suddensurvivalrisk factorPDF download Advertisement
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