Heart Failure In Clinical Practice Research Articles

Use and Risk Management of Carvedilol for the Treatment of Heart Failure in the Community in England

In the UK, the licence for carvedilol was extended in 1998 to include symptomatic heart failure (New York Heart Association [NYHA] class II and III heart failure) with the recommendation that initiation and up-titration should be under the supervision of a hospital physician. A post-marketing surveillance study was conducted to address the UK regulatory authority's request for monitoring the use and safety of carvedilol prescribed for heart failure in clinical practice. To investigate adherence to risk management recommendations for the use of carvedilol for heart failure, monitor how patients' subsequent care was managed and collect event data to evaluate the safety profile of carvedilol used for the treatment of heart failure. An observational cohort study using a modified prescription-event monitoring technique identified patients from dispensed primary care prescriptions in England (August 1999 to June 2001). An eligibility questionnaire was used to identify patients who had been prescribed carvedilol for heart failure for the first time after 31 July 1999. Up to three follow-up questionnaires were sent to the prescribers of eligible patients, requesting demographic information, dosage, supervision of treatment, status of cardiac failure and event information. 2311 patients met the eligibility criteria. For 1666 patients, one or more valid follow-up questionnaires were returned: 68.5% were male; male median age 66 years; female median age 72 years; the observation period was up to 3 years. Hospital physicians supervised initiation of treatment and first up-titration in 85.6% and 61.4% of patients, respectively. 49.2% of patients were prescribed the recommended starting dosage of carvedilol (6.25 mg/day). Approximately 25% of patients started on a lower dose than recommended, and the same proportion were prescribed a higher dose. NYHA status of cardiac failure between starting treatment and the third questionnaire improved for 39.5% of patients, deteriorated for 10.9%, and 11.7% of those for whom NYHA status was given died. Adverse drug reactions (ADRs) were reported for 2.4% of patients; the most commonly reported ADR was malaise/lassitude. Overall, 27.1% of patients stopped taking carvedilol. None of the 163 deaths were attributed to carvedilol. Regulatory guidelines for the use and risk management of carvedilol in heart failure were mostly followed, and most patients appeared to benefit from treatment with carvedilol for heart failure. Malaise/lassitude was the main reason for discontinuing treatment. Further investigations may be warranted to examine the prescribing of carvedilol at lower than recommended doses.

Comparative Effectiveness of Different β-Adrenergic Antagonists on Mortality Among Adults With Heart Failure in Clinical Practice

Randomized trials have demonstrated the efficacy of selected beta-blockers in systolic heart failure, but the comparative effectiveness of different beta-blockers in practice is poorly understood. We compared mortality associated with different beta-blockers following hospitalization for heart failure between 2001 and 2003. Longitudinal exposure to beta-blockers was ascertained from pharmacy databases. Patient characteristics and other medication use were identified from administrative, hospitalization, outpatient, and pharmacy databases. Death was identified from administrative, state mortality, and Social Security Administration databases. Multivariate Cox regression was used to examine the association between different beta-blockers and death. Among 11 326 adults surviving a hospitalization for heart failure, 7976 received beta-blockers (atenolol, 38.5%; metoprolol tartrate, 43.2%; carvedilol, 11.6%; and other, 6.7%) during follow-up. The rate (per 100 person-years) of death during the 12 months after discharge varied by exposure and type of beta-blocker (atenolol, 20.1; metoprolol tartrate, 22.8; carvedilol, 17.7; and no beta-blockers, 37.0). After adjustment for confounders and the propensity to receive carvedilol, the risk of death compared with atenolol was higher for metoprolol tartrate (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.34) and no beta-blockers (HR, 1.63; 95% CI, 1.44-1.84) but was not significantly different for carvedilol (HR, 1.16; 95% CI, 0.92-1.44). Compared with atenolol, the adjusted risks of death were slightly higher with shorter-acting metoprolol tartrate but did not significantly differ for carvedilol in adults with heart failure. Our results should be interpreted cautiously and they suggest the need for randomized trials within real-world settings comparing a broader spectrum of beta-blockers for heart failure.

Management of patients with heart failure in clinical practice: differences between men and women

Objectives:This study evaluated gender differences in clinical characteristics, treatment and outcome among patients with heart failure, and to what extent these differences are due to age and differences in left...

Comparison of Outcomes and Usefulness of Carvedilol Across a Spectrum of Left Ventricular Ejection Fractions in Patients With Heart Failure in Clinical Practice

Heart failure (HF) in the community differs meaningfully from that in clinical trials, particularly the higher prevalence of patients with preserved left ventricular (LV) ejection fraction (EF) typically excluded from clinical trials, thus limiting knowledge of their responsiveness to beta-blocker therapy. From a community-based registry of 4,280 patients with HF starting treatment with the beta blocker carvedilol, we compared characteristics, carvedilol titration, and outcomes of patients according to LVEF >40% or <40% (as in clinical trials) and across the spectrum of LVEF <21%, 21% to 30%, 31% to 40%, and >40%. Patients with preserved EF (LVEF >40%) were older and more often women and hypertensive. Lower LVEF was associated with worse functional class and more HF hospitalizations in the previous year. Carvedilol dose decreased with increasing LVEF. Hospitalization rates for HF related inversely to LVEF before starting carvedilol therapy and decreased from the previous year in all LVEF groups during follow-up. Although 1-year mortality rate decreased from 8% with LVEF < or =20% to 6% with LVEF >40%, adjusted hazard ratios were not significantly different across LVEF groups. Thus, characteristics of community patients with HF vary across the spectrum of LVEF. Patients with HF and preserved EF treated with carvedilol in the community improve symptomatically and experience fewer HF hospitalizations after initiating carvedilol. In conclusion, without a control group, the effect of carvedilol on outcomes is not conclusive and trials of carvedilol in patients with HF and preserved EF should be undertaken.

A Gray Zone Assigned to Inconclusive Results of Quantitative Diagnostic Tests: Application to the Use of Brain Natriuretic Peptide for Diagnosis of Heart Failure in Acute Dyspneic Patients

Most quantitative diagnostic tests do not perfectly differentiate between persons with and without a given disease. We present a simple method to construct a 3-zone partition for quantitative tests results, including positive and negative zones and a gray zone between, and we describe its use in the diagnosis of heart failure by brain natriuretic peptide (BNP) measurement in acute dyspneic patients. We conducted a prospective cohort study of 699 consecutive patients with acute dyspnea who were treated at the emergency department of 3 participating hospitals. Heart failure (acute or decompensated) was assessed independently at discharge by cardiologists blind to the results of BNP measurements. The discriminatory performance of BNP was insufficient to provide a single cutoff value that could be used to correctly diagnose heart failure in clinical practice. Also, the discriminatory performance differed between patients with and without a history of chronic heart failure. The gray zone of inconclusive results was 167-472 ng/L for those without and 0-334 ng/L for those with such a history. Diagnosis of the current episode of heart failure by BNP results and history of heart failure was not enhanced by data from any other sources, including electrocardiography. The gray zone approach applied to the diagnosis of heart failure by BNP might allow sensible cutoff values to be determined for clinical practice according to relevant subgroups of patients. The gray zone approach might be usefully applied to many other quantitative tests and clinical diagnostic or screening problems.

Short-Term Change in Distance Walked in 6 Min Is an Indicator of Outcome in Patients With Chronic Heart Failure in Clinical Practice

The purpose of this study was to investigate the prognostic value of change in distance walked in 6 min in chronic heart failure (CHF). The strongest indication for the 6-min walking test (6MWT) is for measuring the response to therapeutic interventions in patients with CHF. Whether the increase in distance walked after a therapeutic intervention translates into improved clinical outcome is largely unknwon. We studied 476 CHF patients with left ventricular systolic dysfunction who were referred to our institution for adjustment of heart failure therapy because of persisting or worsening symptoms. Adjustment of therapy involved four classes of drugs: angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, beta-blockers, loop diuretics, and aldosterone antagonists. A standardized 6MWT was performed at baseline and at discharge. After 15.2 +/- 8 days, the distance walked increased from 326 +/- 107 m to 408 +/- 109 m (+25%; p = 0.001). During a mean follow-up of 23.9 months, 94 patients died and 12 patients underwent cardiac transplantation. Among a set of variables, New York Heart Association functional class (p = 0.02), serum creatinine concentration (p = 0.01), left ventricular ejection fraction (p = 0.002), distance walked at baseline (p = 0.0002), and change in distance walked (p = 0.002) were significant independent predictors of survival. When the patients were divided into two subgroups according to the median value of the distance walked at baseline, the increase in walking distance was significantly associated with survival only in the subgroup of patients who walked <340 m at baseline. Our data indicate that repeating a 6MWT after drug intervention provides independent prognostic information in CHF patients with more compromised exercise capacity.

Decreased survival in diabetic patients with heart failure due to systolic dysfunction☆

Prognosis of patients with heart failure (HF) has improved in recent years due to advances in therapy. Whether this is also true for diabetic subjects with HF in clinical practice has not been studied in a prospective manner. All patients with HF and left ventricular systolic dysfunction attending the outpatient clinic at our Veteran's Hospital between October 1999 and November 2000 were enrolled in our study and followed prospectively. Electronic medical records were accessed for data on comorbid conditions, medications, echocardiogram results and mortality information. Mean follow-up was 2.7 years. Of 495 patients with HF due to systolic dysfunction enrolled in the study, 293 (59%) had diabetes. Prevalence of hypertension, diuretic use and angiotensin converting enzyme inhibitor use was higher among diabetics. Beta-blocker usage was equal and high in both groups (60%). On follow-up, 109/273 (37%) patients in the diabetic group died, compared with 49/202 (24%) in the non-diabetic group. Independent predictors of death were diabetes (p<0.005, OR=1.73), age at enrollment (p<0.0001, OR=1.06), serum creatinine (p<0.01, OR=1.44) and diuretic use (p=0.038, OR=1.85). Beta-blocker use was associated with a decreased risk of death on univariate analysis only. Our results show that diabetic patients with HF continue to have higher mortality than non-diabetic patients with HF despite advances in therapy.

The Transition From Hypertrophy to Failure

Hypertensive heart disease is a major contributor to cardiovascular morbidity and mortality, especially in African Americans, in whom LV hypertrophy is 2 to 3-fold more common in the general population as compared with whites.1 In the classic paradigm of hypertensive heart disease, concentric hypertrophy (a nondilated, thick-walled left ventricle typically with a normal left ventricular ejection fraction [LVEF]) is a common precursor to LV failure (an increased LV volume with reduced LVEF).2 Although molecular triggers of this transition from concentric hypertrophy to failure have been the subject of intense investigation, there are no previous large, longitudinal cohort studies in humans demonstrating that this progression occurs frequently. The transition from concentric LV hypertrophy to failure has been well demonstrated in animal models including the spontaneously hypertensive rat,3 or after aortic banding4 or transgenic manipulation,5 and also in humans with aortic stenosis6 or familial hypertrophic cardiomyopathy.7 Whether this paradigm faithfully represents the natural history of hypertensive heart disease is not yet known (Figure). An alternative paradigm is that the LV response to elevated blood pressure is either hypertrophy or failure, with transition between the 2 uncommon in the absence of an interval cardiac injury. Potential pathways in progression of hypertensive heart disease. Hypertension can lead to concentric left ventricular hypertrophy (LVH), characterized by nondilated, thick-walled left ventricle (arrow, top left). After “transition to failure,” the LV is dilated with reduced LVEF. Coronary artery disease often via MI is a common contributor to this transition (first horizontal arrow). Whether concentric LVH commonly leads to low EF in absence of an interval MI or significant coronary artery disease is uncertain (second horizontal arrow). If LVH is not common precursor to LV …

Distinguishable Optimal Levels of Plasma B-type Natriuretic Peptide in Heart Failure Management Based on Complicated Atrial Fibrillation

A B-type natriuretic peptide (BNP)-guided strategy is being widely used as a superior management technique for heart failure (HF). However, the optimal target level of BNP to improve the prognosis of HF in clinical practice remains unclear. Several studies have recently demonstrated that the existence of atrial fibrillation (AF) affects plasma BNP levels. We evaluated the prognostic value of BNP assay for HF management and found the optimal target level under the BNP-guided HF management according to the basal cardiac rhythms: AF or sinus rhythm (SR). Patients hospitalized for HF exacerbation between 1996 and 2002 were stratified into SR (n = 129) and chronic AF (CAF, n = 58) groups as basal cardiac rhythms during hospitalization. Cardiac events including death and re-admission for HF exacerbation after discharge were analyzed in relation to the plasma BNP levels at predischarge. Receiver-operating characteristic (ROC) analysis demonstrated that the cut-off values for predischarge BNP, which predict cardiac events at 36 months after discharge, were 125 pg/mL in the SR group and 165 pg/mL in the CAF group. The area under the ROC curve was 0.72 and 0.82, respectively. Stratified subgroup analysis using the Kaplan-Meier method demonstrated that the risk of a cardiac event decreased in a stepwise fashion across a decreasing predischarge BNP range above these cut-off levels, while the minimum decreased risk was recognized at a BNP range below these cut-off levels in each group. In conclusion, the optimal target levels of plasma BNP at predischarge to improve the prognosis of HF should be different and distinguishable depending on with or without AF.

Observational cohort study to monitor the use and safety of carvedilol in the treatment of heart failure in clinical practice in England – 1st interim report

This is an interim report of a prospective observational cohort study to monitor the safety and tolerability of carvedilol in clinical practice when prescribed for heart failure in England. The utilization of carvedilol, management of adverse events in the community and the symptomatic progression of heart failure were examined. It is a non-interventional, observational cohort surveillance study using questionnaires sent to the patients' general practitioners. The general practitioners (GPs) of the patients identified by the Prescription Pricing Authority were sent an eligibility questionnaire if the patient had been newly prescribed carvedilol between September 1999 and July 2001. Further questionnaires requesting baseline clinical information about eligible patients (carvedilol indicated for cardiac failure) and subsequent event data were sent to consenting GPs at 12 months. The questionnaires also requested specific information about initiation and supervision of treatment, including severity of heart failure and treatment withdrawal. The data were analyzed by using descriptive statistics. In addition, the incidence densities (ID) of each event (per 1000 person-months of treatment) were calculated, ranked and the difference between the ID of each event in the first (ID1) and subsequent 5 months of exposure (ID2) was tested by constructing 99% confidence intervals (CI). Selected events of clinical interest would be followed-up for further information to enable causal association with carvedilol to be assessed. In this interim report we have data on a cohort of 847 eligible patients for whom we have received information from the first follow-up questionnaire. The treatment of carvedilol was initiated in a majority of cases by hospital specialists (87%, n = 735), however, for most of them, further supervision of treatment was done under shared care between GPs and hospitals (70%, n = 595). More than 90% of the patients were started on carvedilol in the recommended dose range for the management of cardiac failure. Amongst the patients where NYHA grade of cardiac failure was expressed, the majority of patients treated with carvedilol had NYHA II (37%, n = 281) and III (40%, n = 297) symptoms at the start of carvedilol treatment. On treatment with carvedilol, improvement in NYHA status was reported for 43% (n = 364) of this cohort, whilst less than 2.5% (n = 20) of the patients deteriorated. The events reported with the highest ID1 were malaise/lassitude (14.6), dizziness (12.2), cardiac failure (9.7), dyspnea (9.7) and hypotension (8.5). The most common events reported as reasons for stopping carvedilol were "drug not effective", "dyspnea", "dizziness" and "lassitude". No events were identified as new signals (according to the ID1-ID2 statistic) of adverse events associated with carvedilol. There have been no events identified in this cohort that have required specific follow-up at the time of writing this paper. In summary, the interim results show that there is effective cooperation between hospital specialists and GPs in the use of carvedilol in the management of patients with heart failure. It also shows that carvedilol was well-tolerated and that patients with mild and moderate heart failure benefit symptomatically when treated with carvedilol in routine clinical practice.

Austrian survey of treating heart failure—AUSTRIA

Treatment of chronic heart failure is based on the results of large clinical trials, which form the basis of treatment guidelines, such as those from the European Society of Cardiology (ESC). The aim of this study was to record treatment-modalities and the implementation of guidelines of chronic heart failure in clinical practice in Austria. Overall 96 general physicians, specialists for internal medicine in private practice or in hospital outpatient departments participated in the survey. Physicians were asked to prospectively document 30 consecutive patients with chronic heart failure. 1880 patients were documented. The majority of patients were treated by general physicians (57%). Coronary artery disease was the most frequent aetiology for heart failure (47%). The most frequently used drugs were blockers of the renin-angiotensin-system (RAS-blocker including ACE-inhibitors and angiotensin-receptor-blockers, 78%), diuretics (76%) and beta-blockers (49%). Other drugs like digitalis and spironolactone were used infrequently. Average doses of ACE-inhibitors were approximately 90% of those recommended by the ESC, average doses of beta-blockers were approximately 50% of those recommended. Treatment among the three classes of physicians differed with respect to RAS-blockers and beta-blockers, which were used infrequently by general practitioners. Both groups of drugs were given more frequently to younger patients (<70 years) while digitalis was given more often to elderly patients. Results from this survey suggest that Austrian physicians treating patients with heart failure use the appropriate drugs in dosages that are suggested by recently published guidelines (ACE-inhibitors and beta-blockers). However, dosages of spironolactone clearly differed from current recommendations.

597 Can we use BNP and NTproBNP to rule out heart failure in clinical practice? Results of the UK natriuretic peptide study

597 Can we use BNP and NTproBNP to rule out heart failure in clinical practice? Results of the UK natriuretic peptide study

Cardiac peptides differ in their response to exercise. Implications for patients with heart failure in clinical practice.

Cardiac peptides have diagnostic and prognostic value in heart failure. Their plasma concentrations, however, are sensitive to rapid changes in haemodynamics. As blood sampling under standard conditions is not feasible in clinical practice, it is important to know which peptides are most resistant to change. Therefore, the present study investigated the differences in response to exercise between atrial natriuretic peptide, N-terminal proatrial natriuretic peptide, brain natriuretic peptide and the recently identified N-terminal probrain natriuretic peptide. Fifty-two patients with chronic heart failure performed a symptom-limited graded bicycle exercise. Blood samples for determination of plasma concentrations of cardiac peptides were drawn at rest and at peak exercise. There was a significant difference in percentage increase in response to exercise between the four peptides (P<0.0001). N-terminal proatrial natriuretic peptide increased less than atrial natriuretic peptide (5+/-18% vs 59+/-58%;P<0.0001). The difference in increase between N-terminal probrain natriuretic peptide and brain natriuretic peptide was less distinct but still significant (24+/-24% vs 38+/-52%, P<0.05). Both N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide increased less in response to exercise than their C-terminal counterparts. This implies that the circumstances under which blood sampling for measurements of N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide should be performed are more favourable than the blood sampling conditions for atrial natriuretic peptide and brain natriuretic peptide.

A Comprehensive Management System for Heart Failure Improves Clinical Outcomes and Reduces Medical Resource Utilization

The effectiveness of heart failure management in clinical practice is limited by physicians' suboptimal utilization of effective medications, patients' poor adherence to dietary sodium limitation and optimal drug therapy, and the lack of systematic monitoring of patients after hospitalization. The present study evaluated the feasibility and safety of MULTIFIT, a physician-supervised, nurse-mediated, home-based system for heart failure management that implements consensus guidelines for pharmacologic and dietary therapy using a nurse manager to enhance dietary and pharmacologic adherence and to monitor clinical status by frequent telephone contact. Fifty-one patients with the clinical diagnosis of heart failure were followed for 138 ± 44 days. Daily dietary sodium intake fell by 38%, from 3,393 to 2,088 mg (p = 0.0001); average daily medication doses increased significantly (lisinopril: 17 to 23 mg, p < 0.001; hydralazine: 140 to 252 mg, p = 0.01). Functional status and exercise capacity improved significantly (p = 0.01). Compared with the 6 months before enrollment and normalized for variable follow-up, the frequency of general medical and cardiology visits declined by 23% and 31%, respectively (both p < 0.03); emergency room visits for heart failure and for all causes declined 67% and 53%, respectively (both p < 0.001). Hospitalization rates for heart failure and for all causes declined 87% and 74%, respectively (p = 0.001), compared with the year before enrollment. The MULTIFIT system enhanced the effectiveness of pharmacologic and dietary therapy for heart failure in clinical practice, improving clinical outcomes and reducing medical resource utilization.