Global Variations in Heart Failure Etiology, Management, and Outcomes.

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

Cost-Effectiveness of Coronary Artery Bypass Surgery Versus Medicine in Ischemic Cardiomyopathy: The STICH Randomized Clinical Trial.

BACKGROUND: The STICH Randomized Clinical Trial (Surgical Treatment for Ischemic Heart Failure) demonstrated that coronary artery bypass grafting (CABG) reduced all-cause mortality rates out to 10 years compared with medical therapy alone (MED) in patients with ischemic cardiomyopathy and reduced left ventricular function (ejection fraction ≤35%). We examined the economic implications of these results. METHODS: We used a decision-analytic patient-level simulation model to estimate the lifetime costs and benefits of CABG and MED using patient-level resource use and clinical data collected in the STICH trial. Patient-level costs were calculated by applying externally derived US cost weights to resource use counts during trial follow-up. A 3% discount rate was applied to both future costs and benefits. The primary outcome was the incremental cost-effectiveness ratio assessed from the US health care sector perspective. RESULTS: For the CABG arm, we estimated 6.53 quality-adjusted life-years (95% CI, 5.70-7.53) and a lifetime cost of $140 059 (95% CI, $106 401 to $180 992). For the MED arm, the corresponding estimates were 5.52 (95% CI, 5.06-6.09) quality-adjusted life-years and $74 894 lifetime cost (95% CI, $58 372 to $93 541). The incremental cost-effectiveness ratio for CABG compared with MED was $63 989 per quality-adjusted life-year gained. At a societal willingness-to-pay threshold of $100 000 per quality-adjusted life-year gained, CABG was found to be economically favorable compared with MED in 87% of microsimulations. CONCLUSIONS: In the STICH trial, in patients with ischemic cardiomyopathy and reduced left ventricular function, CABG was economically attractive relative to MED at current benchmarks for value in the United States. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00023595.

Performances on the Montreal Cognitive Assessment Along the Cardiovascular Disease Continuum.

Cardiovascular diseases involve a continuum starting with risk factors, which can progress to coronary heart disease and eventually, to heart failure. Cognitive impairment (CI) is observed as early as cardiovascular risk factors, and in up to 50% of patients with heart failure. Because CI in cardiovascular disease is linked to poorer clinical outcomes, early detection is essential. The Montreal Cognitive Assessment (MoCA) is a screening tool widely used in clinical setting. To date, little is known about MoCA scores along the cardiovascular disease continuum. OBJECTIVE: This study compared performances of different cardiovascular disease profiles on the MoCA and its subscores. METHOD: Eighty participants (>50 years) from two studies conducted at the Montreal Heart Institute were separated into four groups: low cardiovascular risk factors (<2), high cardiovascular risk factors (>2), coronary heart disease, and stable heart failure. ANCOVAs were performed on the total score and on subscores, with sex, age, and education as covariates. RESULTS: Group differences were observed on the MoCA total score (heart failure < low cardiovascular risk), verbal fluency (heart failure < low cardiovascular risk), memory (coronary heart disease < low cardiovascular risk), and orientation (coronary heart disease < low and high cardiovascular risk) subscores. CONCLUSION: Results suggest that the MoCA, particularly verbal fluency and memory subscores, can detect cognitive changes in later stages of the cardiovascular disease continuum, such as heart failure. Detecting cognitive changes earlier on the cardiovascular disease continuum may require more in depth neuropsychological assessments.

Assessing Splanchnic Compartment Using Portal Venous Doppler and Impact of Adding It to the EVEREST Score for Risk Assessment in Heart Failure.

BACKGROUND: The Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) score has proven useful for risk prediction in acute decompensated heart failure (ADHF). However, this score does not include the characterization of the splanchnic compartment, which has been involved in worsening heart failure. Refining this score by integrating an assessment of the splanchnic compartment would allow for a better risk assessment. Therefore, we aimed to characterize the patterns of portal vein pulsatility (PVP), an ultrasound metric used for the assessment of splanchnic compartment and their determinants in patients with ADHF, to explore the relationships between abnormal patterns of PVP and outcomes, and to evaluate the added value of PVP to the EVEREST score for risk assessment in ADHF. METHODS: Portal vein flow was assessed prospectively on admission and at discharge in 95 patients with ADHF using pulsed-wave Doppler. Abnormal PVP was defined for values ≥ 50%. Cox proportional hazards models were used for the assessment of the relationship between PVP and outcomes. RESULTS: Overall, 64% of patients on admission and 24% at discharge had abnormal PVP. PVP on admission was inversely correlated with right ventricular function (tricuspid annular plane systolic excursion, ρ = -0.434) and pulmonary pressure (ρ = 0.346), P < 0.05. Although PVP was associated with all-cause mortality (hazard ratio, 1.028, P < 0.001), the addition of this metric to the EVEREST score had little effect on its C-index (0.813 vs 0.818) for risk assessment. CONCLUSIONS: Abnormal PVP is frequent and associated with right ventricular dysfunction in ADHF. Although abnormal PVP identifies higher-risk patients, this metric does not improve the performance of the EVEREST score for risk assessment.

CONTEXTE: Le score EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) s'avère utile pour la prévision du risque dans les cas d'insuffisance cardiaque décompensée aiguë (ICDA). Cependant, ce score ne permet pas de caractériser le compartiment splanchnique, impliqué dans l'aggravation de l'insuffisance cardiaque. Affiner ce score en y intégrant une évaluation du compartiment splanchnique permettrait une meilleure évaluation du risque. Par conséquent, nous avons entrepris de caractériser les profils de la pulsatilité du flux de la veine porte (PFVP) (mesure échographique permettant d'évaluer le compartiment splanchnique et ses déterminants dans les cas d'ICDA) afin d'examiner les relations entre les profils anormaux de la PFVP et les résultats, et afin d'évaluer la valeur ajoutée de la PFVP dans l'évaluation du risque faisant appel au score EVEREST chez des patients atteints d'ICDA. MÉTHODOLOGIE: Le flux de la veine porte a été évalué prospectivement par échographie Doppler pulsée à l'admission et à la sortie de 95 patients atteints d'ICDA. La définition d'une PFVP anormale ciblait des valeurs de 50 % ou plus. Des modèles à risques proportionnels de Cox ont servi à évaluer la relation entre la PFVP et les résultats. RÉSULTATS: Globalement, la PFVP était anormale à l'admission chez 64 % des patients et à la sortie chez 24 % des patients. Une corrélation inverse a été notée entre la PFVP à l'admission et la fonction ventriculaire droite (excursion annulaire horizontale systolique de la tricuspide, ρ = -0,434) ainsi que la pression pulmonaire (ρ = -0,346), p < 0,05. Bien que la PFVP ait été associée à la mortalité toutes causes confondues (rapport des risques instantanés de 1,028, p < 0,001), l'ajout de cette mesure au score EVEREST a eu peu d'effet sur son indice C (0,813 vs 0,818) pour l'évaluation du risque. CONCLUSIONS: Une PFVP anormale est d'observation courante et se trouve associée à une dysfonctionn ventriculaire droite dans les cas d'ICDA. Bien qu'une PFVP anormale permette de déceler les patients qui présentent un risque plus élevé, son objectivation n'améliore pas la précision du score EVEREST dans l'évaluation du risque.

Income Inequality and Outcomes in Heart Failure: A Global Between-Country Analysis.

OBJECTIVES: This study examined the relationship between income inequality and heart failure outcomes. BACKGROUND: The income inequality hypothesis postulates that population health is influenced by income distribution within a society, with greater inequality associated with worse outcomes. METHODS: This study analyzed heart failure outcomes in 2 large trials conducted in 54 countries. Countries were divided by tertiles of Gini coefficients (where 0% represented absolute income equality and 100% represented absolute income inequality), and heart failure outcomes were adjusted for standard prognostic variables, country per capita income, education index, hospital bed density, and health worker density. RESULTS: Of the 15,126 patients studied, 5,320 patients lived in Gini coefficient tertile 1 countries (coefficient: <33%), 6,124 patients lived in tertile 2 countries (33% to 41%), and 3,772 patients lived in tertile 3 countries (>41%). Patients in tertile 3 were younger than tertile 1 patients, were more often women, and had less comorbidity and several indicators of less severe heart failure, yet the tertile 3-to-1 hazard ratios (HRs) for the primary composite outcome of cardiovascular death or heart failure hospitalization were 1.57 (95% confidence interval [CI]: 1.38 to 1.79) and 1.48 for all-cause death (95% CI: 1.29 to 1.71) after adjustment for recognized prognostic variables. After additional adjustments were made for per capita income, education index, hospital bed density, and health worker density, these HRs were 1.46 (95% CI: 1.25 to 1.70) and 1.30 (95% CI: 1.10 to 1.53), respectively. CONCLUSIONS: Greater income inequality was associated with worse heart failure outcomes, with an impact similar to those of major comorbidities. Better understanding of the societal and personal bases of these findings may suggest approaches to improve heart failure outcomes.

Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial.

AIMS: To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. METHODS AND RESULTS: Overall, 8399 patients with New York Heart Association class II-IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics (n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post-randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on-treatment analysis. CONCLUSION: Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.

Burden of medical co-morbidities and benefit from surgical revascularization in patients with ischaemic cardiomyopathy.

AIMS: The landmark STICH trial found that surgical revascularization compared to medical therapy alone improved survival in patients with heart failure (HF) of ischaemic aetiology and an ejection fraction (EF) ≤ 35%. However, the interaction between the burden of medical co-morbidities and the benefit from surgical revascularization has not been previously described in patients with ischaemic cardiomyopathy. METHODS AND RESULTS: The STICH trial (ClinicalTrials.gov Identifier: NCT00023595) enrolled patients ≥ 18 years of age with coronary artery disease amenable to coronary artery bypass grafting (CABG) and an EF ≤ 35%. Eligible participants were randomly assigned 1:1 to receive medical therapy (MED) (n = 602) or MED/CABG (n = 610). A modified Charlson co-morbidity index (CCI) based on the availability of data and study definitions was calculated by summing the weighted points for all co-morbid conditions. Patients were divided into mild/moderate (CCI 1-4) and severe (CCI ≥ 5) co-morbidity. Cox proportional hazards models were used to evaluate the association between CCI and outcomes and the interaction between severity of co-morbidity and treatment effect. The study population included 349 patients (29%) with a mild/moderate CCI score and 863 patients (71%) with a severe CCI score. Patients with a severe CCI score had greater functional limitations based on 6-min walk test and impairments in health-related quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire. A total of 161 patients (Kaplan-Meier rate = 50%) with a mild/moderate CCI score and 579 patients (Kaplan-Meier rate = 69%) with a severe CCI score died over a median follow-up of 9.8 years. After adjusting for baseline confounders, patients with a severe CCI score were at higher risk for all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.19-1.74; P < 0.001). There was no interaction between CCI score and treatment effect on survival (P = 0.756). CONCLUSIONS: More than 70% of patients had a severe burden of medical co-morbidities at baseline, which was independently associated with increased risk of death. There was not a differential benefit of surgical revascularization with respect to survival based on severity of co-morbidity.

Cost-effectiveness Analysis of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction.

IMPORTANCE: The angiotensin receptor neprilysin inhibitor sacubitril/valsartan was associated with a reduction in cardiovascular mortality, all-cause mortality, and hospitalizations compared with enalapril. Sacubitril/valsartan has been approved for use in heart failure (HF) with reduced ejection fraction in the United States and cost has been suggested as 1 factor that will influence the use of this agent. OBJECTIVE: To estimate the cost-effectiveness of sacubitril/valsartan vs enalapril in the United States. DESIGN, SETTING, AND PARTICIPANTS: Data from US adults (mean [SD] age, 63.8 [11.5] years) with HF with reduced ejection fraction and characteristics similar to those in the PARADIGM-HF trial were used as inputs for a 2-state Markov model simulated HF. Risks of all-cause mortality and hospitalization from HF or other reasons were estimated with a 30-year time horizon. Quality of life was based on trial EQ-5D scores. Hospital costs combined Medicare and private insurance reimbursement rates; medication costs included the wholesale acquisition cost for sacubitril/valsartan and enalapril. A discount rate of 3% was used. Sensitivity analyses were performed on key inputs including: hospital costs, mortality benefit, hazard ratio for hospitalization reduction, drug costs, and quality-of-life estimates. MAIN OUTCOMES AND MEASURES: Hospitalizations, quality-adjusted life-years (QALYs), costs, and incremental costs per QALY gained. RESULTS: The 2-state Markov model of US adult patients (mean age, 63.8 years) calculated that there would be 220 fewer hospital admissions per 1000 patients with HF treated with sacubitril/valsartan vs enalapril over 30 years. The incremental costs and QALYs gained with sacubitril/valsartan treatment were estimated at $35 512 and 0.78, respectively, compared with enalapril, equating to an incremental cost-effectiveness ratio (ICER) of $45 017 per QALY for the base-case. Sensitivity analyses demonstrated ICERs ranging from $35 357 to $75 301 per QALY. CONCLUSIONS AND RELEVANCE: For eligible patients with HF with reduced ejection fraction, the Markov model calculated that sacubitril/valsartan would increase life expectancy at an ICER consistent with other high-value accepted cardiovascular interventions. Sensitivity analyses demonstrated sacubitril/valsartan would remain cost-effective vs enalapril.

Long-term outcome in men and women after CABG; results from the IMAGINE trial.

BACKGROUND: The aim of this study is to determine sex differences in long-term outcome after coronary artery bypass grafting (CABG). METHODS: The international randomized controlled IMAGINE study included 2553 consecutive patients with a left ventricular ejection fraction of >40% who underwent isolated CABG. Median follow-up was 32 months (IQR 17-42 months). The composite endpoint comprised of death, myocardial infarction (MI), cerebrovascular event, angina, revascularization and congestive heart failure. Cox regression analysis was used to examine sex differences in outcome post-CABG. RESULTS: Of the 2553 patients, 2229 were men and 324 (13%) were women. Women were older and more often reported diabetes and hypertension. Smoking and impaired renal function were more prevalent in men. Women experienced a higher event rate during follow-up (composite endpoint 18% vs 12%; P = 0.007). Cox regression showed an increased risk of the composite endpoint in women after adjustment for age (HR 1.48 (95% CI: 1.11-1.97)) which was non-significant after additional adjustment for other confounders (HR 1.26 (95% CI: 0.92-1.72)). CONCLUSION: Women have a worse long-term outcome after CABG than men in univariate analysis. However, after adjusting for potential confounders female sex became a non-significant predictor for prognosis, possibly due to the small sample size of women. Definite answers regarding sex-differences in long-term outcome after CABG should come from future pooling of studies comprising a larger number of women.

Atrial fibrillation in heart failure: drug therapies for rate and rhythm control.

Pharmacological treatment of atrial fibrillation in the context of heart failure poses numerous challenges. Management decisions are limited by contraindications to several drugs and the paucity of robust clinical trials that provide evidence-based guidance. This review proposes a structured action plan for managing atrial fibrillation coexisting with heart failure that considers published clinical guidelines and integrates recent data derived from substudies of randomized trials, including the atrial fibrillation and congestive heart failure (AF-CHF) trial. Areas of uncertainty, such as target heart rates in atrial fibrillation and upstream therapies, are also discussed.

Incremental value of echocardiographic assessment beyond clinical evaluation for prediction of death and development of heart failure after high-risk myocardial infarction.

BACKGROUND: Echocardiographic measurements of left ventricular (LV) function, predominantly LV ejection fraction (LVEF), have been used to define risk in patients after myocardial infarction. However, the extent to which measures of LV structure and function provide incremental prognostic value over clinical variables in survivors of high-risk myocardial infarction has not been well defined. METHODS: Predictors of death and development of heart failure were assessed in 603 patients from the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiographic substudy. We used multivariable proportional hazards models to assess the individual predictive value of echocardiographic measures including left ventricular mass index, LVEF, LV volumes, left atrial volume index, right ventricular fractional area change, mitral regurgitation, and deceleration time. We adjusted for the 11 clinical variables found previously to be most associated with all-cause mortality in this cohort. Receiver operating characteristic curves obtained via binary response regression were used to assess the incremental predictive value of echocardiographic measures in predicting outcomes of death and hospital stay for heart failure. RESULTS: Each echocardiographic measure was independently associated with outcome of death or development of heart failure (all P < .002). Left ventricular ejection fraction alone added minimal prognostic value to the clinical assessment, yet adding additional echocardiographic assessments to a multivariable model improved in predicting 17-month survival free of heart failure significantly, increasing the c-statistic from 0.74 to 0.84 (P < .001). CONCLUSION: Echocardiographic measures of cardiac structure and function beyond LVEF provide important prognostic information beyond the clinical assessment.

CSCI/RCPSC HENRY FRIESEN LECTURE: Clinical research in Canada: the dawn of a new era?

In response to the growing gap between discovery and the optimal application of medical advancements to health care delivery, countries the world over have developed large and well funded programs to reduce these gaps. Although these programs vary in nature, they have generally largely focused more on reducing the gap in bench to bedside research. Canada's strong biomedical and patient oriented research (POR) community has a strong base from which to build, but requires support in order to fill the missing elements needed to take full advantage of the important unmet needs in health related research. In Canada, a coalition of funders of medical research, led by the Canadian Institutes for Health Research (CIHR) is developing a large and comprehensive program to build a Canadian infrastructure that will provide these missing elements, and further strengthen POR in Canada. This coalition proposes to put particular emphasis on bedside to community POR, including phase 3 clinical trials, to take advantage of and improve the sustainability of Canada's unique universal health care system. The major initiatives in POR developed by so many countries, including Canada clearly heralds a new era in clinical research, one that the Canadian research community needs to take full advantage of.

Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program.

BACKGROUND: Atrial fibrillation (AF) is frequent in patients with chronic heart failure (CHF). Experimental and small patient studies have demonstrated that blocking the renin-angiotensin-aldosterone system may prevent AF. In the CHARM program, the effects of the angiotensin receptor blocker candesartan on cardiovascular mortality and morbidity were evaluated in a broad spectrum of patients with symptomatic CHF. CHARM provided the opportunity to prospectively determine the effect of candesartan on the incidence of new AF in this CHF population. METHODS: 7601 patients with symptomatic CHF and reduced or preserved left ventricular systolic function were randomized to candesartan (target dose 32 mg once daily, mean dose 24 mg) or placebo in the 3 component trials of CHARM. The major outcomes were cardiovascular death or CHF hospitalization and all-cause mortality. The incidence of new AF was a prespecified secondary outcome. Median follow-up was 37.7 months. A conditional logistic regression model for stratified data was used. RESULTS: 6379 patients (83.9%) did not have AF on their baseline electrocardiogram. Of these, 392 (6.15%) developed AF during follow-up, 177 (5.55%) in the candesartan group and 215 (6.74%) in the placebo group (odds ratio 0.812, 95% CI 0.662-0.998, P = .048). After adjustment for baseline covariates, the odds ratio was 0.802 (95% CI 0.650-0.990, P = .039). There was no heterogeneity of the effects of candesartan in preventing AF between the 3 component trials (P = .57). CONCLUSIONS: Treatment with the angiotensin receptor blocker candesartan reduced the incidence of AF in a large, broadly-based, population of patients with symptomatic CHF.

Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: assessment of Reduction in Mortality and morbidity (CHARM) program.

BACKGROUND: Atrial fibrillation (AF) is frequent in patients with chronic heart failure (CHF). Experimental and small patient studies have demonstrated that blocking the renin-angiotensin-aldosterone system may prevent AF. In the CHARM program, the effects of the angiotensin receptor blocker candesartan on cardiovascular mortality and morbidity were evaluated in a broad spectrum of patients with symptomatic CHF. CHARM provided the opportunity to prospectively determine the effect of candesartan on the incidence of new AF in this CHF population. METHODS: 7601 patients with symptomatic CHF and reduced or preserved left ventricular systolic function were randomized to candesartan (target dose 32 mg once daily, mean dose 24 mg) or placebo in the 3 component trials of CHARM. The major outcomes were cardiovascular death or CHF hospitalization and all-cause mortality. The incidence of new AF was a prespecified secondary outcome. Median follow-up was 37.7 months. A conditional logistic regression model for stratified data was used. RESULTS: 6446 patients (84.8%) did not have AF on their baseline electrocardiogram. Of these, 392 (6.08%) developed AF during follow-up, 177 (5.55%) in the candesartan group and 215 (6.74%) in the placebo group (odds ratio 0.812, 95% CI 0.662-0.998, P = .048). After adjustment for baseline covariates, the odds ratio was 0.802 (95% CI 0.650-0.990, P = .039). There was no heterogeneity of the effects of candesartan in preventing AF between the 3 component trials (P = .57). CONCLUSIONS: Treatment with the angiotensin receptor blocker candesartan reduced the incidence of AF in a large, broadly-based, population of patients with symptomatic CHF.

The cost of acute myocardial infarction in the new millennium: evidence from a multinational registry.

BACKGROUND: Although geographic variation in the treatment of acute myocardial infarction (AMI) has been recognized, the impact of evidence-based international treatment guidelines on such variation is unclear. We sought to characterize resource use and cost of initial hospitalization for AMI in 9 countries and compare the contribution of length of stay (LOS) and procedure use to cost. METHODS: We applied country-specific cost estimates to data from the international AMI registry associated with the VALIANT trial. The registry includes demographic, medical history, treatment, and discharge information for 5573 patients with AMI admitted to 84 sites in 9 countries from November 1999 to June 2001. Hospitalization cost was estimated by imputed discharge diagnosis-related group code and adjusted for the LOS and procedures. Generalized linear regression was used to adjust cost by country; the contribution of LOS and procedures to cost was assessed by ordinary least squares regression. RESULTS: Unadjusted mean cost for initial AMI hospitalization was 9993 dollars (95% CI 9702 dollars-10,228 dollars). After adjustment for baseline patient-level variation, the lowest average cost was 1605 dollars (Argentina) and the highest was 9196 dollars (United States). Length of stay explained more of the variation in cost (50.7%) than did procedure intensity (31.9%). CONCLUSIONS: International differences in the cost of AMI persist, reflecting variations in procedure use and especially LOS. Relative differences in resource costs and incentives inherent in the provision and financing of health care likely contribute to treatment and cost variation and limit the widespread adoption of international practice guidelines.

Left ventricular assessment in myocardial infarction: the VALIANT registry.

BACKGROUND: How often echocardiography and cardiac catheterization are used to evaluate left ventricular (LV) function in patients with myocardial infarction (MI) and how they are associated with quality of care is unknown. METHODS: Patients with MI in the Valsartan in Acute Myocardial Infarction (VALIANT) registry were divided into those with (n = 1423) and without (n = 3968) heart failure (HF), and the use of either echocardiography or cardiac catheterization for LV assessment in each group was compared along with associated baseline characteristics. We evaluated the association between LV assessment and discharge medications. Using a multivariable model with a propensity analysis, we evaluated the association of LV assessment with in-hospital outcomes. RESULTS: Of the patients with HF, 322 (22.6%) had no LV assessment. Patients with HF with LV assessment were discharged more frequently under treatment with aspirin (81.3% vs 70.0%; P<.001), beta-blockers (65.6% vs 56.4%; P = .008), clopidogrel (30.4% vs 14.0%; P<.001), and statins (45.9% vs 34.2%; P<.001). Patients without HF who underwent LV assessment were discharged more frequently under treatment with an angiotensin-converting enzyme inhibitor (53.8% vs 41.5%; P<.001). After adjustment for regional use, other covariates, and revascularization, LV assessment was associated with lower in-hospital mortality in patients with HF (adjusted odds ratio [OR], 0.45; P<.001) and in patients without HF (adjusted OR, 0.30; P<.001). After excluding deaths during the first 2 days, LV assessment remained associated with lower mortality in patients with HF (adjusted OR, 0.59; P = .03) and in patients without HF (adjusted OR, 0.41; P<.001). CONCLUSION: Left ventricular assessment was frequently not performed during the in-hospital stay of patients with acute MI, including those with clinical HF, and its use was associated with better quality of care.

Treatment of congestive heart failure: present and future.

The treatment of patients with congestive heart failure has markedly improved over the past 25 years. The most successful therapy has been attenuation of neurohumoral overactivation with antagonists of the renin-angiotensin-aldosterone system, as well as beta-adrenergic blockade. Cardiac surgical interventions, which include not only aortocoronary artery bypass surgery but also interventions that remodel the heart and repair the mitral valve, have also been advocated. However, randomized clinical trials to prove their benefit and to identify which patients could derive the most benefit from these interventions are lacking. Cardiac devices, such as biventricular pacemakers (for cardiac resynchronization) and implantable cardiac defibrillators, have proved useful in improving survival and quality of life. The treatment of sleep apnea with continuous positive airway pressure has shown some promise, as has immune modulation therapy, but more research to conclusively prove their efficacy is necessary. Cell therapy with skeletal myoblasts or pluripotential stem cells is an interesting and emerging area of research that shows enormous promise. However, fundamental questions regarding the optimal use of this therapy remain unanswered. Finally, although exciting, these developments, along with the changing demographics of the Canadian population, will require a change in the way we provide care for patients with congestive heart failure. These changes will require greater involvement of health care professionals other than physicians, and greater emphasis on outpatient care, early detection and prevention, and evidence-based practice.

Comparison of coding of heart failure and comorbidities in administrative and clinical data for use in outcomes research.

BACKGROUND: Despite the potential usefulness of administrative databases for evaluating outcomes, coding of heart failure and associated comorbidities have not been definitively compared with clinical data. OBJECTIVE: To compare the predictive value of heart failure diagnoses and secondary conditions identified in a large administrative database with chart-based records. METHODS: The authors studied 1808 patient records sampled from 14 acute care hospitals and compared clinically recorded data with administrative records from the Canadian Institute for Health Information. The impact of comorbidity coding in the administrative data set according to the Charlson classification was examined in models of 30-day mortality. RESULTS: The positive predictive value (PPV) of a primary diagnosis ICD-9 428 was 94.3% using the Framingham criteria and 88.6% using criteria previously validated with pulmonary capillary wedge pressure. There was reduced prevalence of secondary comorbid conditions in administrative data in comparison with clinical chart data. The specificities and PPV/negative predictive values of administratively identified index comorbidities were high. The sensitivities of index comorbidities were low, but were enhanced by examination of hospitalizations within 1 year prior to the index heart failure admission. Using information from prior hospitalizations modestly enhanced 30-day mortality model performance; however, the odds ratio point estimates of the index and enhanced administrative data sets were consistent with the clinical model. CONCLUSION: The ICD-9 428 primary diagnosis is highly predictive of heart failure using clinical criteria. Examination of hospitalization data up to 1 year prior to the index admission improves comorbidity detection and may provide enhancements to future studies of heart failure mortality.