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1.  Chronic kidney disease increases cardiovascular unfavourable outcomes in outpatients with heart failure 
BMC Nephrology  2009;10:31.
Chronic heart failure (CHF) has a high morbidity and mortality. Chronic kidney disease (CKD) has consistently been found to be an independent risk factor for unfavorable cardiovascular (CV) outcomes. Early intervention on CKD reduces the progression of CHF, hospitalizations and mortality, yet there are very few studies about CKD as a risk factor in the early stages of CHF. The aims of our study were to assess the prevalence and the prognostic importance of CKD in patients with systolic CHF stages B and C.
This is a prospective cohort study, dealing with prognostic markers for CV endpoints in patients with systolic CHF (ejection fraction ≤ 45%).
CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 and CV endpoints as death or hospitalization due to CHF, in 12 months follow-up. Eighty three patients were studied, the mean age was 62.7 ± 12 years, and 56.6% were female. CKD was diagnosed in 49.4% of the patients, 33% of patients with CHF stage B and 67% in the stage C. Cardiovascular endpoints were observed in 26.5% of the patients. When the sample was stratified into stages B and C of CHF, the occurrence of CKD was associated with 100% and 64.7%, respectively, of unfavorable CV outcomes. After adjustments for all other prognostic factors at baseline, it was observed that the diagnosis of CKD increased in 3.6 times the possibility of CV outcomes (CI 95% 1.04-12.67, p = 0.04), whereas higher ejection fraction (R = 0.925, IC 95% 0.862-0.942, p = 0.03) and serum sodium (R = 0.807, IC 95% 0.862-0.992, p = 0.03) were protective.
In this cohort of patients with CHF stages B and C, CKD was prevalent and independently associated with increased risk of hospitalization and death secondary to cardiac decompensation, especially in asymptomatic patients.
PMCID: PMC2771010  PMID: 19843342
2.  Factors related to time to admission to specialized multidisciplinary clinics in patients with congestive heart failure 
The Canadian Journal of Cardiology  2009;25(10):e347-e352.
Congestive heart failure (CHF) is a common cause of hospitalization and has a poor prognosis. Specialized multidisciplinary clinics are effective in the management of CHF.
To measure time of admission to the specialized clinics and explore factors related to the time of admission to these clinics.
Patients who were newly admitted to one of six CHF multidisciplinary clinics in the province of Quebec were enrolled in the study. Data were collected from the common clinical database used at these clinics as well as from questionnaires administered to the patients.
A total of 531 patients with a mean age of 65.9 years were enrolled. Only 26% were women. The median duration of disease before admission to the CHF clinic was 1.2 years. The majority of patients (62%) were referred by a cardiologist or an internist, while 24% were referred by other specialists, and 14% by general practitioners. One-fifth of patients did not have regular follow-up for their CHF before being admitted to the clinic. Factors associated with shorter disease duration at admission to the clinic were referral by a specialist, not having regular medical follow-up for CHF, having a higher income and having visited the emergency room for CHF.
There may be a need to improve dissemination of information regarding availability and benefits of CHF clinics and criteria for referral.
PMCID: PMC2782508  PMID: 19812808
Congestive heart failure; Multidisciplinary heart failure clinics; Referral
3.  Cardiopulmonary Exercise Testing in Patients with Chronic Heart Failure: Prognostic Comparison from Peak VO2 and VE/VCO2 Slope 
Cardiopulmonary exercise testing with ventilatory expired gas analysis (CPET) has proven to be a valuable tool for assessing patients with chronic heart failure (CHF). The maximal oxygen uptake (peak V02) is used in risk stratification of patients with CHF. The minute ventilation-carbon dioxide production relationship (VE/VCO2 slope) has recently demonstrated prognostic significance in patients with CHF.
Between January 2006 and December 2007 we performed CPET in 184 pts (146 M, 38 F, mean age 59.8 ± 12.9 years), with stable CHF (96 coronary artery disease, 88 dilated cardiomyopathy), in NYHA functional class II (n.107) - III (n.77), with left ventricular ejection fraction (LVEF) ≤ 45%,. The ability of peak VO2 and VE/VCO2 slope to predict cardiac related mortality and cardiac related hospitalization within 12 months after evaluation was examined.
Peak VO2 and VE/VCO2 slope were demonstrated with univariate Cox regression analysis both to be significant predictor of cardiac-related mortality and hospitalization (p < 0.0001, respectively). Non survivors had a lower peak VO2 (10.49 ± 1.70 ml/kg/min vs. 14.41 ± 3.02 ml/kg/min, p < 0.0001), and steeper Ve/VCO2 slope (41.80 ± 8.07 vs. 29.84 ± 6.47, p < 0.0001) than survivors. Multivariate survival analysis revealed that VE/VCO2 slope added additional value to VO2 peak as an independent prognostic factor (χ2: 56.48, relative risk: 1.08, 95% CI: 1.03 – 1.13, p = 0.001). The results from Kaplan-Meier analysis revealed a 1-year cardiac-related mortality of 75% in patients with VE/VCO2 slope ≥ 35.6 and 25% in those with VE/VCO2 slope < 35.6 (log rank χ2: 67.03, p < 0.0001) and 66% in patients with peak VO2 ≤ 12.2 ml/kg/min and 34% in those with peak VO2 > 12.2 ml/kg/min (log rank χ2: 50.98, p < 0.0001). One-year cardiac-related hospitalization was 77% in patients with VE/VCO2 slope ≥ 32.5 and 23% in those with VE/VCO2 slope < 32.5 (log rank χ2: 133.80, p < 0.0001) and 63% in patients with peak VO2 ≤ 12.3 ml/kg/min and 37% in those with peak VO2 > 12.3 ml/kg/min (log rank χ2: 72.86, p < 0.0001). The VE/VCO2 slope was demonstrated with receiver operating characteristic curve analysis to be equivalent to peak VO2 in predicting cardiac-related mortality (0.89 vs. 0.89). Although area under the receiver operating characteristic curve for the VE/VCO2 slope was greater than peak VO2 in predicting cardiac-related hospitalization (0.88 vs 0.82), the difference was no statistically significant (p = 0.13).
These results add to the present body of knowledge supporting the use of CPET in CHF patients. The VE/VCO2 slope, as an index of ventilatory response to exercise, is an excellent prognostic parameter and improves the risk stratification of CHF patients. It is easier to obtain than parameters of maximal exercise capacity and is of equivalent prognostic importance than peak VO2.
PMCID: PMC2908890  PMID: 20657715
Congestive heart failure; exercise capacity; gas exchange; ventilation; prognosis.
4.  Effects of congestive heart failure on plasma von Willebrand factor and soluble P-selectin concentrations in patients with non-valvar atrial fibrillation 
Heart  2005;91(6):759-763.
Objective: To examine further the relations of plasma von Willebrand factor (vWf, an index of endothelial damage and dysfunction) and soluble P-selectin (sP-sel, an index of platelet activation) concentrations to the presence and onset of clinical congestive heart failure (CHF) and the degree of left ventricular (LV) dysfunction in patients taking part in the SPAF (stroke prevention in atrial fibrillation) study.
Methods: Plasma concentrations of vWf and sP-sel were measured by enzyme linked immunosorbent assay (ELISA) in 1321 participants in the SPAF III study and related to the presence and onset of clinical CHF, as well as echocardiographic findings. Of the 1321 patients with atrial fibrillation (AF), 331 (25%) had a documented history of clinical heart failure, of which 168 cases were related to a new or recurrent episode of acute decompensated heart failure occurring within the preceding three months.
Results: Mean plasma vWf was higher among patients with AF and CHF (154 (29) v 144 (31) IU/dl, p < 0.001), particularly those with acute or recent decompensated symptoms. Patients with severe LV dysfunction on two dimensional echocardiography and low fractional shortening also had significantly higher vWf concentrations than those with no LV dysfunction. CHF patients with clinical features—with (156 (28) IU/dl) and without (152 (31) IU/dl) LV dysfunction—also had higher mean vWf concentrations than patients with asymptomatic LV dysfunction (146 (31) IU/dl, p < 0.001). The presence of mitral regurgitation in CHF was associated with lower vWf concentrations. Plasma sP-sel concentrations were not affected by presence, onset, or severity of heart failure.
Conclusions: CHF may contribute to hypercoagulability and thrombotic risk in AF through increased endothelial damage and dysfunction. Patients with acute or recent decompensated features have the highest degree of endothelial damage and dysfunction. The presence of CHF clinical features was an important determinant of plasma vWf concentrations.
PMCID: PMC1768962  PMID: 15894770
von Willebrand factor; soluble P-selectin; stroke; heart failure; atrial fibrillation
5.  Self-perceived symptoms and care needs of patients with severe to very severe chronic obstructive pulmonary disease, congestive heart failure or chronic renal failure and its consequences for their closest relatives: the research protocol 
Recent research shows that the prevalence of patients with very severe chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and chronic renal failure (CRF) continues to rise over the next years. Scientific studies concerning self-perceived symptoms and care needs in patients with severe to very severe COPD, CHF and CRF are scarce.
Consequently, it will be difficult to develop an optimal patient-centred palliative care program for patients with end-stage COPD, CHF or CRF. The present study has been designed to assess the symptoms, care needs, end-of-life care treatment preferences and communication needs of patients with severe to very severe COPD, CHF or CRF. Additionally, family distress and care giving burden of relatives of these patients will be assessed.
A cross-sectional comparative and prospective longitudinal study in patients with end-stage COPD, CHF or CRF has been designed. Patients will be recruited by their treating physician specialist. Patients and their closest relatives will be visited at baseline and every 4 months after baseline for a period of 12 months. The following outcomes will be assessed during home visits: self-perceived symptoms and care needs; daily physical functioning; general health status; end-of-life care treatment preferences; end-of-life care communication and care-giver burden of family caregivers. Additionally, end-of-life care communication and prognosis of survival will be assessed with the physician primarily responsible for the management of the chronic organ failure. Finally, if patients decease during the study period, the baseline preferences with regard to life-sustaining treatments will be compared with the real end-of-life care.
To date, the symptoms, care needs, caregiver burden, end-of-life care treatment preferences and communication needs of patients with very severe COPD, CHF or CRF remain unknown. The present study will increase the knowledge about the self-perceived symptoms, care-needs, caregiver burden, end-of-life care treatment preferences and communication needs from the views of patients, their loved ones and their treating physician. This knowledge is necessary to optimize palliative care for patients with COPD, CHF or CRF. Here, the design of the present study has been described. A preliminary analysis of the possible strengths, weaknesses and clinical consequences is outlined.
PMCID: PMC2391145  PMID: 18460203
6.  Changing trends in mortality and admissions to hospital for elderly patients with congestive heart failure in Montreal 
Congestive heart failure (CHF) is a common disease requiring admission to hospital among elderly people and is associated with a high mortality rate. The objective of this study was to examine trends in CHF mortality and admissions to hospital in Montreal between 1990 and 1997 for individuals aged 65 years or more.
We obtained information about deaths from the Quebec Death Certificate Registry database and information about admissions to hospital from the Québec Med-Écho database. Patients with a primary diagnosis that was classified as ICD-9 code 428 were considered cases of CHF.
Although age-adjusted rates of mortality from CHF did not change significantly between 1990 and 1997, the annual rate of admission to hospital for CHF increased from 92 per 10 000 population in 1990/91 to 124 per 10 000 population in 1997/98 (p < 0.01). Deaths due to CHF, expressed as a proportion of all cardiovascular deaths, increased among women from 5.6% in 1990 to 6.2% in 1997 (p = 0.01). The rate of readmission for all causes following a first admission for CHF during that year rose over the study period from 16.6% to 22.0% within one month (p < 0.001) and from 46.7% to 49.4% within 6 months (p = 0.03). Conversely, mean annual length of stay per admission decreased from 16.4 days in 1990/91 to 12.2 days in 1997/98.
The increase in rates of admission to hospital for CHF and the stable rates of CHF mortality suggest that the management of CHF and its antecedents has improved in recent years.
PMCID: PMC81537  PMID: 11699698
7.  Prognostic factors of mid-term clinical outcome in congestive heart failure patients discharged after acute decompensation 
Risk stratification in congestive heart failure (CHF) patients is based on a variety of clinical and laboratory variables. We analysed renal function, BNP, water composition, echocardiographic and functional determinations in predicting mid-term outcome in CHF patients discharged after decompensation.
Material and methods
All subjects with NYHA class II-IV were enrolled at hospital discharge. NYHA class, BNP, water body composition, non-invasive cardiac output and echocardiogram were analysed. Death, cardiac transplantation and hospital readmission for CHF were scheduled.
Two-hundred and thirty-seven (64.5% males, age 71.1±10.1) patients were discharged after obtaining normal hydration; left ventricular ejection fraction (LVEF) was 43.2±16.2%, cardiac output was 3.8±1.1 l/min and BNP at discharge resulted 401.3±501.7 pg/ml. During the 14-month follow-up 15 patients (6.3%) died, 1 (0.4%) underwent cardiac transplantation and 18 (7.6%) were readmitted for CHF (event group); in 203 (85.6%) no events were observed (no-event group). Higher NYHA class (2.1±0.7 vs. 1.9±0.4, p=0.01), BNP at discharge (750.2±527.3 pg/ml vs. 340.7±474.3 pg/ml, p=0.002) and impaired LVEF (33.7±15.7% vs. 44.5±15.8%, p=0.0001) and creatinine (1.7±0.6 vs. 1.2±0.8 mg/dl, p=0.004) were noticed in the event group. At multivariate Cox analysis LVEF (p=0.0009), plasma creatinine (p=0.006) and BNP at discharge (p=0.001) were associated with adverse mid-term outcome. Kaplan-Meier survival curves demonstrated that adding cut-off points for creatinine 1.5 mg/dl and discharged BNP of 250 pg/ml discriminated significantly prognosis (p=0.0001; log rank 21.09).
In predicting mid-term clinical prognosis in CHF patients discharged after acute decompensation, BNP at discharge ≥ 250 pg/ml added with plasma creatinine > 1.5 mg/dl are strong adverse predictors.
PMCID: PMC3400912  PMID: 22852001
congestive heart failure; prognosis; natriuretic peptide
8.  Statins in the Treatment of Chronic Heart Failure: A Systematic Review 
PLoS Medicine  2006;3(8):e333.
The efficacy of statin therapy in patients with established chronic heart failure (CHF) is a subject of much debate.
Methods and Findings
We conducted three systematic literature searches to assess the evidence supporting the prescription of statins in CHF. First, we investigated the participation of CHF patients in randomized placebo-controlled clinical trials designed to evaluate the efficacy of statins in reducing major cardiovascular events and mortality. Second, we assessed the association between serum cholesterol and outcome in CHF. Finally, we evaluated the ability of statin treatment to modify surrogate endpoint parameters in CHF.
Using validated search strategies, we systematically searched PubMed for our three queries. In addition, we searched the reference lists from eligible studies, used the “see related articles” feature for key publications in PubMed, consulted the Cochrane Library, and searched the ISI Web of Knowledge for papers citing key publications.
Search 1 resulted in the retrieval of 47 placebo-controlled clinical statin trials involving more than 100,000 patients. CHF patients had, however, been systematically excluded from these trials. Search 2 resulted in the retrieval of eight studies assessing the relationship between cholesterol levels and outcome in CHF patients. Lower serum cholesterol was consistently associated with increased mortality. Search 3 resulted in the retrieval of 18 studies on the efficacy of statin treatment in CHF. On the whole, these studies reported favorable outcomes for almost all surrogate endpoints.
Since CHF patients have been systematically excluded from randomized, controlled clinical cholesterol-lowering trials, the effect of statin therapy in these patients remains to be established. Currently, two large, randomized, placebo-controlled statin trials are under way to evaluate the efficacy of statin treatment in terms of reducing clinical endpoints in CHF patients in particular.
A systematic review found that patients with heart failure have been excluded from randomised controlled trials on the use of statins. Evidence from other studies on the effectiveness of statins for patients with heart failure is weak and conflicting.
Editors' Summary
When medical researchers test a drug—or some other treatment—for a particular medical condition, they often decide not to include in their study anyone who has, in addition to the disease they are interested in, certain other health problems. This is because including patients with two or more conditions can complicate the analysis of the results and make it hard to reach firm conclusions. However, excluding patients in this way can result in uncertainty as to whether treatments are effective for anyone who suffers from the disease in question, or just for people like those who took part in the research.
A great deal of research has been conducted with drugs known as statins, which lower cholesterol levels in the blood. (A raised level of cholesterol is known to be a major risk factor for cardiovascular disease, which causes heart attacks and strokes.) As a result of this research, statins have been accepted as effective and safe. They are now, in consequence, among the most commonly prescribed medicines. Heart failure, however, is not the same thing as a heart attack. It is the name given to the condition where the muscles of the heart have become weakened, most often as a result of aging, and the heart becomes gradually less efficient at pumping blood around the body. (Some people with heart failure live for many years, but 70% of those with the condition die within ten years.) It is common for people with cardiovascular disease also to have heart failure. Nevertheless, some researchers who have studied the effects of statins have made the decision not to include in their studies any patients with cardiovascular disease who, in addition, have heart failure.
Why Was This Study Done?
The researchers in this study were aware that patients with heart failure have often been excluded from statin trials. They felt it was important to assess the available evidence supporting the prescription of statins for such patients. Specifically, they wanted to find out the following: how often have patients with heart failure been included in statin trials, what evidence is available as to whether it is beneficial for patients with heart failure to have low cholesterol, and what evidence is there that prescribing statins helps these patients?
What Did the Researchers Do and Find?
They did not do any new work involving patients. Instead, they did a very thorough search for all relevant studies of good quality that had already been published and they reviewed the results. “Randomized clinical trials” (RCTs) are the most reliable type of medical research. The researchers found there had been 47 such trials (involving over 100,000 patients) on the use of statins for treating cardiovascular disease, but all these trials had excluded heart failure patients. They found eight studies (which were not RCTs) looking at cholesterol levels and heart failure. These studies found, perhaps surprisingly, that death rates were higher in those patients with heart failure who had low cholesterol. However, they also found 18 studies (again not RCTs) on the use of statins in patients with heart failure. These 18 studies seemed to suggest that statins were of benefit to the patients who received them.
What Do These Findings Mean?
The evidence for or against prescribing statins for people with heart failure is limited, conflicting, and unclear. Further research involving RTCs is necessary. (Two such trials are known to be in progress.)
Additional Information.
Please access these Web sites via the online version of this summary at
General information about statins is available from the Web site of Patient UK
The American Heart Association Web site is a good source of information about all types of heart disease, including heart attacks and heart failure
For a definition of randomized controlled trials see Wikipedia, a free online encyclopedia that anyone can edit
More detailed information about the quality of evidence from medical research may be found in the James Lind Library
PMCID: PMC1551909  PMID: 16933967
9.  Serial pulmonary function tests to diagnose COPD in chronic heart failure 
It is unknown whether serial pulmonary function tests are necessary for the correct diagnosis of chronic obstructive pulmonary disease (COPD) in patients with stable non-congested chronic heart failure (CHF). The aim of this study was to determine the prevalence of COPD in outpatients with stable CHF without pulmonary congestion using initial as well as confirmatory spirometry three months after treatment for COPD.
Spirometry was performed in 187 outpatients with stable CHF without pulmonary congestion on chest radiograph who had a left ventricular ejection fraction < 40% (mean age 69 ± 10 years, 78% men). COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. The diagnosis of COPD was confirmed three months after treatment with tiotropium in newly diagnosed COPD patients.
Using a three month follow-up spirometry to confirm initial diagnosis of de novo COPD did not change COPD prevalence significantly: 32.6% initially versus 32.1% after three months of follow-up. Only 1 of 25 (4%) patients with newly diagnosed COPD was not reproducibly obstructed at follow-up. COPD was greatly under- (19%) and overdiagnosed (32%).
Spirometry should be used under stable and euvolemic conditions to decrease the burden of undiagnosed or overdiagnosed COPD in patients with CHF. Under these conditions, a confirmatory spirometry is unnecessary, as it does not change a newly established diagnosis of COPD in the vast majority of patients with CHF.
Trial registration Identifier NCT01429376.
PMCID: PMC4177105  PMID: 25285269
Chronic obstructive pulmonary disease; Chronic heart failure; Prevalence; Serial pulmonary function tests; Underdiagnosis; Overdiagnosis
10.  Quality of congestive heart failure care 
Canadian Family Physician  2010;56(12):e432-e437.
To study the feasibility of using electronic medical record (EMR) data from the Deliver Primary Healthcare Information (DELPHI) database to measure quality of care for patients with congestive heart failure (CHF) in primary care and to determine the percentage of patients with CHF receiving the recommended care.
Items listed on the Ontario Ministry of Health and Long-Term Care Heart Failure Patient Care Flow Sheet (CHF flow sheet) were assessed and measured using EMRs of patients diagnosed with CHF between October 1, 2005, and September 30, 2008.
Ten primary health care practices in southwestern Ontario.
Four hundred eighty-eight patients who were considered to have CHF because at least 1 of the following was indicated in their EMRs: an International Classification of Diseases billing code for CHF (category 428), an International Classification of Primary Care diagnosis code for heart failure (ie, K77), or “CHF” reported on the problem list.
Number of CHF flow sheet items that were measurable using EMR data from the DELPHI database. Percentage of patients with CHF receiving required quality-of-care items since the date of diagnosis.
The DELPHI database contained information on 60 (65.9%) of the 91 items identified using the CHF flow sheet. The recommended tests and procedures were recorded infrequently: 55.5% of patients with CHF had chest radiographs; 32.6% had electrocardiograms; 32.2% had echocardiograms; 30.5% were prescribed angiotensin-converting enzyme inhibitors; 20.9% were prescribed β-blockers; and 15.8% were prescribed angiotensin II receptor blockers.
Low frequencies of recommended care items for patients with CHF were recorded in the EMR. Physicians explained that CHF care was documented in areas of the EMR that contained patient identifiers, such as the encounter notes, and was therefore not part of the DELPHI database. Extractable information from the EMR does not provide a complete picture of the quality of care provided to patients with CHF.
PMCID: PMC3001951  PMID: 21156884
11.  Comorbidities as a driver of the excess costs of community-acquired pneumonia in U.S. commercially-insured working age adults 
Adults with certain comorbid conditions have a higher risk of pneumonia than the overall population. If treatment of pneumonia is more costly in certain predictable situations, this would affect the value proposition of populations for pneumonia prevention. We estimate the economic impact of community-acquired pneumonia (CAP) for adults with asthma, diabetes, chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF) in a large U.S. commercially-insured working age population.
Data sources consisted of 2003 through 2007 Thomson Reuters MarketScan Commercial Claims and Encounters and Thomson Reuters Health Productivity and Management (HPM) databases. Pneumonia episodes and selected comorbidities were identified by ICD-9-CM diagnosis codes. By propensity score matching, controls were identified for pneumonia patients. Excess direct medical costs and excess productivity cost were estimated by generalized linear models (GLM).
We identified 402,831 patients with CAP between 2003 through 2007, with 25,560, 32,677, 16,343, and 5,062 episodes occurring in patients with asthma, diabetes, COPD and CHF, respectively. Mean excess costs (and standard error, SE) of CAP were $14,429 (SE=44) overall. Mean excess costs by comorbidity subgroup were lowest for asthma ($13,307 (SE=123)), followed by diabetes ($21,395 (SE=171)) and COPD ($23,493 (SE=197)); mean excess costs were highest for patients with CHF ($34,436 (SE=549)). On average, indirect costs comprised 21% of total excess costs, ranging from 8% for CHF patients to 27% for COPD patients.
Compared to patients without asthma, diabetes, COPD, or CHF, the excess cost of CAP is nearly twice as high for patients with diabetes and COPD and nearly three times as high for patients with CHF. Indirect costs made up a significant but varying portion of excess CAP costs. Returns on prevention of pneumonia would therefore be higher in adults with these comorbidities.
PMCID: PMC3585380  PMID: 23113880
Community-acquired pneumonia (CAP); Medical cost; Productivity cost; Economic evaluation; Asthma; Diabetes; Chronic Obstructive Pulmonary Disease (COPD); Congestive Heart Failure (CHF)
12.  Ivabradine Treatment in a Chronic Heart Failure Patient Cohort: Symptom Reduction and Improvement in Quality of Life in Clinical Practice 
Advances in Therapy  2014;31(9):961-974.
In the prospective, open-label multicenter INTENSIFY study, the effectiveness and tolerability of ivabradine as well as its impact on quality of life (QOL) in chronic systolic heart failure (CHF) patients were evaluated over a 4-month period.
In CHF patients with an indication for treatment with ivabradine, resting heart rate (HR), heart failure symptoms [New York Heart Association (NYHA) class, signs of decompensation], left ventricular ejection fraction, brain natriuretic peptide (BNP) values, QOL, and concomitant medication with focus on beta-blocker therapy were documented at baseline, after 4 weeks, and after 4 months. The results were analyzed using descriptive statistical methods.
Thousand nine hundred and fifty-six patients with CHF were included. Their mean age was 67 ± 11.7 years and 56.9% were male. 77.8% were receiving beta-blockers. Other concomitant medications included angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (83%), diuretics (61%), aldosterone antagonists (18%), and cardiac glycosides (8%). At baseline, the mean HR of patients was 85 ± 11.8 bpm, 51.1% and 37.2% of patients were classified as NYHA II and III, respectively, and 22.7% showed signs of decompensation. BNP concentrations were tracked in a subgroup, and values exceeding 400 pg/mL were noted in 53.9% of patients. The mean value of the European quality of life-5 dimensions (EQ-5D) QOL index was 0.64 ± 0.28. After 4 months of treatment with ivabradine, HR was reduced to 67 ± 8.9 bpm. Furthermore, the proportion of patients presenting with signs of decompensation decreased to 5.4% and the proportion of patients with BNP levels >400 pg/mL dropped to 26.7%, accompanied by a shift in NYHA classification towards lower grading (24.0% and 60.5% in NYHA I and II, respectively). EQ-5D index improved to 0.79 ± 0.21.
Over 4 months of treatment, ivabradine effectively reduced HR and symptoms in CHF patients in this study reflecting daily clinical practice. These benefits were accompanied by improved QOL and good general tolerability.
Electronic supplementary material
The online version of this article (doi:10.1007/s12325-014-0147-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4177104  PMID: 25160945
Cardiology; Chronic heart failure; Heart rate; Ivabradine; NYHA class; Quality of life; Symptom reduction
13.  Can Peak Expiratory Flow Measurements Differentiate Chronic Obstructive Pulmonary Disease from Congestive Heart Failure? 
Dyspneic patients are commonly encountered by Emergency Medical Service (EMS). Frequent causes include Chronic Obstructive Pulmonary Disease (COPD) and Congestive Heart Failure (CHF). Measurement of peak expiratory flow rate (PEFR) has been proposed to help differentiate COPD from CHF. This prospective, cohort, pilot study was conducted to determine if PEFR in patients with an exacerbation of COPD were significantly different than CHF. Included were patients presenting with dyspnea plus a history of COPD and/or CHF. A PEFR was measured, values were compared to predicted average, and a percentage was calculated. Twenty-one patients were enrolled. Six had a diagnosis of COPD, 12 CHF; 3 had other diagnoses. Mean percentage of predicted PEFR with COPD was 26.36%, CHF 48.9% (P = 0.04). Patients presenting with acute COPD had significantly lower percentage of predicted PEFR than those with CHF. These results suggest that PEFR may be useful in differentiating COPD from CHF. This study should be expanded to the prehospital setting with a larger number of subjects.
PMCID: PMC3205738  PMID: 22114739
14.  Heart rate variability and its relation to ventricular arrhythmias in congestive heart failure. 
British Heart Journal  1994;71(4):322-328.
BACKGROUND--It has been shown that heart rate variability is decreased in patients with congestive heart failure and that depressed heart rate variability is associated with a propensity to ventricular arrhythmias. Little is known, however, about heart rate variability in patients with both congestive heart failure and ventricular arrhythmias. METHODS--Spectral heart rate variability was analysed from 24 hour ambulatory electrocardiograms in 15 controls, 15 patients with non-sustained ventricular tachycardia associated with clinically normal hearts (NHVT group), and 40 patients with congestive heart failure (CHF group) secondary to either ischaemic heart disease (n = 15) or idiopathic dilated cardiomyopathy (n = 25). Of the 40 patients with congestive heart failure 15 had no appreciable ventricular arrhythmias (ventricular extrasystoles < 10 beats/h and no salvos) and formed the CHF-VA- group. Another 15 patients with congestive heart failure and non-sustained ventricular tachycardia formed the CHF-NSVT group. RESULTS--Heart rate variability was significantly lower in the CHF group than in controls (mean (SD) total frequency 23 (12) v 43 (13) ms; low frequency 12 (8) v 28 (9) ms; high frequency 8 (5) v 14 (7) ms; p < 0.001). The differences in heart rate variability between controls and the NHVT group, between ischaemic heart disease and dilated cardiomyopathy, and between the CHF-VA- and CHF-NSVT groups were not significant. In the CHF group heart rate variability was significantly related to left ventricular ejection fraction but not associated with ventricular arrhythmias. The frequency of ventricular extrasystoles was significantly related to the high frequency component of heart rate variability (r = 0.54, p < 0.05) in the NHVT group. Stepwise multiple regression analysis showed that in the CHF group, heart rate variability was predominantly related to left ventricular ejection fraction (p < 0.05). There was no significant difference in heart rate variability between survivors (n = 34) and those who died suddenly (n = 6) at one year of follow up in the CHF group. CONCLUSION--In patients with congestive heart failure, heart rate variability is significantly decreased. The depressed heart rate variability is principally related to the degree of left ventricular impairment and is independent of aetiology and the presence of ventricular arrhythmias. The data suggest that analysis of heart rate variability does not help the identification of patients with congestive heart failure at increased risk of sudden death.
PMCID: PMC483680  PMID: 8198881
15.  Association of Hospital Spending Intensity With Mortality and Readmission Rates in Ontario Hospitals 
Jama  2012;307(10):1037-1045.
The extent to which better spending produces higher-quality care and better patient outcomes in a universal health care system with selective access to medical technology is unknown.
To assess whether acute care patients admitted to higher-spending hospitals have lower mortality and readmissions.
Design, Setting, and Patients
The study population comprised adults (> 18 years) in Ontario, Canada, with a first admission for acute myocardial infarction (AMI) (n=179 139), congestive heart failure (CHF) (n=92 377), hip fracture (n=90 046), or colon cancer (n=26 195) during 1998–2008, with follow-up to 1 year. The exposure measure was the index hospital’s end-of-life expenditure index for hospital, physician, and emergency department services.
Main Outcome Measures
The primary outcomes were 30-day and 1-year mortality and readmissions and major cardiac events (readmissions for AMI, angina, CHF, or death) for AMI and CHF.
Patients’ baseline health status was similar across hospital expenditure groups. Patients admitted to hospitals in the highest- vs lowest-spending intensity terciles had lower rates of all adverse outcomes. In the highest- vs lowest-spending hospitals, respectively, the age- and sex-adjusted 30-day mortality rate was 12.7% vs 12.8% for AMI, 10.2% vs 12.4% for CHF, 7.7% vs 9.7% for hip fracture, and 3.3% vs 3.9% for CHF; fully adjusted relative 30-day mortality rates were 0.93 (95% CI, 0.89–0.98) for AMI, 0.81 (95% CI, 0.76–0.86) for CHF, 0.74 (95% CI, 0.68–0.80) for hip fracture, and 0.78 (95% CI, 0.66–0.91) for colon cancer. Results for 1-year mortality, readmissions, and major cardiac events were similar. Higher-spending hospitals had higher nursing staff ratios, and their patients received more inpatient medical specialist visits, interventional (AMI cohort) and medical (AMI and CHF cohorts) cardiac therapies, preoperative specialty care (colon cancer cohort), and postdischarge collaborative care with a cardiologist and primary care physician (AMI and CHF cohorts).
Among Ontario hospitals, higher spending intensity was associated with lower mortality, readmissions, and cardiac event rates.
PMCID: PMC3339410  PMID: 22416099
16.  An Internet-Based Counseling Intervention With Email Reminders that Promotes Self-Care in Adults With Chronic Heart Failure: Randomized Controlled Trial Protocol 
JMIR Research Protocols  2014;3(1):e5.
Chronic heart failure (CHF) is a public health priority. Its age-standardized prevalence has increased over the past decade. A major challenge for the management of CHF is to promote long-term adherence to self-care behaviors without overtaxing available health care resources. Counseling by multidisciplinary health care teams helps to improve adherence to self-care behaviors and to reduce the rate of death and hospitalization. In the absence of intervention, adherence to self-care is below recommended standards.
This trial aims to establish and evaluate a Canadian e-platform that will provide a core, standardized protocol of behavioral counseling and education to facilitate long-term adherence to self-care among patients with CHF.
Canadian e-Platform to Promote Behavioral Self-Management in Chronic Heart Failure (CHF-CePPORT) is a multi-site, double blind, randomized controlled trial with a 2 parallel-group (e-Counseling + Usual Care vs e-Info Control + Usual Care) by 3 assessments (baseline, 4-, and 12-month) design. We will identify subjects with New York Heart Association Class II or III systolic heart failure from collaborating CHF clinics and then recruit them (n=278) by phone. Subjects will be randomized in blocks within each site (Toronto, Montreal, and Vancouver). The primary outcome will be improved quality of life, defined as an increased number of subjects with an improvement of ≥5 points on the summary score of the Kansas City Cardiomyopathy Questionnaire. We will also assess the following secondary outcomes: (1) diet habits, depression, anxiety, smoking history, stress level, and readiness for change using self-report questionnaires, (2) physical activity level, current smoking status, and vagal-heart rate modulation by physiological tests, and (3) exercise capacity, prognostic indicators of cardiovascular functioning, and medication adherence through medical chart review. The primary outcome will be analyzed using generalized estimation equations with repeated measures on an intention-to-treat basis. Secondary outcomes will be analyzed using repeated-measures linear mixed models with a random effects intercept. All significant main effects or interactions in the statistical models will be followed up with post hoc contrasts using a Bonferroni correction with a 2-sided statistical significance criterion of P<.05.
This 3.5-year, proof-of-principle trial will establish the e-infrastructure for a pan-Canadian e-platform for CHF that is comprised of a standardized, evidence-based protocol of e-Counseling.
CHF-CePPORT is designed to improve long-term adherence to self-care behaviors and quality of life among patients with CHF. It will demonstrate a distinct Canadian initiative to build capacity for preventive eHealth services for patients with CHF.
Trial Registration NCT01864369; (Archived by WebCite at
PMCID: PMC3936276  PMID: 24480783
e-counseling; chronic heart failure; lifestyle intervention; Internet-based intervention; quality of life
17.  Pioglitazone Initiation and Subsequent Hospitalisation for Congestive Heart Failure 
Thiazolidinediones (TZD) have been associated with an expansion in plasma volume and the development of peripheral oedema. A recent study reported an association between the use of TZDs and development of congestive heart failure (CHF). The objective of this study was to determine if short-term use of pioglitazone, a TZD, is associated with increased risk of CHF hospitalisation in a well-characterised, community-based cohort of type 2 diabetic patients without prevalent CHF.
A cohort study of all patients in the Kaiser Permanente Medical Care Program with type 2 diabetes (Kaiser Permanente Northern California Diabetes Registry) who initiated any diabetes pharmacotherapy (n=23,440) between October, 1999 and November, 2001. Only patients initiating single new therapies (“new users”) were included to reduce confounding and create mutually-exclusive exposure groups. We constructed Cox proportional hazards models (with sulfonylureas initiators specified as the reference group) to evaluate the impact of initiating new diabetes therapies on time to incident CHF hospitalisation, defined by primary hospital discharge diagnosis.
Patients initiated pioglitazone (15.2%), sulfonylureas (25.3%), metformin (50.9%), and insulin (8.6%) alone or as additions to pre-existing or maintained therapies. Three hundred and twenty CHF hospitalisations were observed during the follow-up (10.2 months on average) after initiation. Relative to sulfonylurea initiators, there were no significant increases in the incidence of CHF hospitalisation among those initiating pioglitazone (hazard ratio (HR) = 1.28; 95% confidence interval (CI): 0.85 – 1.92) after adjusting for demographic, behavioural, and clinical factors. There was a significantly higher incidence among those initiating insulin (HR = 1.56; 95% CI: 1.00 – 2.45) and lower incidence among those initiating metformin, (HR = 0.70; 95% CI: 0.49 – 0.99).
This study of patients with type 2 diabetes failed to find evidence that short-term pioglitazone use was associated with an elevated risk of CHF hospitalisation relative to the standard, first line diabetes therapy.
PMCID: PMC3557913  PMID: 16026362
diabetes mellitus; congestive heart failure; thiazolidinediones; pioglitazone; hypoglycaemic agents; pharmacoepidemiology; new user design
18.  The Methionine 196 Arginine Polymorphism of the TNF Receptor 2 Gene (TNFRSF1B) is Not Associated with Worse Outcomes in Heart Failure 
Cytokine  2012;60(3):838-842.
Tumor necrosis factor α (TNFα) may contribute to the pathologic process of congestive heart failure (CHF). TNFα signaling occurs through two receptors; TNFR1 (TNFRSF1A) and TNFRII (TNFRSF1B). In humans a single nucleotide polymorphism (rs1061622 in TNFRSF1B exon 6; T587G) encodes two different amino acids (M196R) in the transmembrane region . The 587G allele is associated with greater severity and/or prevalence of some inflammatory diseases, but its role in CHF in unknown. This study sought to test the hypothesis that the 587G allele is associated with a worse outcome or more severe phenotype in CHF. Peripheral blood DNA was isolated and genotyped from 379 heart failure patients enrolled in a genetic outcome study (GRACE); (44.7% ischemic, 70.4% male, 8.5% black race, age 55.6+/−11.7 yr (SD), LVEF 0.245+/−8.3%, NYHA 2.53+/−0.64). Genotyping was performed by PCR-RFLP. Cardiac function was assessed from medical records at study entry. The distribution of genotypes in this population was 54% T/T, 38.4% G/T, and 7.7% G/G. Mean LV ejection fraction (T/T 24.4+/−8.2, T/G 25.0+/−8.4, G/G 23.3+/−8.6, n=352, p=ns) and LV end-diastolic dimensions (T/T 6.57+/−0.93, T/G 6.53+/−1.0, G/G 6.57+/−0.78, n=211, p=ns) were comparable in all groups. Transplant-free survival (median 23 months (range 1–62 months) did not vary by genotype (p=0.95). A lack of effect (p=0.74) on transplant-free survival was also observed in a subset of patients with ischemic heart failure (n=169). The TNFRSF1B 587G allele is not associated with the severity of heart failure phenotype or clinical outcomes in patients with chronic CHF.
PMCID: PMC3592567  PMID: 22921902
Tumor Necrosis Factor α; TNF receptor; polymorphisms; heart failure
19.  Heart failure in patients with preserved and deteriorated left ventricular ejection fraction 
Heart  2005;91(4):489-494.
Objectives: To determine clinical and prognostic differences between preserved and deteriorated systolic function (defined as left ventricular (LV) ejection fractions ⩾ 50% and < 50%, respectively) in patients with heart failure satisfying modified Framingham criteria.
Patients and methods: Records were studied of 1252 patients with congestive heart failure (CHF) (mean (SD) age 69.4 (11.7) years; 485 women, 767 men) who had been admitted to a cardiology service for CHF in the period 1991–2002 and whose LV systolic function had been echocardiographically evaluated within two weeks of admission. Data were collected on the main clinical findings, supplementary examinations, treatment, and duration of hospitalisation. Whether the patient was alive in the spring of 2003 was evaluated by searching the general archives of the hospital and by telephone survey.
Results: LV systolic function was preserved in 39.8% of patients. Age, female to male sex ratio, and prevalence of atrial fibrillation, valve disease, and other non-ischaemic, non-dilated cardiopathies were all significantly greater in the group with preserved systolic function. New York Heart Association functional class IV, third heart sound, jugular vein congestion, cardiomegaly, radiological signs of lung oedema, pathological Q waves, left bundle branch block, sinus rhythm, ischaemic cardiopathy, and dilated cardiomyopathy were all significantly more prevalent in the group with deteriorated systolic function, as was treatment with angiotensin converting enzyme inhibitors and most other antihypertensive drugs on discharge from hospital. There was no significant difference in survival between the groups with preserved and deteriorated systolic function (either survival regardless of age at admission or in subgroups aged < 75 and ⩾ 75 years at admission). In the whole group, survival rates after one, three, and five years were 84.0%, 66.7%, and 50.9%, respectively.
Conclusion: In view of the poor prognosis of patients with CHF with preserved LV systolic function, who are currently treated empirically, it is to be hoped that relevant controlled clinical trials under way will afford information allowing optimisation of their treatment.
PMCID: PMC1768853  PMID: 15772209
heart failure; prognosis; preserved systolic function; deteriorated systolic function
20.  Incidence and Cost of Pneumonia in Older Adults with COPD in the United States 
PLoS ONE  2013;8(10):e75887.
To estimate the incidence of pneumonia by COPD status and the excess cost of inpatient primary pneumonia in elders with COPD.
Study Design
A retrospective, longitudinal study using claims linked to eligibility/demographic data for a 5% sample of fee-for-service Medicare beneficiaries from 2005 through 2007.
Incidence rates of pneumonia were calculated for elders with and without COPD and for elders with COPD and coexistent congestive heart failure (CHF). Propensity-score matching with multivariate generalized linear regression was used to estimate the excess direct medical cost of inpatient primary pneumonia in elders with COPD as compared with elders with COPD but without a pneumonia hospitalization.
Elders with COPD had nearly six-times the incidence of pneumonia compared with elders without COPD (167.6/1000 person-years versus 29.5/1000 person-years; RR=5.7, p <0 .01); RR increased to 8.1 for elders with COPD and CHF compared with elders without COPD. The incidence of inpatient primary pneumonia among elders with COPD was 54.2/1000 person-years compared with 7/1000 person-years for elders without COPD; RR=7.7, p<0.01); RR increased to 11.0 for elders with COPD and CHF compared with elders without COPD. The one-year excess direct medical cost of inpatient pneumonia in COPD patients was $ 22,697 ($45,456 in cases vs. $ 22,759 in controls (p <0.01)); 70.2% of this cost was accrued during the quarter of the index hospitalization. During months 13 through 24 following the index hospitalization, the excess direct medical cost was $ 5,941 ($23,215 in cases vs. $ 17,274 in controls, p<0.01).
Pneumonia occurs more frequently in elders with COPD than without COPD. The excess direct medical cost in elders with inpatient pneumonia extends up to 24 months following the index hospitalization and represents $28,638 in 2010 dollars.
PMCID: PMC3794002  PMID: 24130749
21.  Plasma Leptin Levels and Incidence of Heart Failure, Cardiovascular Disease, and Total Mortality in Elderly Individuals 
Diabetes Care  2008;32(4):612-616.
Obesity predisposes individuals to congestive heart failure (CHF) and cardiovascular disease (CVD). Leptin regulates energy homeostasis, is elevated in obesity, and influences ventricular and vascular remodeling. We tested the hypothesis that leptin levels are associated with greater risk of CHF, CVD, and mortality in elderly individuals.
We evaluated 818 elderly (mean age 79 years, 62% women) Framingham Study participants attending a routine examination at which plasma leptin was assayed.
Leptin levels were higher in women and strongly correlated with BMI (P < 0.0001). On follow-up (mean 8.0 years), 129 (of 775 free of CHF) participants developed CHF, 187 (of 532 free of CVD) experienced a first CVD event, and 391 individuals died. In multivariable Cox regression models adjusting for established risk factors, log-leptin was positively associated with incidence of CHF and CVD (hazard ratio [HR] per SD increment 1.26 [95% CI 1.03–1.55] and 1.28 [1.09–1.50], respectively). Additional adjustment for BMI nullified the association with CHF (0.97 [0.75–1.24]) but only modestly attenuated the relation to CVD incidence (1.23 [1.00–1.51], P = 0.052). We observed a nonlinear, U-shaped relation between log-leptin and mortality (P = 0.005 for quadratic term) with greater risk of death evident at both low and high leptin levels.
In our moderate-sized community-based elderly sample, higher circulating leptin levels were associated with a greater risk of CHF and CVD, but leptin did not provide incremental prognostic information beyond BMI. Additional investigations are warranted to elucidate the U-shaped relation of leptin to mortality.
PMCID: PMC2660448  PMID: 19114611
22.  Social deprivation increases cardiac hospitalisations in chronic heart failure independent of disease severity and diuretic non-adherence 
Heart  2000;83(1):12-16.
OBJECTIVE—To examine whether social deprivation has any independent effect on emergency cardiac hospitalisations in patients with chronic heart failure (CHF).
DESIGN—Cohort study of 478 patients with CHF who had been hospitalised before 1993 and who were followed up during 1993 and 1994.
SETTING—Emergency admissions within Tayside acute hospitals.
PATIENTS—478 CHF patients who had a previous myocardial infarction, a previous CHF admission, and were on diuretic treatment.
MAIN OUTCOME MEASURES—Emergency hospital admissions are divided into those for all causes and those for cardiac causes only.
RESULTS—Social deprivation was significantly associated with an increase in the number of cardiac hospitalisations (p = 0.007). This effect was mainly caused by increasing the proportion of patients hospitalised in each deprivation category (26% in deprivation category 1-2 versus 40% in deprivation category 5-6, p = 0.03). This effect of deprivation was independent of disease severity, as judged by the dose of prescribed diuretic, the death rate, and the duration of each hospital stay. Non-adherence with diuretic treatment could not account for these findings either.
CONCLUSIONS—Social deprivation increases the chance of a CHF patient being rehospitalised independently of disease severity. Possible explanations are that doctors who look after socially deprived patients have a lower threshold for cardiac hospitalisation of their patients, or that social deprivation alters the way a CHF patient accesses medical care during decompensation. Understanding how social deprivation influences both doctor and patient behaviour in the prehospital phase is now crucial in order to reduce the amplifying effect that social deprivation appears to have on cardiac hospitalisations.

Keywords: chronic heart failure; hospitalisations; social deprivation
PMCID: PMC1729263  PMID: 10618326
23.  Prevention of relapse in patients with congestive heart failure: the role of precipitating factors 
Heart  1998;80(5):432-436.
Relapse of congestive heart failure (CHF) frequently occurs and has serious consequences in terms of morbidity, mortality, and health care expenditure. Many studies have investigated the aetiological and prognostic factors of CHF, but there are only limited data on the role of precipitating factors that trigger relapse of CHF. Knowledge of potential precipitating factors may help to optimise treatment and provide guidance for patients with CHF. The literature was reviewed to identify factors that may influence haemodynamic homeostasis in CHF. Precipitating factors that may offer opportunities for preventing relapse of CHF were selected. Potential precipitating factors are discussed in relation to the pathophysiology of CHF: alcohol, smoking, psychological stress, uncontrolled hypertension, cardiac arrhythmias, myocardial ischaemia, poor treatment compliance, and inappropriate medical treatment. Poor treatment compliance in particular is frequently encountered in patients with CHF. Furthermore, studies of medical treatment under everyday circumstances indicate that some aspects of the management of CHF can be improved. In conclusion, the identification of precipitating factors for relapse of CHF may strongly contribute to optimal treatment. Improvement of treatment compliance and optimalisation of medical treatment may offer important possibilities to clinicians to reduce the number of relapses in patients with CHF.

 Keywords: congestive heart failure;  precipitating factors;  prevention
PMCID: PMC1728829  PMID: 9930039
24.  The Effect of Congestive Heart Failure on Sensor Accuracy Among Hospitalized Patients with Type 2 Diabetes 
Diabetes Technology & Therapeutics  2013;15(10):817-824.
Congestive heart failure (CHF) features disturbances in the interstitial environment that may affect the accuracy of subcutaneous continuous glucose monitoring (CGM).
Subjects and Methods
A pooled analysis of two studies of hospitalized patients with type 2 diabetes randomized to intravenous or subcutaneous insulin was conducted. One study enrolled patients with CHF exacerbation, whereas history of CHF was an exclusion criterion in the other. All patients wore a professional CGM device for at least 24 h. Intravenous insulin was administered according to the institution's nursing-run protocol (duration of 12 and 48 h in non-CHF and CHF protocols, respectively). Subcutaneous insulin was delivered similarly in both groups.
Subjects with CHF (n=43) had higher admission glucose and hemoglobin A1c compared with non-CHF subjects (n=32), but the sensor glucose values were similar. Overall mean absolute relative difference (MARD) was similar between CHF and non-CHF subjects (0.11 vs. 0.08, respectively; P=0.12). MARD was higher in the 100–149 mg/dL (P=0.003) and >199 mg/dL (P=0.02) strata among CHF subjects. Static glucose and continuous glucose error grid analyses favored the non-CHF group. In multivariable analyses, only glucose coefficient of variation and log sensor time were independent predictors of elevated overall MARD >0.10. After adjustment for other factors, only increasing log sensor time was a significant predictor of elevated MARD in the 100–149 mg/dL strata.
Among hospitalized subjects with type 2 diabetes, CHF exacerbation is not associated with lower sensor accuracy after adjustment for other factors, but this requires confirmation over a wider glucose range.
PMCID: PMC3781123  PMID: 24050738
25.  Community-Based Care for the Specialized Management of Heart Failure 
Executive Summary
In August 2008, the Medical Advisory Secretariat (MAS) presented a vignette to the Ontario Health Technology Advisory Committee (OHTAC) on a proposed targeted health care delivery model for chronic care. The proposed model was defined as multidisciplinary, ambulatory, community-based care that bridged the gap between primary and tertiary care, and was intended for individuals with a chronic disease who were at risk of a hospital admission or emergency department visit. The goals of this care model were thought to include: the prevention of emergency department visits, a reduction in hospital admissions and re-admissions, facilitation of earlier hospital discharge, a reduction or delay in long-term care admissions, and an improvement in mortality and other disease-specific patient outcomes.
OHTAC approved the development of an evidence-based assessment to determine the effectiveness of specialized community based care for the management of heart failure, Type 2 diabetes and chronic wounds.
Please visit the Medical Advisory Secretariat Web site at: to review the following reports associated with the Specialized Multidisciplinary Community-Based care series.
Specialized multidisciplinary community-based care series: a summary of evidence-based analyses
Community-based care for the specialized management of heart failure: an evidence-based analysis
Community-based care for chronic wound management: an evidence-based analysis
Please note that the evidence-based analysis of specialized community-based care for the management of diabetes titled: “Community-based care for the management of type 2 diabetes: an evidence-based analysis” has been published as part of the Diabetes Strategy Evidence Platform at this URL:
Please visit the Toronto Health Economics and Technology Assessment Collaborative Web site at: to review the following economic project associated with this series:
Community-based Care for the specialized management of heart failure: a cost-effectiveness and budget impact analysis.
The objective of this evidence-based analysis was to determine the effectiveness of specialized multidisciplinary care in the management of heart failure (HF).
Clinical Need: Target Population and Condition
HF is a progressive, chronic condition in which the heart becomes unable to sufficiently pump blood throughout the body. There are several risk factors for developing the condition including hypertension, diabetes, obesity, previous myocardial infarction, and valvular heart disease.(1) Based on data from a 2005 study of the Canadian Community Health Survey (CCHS), the prevalence of congestive heart failure in Canada is approximately 1% of the population over the age of 12.(2) This figure rises sharply after the age of 45, with prevalence reports ranging from 2.2% to 12%.(3) Extrapolating this to the Ontario population, an estimated 98,000 residents in Ontario are believed to have HF.
Disease management programs are multidisciplinary approaches to care for chronic disease that coordinate comprehensive care strategies along the disease continuum and across healthcare delivery systems.(4) Evidence for the effectiveness of disease management programs for HF has been provided by seven systematic reviews completed between 2004 and 2007 (Table 1) with consistency of effect demonstrated across four main outcomes measures: all cause mortality and hospitalization, and heart-failure specific mortality and hospitalization. (4-10)
However, while disease management programs are multidisciplinary by definition, the published evidence lacks consistency and clarity as to the exact nature of each program and usual care comparators are generally ill defined. Consequently, the effectiveness of multidisciplinary care for the management of persons with HF is still uncertain. Therefore, MAS has completed a systematic review of specialized, multidisciplinary, community-based care disease management programs compared to a well-defined usual care group for persons with HF.
Evidence-Based Analysis Methods
Research Questions
What is the effectiveness of specialized, multidisciplinary, community-based care (SMCCC) compared with usual care for persons with HF?
Literature Search Strategy
A comprehensive literature search was completed of electronic databases including MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Library and Cumulative Index to Nursing & Allied Health Literature. Bibliographic references of selected studies were also searched. After a review of the title and abstracts, relevant studies were obtained and the full reports evaluated. All studies meeting explicit inclusion and exclusion criteria were retained. Where appropriate, a meta-analysis was undertaken to determine the pooled estimate of effect of specialized multidisciplinary community-based care for explicit outcomes. The quality of the body of evidence, defined as one or more relevant studies was determined using GRADE Working Group criteria. (11)
Inclusion Criteria
Randomized controlled trial
Systematic review with meta analysis
Population includes persons with New York Heart Association (NYHA) classification 1-IV HF
The intervention includes a team consisting of a nurse and physician one of which is a specialist in HF management.
The control group receives care by a single practitioner (e.g. primary care physician (PCP) or cardiologist)
The intervention begins after discharge from the hospital
The study reports 1-year outcomes
Exclusion Criteria
The intervention is delivered predominately through home-visits
Studies with mixed populations where discrete data for HF is not reported
Outcomes of Interest
All cause mortality
All cause hospitalization
HF specific mortality
HF specific hospitalization
All cause duration of hospital stay
HF specific duration of hospital stay
Emergency room visits
Quality of Life
Summary of Findings
One large and seven small randomized controlled trials were obtained from the literature search.
A meta-analysis was completed for four of the seven outcomes including:
All cause mortality
HF-specific mortality
All cause hospitalization
HF-specific hospitalization.
Where the pooled analysis was associated with significant heterogeneity, subgroup analyses were completed using two primary categories:
direct and indirect model of care; and
type of control group (PCP or cardiologist).
The direct model of care was a clinic-based multidisciplinary HF program and the indirect model of care was a physician supervised, nurse-led telephonic HF program.
All studies, except one, were completed in jurisdictions outside North America. (12-19) Similarly, all but one study had a sample size of less than 250. The mean age in the studies ranged from 65 to 77 years. Six of the studies(12;14-18) included populations with a NYHA classification of II-III. In two studies, the control treatment was a cardiologist (12;15) and two studies reported the inclusion of a dietitian, physiotherapist and psychologist as members of the multidisciplinary team (12;19).
All Cause Mortality
Eight studies reported all cause mortality (number of persons) at 1 year follow-up. (12-19) When the results of all eight studies were pooled, there was a statistically significant RRR of 29% with moderate heterogeneity (I2 of 38%). The results of the subgroup analyses indicated a significant RRR of 40% in all cause mortality when SMCCC is delivered through a direct team model (clinic) and a 35% RRR when SMCCC was compared with a primary care practitioner.
HF-Specific Mortality
Three studies reported HF-specific mortality (number of persons) at 1 year follow-up. (15;18;19) When the results of these were pooled, there was an insignificant RRR of 42% with high statistical heterogeneity (I2 of 60%). The GRADE quality of evidence is moderate for the pooled analysis of all studies.
All Cause Hospitalization
Seven studies reported all cause hospitalization at 1-year follow-up (13-15;17-19). When pooled, their results showed a statistically insignificant 12% increase in hospitalizations in the SMCCC group with high statistical heterogeneity (I2 of 81%). A significant RRR of 12% in all cause hospitalization in favour of the SMCCC care group was achieved when SMCCC was delivered using an indirect model (telephonic) with an associated (I2 of 0%). The Grade quality of evidence was found to be low for the pooled analysis of all studies and moderate for the subgroup analysis of the indirect team care model.
HF-Specific Hospitalization
Six studies reported HF-specific hospitalization at 1-year follow-up. (13-15;17;19) When pooled, the results of these studies showed an insignificant RRR of 14% with high statistical heterogeneity (I2 of 60%); however, the quality of evidence for the pooled analysis of was low.
Duration of Hospital Stay
Seven studies reported duration of hospital stay, four in terms of mean duration of stay in days (14;16;17;19) and three in terms of total hospital bed days (12;13;18). Most studies reported all cause duration of hospital stay while two also reported HF-specific duration of hospital stay. These data were not amenable to meta-analyses as standard deviations were not provided in the reports. However, in general (and in all but one study) it appears that persons receiving SMCCC had shorter hospital stays, whether measured as mean days in hospital or total hospital bed days.
Emergency Room Visits
Only one study reported emergency room visits. (14) This was presented as a composite of readmissions and ER visits, where the authors reported that 77% (59/76) of the SMCCC group and 84% (63/75) of the usual care group were either readmitted or had an ER visit within the 1 year of follow-up (P=0.029).
Quality of Life
Quality of life was reported in five studies using the Minnesota Living with HF Questionnaire (MLHFQ) (12-15;19) and in one study using the Nottingham Health Profile Questionnaire(16). The MLHFQ results are reported in our analysis. Two studies reported the mean score at 1 year follow-up, although did not provide the standard deviation of the mean in their report. One study reported the median and range scores at 1 year follow-up in each group. Two studies reported the change scores of the physical and emotional subscales of the MLHFQ of which only one study reported a statistically significant change from baseline to 1 year follow-up between treatment groups in favour of the SMCCC group in the physical sub-scale. A significant change in the emotional subscale scores from baseline to 1 year follow-up in the treatment groups was not reported in either study.
There is moderate quality evidence that SMCCC reduces all cause mortality by 29%. There is low quality evidence that SMCCC contributes to a shorter duration of hospital stay and improves quality of life compared to usual care. The evidence supports that SMCCC is effective when compared to usual care provided by either a primary care practitioner or a cardiologist. It does not, however, suggest an optimal model of care or discern what the effective program components are. A field evaluation could address this uncertainty.
PMCID: PMC3377506  PMID: 23074521

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