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Rassegna bibliografica di articoli selezionati apparsi in ...

  1. 1. Rassegna bibliografica di articoli selezionati apparsi in letteratura nel periodo 1999 – Maggio 2004 inerenti la “DISFUNZIONE RENALE” nello “scompenso cardiaco congestizio” Note esplicative: Cliccando sull’icona della Rivista si può accedere al suo sito On-line (se disponibile) Cliccando sull’icona (clicca qui per andare su PUBMED) si visualizza l’ABS su PUBMED (da dove poi si può espandere ulteriormente la ricerca) Alcune riviste forniscono un libero accesso agli articoli in formato PDF (richiede Adobe acrobat reader che si può scaricare dal sito ANMCO). In tal caso, sotto la citazione compare l’immagine interattiva : che basterà cliccare per scaricare direttamente l’articolo. Per ulteriori informazioni sulle riviste a libero accesso (lodevole inziativa che consente la libera circolazione delle idee) rimandiamo al sito: The Free Medical Journals Site (dove tra l’altro è inserito nella lista anche il nostro giornale.) L’indirizzo e.mail (se disponibile) che appare su alcuni abs consente una migliore interazione con gli autori (cosa di solito molto gradita) per eventuali chiarimenti, richieste di reprint etc. etc. Buona lettura Luigi Tarantini, Giovanni Pulignano, Guido Gigli Butler J, Forman DE, Abraham WT, Gottlieb SS, Loh E, Massie BM, O'Connor CM, Rich MW, Stevenson LW, Wang Y, Young JB, Krumholz HM. Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. Am Heart J. 2004 Feb;147(2):331-8. clicca qui per andare su PUBMED Vanderbilt University, Nashville, Tenn, USA. javed.butler@vanderbilt.edu Comment: Lapman PG, Golduber GN, Le Jemtel TH. Heart failure treatment and renal function. Am Heart J. 2004 Feb;147(2):193-4.
  2. 2. BACKGROUND: Among patients who are hospitalized with heart failure (HF), worsening renal function (WRF) is associated with worse outcomes. Whether treatment for HF contributes to WRF is unknown. In this study, we sought to assess whether acute treatment for patients who were hospitalized with HF contributes to WRF. METHODS: Data were collected in a nested case-control study on 382 subjects who were hospitalized with HF (191 patients with WRF, defined as a rise in serum creatinine level >26.5 micromol/L [0.3 mg/dL], and 191 control subjects). The association of medications, fluid intake/output, and weight with WRF was assessed. RESULTS: Calcium channel blocker (CCB) use and loop diuretic doses were higher in patients on the day before WRF (25% vs 10% for CCB; 199 +/- 195 mg vs 143 +/- 119 mg for loop diuretics; both P <.05). There were no significant differences in the fluid intake/output or weight changes in the 2 groups. Angiotensin-converting enzyme (ACE) inhibitor use was not associated with WRF. Other predictors of WRF included elevated creatinine level at admission, uncontrolled hypertension, and history of HF or diabetes mellitus. Higher hematocrit levels were associated with a lower risk. Vasodilator use was higher among patients on the day before WRF (46% vs 35%, P <.05), but was not an independent predictor in the multivariable analysis. CONCLUSIONS: Several medical strategies, including the use of CCBs and a higher dose of loop diuretics, but not ACE inhibitors, were associated with a higher risk of WRF. Although assessment of inhospital diuresis was limited, WRF could not be explained by greater fluid loss in these patients. Determining whether these interventions are responsible for WRF or are markers of higher risk requires further investigation. Walsh CR, O'Donnell CJ, Camargo CA Jr, Giugliano RP, Lloyd-Jones DM. Elevated serum creatinine is associated with 1-year mortality after acute myocardial infarction. Am Heart J. 2002 Dec;144(6):1003-11. clicca qui per andare su PUBMED Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA. BACKGROUND: Cardiovascular mortality is high in individuals with end-stage renal disease. However, less is known about the prognostic importance of moderate renal insufficiency in patients with acute myocardial infarction. METHODS: We studied all patients with acute myocardial infarction admitted through the emergency department to an urban, academic hospital over 1 year. Patients were classified as having elevated (>133 micromol/L [1.5 mg/dL]) or normal (< or =133 micromol/L) serum creatinine at presentation. RESULTS: Of 483 patients, 22% had elevated creatinine and 78% had normal creatinine. By 1 year, 46% of patients with elevated creatinine and 15% of patients with normal creatinine had died (P <.001). The unadjusted hazard ratio for 1-year mortality was increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 3.85, 95% CI 2.61-5.67). After adjustment for baseline characteristics and treatment, the multivariable-adjusted hazard ratio for 1- year mortality remained increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 2.40, 95% CI 1.55-3.72). There was an important modification of the prognostic value of creatinine by the presence of congestive heart failure at presentation (P value for interaction =.04). The adjusted hazard ratio for 1-year death associated with elevated creatinine compared with normal creatinine was 3.89 (95% CI 1.87-8.07) in patients without congestive heart failure and 1.92 (95% CI 1.10-3.36) in patients with congestive heart failure. CONCLUSIONS: Elevated serum creatinine at presentation is associated with 1-year mortality after acute myocardial infarction. Further study is needed to optimize treatment after myocardial infarction in this high-risk group. Havranek EP, Masoudi FA, Westfall KA, Wolfe P, Ordin DL, Krumholz HM.
  3. 3. Spectrum of heart failure in older patients: results from the National Heart Failure project. Am Heart J. 2002 Mar;143(3):412-7. clicca qui per andare su PUBMED Colorado Foundation for Medical Care, Aurora, Colo, USA. EHavrane@DHHA.org BACKGROUND: The elderly make up the majority of patients with heart failure (HF), but information on this segment of the HF population is lacking because clinical trials typically enroll younger patients and population-based studies lack clinical detail. We sought to describe a contemporary national sample of elderly patients with HF and to examine the sample for age-related trends in clinical characteristics. METHODS: We studied the charts of 800 Medicare patients per state who were hospitalized with a principal diagnosis of HF between April 1998 and March 1999. There were 34,587 patients in the sample after exclusion of patients who were <65 years old, repeat discharges, discharges to another acute care facility or against medical advice, or receiving long-term hemodialysis. RESULTS: Comorbidity was common. About one third of patients had chronic obstructive pulmonary disease, about 40% had diabetes, more than half had coronary heart disease, and more than half had a history of hypertension, but comorbidity rates declined with age. Left ventricular ejection fraction was <40% in only 50.4% of patients in whom it was assessed. Associated laboratory abnormalities were relatively constant across the age spectrum, but renal insufficiency was more common with advancing age. The likelihood that patients were in long-term care facilities before admission rose quite steeply with age. CONCLUSIONS: Elderly patients with HF are a heterogeneous group and appear to differ substantially from patients enrolled in clinical trials. Evidence-based guidance for treatment in the context of multiple comorbid conditions, poor renal function, HF with preserved left ventricular systolic function, and residence in long-term care facilities is urgently needed. Devereux RB, Roman MJ, Paranicas M, Lee ET, Welty TK, Fabsitz RR, Robbins D, Rhoades ER, Rodeheffer RJ, Cowan LD, Howard BV. A population-based assessment of left ventricular systolic dysfunction in middle-aged and older adults: the Strong Heart Study. Am Heart J. 2001 Mar;141(3):439-46. clicca qui per andare su PUBMED Department of Medicine, Cornell Medical Center, New York, NY, USA. rbdevere@med.cornell.edu BACKGROUND: Although clinical congestive heart failure (CHF) is increasingly common, few data document the prevalence and correlates of underlying left ventricular (LV) systolic dysfunction (D) in population-based samples. METHODS: Echocardiography was used in the second Strong Heart Study (SHS) examination to identify mild and severe LVD (LV ejection fraction [EF] 40%-54% and <40%, respectively) in 3184 American Indians. RESULTS: Mild and severe LVD were more common in men than women (17.4% vs 7.2% and 4.7% vs 1.8%) and in diabetic than nondiabetic participants (12.7% vs 9.1% and 3.5% vs 1.6%). Stepwise increases were observed from participants with normal EF to those with mild and severe LVD in age (mean 60 vs 61 and 63 years, P <.001), prevalence of overt CHF (2% vs 6% and 28%) and definite coronary heart disease (3% vs 11% and 32%), systolic pressure (129 vs 135 and 136 mm Hg), serum creatinine level (0.98 vs 1.34 and 2.16 mg/dL), and log urinary albumin/creatinine level (3.2 vs 3.7 and 4.7); a negative relation was seen with body mass index (31.1 vs 31.0 and 28.4 kg/m(2)) (all P <.001). In multivariate analyses lower LVEFs were independently associated with clinical CHF and coronary heart disease, lower myocardial contractility, male sex, hypertension, overweight, arterial stiffening (higher pulse pressure/stroke volume) and renal dysfunction (higher serum creatinine level), higher LV mass, and lower relative wall thickness. CONCLUSIONS: LVD, present in approximately 14% of middle-aged to elderly adults, is independently
  4. 4. associated with overt heart failure and coronary heart disease, male sex, hypertension, overweight, arterial stiffening, and renal target organ damage and, less consistently, with older age and diabetes. Echemann M, Zannad F, Briancon S, Juilliere Y, Mertes PM, Virion JM, Villemot JP. Determinants of angiotensin-converting enzyme inhibitor prescription in severe heart failure with left ventricular systolic dysfunction: the EPICAL study. Am Heart J. 2000 Apr;139(4):624-31. clicca qui per andare su PUBMED Service d'Epidemiologie et d'Evaluation Cliniques, Hopital Marin, France. BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have been demonstrated to reduce morbidity and mortality rates in patients with heart failure with left ventricular systolic dysfunction. Nevertheless, these drugs are underutilized in current practice and prescribed at doses below those usually recommended. The aim of this work was to identify the social, demographic, laboratory, clinical, and therapeutic factors associated with nonprescription of ACE inhibitors and/or their prescription at doses below those recommended in the treatment of severe long-term congestive heart failure (CHF). METHODS AND RESULTS: An epidemiologic observational study, EPICAL (EPidemiologie de l'Insuffisance Cardiaque Avancee en Lorraine), studied 417 patients with severe CHF surviving after the index hospitalization. Multivariate logistic regression determined the factors associated with ACE inhibitor nonprescription and with their prescription at lower-than-recommended doses. ACE inhibitors were taken by 75% of the patients but 38% took lower-than-recommended doses. Factors shown to be associated with nonprescription included patients >65 years of age with renal impairment (odds ratio 19.5, confidence interval [CI] 7.9-48.0), nonsinus cardiac rhythm (odds ratio 2.0, CI 1.2-3.2), and prescription of potassium-sparing diuretics (odds ratio 2.4, CI 1. 2-4.7). Renal impairment was the single most important factor associated with prescription of lower-than-recommended doses, particularly in elderly patients. CONCLUSIONS: Our results underline the need for optimal and better use of ACE inhibitor therapy. CHF treatment guidelines must be more uniformly applied by all physicians caring for patients with heart failure. Knight EL, Glynn RJ, McIntyre KM, Mogun H, Avorn J. Predictors of decreased renal function in patients with heart failure during angiotensin-converting enzyme inhibitor therapy: results from the studies of left ventricular dysfunction (SOLVD) Am Heart J. 1999 Nov;138(5 Pt 1):849-55. clicca qui per andare su PUBMED Editoriale: Bart BA. Concern for azotemia with angiotensin-converting enzyme inhibitors: public health implications and clinical relevance. Am Heart J. 1999 Nov;138(5 Pt 1):801-3. clicca qui per andare su PUBMED Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. BACKGROUND: Although angiotensin-converting enzyme inhibitor therapy reduces mortality rates in patients with congestive heart failure (CHF), it may also cause decreased renal function. Little information is available to predict which patients are at highest risk for this complication. OBJECTIVE: To quantify specific clinical predictors of reduction in renal function in patients with CHF who are prescribed angiotensin-converting enzyme inhibitor therapy. METHOD: We
  5. 5. analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized, double-blind, placebo-controlled trial of enalapril for the treatment of CHF. There were 3379 patients randomly assigned to enalapril with a median follow-up of 974 days and 3379 patients randomly assigned to placebo with a mean follow-up of 967 days. Decreased renal function was defined as a rise in serum creatinine >/=0.5 mg/dL (44 micromol/L) from baseline. We used time-to-event analysis to identify potential predictors of decrease in renal function including age, baseline ejection fraction, baseline creatinine, low systolic blood pressure (<100 mm Hg), history of hypertension, diabetes, and use of antiplatelet, diuretic, and beta-blocker therapy. RESULTS: Patients randomly assigned to enalapril had a 33% greater likelihood of decreased renal function than controls (P =.003). By multivariate analysis, in both the placebo and enalapril groups older age, diuretic therapy, and diabetes were associated with decreased renal function, whereas beta-blocker therapy and higher ejection fraction were renoprotective. Older age was associated with a greater risk of developing decreased renal function in both groups, but significantly more so in the enalapril group (enalapril: risk ratio [RR] 1.42 per 10 years, 95% confidence interval [CI] 1.32-1.52 with enalapril; placebo: RR 1.18, 95% CI 1.12-1.25). Diuretic therapy was likewise associated with a greater risk of decreased renal function in the enalapril group (RR 1.89, 95% CI 1.70-2.08) than in the placebo group (RR 1.35, 95% CI 1.09-1.66). Conversely, enalapril had a relative renoprotective effect (RR 1.33, 95% CI 1.13-1.53) compared with placebo (RR 1.96, 95% CI 1.57-2.44) in patients with diabetes. A lower risk of renal impairment was seen in both groups with beta-blocker therapy (RR 0.70, 95% CI 0.57-0.85) and higher baseline ejection fraction (RR 0.93 per 5% increment, 95% CI 0.91-0. 96). CONCLUSIONS: Enalapril use caused a 33% increase in the risk of decreased renal function in patients with CHF. Diuretic use and advanced age increased this risk. Diabetes was associated with an increased risk of renal impairment in all patients with CHF, but this risk was reduced in the enalapril group compared with the placebo group. beta-Blocker therapy and higher ejection fraction were renoprotective in all patients regardless of therapy. Weinfeld MS, Chertow GM, Stevenson LW. Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure. Am Heart J. 1999 Aug;138(2 Pt 1):285-90. clicca qui per andare su PUBMED Comment in: Bart BA, Goldsmith SR. Aggravated renal dysfunction and the acute management of advanced chronic heart failure. Am Heart J. 1999 Aug;138(2 Pt 1):200-2. clicca qui per andare su PUBMED Cardiovascular Division, Department of Medicine, Brigham Women's Hospital, Boston, MA 02115, USA. BACKGROUND: Chronic heart failure is associated with impaired renal function, which may worsen during therapy. The incidence, predictors, and consequences of aggravated renal dysfunction (ARD) in patients undergoing intensive therapy for advanced chronic heart failure are unknown. METHODS: We reviewed the experience of 48 consecutive patients hospitalized for treatment of advanced chronic heart failure who underwent intravenous diuretic therapy with a weight loss of >/=2 kg. Evaluation included baseline renal function and echocardiography in all patients and hemodynamic measurements in 38 (79%) patients. RESULTS: ARD, defined as >/=25% increase in serum creatinine concentration to >/=2 mg/dL, developed in 10 (21%) patients. Patients with ARD developing were older (aged 58 +/- 16 years vs 51 +/- 13 years; P =.006) and had lower baseline creatinine clearance (49 +/- 21 mL/min vs 74 +/- 26 mL/min; P =.01) but had the same serum creatinine at baseline. They were more likely to have atrial fibrillation (70%
  6. 6. vs 29%, P =.02) but did not have lower filling pressures, cardiac output, or estimated renal perfusion pressure. Length of stay was longer if ARD developed (median 17 vs 9 days, P =.02). Mortality rate after discharge was increased in the patients with ARD (relative risk 5.3, P =.002). CONCLUSIONS: In patients undergoing intensive treatment for heart failure, ARD is common and clinically significant. The relation among baseline factors, ARD, and worsened outcome may reflect complex cardiorenal interactions. Better understanding of the causes and prevention of ARD during heart failure therapy may in the future lead to better outcomes. Bello D, Shah NB, Edep ME, Tateo IM, Massie BM. Self-reported differences between cardiologists and heart failure specialists in the management of chronic heart failure. Am Heart J. 1999 Jul;138(1 Pt 1):100-7. clicca qui per andare su PUBMED Comment in: Smith JJ, Konstam MA. Heart failure: A case for subspecialized care management. Am Heart J. 1999 Jul;138(1 Pt 1):14-6. clicca qui per andare su PUBMED Department of Medicine and Cardiovascular Research Institute of the University of California, San Francisco, USA. BACKGROUND: Heart failure (HF) is responsible for considerable mortality morbidity rates and resource utilization. Recently, several studies have reported improved outcomes when patients are managed by special HF clinics, but it is uncertain whether this improvement reflects differences in physician practices or other aspects of the operation of these clinics. OBJECTIVES: This study was designed to identify differences in HF management practices between general cardiologists and cardiologists specializing in the treatment of patients with HF. METHODS: A survey examining diagnostic and treatment practices in patients with HF was sent to a sample of cardiologists derived from the American Medical Association Masterfile and to HF specialists who were members of the Society of Transplant Cardiologists or principal investigators in HF trials. Responses were examined in relation to guidelines issued by the Agency for Health care Policy and Research released 9 months previously. RESULTS: In general both groups practice in conformity with published guidelines. However, there were important differences between the practice patterns of general cardiologists and HF specialists. For instance, in patients being evaluated for the first time, cardiologists reported using a chest radiograph to assist in the diagnosis more than did HF specialists (47% vs 12%), whereas HF specialists were more likely to use an echocardiogram (73% vs 48%). Both groups were likely to evaluate their patients for ischemia and possible revascularization, even in patients not having angina. However, HF specialists tended to use coronary angiography as the initial diagnostic test, whereas cardiologists were more likely to use stress testing. HF specialists more often used angiotensin-converting enzyme inhibitors as part of their initial therapy in patients with mild to moderate HF (94% vs 86%) and during maintenance therapy (91% vs 80%). Also, HF specialists were more likely than cardiologists to titrate angiotensin-converting enzyme inhibitors to higher doses (75% vs 35%), even in the presence of renal dysfunction. CONCLUSION: Cardiologists and HF specialists generally manage their patients in conformity with guidelines. However, in many areas, such as angiotensin-converting enzyme inhibitor use, HF specialists do so more aggressively. These approaches may, in part, explain the success of the HF clinic model and raise the possibility that some portion of the HF population may be more optimally managed by cardiologists with a special interest in and additional training or experience with this condition.
  7. 7. McAlister FA, Teo KK, Taher M, Montague TJ, Humen D, Cheung L, Kiaii M, Yim R, Armstrong PW. Insights into the contemporary epidemiology and outpatient management of congestive heart failure. Am Heart J. 1999 Jul;138(1 Pt 1):87-94. clicca qui per andare su PUBMED Comment in: Ghali JK. Contemporary issues in heart failure. Am Heart J. 1999 Jul;138(1 Pt 1):5-8. clicca qui per andare su PUBMED Division of General Internal Medicine, University of Alberta, Edmonton, Canada. OBJECTIVES: To evaluate the epidemiology, prognosis, and patterns of practice in patients with chronic congestive heart failure (CHF) treated and followed at a specialized clinic. METHODS: Prospective cohort study of consecutive patients referred to and followed up in a specialized heart failure clinic between September 1989 and March 1996. RESULTS: Of the 628 patients referred, 566 were confirmed to have CHF. Mean duration of follow-up was 518 +/- 490 days (range 1 to 2192 days). Vital status was available for 99.3% of patients. Mean age at enrollment was 66 years, 68% were men, 67% had an ischemic cause of heart disease, and 78% had systolic dysfunction. Patients with preserved systolic function were older, more often female, had higher mean systolic blood pressures, and a lower prevalence of ischemic heart disease, ventricular arrhythmias, or impaired renal function when compared with those with systolic dysfunction (all P </=.001). Although there was a significant negative trend in survival with decreasing ejection fraction (P =. 03), the survival experience of those with CHF and preserved systolic function did not significantly differ from those with systolic failure (P =.25). Multiple logistic regression analysis showed increased mortality risk was associated with increasing age, New York Heart Association class IV, ischemic cause of disease, elevated serum creatinine level, use of diuretics, and systolic dysfunction, whereas use of beta-blockers was associated with reduced risk. CONCLUSIONS: Our data suggest that a specialized outpatient clinic can improve practice patterns in patients with CHF. The high mortality risk in CHF with preserved systolic function suggests the need to find efficacious (and effective) therapies for this condition. Kawai K, Hata K, Tanaka K, Kubota Y, Inoue R, Masuda E, Miyazaki T, Yokoyama M. Attenuation of biologic compensatory action of cardiac natriuretic peptide system with aging. Am J Cardiol. 2004 Mar 15;93(6):719-23. clicca qui per andare su PUBMED Department of Internal Medicine, Kanzaki General Municipal Hospital, Hyogo, Japan. kkwai@river.sannet.ne.jp Although plasma B-type natriuretic peptide (BNP) levels increase with age, the mechanisms responsible for this increase are unknown. We investigated the predictors of elevated BNP in older subjects without cardiac systolic
  8. 8. dysfunction and overt renal dysfunction. Furthermore, we analyzed the relations between BNP and its second messenger, cyclic guanosine monophosphate (cGMP), to aging. In 252 subjects (mean age 69 +/- 12 years) with left ventricular ejection fraction >/=50% and creatinine levels <==1.5 mg/dl, plasma levels of BNP, cGMP, blood urea nitrogen, creatinine, and beta2-microglobulin (an endogenous marker of renal function), estimated glomerular filtration rate, and echocardiographic data were prospectively evaluated. Plasma BNP levels increased with age (r = 0.4, p <0.0001). With use of multivariate analysis, predictors of elevated BNP levels were age, use of beta blockers, and serum beta2-microglobulin levels. The molar ratio of cGMP to BNP significantly decreased with aging (r = 0.55, p <0.0001). Elevated BNP in older subjects with normal cardiac systolic function may be due in part to renal impairment. With aging, biologic compensation of the cardiac natriuretic peptide system may be attenuated. Cioffi G, Stefenelli C, Tarantini L, Opasich C. Hemodynamic response to intensive unloading therapy (furosemide and nitroprusside) in patients >70 years of age with left ventricular systolic dysfunction and decompensated chronic heart failure. Am J Cardiol. 2003 Nov 1;92(9):1050-6. clicca qui per andare su PUBMED Department of Cardiology, Villa Bianca Hospital, Trento, Italy. gcioffi@albaclick.com In patients with decompensated chronic congestive heart failure (CHF), intensive unloading therapy allows an acute decrease in ventricular filling pressures and improves long-term prognosis. Because elderly patients do not routinely undergo invasive hemodynamic evaluation, they are generally denied such a pharmacologic approach. We prospectively characterized the acute hemodynamic response to intensive unloading and its prognostic significance in a elderly population with CHF who were hospitalized for cardiac decompensation. Fifty-nine patients aged >70 years with left ventricular systolic dysfunction underwent intensive unloading therapy (furosemide and nitroprusside) tailored to reduce ventricular filling pressures to near-normal levels. The hemodynamic parameters were monitored by Doppler echocardiography. At baseline, left and right ventricular filling pressures were 21 +/- 3 and 10 +/- 3 mm Hg, respectively. Although all patients experienced a relevant improvement in clinical status during hospital stay, a significant reduction of ventricular filling pressures was detected at discharge in only 40 of them (68%) (responders), whereas 19 patients (32%) had a deficient response to therapy (nonresponders). This unfavorable behavior was predicted by the presence of renal dysfunction at admission. During 19-month follow-up, death due to cardiovascular causes occurred in 8 of 40 responders (20%) and in 9 of 19 nonresponders (47%) (p <0.005). Hospitalizations for cardiovascular causes were more frequent in the nonresponders (58% vs 8%, p <0.0001). Thus, a deficient hemodynamic response to intensive unloading treatment is not infrequent in elderly patients with decompensated CHF. This behavior is predicted by renal dysfunction at admission and is associated with poorer outcome. Chae CU, Albert CM, Glynn RJ, Guralnik JM, Curhan GC Mild renal insufficiency and risk of congestive heart failure in men and women > or =70 years of age. Am J Cardiol. 2003 Sep 15;92(6):682-6. clicca qui per andare su PUBMED Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215-1204, USA. cchae@partners.org
  9. 9. Mild renal insufficiency is increasingly recognized as an independent risk factor for cardiovascular disease. However, few data exist regarding its relation to risk of congestive heart failure (CHF), a major public health problem in the elderly. To determine if mild renal insufficiency is associated with risk of incident CHF in the elderly, we analyzed data from 3,618 participants in the prospective, community-based Established Populations for Epidemiologic Studies of the Elderly (EPESE), who had no known CHF and had serum creatinine levels measured from 1987 to 1989. Mean age of the study population was 78.3 +/- 5.4 years; 84% had creatinine values <1.5 mg/dl and 98% had creatinine values < or =2.0 mg/dl. Creatinine clearance (CrCl) was calculated using the Cockcroft-Gault equation. During 3.9 years of follow-up, 488 subjects developed incident CHF as defined by hospital discharge and death certificate data. In a multivariate proportional hazards model, CrCl was inversely associated with CHF risk (p value for trend <0.001). Those in the lowest quartile of CrCl (< or =36.9 ml/min) had a nearly twofold (hazards ratio [HR] 1.99, 95% confidence intervals [CI] 1.43 to 2.79) greater risk of incident CHF compared with those in the highest quartile (>57.4 ml/min). Renal insufficiency, defined as creatinine > or =1.5 mg/dl in men and > or =1.3 mg/dl in women, was also associated with increased CHF risk (multivariate HR 1.43, 95% CI 1.17 to 1.74). Thus, mild renal insufficiency was a strong independent predictor of CHF in this cohort, suggesting that serum creatinine may offer a readily accessible tool to identify elderly patients at risk for CHF. Devereux RB, Roman MJ, Liu JE, Welty TK, Lee ET, Rodeheffer R, Fabsitz RR, Howard BV. Congestive heart failure despite normal left ventricular systolic function in a population-based sample: the Strong Heart Study. Am J Cardiol. 2000 Nov 15;86(10):1090-6. clicca qui per andare su PUBMED Department of Medicine, The New York Presbyterian Hospital-Weill Cornell Medical Center, New York 10021, USA. rbdevere@med.cornell.edu In selected clinical series, > or = 50% of adults with congestive heart failure (CHF) do not have left ventricular (LV) systolic dysfunction. Little is known of the prevalence of this phenomenon in population samples. Therefore, clinical examination and echocardiography were used in the second examination of the Strong Heart Study (3,184 men and women, 47 to 81 years old) to identify 95 participants with CHF, 50 of whom had normal LV ejection fraction (EF) (> 54%), 19 of whom had mildly reduced EF (40% to 54%), and 26 of whom had EF < or = 40%. Compared with those with no CHF, participants with CHF and no, mild, or severe decrease in EF had higher creatinine levels (2.34 to 2.85 vs 1.01 mg/dl, p < 0.001) and higher prevalences of diabetes (60% to 70% vs 50%) and hypertension (75% to 96% vs 46%, p < 0.05). Compared with those with no CHF, participants with CHF and normal EF had prolonged deceleration time (233 vs 204 ms, p < 0.05) and a reduced E/A, whereas those with CHF and EF < or = 40% had short deceleration time (158 ms, p < 0.05) and high E/A (1.70, p < 0.001); patients with CHF and normal EF had higher LV mass (98 vs 84 g/m2, p < 0.001) and relative wall thickness (0.37 vs 0.35, p < 0.05) than those without CHF. Patients with CHF with normal EF were, compared with those without CHF or with CHF and EF < or = 40%, disproportionately women (mean 84% vs 63% and 42%, p < 0.001), older (mean 64 vs 60 years and 63 years, respectively, p < 0.01), had higher body mass index (mean 33.1 vs 31.0 and 27.7 kg/m2, p < 0.05), and higher systolic blood pressure (mean 137 vs 130 and 128 mm Hg, both p < 0.05). Thus, in a population-based sample, patients with CHF and normal LV EF were older and overweight, more often women, had renal dysfunction, impaired early diastolic LV relaxation, and concentric LV geometry, whereas patients with CHF and severe LV dysfunction were more often men, had lower body mass index, a restrictive pattern of LV filling, and eccentric LV hypertrophy.
  10. 10. Krumholz HM, Chen YT, Vaccarino V, Wang Y, Radford MJ, Bradford WD, Horwitz RI. Correlates and impact on outcomes of worsening renal function in patients > or =65 years of age with heart failure. Am J Cardiol. 2000 May 1;85(9):1110-3. clicca qui per andare su PUBMED Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520-8025, USA. harlan.krumholz@yale.edu Despite the potential importance of a rising creatinine level in patients hospitalized for heart failure, there is little information about factors that may predispose patients to this condition or its association with outcomes. We sought to determine the incidence and identify factors associated with the development of worsening renal function in elderly patients admitted with heart failure, and to examine the impact of worsening renal function on clinical and economic outcomes. The study sample included 1,681 patients aged 65 years, discharged with heart failure at 18 Connecticut hospitals, who did not have clear precipitants for renal dysfunction. Worsening renal function (defined as an increase in serum creatinine level of >0.3 mg/dl during hospitalization from admission) occurred in 28% of the cohort and was associated with male gender, hypertension, rales > basilar, pulse >100 beats/min, systolic blood pressure >200 mm Hg, and admission creatinine >1.5 mg/dl. Based on the number of these factors, a patient's risk for developing worsening renal function ranged between 16% ( 1 factor) and 53% ( 5 factors). After adjusting for confounding effects, worsening renal function was associated with a significantly longer length of stay by 2.3 days, higher in-hospital cost by $1,758, and an increased risk of in-hospital mortality (odds ratio 2.72; 95% confidence interval 1.62 to 4.58). In conclusion, worsening renal function, an event that frequently occurs in elderly patients hospitalized with heart failure, confers a substantial burden to patients and the healthcare system and can be predicted by 6 admission characteristics McCullough PA, Duc P, Omland T, McCord J, Nowak RM, Hollander JE, Herrmann HC, Steg PG, Westheim A, Knudsen CW, Storrow AB, Abraham WT, Lamba S, Wu AH, Perez A, Clopton P, Krishnaswamy P, Kazanegra R, Maisel AS; Breathing Not Properly Multinational Study Investigators. B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the Breathing Not Properly Multinational Study. Am J Kidney Dis. 2003 Mar;41(3):571-9. clicca qui per andare su PUBMED University of California, San Diego Veteran's Affairs Medical Center, San Diego, CA, USA. mailto:pmc975@yahoo.com BACKGROUND: Both B-type natriuretic peptide (BNP) and renal function are prognostic indicators of survival in patients with congestive heart failure (CHF). However, relationships between BNP, renal function, and heart failure as an emergency diagnosis are unknown. METHODS: The Breathing Not Properly
  11. 11. Multinational Study was a prospectively designed diagnostic test evaluation study conducted in seven centers. Of 1,586 participants who presented with acute dyspnea, 1,452 patients (91.6%) had both BNP level and baseline estimated glomerular filtration rate (eGFR) available. Patients with an eGFR less than 15 mL/min/1.73 m2 and those on dialysis therapy were excluded. The final diagnosis was adjudicated by two independent cardiologists who were blinded to BNP results. RESULTS: The final diagnosis was CHF in 715 patients (49.2%). Raw and log-log transformed correlations between BNP and eGFR values were r = -0.19 and r = -0.17 for those with CHF and r = -0.20 and r = -0.31 for those without CHF (both P < 0.0001 for r not equal 0). Mean BNP levels were 561.6 pg/mL (162.3 fmol/mL), 647.5 pg/mL (187.1 fmol/mL), 745.6 pg/mL (215.5 fmol/mL), and 850.7 pg/mL (245.8 fmol/mL) for those with CHF and 85.4 pg/mL (24.7 fmol/mL), 131.7 pg/mL (38.1 fmol/mL), 297.2 pg/mL (85.9 fmol/mL), and 285.0 pg/mL (82.3 fmol/mL) for those without CHF in eGFR categories of 90 or greater, 89 to 60, 59 to 30, and less than 30 mL/min/1.73 m2, respectively. The area under the receiver operating characteristic curve and optimum cut points for BNP were 0.91 and 70.7 pg/mL (20.4 fmol/mL), 0.90 and 104.3 pg/mL (30.1 fmol/mL), 0.81 and 201.2 pg/mL (58.1 fmol/mL), and 0.86 and 225.0 pg/mL (65.0 fmol/mL) for the eGFR categories of 90 or greater, 89 to 60, 59 to 30, and less than 30 mL/min/1.73 m2, respectively. CONCLUSION: Renal function correlates weakly with BNP and influences the optimal cut point for BNP, particularly in those with an eGFR less than 60 mL/min/1.73 m2. Krumholz HM, Chen YT, Bradford WD, Cerese J. Variations in and correlates of length of stay in academic hospitals among patients with heart failure resulting from systolic dysfunction. Am J Manag Care. 1999 Jun;5(6):715-23. clicca qui per andare su PUBMED Comment in: Weintraub WS, Deaton C. Variation in length of stay in patients hospitalized with congestive heart failure. Am J Manag Care. 1999 Jun;5(6):800-2. clicca qui per andare su PUBMED Yale University School of Medicine, New Haven, CT, USA. harlan.krumholz@yale.edu OBJECTIVE: Given the high cost of caring for patients with congestive heart failure, there are strong incentives to decrease hospital costs by shortening length of hospital stay. We sought to identify factors associated with length of stay among patients admitted for the treatment of heart failure resulting from systolic dysfunction. STUDY DESIGN: Retrospective cohort study. METHODS: We examined data from patients with a principal discharge diagnosis of congestive heart failure who had been admitted to 1 of the 49 academic hospitals across the United States that participated in the CHF Benchmark Project, a large collaborative quality improvement project coordinated by the University HealthSystem Consortium. Patients were discharged between January 1 and June 30, 1996. We obtained patient characteristics and hospitalization data by retrospectively reviewing medical records. We used linear regression models to identify major determinants of length of stay. RESULTS: Among the 1046 patients eligible for the study, 59% were women, 55% were white, and 58% were aged 65 years or older. Adjusting for patient demographic and admission clinical
  12. 12. characteristics, the mean length of stay was 4.9 +/- 0.9 days. Length of stay varied significantly among hospitals, even after adjusting for differences in patient characteristics. In multivariate regression models, factors that were independently associated with a significantly longer length of stay were prior renal failure, peripheral edema, atrial fibrillation, hyponatremia, urinary catheter on admission, initiation of an antiarrhythmic or warfarin, and major complications. Patient characteristics and hospital events combined explained 16% of the variation in the length of stay. Adjusting for the individual hospitals explained an additional 10% of the variation in the length of stay. CONCLUSIONS: Although a number of patient and hospitalization factors were associated with length of stay in patients with congestive heart failure resulting from systolic dysfunction, much unexplained variation remained. Clinical factors alone explained about 50% more variation than did factors specific to the individual hospitals. Aronson D, Mittleman MA, Burger AJ. Elevated blood urea nitrogen level as a predictor of mortality in patients admitted for decompensated heart failure. Am J Med. 2004 Apr 1;116(7):466-73. clicca qui per andare su PUBMED Division of Cardiology, Rambam Medical Center, Haifa, Israel. BACKGROUND: Hospitalization for decompensated heart failure is associated with high mortality after discharge. In heart failure, renal function involves both cardiovascular and hemodynamic properties. We studied the relation between renal dysfunction and mortality in patients admitted for decompensated heart failure. METHODS: The prognostic importance of four measures of renal function-blood urea nitrogen, serum creatinine, blood urea nitrogen/creatinine ratio, and estimated creatinine clearance-was evaluated in 541 patients (mean [+/- SD] age, 63 +/- 14 years; 377 men [70%]) with a previous diagnosis of heart failure (96% with New York Heart Association class III or IV symptoms) who were admitted for clinical decompensation. RESULTS: During a mean follow-up of 343 +/- 185 days, 177 patients (33%) died. In multivariable Cox regression models, the risk of all-cause mortality increased with each quartile of blood urea nitrogen, with an adjusted relative risk of 2.3 in patients in the upper compared with the lower quartiles (95% confidence interval [CI]: 1.3 to 4.1; P = 0.005). Creatinine and estimated creatinine clearance were not significant predictors of mortality after adjustment for other covariates. Blood urea nitrogen/creatinine ratio yielded similar prognostic information as blood urea nitrogen (adjusted relative risk = 2.3; 95% CI: 1.4 to 3.8; P = 0.0007 for patients in the upper compared with the lower quartiles). CONCLUSION: Blood urea nitrogen is a simple clinical variable that provides useful prognostic information in patients admitted for decompensated heart failure. In this setting, elevated blood urea nitrogen levels probably reflect the cumulative effects of hemodynamic and neurohormonal alterations that result in renal hypoperfusion. Brophy JM, Dagenais GR, McSherry F, Williford W, Yusuf S. A multivariate model for predicting mortality in patients with heart failure and
  13. 13. systolic dysfunction. Am J Med. 2004 Mar 1;116(5):300-4. clicca qui per andare su PUBMED Division of Cardiology and Clinical Epidemiology, McGill University Health Center, Montreal, Quebec, Canada. jbroph@po-box.mcgill.ca BACKGROUND: Heart failure is a leading cause of morbidity and mortality, but there are no reliable models based on readily available clinical variables to predict outcomes in patients taking angiotensin-converting enzyme (ACE) inhibitors. METHODS: A multivariate statistical model to predict mortality was developed in a random sample (n = 4277 patients [67%]) of the 6422 patients enrolled in the Digitalis Investigation Group trial who had a depressed ejection fraction (<or=45%), were in sinus rhythm, and were taking ACE inhibitors. The model was then validated in the remaining 2145 patients. RESULTS: Total mortality in the derivation sample was 11.2% (n = 480) at 12 months and 29.9% (n = 1277) at 36 months. Lower ejection fraction, worse renal function, cardiomegaly, worse functional class, signs or symptoms of heart failure, lower blood pressure, and lower body mass index were associated with reduced 12-month survival. This model provided good predictions of mortality in the verification sample. The same variables, along with age and the baseline use of nitrates, were also predictive of 36-month mortality. CONCLUSION: Routine clinical variables can be used to predict short- and long-term mortality in patients with heart failure and systolic dysfunction who are treated with ACE inhibitors. Marenzi G, Lauri G, Guazzi M, Assanelli E, Grazi M, Famoso G, Agostoni P. Cardiac and renal dysfunction in chronic heart failure: relation to neurohumoral activation and prognosis. Am J Med Sci. 2001 Jun;321(6):359-66. clicca qui per andare su PUBMED IRCCS, Institute of Cardiology, University of Milan, Italy. giancarlo.marenzi@cardiologicomonzino.it BACKGROUND: In chronic heart failure (CHF), cardiac dysfunction is considered the major determinant of neurohumoral activation but the role of renal impairment has not been defined. We investigated the relationship between both cardiac and renal dysfunction and neurohumoral activation, and their possible influence on prognosis. METHODS: Hemodynamics, renal function, plasma neurohormones, and long-term follow-up were evaluated in 148 CHF patients, grouped according to systolic volume index (SVI) and serum creatinine (CRE) values: SVI > 28 mL/m2 and CRE < 1.5 mg/dL (group I, n = 55), SVI < 28 mL/m2 and CRE < 1.5 mg/dL (group II, n = 37), SVI > 28 mL/m2 and CRE > 1.5 mg/dL (group III, n = 25), SVI < 28 mL/m2 and CRE > 1.5 mg/dL (group IV, n = 31). RESULTS: Neurohormones progressively increased from Group I through IV and correlated with both cardiac and renal function. The hemodynamic pattern was similar in patients with normal or abnormal renal function, whereas neurohormones were only
  14. 14. moderately increased in the former group and markedly increased in the latter group. Long-term survival progressively decreased from Group I through IV and was significantly poorer in patients with renal dysfunction. CONCLUSIONS: Our study confirms that, in CHF, neurohumoral activation is strictly related to long-term survival and that many factors contribute to its development and progression; among these, cardiac and renal dysfunction seem to play a major role. Massie BM, Armstrong PW, Cleland JG, Horowitz JD, Packer M, Poole-Wilson PA, Ryden L. Toleration of high doses of angiotensin-converting enzyme inhibitors in patients with chronic heart failure: results from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival. Arch Intern Med. 2001 Jan 22;161(2):165-71. clicca qui per andare su PUBMED Department of Medicine, University of California-San Francisco and the Department of Veterans Affairs Medical Center, USA. Barry.Massie@med.va.gov BACKGROUND: Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high- compared with low-dose lisinopril in CHF. METHODS: The Assessment of Lisinopril and Survival study was a multicenter, randomized, double-blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium-dose lisinopril (12.5 or 15.0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0.30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction. RESULTS: Of 405 patients not previously receiving an ACE inhibitor, doses in only 4.2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2.0%) or because of renal dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients in the high- and low-dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, <120 mm Hg; creatinine, > or =132.6 micromol/L [> or =1.5 mg/dL]; age, > or =70 years; and patients with diabetes) generally tolerated the high-dose strategy. CONCLUSIONS: These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted.
  15. 15. McAlister FA, Ezekowitz J, Tonelli M, Armstrong PW. Renal insufficiency and heart failure: prognostic and therapeutic implications from a prospective cohort study. Circulation. 2004 Mar 2;109(8):1004-9. Epub 2004 Feb 09. clicca qui per andare su PUBMED Division of General Internal Medicine, University of Alberta, Edmonton, Canada. Finlay.McAlister@ualberta.ca BACKGROUND: The prevalence, prognostic import, and impact of renal insufficiency on the benefits of ACE inhibitors and beta-blockers in community-dwelling patients with heart failure are uncertain. METHODS AND RESULTS: We analyzed data from a prospective cohort of 754 patients with heart failure who had ejection fraction, serum creatinine, and weight measured at baseline. Median age was 69 years, and 43% had an ejection fraction > or =35%. By the Cockcroft-Gault equation, 118 patients (16%) had creatinine clearances < or =30 mL/min and 301 (40%) had creatinine clearances between 30 and 59 mL/min. During follow-up (median 926 days), 385 patients (37%) died. Even after adjustment for all other prognostic factors, survival was significantly associated with renal function (P=0.002) in patients with either systolic or diastolic dysfunction; patients exhibited a 1% increase in mortality for each 1-mL/min decrease in creatinine clearance. The associations with 1-year mortality reductions were similar for ACE inhibitors (OR 0.46 [95% CI 0.26 to 0.82] versus OR 0.28 [95% CI 0.11 to 0.70]) and beta-blockers (OR 0.40 [95% CI 0.23 to 0.70] versus OR 0.41 [95% CI 0.19 to 0.85]) in patients with creatinine clearances <60 mL/min versus > or =60 mL/min, although these drugs were used less frequently in patients with renal insufficiency. CONCLUSIONS: Renal insufficiency is more prevalent in patients with heart failure than previously reported and is an independent prognostic factor in diastolic and systolic dysfunction. ACE inhibitors and beta-blockers were associated with similar reductions in mortality in patients with and without renal insufficiency. Arnold JM, Yusuf S, Young J, Mathew J, Johnstone D, Avezum A, Lonn E, Pogue J, Bosch J; HOPE Investigators. Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation. 2003 Mar 11;107(9):1284-90 London Health Sciences Centre, London, Canada. malcolm.arnold@lhsc.on.ca BACKGROUND: Previous trials in the prevention of heart failure have been restricted to patients with low ejection fraction or hypertension. We assessed an angiotensin-converting enzyme (ACE) inhibitor, ramipril, to prevent the development of heart failure in high-risk patients without known low ejection fraction or heart failure. METHODS AND RESULTS: We randomly assigned 9297 patients to receive double-blind ramipril (10 mg daily) or matching placebo for 4.5 years. Death attributable to heart failure, hospitalization for heart failure, initiation of open-label ACE inhibitor for heart failure, or development of typical signs or symptoms of heart failure developed in 951 patients and was associated with a 4.01-fold increase in the risk of death
  16. 16. (P<0.0001). The rate of developing heart failure was significantly increased with coronary disease (risk ratio, 2.17), microalbuminuria (1.82), left ventricular hypertrophy (1.47), increasing age (by decade, 1.37), and diabetes (1.36). Ramipril reduced new-onset heart failure rate from 11.5% to 9.0% (relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.0001). Ramipril consistently reduced heart failure rate both in those with (relative risk, 0.87) and those without an interim myocardial infarction (relative risk, 0.78). Ramipril also reduced the heart failure rate more in patients with baseline systolic pressure above the median (139 mm Hg) (relative risk, 0.67) compared with those below the median (relative risk, 0.91; P=0.024 for interaction of group by treatment). CONCLUSION: Ramipril significantly reduces the rate of development of heart failure in patients at high risk of cardiovascular events. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW; American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003 Oct 28;108(17):2154-69 Schoolwerth AC, Sica DA, Ballermann BJ, Wilcox CS; Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation. 2001 Oct 16;104(16):1985-91 Hillege HL, Girbes AR, de Kam PJ, Boomsma F, de Zeeuw D, Charlesworth A, Hampton JR, van Veldhuisen DJ. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation. 2000 Jul 11;102(2):203-10. Department of Clinical Pharmacology, State University Groningen, The Netherlands. BACKGROUND: Because renal function is affected by chronic heart failure (CHF) and it relates to both cardiovascular and hemodynamic properties, it should have additional prognostic value. We studied whether renal function is a predictor for mortality in advanced CHF, and we assessed its relative contribution
  17. 17. compared with other established risk factors. In addition, we studied the relation between renal function and neurohormonal activation. METHODS AND RESULTS: The study population consisted of 1906 patients with CHF who were enrolled in a recent survival trial (Second Prospective Randomized study of Ibopamine on Mortality and Efficacy). In a subgroup of 372 patients, plasma neurohormones were determined. The baseline glomerular filtration rate (GFR(c)) was calculated using the Cockroft Gault equation. GFR(c) was the most powerful predictor of mortality; it was followed by New York Heart Association functional class and the use of angiotensin-converting enzyme inhibitors. Patients in the lowest quartile of GFR(c) values (<44 mL/min) had almost 3 times the risk of mortality (relative risk, 2. 85; P<0.001) of patients in the highest quartile (>76 mL/min). Impaired left ventricular ejection fraction (LVEF) was only modestly predictive (P=0.053). GFR(c) was inversely related with N-terminal atrial natriuretic peptide (ANP; r=-0.53) and, to a lesser extent, with ANP itself (r=-0.35; both P<0.001). CONCLUSIONS: Impaired renal function (GFR(c)) is a stronger predictor of mortality than impaired cardiac function (LVEF and New York Heart Association class) in advanced CHF, and it is associated with increased levels of N-terminal ANP. Moreover, impaired renal function was not related to LVEF, which suggests that factors other than reduced cardiac output are causally involved. Middlekauff HR, Nitzsche EU, Hoh CK, Hamilton MA, Fonarow GC, Hage A, Moriguchi JD. Exaggerated renal vasoconstriction during exercise in heart failure patients. Circulation. 2000 Feb 22;101(7):784-9. Division of Cardiology, Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095, USA. BACKGROUND: During static exercise in normal healthy humans, reflex renal cortical vasoconstriction occurs. Muscle metaboreceptors contribute importantly to this reflex renal vasoconstriction. In patients with heart failure, in whom renal vascular tone is already increased at rest, it is unknown whether there is further reflex renal vasoconstriction during exercise. METHODS AND RESULTS: Thirty-nine heart failure patients (NYHA functional class III and IV) and 38 age-matched control subjects (controls) were studied. Renal blood flow was measured by dynamic positron emission tomography. Graded handgrip exercise and post-handgrip ischemic arrest were used to clarify the reflex mechanisms involved. During sustained handgrip (30% maximum voluntary contraction), peak renal vasoconstriction was significantly increased in heart failure patients compared with controls (70+/-13 versus 42+/-1 U, P=0.02). Renal vasoconstriction returned to baseline in normal humans by 2 to 5 minutes but remained significantly increased in heart failure patients at 2 to 5 minutes and had returned to baseline at 20 minutes. In contrast, during post-handgrip circulatory arrest, which isolates muscle metaboreceptors, peak renal vasoconstriction was not greater in heart failure patients than in normal controls. In fact, the increase in renal vasoconstriction was blunted in heart failure patients compared with controls (20+/-5 versus 30+/-2 U, P=0.05). CONCLUSIONS: During sustained handgrip exercise in heart failure, both the magnitude and duration of reflex renal vasoconstriction are exaggerated in heart failure patients compared with normal healthy humans. The contribution of the muscle metaboreceptors to reflex renal vasoconstriction is blunted in heart failure patients compared with normal controls.
  18. 18. Silverberg DS, Wexler D, Blum M, Tchebiner J, Sheps D, Keren G, Schwartz D, Baruch R, Yachnin T, Shaked M, Zubkov A, Steinbruch S, Iaina A. The correction of anemia in severe resistant heart failure with erythropoietin and intravenous iron prevents the progression of both the heart and the renal failure and markedly reduces hospitalization. Clin Nephrol. 2002 Jul;58 Suppl 1:S37-45. clicca qui per andare su PUBMED Department of Nephrology and Cardiology, Tel Aviv Medical Center, Israel. donald@netvision.net.il Both Congestive Heart Failure (CHF) and Chronic Renal Failure (CRF) are increasing steadily in the community. We propose that there is a vicious circle established whereby CHF and CRF both cause anemia and the anemia then worsens both the CHF and CRF causing more anemia and so on. We call this the Cardio Renal Anemia (CRA) syndrome. By the combination of active treatment of the CHF and control of the anemia with subcutaneous erythropoietin and intravenous iron, the progression of both the CHF and the CRF can be slowed or stopped in most cases, the quality of life improved and the need for recurrent hospitalization reduced. This will involve cooperation between internists, cardiologists, and nephrologists to allow early and maximal therapy of both the CHF and the anemia. Capes SE, Gerstein HC, Negassa A, Yusuf S. Enalapril prevents clinical proteinuria in diabetic patients with low ejection fraction. Diabetes Care. 2000 Mar;23(3):377-80. Department of Medicine, McMaster University, Hamilton, Ontario, Canada. scapes@fhs.csu.mcmaster.ca OBJECTIVE: Clinical proteinuria is a risk factor for both end-stage renal disease and cardiovascular disease. The prevalence of clinical proteinuria, its correlates and predictive value, and the effect of ACE inhibitors in preventing clinical proteinuria in diabetic and nondiabetic patients with left ventricular (LV) dysfunction are unknown. RESEARCH DESIGN AND METHODS: The Studies of Left Ventricular Dysfunction (SOLVD) trials were analyzed to determine the baseline distribution of clinical proteinuria and related cardiovascular risk factors, the effect of baseline proteinuria on the risk of hospitalization for congestive
  19. 19. heart failure (CHF) and mortality, and the effect of enalapril in preventing new clinical proteinuria. RESULTS: A total of 5,487 out of 6,797 SOLVD participants (81%) were assessed for proteinuria at baseline. A total of 177 patients (3.2%) had baseline proteinuria. These patients had significantly higher systolic (137 vs. 125 mmHg, P < or = 0.001) and diastolic (83 vs. 77 mmHg, P < or = 0.001) blood pressure levels, a higher prevalence of diabetes (41 vs. 18%, P < or = 0.001), a lower ejection fraction (26.2 vs. 27.3%, P < or = 0.05), and greater degree of CHF (New York Heart Association [NYHA] class III/IV in 22 vs. 10%, P < or = 0.001) than patients without baseline proteinuria. Patients with baseline proteinuria also had higher rates of hospitalization for CHF (relative risk 1.81 [95% CI 1.37-2.41], P = 0.0001) and mortality (1.73 [1.34-2.24], P = 0.0001). Enalapril prevented clinical proteinuria in diabetic patients (0.38 [0.17-0.81], P = 0.0123) but not in nondiabetic patients (1.43 [0.77-2.63], P = 0.2622) without baseline proteinuria. CONCLUSIONS: Clinical proteinuria is an independent predictor of hospitalization for CHF and mortality in diabetic and nondiabetic patients with LV dysfunction. Enalapril significantly reduces the risk of clinical proteinuria in diabetic patients with LV dysfunction. Komajda M, Follath F, Swedberg K, Cleland J, Aguilar JC, Cohen-Solal A, Dietz R, Gavazzi A, Van Gilst WH, Hobbs R, Korewicki J, Madeira HC, Moiseyev VS, Preda I, Widimsky J, Freemantle N, Eastaugh J, Mason J; Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology. The EuroHeart Failure Survey programme--a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Heart J. 2003 Mar;24(5):464-74. clicca qui per andare su PUBMED BACKGROUND: National surveys suggest that treatment of heart failure in daily practice differs from guidelines and is characterized by underuse of recommended medications. Accordingly, the Euro Heart Failure Survey was conducted to ascertain how patients hospitalized for heart failure are managed in Europe and if national variations occur in the treatment of this condition. METHODS: The survey screened discharge summaries of 11304 patients over a 6-week period in 115 hospitals from 24 countries belonging to the ESC to study their medical treatment. RESULTS: Diuretics (mainly loop diuretics) were prescribed in 86.9% followed by ACE inhibitors (61.8%), beta-blockers (36.9%), cardiac glycosides (35.7%), nitrates (32.1%), calcium channel blockers (21.2%) and spironolactone (20.5%). 44.6% of the population used four or more different drugs. Only 17.2% were under the combination of diuretic, ACE inhibitors and beta-blockers. Important local variations were found in the rate of prescription of ACE inhibitors and particularly beta-blockers. Daily dosage of ACE inhibitors and particularly of beta-blockers was on average below the recommended target dose. Modelling-analysis of the prescription of treatments indicated that the aetiology of heart failure, age, co-morbid factors and type of hospital ward influenced the rate of prescription. Age <70 years, male gender and ischaemic aetiology were associated with an increased odds ratio for receiving an ACE
  20. 20. inhibitor. Prescription of ACE inhibitors was also greater in diabetic patients and in patients with low ejection fraction (<40%) and lower in patients with renal dysfunction. The odds ratio for receiving a beta-blocker was reduced in patients >70 years, in patients with respiratory disease and increased in cardiology wards, in ischaemic heart failure and in male subjects. Prescription of cardiac glycosides was significantly increased in patients with supraventricular tachycardia/atrial fibrillation. Finally, the rate of prescription of antithrombotic agents was increased in the presence of supraventricular arrhythmia, ischaemic heart disease, male subjects but was decreased in patients over 70. CONCLUSION: Our results suggest that the prescription of recommended medications including ACE inhibitors and beta-blockers remains limited and that the daily dosage remains low, particularly for beta-blockers. The survey also identifies several important factors including age, gender, type of hospital ward, co morbid factors which influence the prescription of heart failure medication at discharge. Hillege HL, van Gilst WH, van Veldhuisen DJ, Navis G, Grobbee DE, de Graeff PA, de Zeeuw D; CATS Randomized Trial. Accelerated decline and prognostic impact of renal function after myocardial infarction and the benefits of ACE inhibition: the CATS randomized trial. Eur Heart J. 2003 Mar;24(5):412-20. clicca qui per andare su PUBMED Comment in: Mann JF, Dulau-Florea I, Franke J. Looking for people at high cardiovascular risk? Look at serum-creatinine Eur Heart J. 2003 Mar;24(5):381-3. clicca qui per andare su PUBMED Department of Cardiology/Thoraxcenter, University Hospital Groningen, Hanzeplein 1, 9700 Groningen, The Netherlands. h.hillege@tcc.azg.nl AIMS: Information regarding the cardiorenal axis in patients after a myocardial infarction (MI) is limited. We examined the change in renal function after a first MI, the protective effect of angiotensin converting enzyme (ACE) inhibition and the prognostic value of baseline renal function. METHODS AND RESULTS: The study population consisted of 298 patients with a first anterior wall MI who were randomized to the ACE inhibitor captopril or placebo after completion of streptokinase infusion. Renal function, by means of glomerular filtration rate (GFR), was calculated using the Cockroft-Gault equation (GFR(c)). In the placebo group, renal function (GFR(c)) declined by 5.5 min(-1)within 1 year, vs only 0.5 ml min(-1)in the ACE inhibitor group (P<0.05). This beneficial effect of captopril was most pronounced in patients with the most compromised renal function at baseline. The incidence of chronic heart failure (CHF) within 1 year increased significantly with decreasing GFR(c)(divided into tertiles: 24.0, 28.9, and 41.2%; P<0.01). The risk-ratio for GFR(c)<81 ml min(-1)vs >103 mL min(-1)was 1.86 (95% CI 1.11-3.13; P=0.019). CONCLUSIONS: Renal function markedly deteriorates after a first MI, but is significantly preserved by ACE inhibition. Furthermore, an impaired baseline renal function adds to the prognostic risk of developing CHF in patients after a first anterior MI.
  21. 21. Maxwell AP, Ong HY, Nicholls DP. Influence of progressive renal dysfunction in chronic heart failure. Eur J Heart Fail. 2002 Mar;4(2):125-30. clicca qui per andare su PUBMED Regional Nephrology Unit, Belfast City Hospital, Northern Ireland, Belfast, UK. Chronic heart failure (CHF) is often associated with impaired renal function due to hypoperfusion. Such patients are very sensitive to changes in renal perfusion pressure, and may develop acute tubular necrosis if the pressure falls too far. The situation is complicated by the use of diuretics, ACE inhibitors and spironolactone, all of which may affect renal function and potassium balance. Chronic renal failure (CRF) may also be associated with fluid overload. Anaemia and hypertension in CRF contribute to the development of left ventricular hypertrophy (LVH), which carries a poor prognosis, so correction of these factors is important. Bouvy ML, Heerdink ER, Leufkens HG, Hoes AW. Predicting mortality in patients with heart failure: a pragmatic approach. Heart. 2003 Jun;89(6):605-9. clicca qui per andare su PUBMED Comment in: Cowie MR. Estimating prognosis in heart failure: time for a better approach. Heart. 2003 Jun;89(6):587-8. clicca qui per andare su PUBMED Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, Netherlands. m.bouvy@pharm.uu.nl OBJECTIVE: To develop a comprehensive and easily applicable prognostic model predicting mortality risk in patients with moderate to severe heart failure. DESIGN: Prospective follow up study. SETTING: Seven general hospitals in the Netherlands. PATIENTS: 152 outpatients with heart failure or patients admitted to hospital because of heart failure, who were included in a randomised trial to assess the impact of a pharmacist led intervention to improve drug compliance. Duration of follow up was at least 18 months. MAIN OUTCOME MEASURES: Multivariable logistic regression modelling was used to evaluate information from history, physical examination (for example, blood pressure), drug use, and quality of life questionnaires that independently contributed to the prediction of death. The area under receiver operating characteristic curves (AUC) was used
  22. 22. to estimate the predictive ability of the prognostic models. RESULTS: During the 18 months of follow up, 51 patients (34%) died. Independent predictors of mortality were diabetes mellitus, a history of renal dysfunction (or higher creatinine), New York Heart Association (NYHA) functional class III or IV, lower weight or body mass index, lower blood pressure, ankle oedema, and higher scores on a disease specific quality of life questionnaire. The use of beta blockers was predictive of a better prognosis. These factors were used to derive various prediction formulas. A model based on medical history, weight, presence of oedema, and lower blood pressure had an AUC of 0.77. Addition of use of beta blockers to this model improved the AUC to 0.80. Addition of NYHA class increased the AUC to 0.84. Data on quality of life did not improve the AUC further (AUC 0.85). CONCLUSIONS: A prognostic model produced on the basis of easily obtainable information from medical history and physical examination can adequately stratify heart failure patients according to their short term risk of death. Juenger J, Schellberg D, Kraemer S, Haunstetter A, Zugck C, Herzog W, Haass M. Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables. Heart. 2002 Mar;87(3):235-41. clicca qui per andare su PUBMED Departments of General Internal and Psychosomatic Medicine, University of Heidelberg, Heidelberg, Germany. jana_juenger@med.uni-heidelberg.de OBJECTIVE: To assess health related quality of life of patients with congestive heart failure; to compare their quality of life with the previously characterised general population and in those with other chronic diseases; and to correlate the different aspects of quality of life with relevant somatic variables. SETTING: University hospital. PATIENTS AND DESIGN: A German version of the generic quality of life measure (SF-36) containing eight dimensions was administered to 205 patients with congestive heart failure and systolic dysfunction. Cardiopulmonary evaluation included assessment of New York Heart Association (NYHA) functional class, left ventricular ejection fraction, peak oxygen uptake, and the distance covered during a standardised six minute walk test. RESULTS: Quality of life significantly decreased with NYHA functional class (linear trend: p < 0.0001). In NYHA class III, the scores of five of the eight quality of life domains were reduced to around one third of those in the general population. The pattern of reduction was different in patients with chronic hepatitis C and major depression, and similar in patients on chronic haemodialysis. Multiple regression analysis showed that only the NYHA functional class was consistently and closely associated with all quality of life scales. The six minute walk test and peak oxygen uptake added to the explanation of the variance in only one of the eight quality of life domains (physical functioning). Left ventricular ejection fraction, duration of disease, and age showed no clear association with quality of life. CONCLUSIONS: In congestive heart failure, quality of life decreases as NYHA functional class worsens. Though NYHA functional class was the most dominant predictor among the somatic variables studied, the major determinants of reduced quality of life remain unknown.
  23. 23. Silverberg DS, Wexler D, Blum M, Schwartz D, Keren G, Sheps D, Iaina A Effect of correction of anemia with erythropoietin and intravenous iron in resistant heart failure in octogenarians. Isr Med Assoc J. 2003 May;5(5):337-9. clicca qui per andare su PUBMED Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. donald@netvision.net.il BACKGROUND: Congestive heart failure is extremely common in octogenarians and is associated with severe fatigue, shortness of breath, recurrent hospitalizations, and death. These patients, many of whom are anemic, are often resistant to standard CHF therapy including angiotensin-converting enzyme inhibitors, beta-blockers and diuretics. OBJECTIVES: To examine whether correction of the anemia (hemoglobin < 12 g/dl) in CHF patients can improve their clinical condition. METHODS: Forty octogenarians with anemia and severe resistant CHF were administered a combination of subcutaneous erythropoietin and intravenous iron sucrose. RESULTS: This combination therapy led to a marked improvement in cardiac function, shortness of breath and fatigue, a marked reduction in the rate of hospitalization and a stabilizing of renal function. CONCLUSION: Anemia appears to be an important but ignored contributor to the progression of CHF, and its correction may improve cardiac and renal status as well as the quality of life in elderly patients. Troughton RW, Prior DL, Pereira JJ, Martin M, Fogarty A, Morehead A, Yandle TG, Richards AM, Starling RC, Young JB, Thomas JD, Klein AL. Plasma B-type natriuretic peptide levels in systolic heart failure: importance of left ventricular diastolic function and right ventricular systolic function. J Am Coll Cardiol. 2004 Feb 4;43(3):416-22. clicca qui per andare su PUBMED Department of Cardiovascular Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. OBJECTIVES: This study was designed to characterize the importance of echocardiographic indexes, including newer indexes of diastolic function, as determinants of plasma B-type natriuretic peptide (BNP) levels in patients with systolic heart failure (SHF). BACKGROUND: Plasma BNP levels have utility for diagnosing and managing heart failure. However, there is significant heterogeneity in BNP levels that is not explained by left ventricular size and function alone. METHODS: In 106 patients with symptomatic SHF (left ventricular ejection fraction [LVEF] <0.35), we measured plasma BNP levels and performed comprehensive echocardiography with assessment of left ventricular diastolic function, including color M-mode (CMM) and tissue Doppler imaging (TDI), and of right ventricular (RV) function. RESULTS: Median plasma BNP levels were elevated and increased with greater severity of diastolic dysfunction. We found significant correlations (p < 0.001 for all) between BNP and indexes of myocardial relaxation (early diastolic velocity: r = -0.26), compliance (deceleration time: r = -0.55), and filling pressure (early transmitral to early
  24. 24. annular diastolic velocity ratio: r = 0.51; early transmitral flow to the velocity of early left ventricular flow propagation ratio: r = 0.41). In multivariate analysis, overall diastolic stage, LVEF, RV systolic dysfunction, mitral regurgitation (MR) severity, age and creatinine clearance were independent predictors of BNP levels (model fit r = 0.8, p < 0.001). CONCLUSIONS: Plasma BNP levels are significantly related to newer diastolic indexes measured from TDI and CMM in SHF. Heterogeneity of BNP levels in patients with SHF reflects the severity of diastolic abnormality, RV dysfunction, and MR in addition to LVEF, age, and renal function. These findings may explain the powerful relationship of BNP to symptoms and prognosis in SHF. Forman DE, Butler J, Wang Y, Abraham WT, O'Connor CM, Gottlieb SS, Loh E, Massie BM, Rich MW, Stevenson LW, Young JB, Krumholz HM. Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol. 2004 Jan 7;43(1):61-7. clicca qui per andare su PUBMED Section of Cardiology, Boston Medical Center, Boston, Massachusetts 02188, USA. Daniel.Forman@bmc.org OBJECTIVES: The goal of this study was to determine the prevalence of worsening renal function (WRF) among hospitalized heart failure (HF) patients, clinical predictors of WRF, and hospital outcomes associated with WRF. BACKGROUND: Impaired renal function is associated with poor outcomes among chronic HF patients. METHODS: Chart reviews were performed on 1,004 consecutive patients admitted for a primary diagnosis of HF from 11 geographically diverse hospitals. Cox regression model analysis was used to identify independent predictors for WRF, defined as a rise in serum creatinine of >0.3 mg/dl (26.5 micromol/l). Bivariate analysis was used to determine associations of development of WRF with outcomes (in-hospital death, in-hospital complications, and length of stay). RESULTS: Among 1,004 HF patients studied, WRF developed in 27%. In the majority of cases, WRF occurred within three days of admission. History of HF or diabetes mellitus, admission creatinine > or =1.5 mg/dl (132.6 micromol/l), and systolic blood pressure >160 mm Hg were independently associated with higher risk of WRF. A point score based on these characteristics and their relative risk ratios predicted those at risk for WRF. Hospital deaths (adjusted risk ratio [ARR] 7.5; 95% confidence intervals [CI] 2.9, 19.3), complications (ARR 2.1; CI 1.5, 3.0), and length of hospitalizations >10 days (ARR 3.2, CI 2.2, 4.9) were greater among patients with WRF. CONCLUSIONS: Worsening renal function occurs frequently among hospitalized HF patients and is associated with significantly worse outcomes. Clinical characteristics available at hospital admission can be used to identify patients at increased risk for developing WRF. Gibson CM, Pinto DS, Murphy SA, Morrow DA, Hobbach HP, Wiviott SD, Giugliano RP, Cannon CP, Antman EM, Braunwald E; TIMI Study Group. Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality. J Am Coll Cardiol. 2003 Nov 5;42(9):1535-43. clicca qui per andare su PUBMED TIMI Study Chairman's Office, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. mgibson@tini.org Comment in: French WJ, Wright RS. Renal insufficiency and worsened prognosis with STEMI: a call for action. J Am Coll Cardiol. 2003 Nov 5;42(9):1544-6. clicca qui per andare su PUBMED
  25. 25. OBJECTIVES: We hypothesized that impaired renal function would also be associated with poorer clinical outcomes among patients with ST-segment elevation myocardial infarction (STEMI) treated with fibrinolysis. BACKGROUND: Previous studies have demonstrated that impaired renal function is associated with poorer clinical outcomes in the setting of unstable angina and non-STEMI and after percutaneous coronary intervention. METHODS: Data were drawn from the Thrombolysis In Myocardial Infarction (TIMI)-10, TIMI-14, and Intravenous nPA for the Treatment of Infarcting Myocardium Early (InTIME-II) trials. RESULTS: Within each TIMI risk score (TRS) for STEMI category (0 to 2, 3 to 4, >/=5), 30-day mortality increased stepwise among patients with normal (creatinine [Cr] </=1.2 mg/dl), mildly (Cr >1.2 to 2 mg/dl), and severely (Cr >2.0 mg/dl) impaired renal function (p < 0.001) and in patients with normal (creatinine clearance [CrCl] >/=90 ml/min), mildly (60 to <90 ml/min), moderately (30 to <60 ml/min), and severely (<30 ml/min) impaired CrCl (p < 0.001). Impaired renal function was associated with increased mortality after adjusting for previously identified correlates of mortality (using Cr: odds ratio [OR] for mild impairment 1.52, 95% confidence interval [CI] 1.30 to 1.77, p < 0.001; OR for severe impairment 3.73, 95% CI 2.55 to 5.45, p < 0.001; using CrCl: OR for mild impairment 1.38, 95% CI 1.10 to 1.73, p = 0.006; OR for moderate impairment 2.06, 95% CI 1.59 to 2.66, p < 0.001; OR for severe impairment 3.81, 95% CI 2.57 to 5.65, p < 0.001). CONCLUSIONS: In the setting of STEMI, elevated Cr and/or impaired CrCl on presentation is associated with increased mortality, independent of other conventional risk factors and TRS. This association does not appear to be mediated by reduced fibrinolytic efficacy among patients with impaired renal function or by the presence of congestive heart failure on presentation. Kittleson M, Hurwitz S, Shah MR, Nohria A, Lewis E, Givertz M, Fang J, Jarcho J, Mudge G, Stevenson LW. Development of circulatory-renal limitations to angiotensin-converting enzyme inhibitors identifies patients with severe heart failure and early mortality. J Am Coll Cardiol. 2003 Jun 4;41(11):2029-35. clicca qui per andare su PUBMED Departments of Medicine and Cardiology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. OBJECTIVES: This study examined the hypothesis that patients who develop angiotensin-converting enzyme inhibitor intolerance attributable to circulatory-renal limitations (CRLimit) have more severe underlying disease and worse outcome. BACKGROUND: Although the renin-angiotensin system contributes to the progression of heart failure (HF), it also supports the failing circulation. Patients with the most severe disease may not tolerate inhibition of this system. METHODS: Consecutive inpatient admissions to the cardiomyopathy service of the Brigham and Women's Hospital between 2000 and 2002 were reviewed retrospectively for initial profiles, discharge medications, and documented reasons for discontinuation of angiotensin-converting enzyme inhibitors. Outcomes of death and transplantation were determined. RESULTS: Of the 259 patients, 86 were not on an angiotensin-converting enzyme inhibitor at discharge. Circulatory-renal limitations of symptomatic hypotension, progressive renal dysfunction, or hyperkalemia were documented in 60 patients (23%); other adverse effects, including cough, in 24 patients; and absent reasons in 2 patients. Compared with patients on angiotensin-converting enzyme inhibitors, patients with CRLimit were older (60 vs. 55 years; p = 0.006), with longer history of HF (5 vs. 2 years; p = 0.009), lower systolic blood pressure (104 vs. 110 mm Hg; p = 0.05), lower sodium (135 vs. 138 mEql/l; p = 0.002), and higher initial creatinine (2.5 vs. 1.2 mg/dl; p = 0.0001). Mortality was 57% in patients with CRLimit and 22% in the patients on angiotensin-converting enzyme
  26. 26. inhibitors during a median 8.5-month follow-up (p = 0.0001). CONCLUSIONS: Development of CRLimit to angiotensin-converting enzyme inhibitor intolerance identifies patients with severe disease who are likely to die during the next year. New treatment strategies should be targeted to this population. Fried LF, Shlipak MG, Crump C, Bleyer AJ, Gottdiener JS, Kronmal RA, Kuller LH, Newman AB. Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. J Am Coll Cardiol. 2003 Apr 16;41(8):1364-72. clicca qui per andare su PUBMED Renal Section, VA Pittsburgh Healthcare System, Pennsylvania 15240, USA. lff9+@pitt.edu OBJECTIVES: This study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events. BACKGROUND: End-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear. METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level > or =1.5 mg/dl in men or > or =1.3 mg/dl in women. RESULTS: An elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all- cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine. CONCLUSIONS: Elevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease. Khot UN, Mishra M, Yamani MH, Smedira NG, Paganini E, Yeager M, Buda T, McCarthy PM, Young JB, Starling RC. Severe renal dysfunction complicating cardiogenic shock is not a contraindication to mechanical support as a bridge to cardiac transplantation. J Am Coll Cardiol. 2003 Feb 5;41(3):381-5. clicca qui per andare su PUBMED Department of Cardiovascular Medicine, Kaufman Center for Heart Failure, The Cleveland Clinic Foundation, Cleveland, Ohio, USA. khot@cvresearch.net OBJECTIVES: This study investigated outcomes in patients with cardiogenic shock and severe renal dysfunction treated with ventricular assist devices (VAD) as a bridge to cardiac transplantation. BACKGROUND: Previous reports have documented poor survival in patients with cardiogenic shock and severe renal dysfunction treated with VAD. METHODS: We surveyed 215 consecutive patients who received a VAD from 1992 to 2000 and selected patients who had a serum creatinine > or =3.0 mg/dl at the time of VAD placement. Demographic, laboratory, and clinical outcome data were collected. RESULTS: Eighteen patients met the inclusion
  27. 27. criteria. Mean serum creatinine at the time of VAD placement was 4.0 +/- 0.7 mg/dl (range 3.0 to 5.2 mg/dl). Seven patients required temporary renal support with continuous venovenous hemodialysis (CVVHD). Eleven patients underwent cardiac transplantation. At six months post-transplantation, mean serum creatinine was 2.0 +/- 0.6 mg/dl (range 1.3 to 3.5 mg/dl). None of the transplanted patients required subsequent renal support. Seven patients died with a VAD before transplantation. Three died early (<1 month) after VAD placement, and all three required CVVHD until death. Four patients survived for >1 month after VAD placement; all four had resolution of renal dysfunction with mean serum creatinine of 1.9 +/- 1.2 mg/dl (range 0.8 to 3.6 mg/dl) without the need for renal support. Overall 30-day and six-month survival after VAD placement, survival to transplantation, and survival one year post-transplantation were similar to patients without severe renal dysfunction. CONCLUSIONS: Contemporary use of VAD leads to resolution of severe renal dysfunction in most cardiogenic shock patients and comparable long-term outcomes to patients without renal dysfunction. Mahon NG, Blackstone EH, Francis GS, Starling RC 3rd, Young JB, Lauer MS. The prognostic value of estimated creatinine clearance alongside functional capacity in ambulatory patients with chronic congestive heart failure. J Am Coll Cardiol. 2002 Sep 18;40(6):1106-13. clicca qui per andare su PUBMED Comment in: Lepor NE. Renal insufficiency. The prognostic value of renal function in patients with congestive heart failure and acute myocardial infarction. Rev Cardiovasc Med. 2003 Summer;4(3):192-4. Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. OBJECTIVES: The goal of this study was to determine the prognostic significance of estimated creatinine clearance (CrCl) in relation to 6-min walk distance in ambulatory patients with congestive heart failure (HF). BACKGROUND: Although measurement of renal function is integral to the management of chronic congestive HF, its prognostic implications are not well described and have not been formally evaluated relative to measures of functional capacity. METHODS: We analyzed outcomes of the 585 participants of the 6-min walk substudy of the Digitalis Investigation Group (DIG) trial. The CrCl was estimated using the Cockcroft-Gault equation. Predictors of all-cause mortality were identified using semiparametric Cox proportional hazards regression and completely parametric hazard analyses. RESULTS: Most subjects (85%) were New York Heart Association functional class II and III. Mean age was 65 (+/-12) years and mean ejection fraction (EF) 35% (+/-13%). There were 153 (26%) deaths during a median of 2.6 years of follow-up. Mortality by increasing quartiles of estimated CrCl was 37% (18 to 48 ml/min), 29% (47 to 64 ml/min), 18% (64 to 86 ml/min), and 21% (86 to 194 ml/min) with corresponding hazard ratios (HRs) relative to the top quartile of 2.1 (95% confidence interval [CI], 1.4 to 3.3), 1.6 (95% CI, 1.0 to 2.5), and 0.9 (95% CI, 0.5 to 1.5), respectively. In Cox regression analyses, independent predictors of mortality were estimated CrCl (adjusted HR [quartile 1:quartile 4] 1.5; 95% CI, 1.1 to 2.1), 6-min walk distance < or =262 m [adjusted HR, 1.63; 95% CI, 1.12 to 2.27]), EF, recent hospitalization for worsening HF, and need for diuretic treatment. Parametric (hazard) analysis confirmed consistent effects of estimated CrCl on mortality in several subgroups including that of patients with EF >45%. CONCLUSION: In ambulatory patients with congestive HF, estimated CrCl predicts all-cause mortality independently of established prognostic variables.
  28. 28. Kearney MT, Fox KA, Lee AJ, Prescott RJ, Shah AM, Batin PD, Baig W, Lindsay S, Callahan TS, Shell WE, Eckberg DL, Zaman AG, Williams S, Neilson JM, Nolan J. Predicting death due to progressive heart failure in patients with mild-to- moderate chronic heart failure. J Am Coll Cardiol. 2002 Nov 20;40(10):1801-8 clicca qui per andare su PUBMED Department of Cardiology, GKT School of Medicine, King's College London, Bessemer Road, Denmark Hill, London SE5 9PJ, United Kingdom. mark.kearney@kcl.ac.uk OBJECTIVES: The aim of this study was to explore the value of noninvasive predictors of death/mode of death in ambulant outpatients with chronic heart failure (HF). BACKGROUND: Mortality in chronic HF remains high, with a significant number of patients dying of progressive disease. Identification of these patients is important. METHODS: We recruited 553 ambulant outpatients age 63 +/- 10 years with symptoms of chronic HF (New York Heart Association functional class, 2.3 +/- 0.5) and objective evidence of left ventricular dysfunction (ejection fraction <45%, cardiothoracic ratio >0.55, or pulmonary edema on chest radiograph). After 2,365 patient-years of follow-up, 201 patients had died, with 76 events due to progressive HF. RESULTS: Independent predictors of all-cause mortality assessed with the Cox proportional hazards model were as follows: a low standard deviation of all normal-to-normal RR intervals (SDNN); lower serum sodium and higher creatinine levels; higher cardiothoracic ratio; nonsustained ventricular tachycardia; higher left ventricular end-systolic diameter; left ventricular hypertrophy; and increasing age. Independent predictors of death specific to progressive HF were SDNN, serum sodium and creatinine levels. The hazard ratio of progressive HF death for a 10% decrease in SDNN was 1.06 (95% confidence interval [CI], 1.01 to 1.12); for a 2 mmol/l decrease in serum sodium, 1.22 (95% CI, 1.08 to 1.38); and for a 10 micromol/l increase in serum creatinine, 1.14 (95% CI, 1.09 to 1.19) (all p < 0.01). CONCLUSIONS: In ambulant outpatients with chronic HF, low serum sodium and SDNN and high serum creatinine identify patients at increased risk of death due to progressive HF. 283: Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC Jr. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol. 2002 Sep 4;40(5):976-82. clicca qui per andare su PUBMED Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. redfield.margaret@mayo.edu OBJECTIVES: We wished to examine the effects of age and gender on plasma brain natriuretic peptide (BNP) concentration in a population-based study. BACKGROUND: Measurement of BNP concentration is approved for use in the diagnosis of heart failure and may aid in the detection of left ventricular dysfunction. Although BNP is approved for clinical use, there are few data regarding the range of BNP observed in persons without cardiovascular disease or cardiac dysfunction. These data are essential for the interpretation of BNP. METHODS: In 2,042 randomly selected residents of Olmsted County, Minnesota, >44 years old, BNP (Shionogi and Biosite assays), Doppler echocardiography, and medical record review were performed. A normal subset of subjects (n = 767) in sinus rhythm without cardiovascular, renal, or pulmonary disease or diabetes; on no cardiovascular medications; and with normal systolic, diastolic, and valvular function was identified. RESULTS: Within the normal subset, the distribution of BNP differed by age, gender, and assay system. With both assays, BNP increased significantly with age and was significantly higher in women than men, leading to age-, gender-, and assay-specific reference ranges. Receiver operating characteristic
  29. 29. analysis for the ability of BNP to detect an ejection fraction < or = 40% was performed in each age/gender stratum in the entire cohort (n = 2,042) and confirmed that discriminatory values for BNP for detection of reduced ejection fraction were higher in women and older persons and were different between the two assays. CONCLUSIONS: Interpretation of BNP should include consideration of age-, gender-, and assay-specific partition values. Krumholz HM, Chen J, Chen YT, Wang Y, Radford MJ. Predicting one-year mortality among elderly survivors of hospitalization for an acute myocardial infarction: results from the Cooperative Cardiovascular Project. J Am Coll Cardiol. 2001 Aug;38(2):453-9. clicca qui per andare su PUBMED Comment in: Teo KK, Catellier DJ. Risk prediction after myocardial infarction in the elderly J Am Coll Cardiol. 2001 Aug;38(2):460-3. clicca qui per andare su PUBMED Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8025, USA. OBJECTIVES: We sought to develop a model based on information available from the medical record that would accurately stratify elderly patients who survive hospitalization with an acute myocardial infarction (AMI) according to their risk of one-year mortality. BACKGROUND: Prediction of the risk of mortality among older survivors of an AMI has many uses, yet few studies have determined the prognostic importance of demographic, clinical and functional data that are available on discharge in a population-based sample. METHODS: In a cohort of patients aged > or = 65 years who survived hospitalization for a confirmed AMI from 1994 to 1995 at acute care, nongovernmental hospitals in the U.S., we developed a parsimonious model to stratify patients by their risk of one-year mortality. RESULTS: The study sample of 103,164 patients, with a mean age of 76.8 years, had a one-year mortality of 22%. The factors with the strongest association with mortality were older age, urinary incontinence, assisted mobility, presence of heart failure or cardiomegaly any time before discharge, presence of peripheral vascular disease, body mass index <20 kg/m2, renal dysfunction (defined as creatinine >2.5 mg/dl or blood urea nitrogen >40 mg/dl) and left ventricular dysfunction (left ventricular ejection fraction <40%). On the basis of the coefficients in the model, patients were stratified into risk groups ranging from 7% to 49%. CONCLUSIONS: We demonstrate that a simple risk model can stratify older patients well by their risk of death one year after discharge for AMI. Silverberg DS, Wexler D, Blum M, Keren G, Sheps D, Leibovitch E, Brosh D, Laniado S, Schwartz D, Yachnin T, Shapira I, Gavish D, Baruch R, Koifman B, Kaplan C, Steinbruch S, Iaina A. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol. 2000 Jun;35(7):1737-44. clicca qui per andare su PUBMED Department of Nephrology and Cardiology, Tel Aviv Medical Center, Israel. OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on
  30. 30. cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization. Dries DL, Exner DV, Domanski MJ, Greenberg B, Stevenson LW. The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol. 2000 Mar 1;35(3):681-9. clicca qui per andare su PUBMED Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. OBJECTIVES: The present analysis examines the prognostic implications of moderate renal insufficiency in patients with asymptomatic and symptomatic left ventricular systolic dysfunction. BACKGROUND: Chronic elevations in intracardiac filling pressures may lead to progressive ventricular dilation and heart failure progression. The ability to maintain fluid balance and prevent increased intracardiac filling pressures is critically dependent on the adequacy of renal function. METHODS: This is a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) Trials, in which moderate renal insufficiency is defined as a baseline creatinine clearance <60 ml/min, as estimated from the Cockroft-Gault equation. RESULTS: In the SOLVD Prevention Trial, multivariate analyses demonstrated moderate renal insufficiency to be associated with an increased risk for all-cause mortality (Relative Risk [RR] 1.41; p = 0.001), largely explained by an increased risk for pump-failure death (RR 1.68; p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.33; p = 0.001). Likewise, in the Treatment Trial, multivariate analyses demonstrated moderate renal insufficiency to be associated with an increased risk for all-cause mortality (RR 1.41; p = 0.001), also largely explained by an increased risk for pump-failure death (RR 1.49; p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.45; p = 0.001). CONCLUSIONS: Even moderate degrees of renal insufficiency are independently associated with an increased risk for all-cause mortality in patients with heart failure, largely explained by an increased risk of heart failure progression. These data suggest that, rather than simply being a marker of the severity of underlying disease, the adequacy of renal function may be a primary determinant of compensation in patients with heart failure, and therapy capable of improving renal function may delay disease progression.

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